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Chemical Structure| 133627-45-9 Chemical Structure| 133627-45-9

Structure of 133627-45-9

Chemical Structure| 133627-45-9

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CAS No.: 133627-45-9

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Product Details of [ 133627-45-9 ]

CAS No. :133627-45-9
Formula : C6H7ClN2
M.W : 142.59
SMILES Code : C1=C(C(=C(N=C1)Cl)N)C
MDL No. :MFCD00673152
InChI Key :UOBCYTOUXLAABU-UHFFFAOYSA-N
Pubchem ID :2756387

Safety of [ 133627-45-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P337+P313-P301+P312+P330

Computational Chemistry of [ 133627-45-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 6
Fraction Csp3 0.17
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 38.62
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

38.91 ?2

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.45
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.5
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

1.63
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

0.75
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

1.74
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.42

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.16
Solubility 0.981 mg/ml ; 0.00688 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.92
Solubility 1.7 mg/ml ; 0.0119 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-2.64
Solubility 0.324 mg/ml ; 0.00227 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

 High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

 Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

 No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

 No
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

 No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

 No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

 No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

 No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.1 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

 0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

 None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

 0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

 0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

 1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

 No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

 1.54

Application In Synthesis of [ 133627-45-9 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 133627-45-9 ]

[ 133627-45-9 ] Synthesis Path-Downstream   1~33

  • 1
  • [ 49609-84-9 ]
  • [ 133627-45-9 ]
  • [ 133627-46-0 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In ethyl acetate; at 75 - 80℃; for 14h;Product distribution / selectivity; Example-3: Preparation of 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3 -pyridine carboxamide (V) [utilizing ethyl acetate as solvent during acylation]2-Chloro nicotinic acid (1.33kg; 8.44moles) was added to toluene (S.Olitres) and thionyl chloride (0.75 litres; 10.42 moles) and dimethyl formamide (100ml; 0.18moles) were added and the mixture refluxed at 80C-90C till completion of reaction. The reaction mixture was concentrated under reduced pressure and cooled between 25C and 300C. Ethyl acetate (8.0 litres) was added to the mixture followed by potassium carbonate (2.0kg; 15.15 moles). 3-Amino-2-chloro-4-methyl pyridine of formula (IIotaI).was dissolved in ethyl acetate and added to the acid chloride (IV). The mixture was refluxed at 75C to 8O0C for 14 hours. The reaction mixture was concentrated after completion of the reaction and water (5.0 litres) was added. The reaction mass was cooled between 10-150C, filtered and dried between 600C and 700C under reduced pressure..Yield: 1.73 kg. % Yield: 87.80%. HPLC Purity: 99.9%.
With potassium carbonate; In toluene; at 75 - 80℃; for 14h;Product distribution / selectivity; Example-4: Preparation of 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3 -pyridine carboxamide (V) [utilizing toluene as solvent and potassium carbonate as inorganic base during acylation]2-Chloro nicotinic acid (1.33kg; 8.44moles) was added to toluene (5.01itres) and thionyl chloride (0.75 litres; 10.42 moles) and dimethyl formamide (100ml; 0.18moles) were added and the mixture refluxed at 800C -9O0C till completion of reaction. The reaction EPO <DP n="20"/>mixture was concentrated under reduced pressure and cooled between 25C and 300C. Toluene (8.0 litres) was added to the residue containing compound (IV), followed by addition of potassium carbonate (2.0kg; 15.15 moles). 3-Amino-2-chloro-4-methyl pyridine of formula (III) dissolved in toluene was added to the acid chloride (IV). The mixture was refluxed at 750C to 800C for 14 hours. The reaction mixture was concentrated after completion of the reaction and quenched with water (5.0 litres). The reaction mass was cooled between 10-150C and filtered.Yield: 1.73 kg. % Yield: 87.80%. HPLC Purity: 99.9%.
With triethylamine; In toluene; at 25 - 32℃;Product distribution / selectivity; Example-5: Preparation of 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3 -pyridine carboxamide (V) [utilizing toluene as solvent during acylation and triethyl amine as organic base]2-Chloro nicotinic acid (1.33kg; 8.44moles) was added to toluene (5.01itres) and thionyl chloride (0.75 litres; 10.42 moles) and dimethyl formamide (100ml; 0.18moles) were added and the mixture refluxed at 800C -9O0C till completion of reaction. The reaction mixture was concentrated under reduced pressure. Toluene (8.0 litres) was added to the mixture. 3-Amino-2-chloro-4-methyl pyridine of formula (III) dissolved in toluene was added to the acid chloride (IV) and triethyl amine was added to the reaction mixture to adjust pH. The mixture was stirred at 250C to 32C. Impurity formation up to 30-40% was formed in the reaction mixture, therefore, the reaction was not worked up for isolation of compound (V).
With pyridine; In 1,4-dioxane; cyclohexane; at 25 - 32℃; for 2.5h;Product distribution / selectivity; Example 6: Preparation of 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridine carboxamide (V) [utilizing toluene as solvent during acylation and pyridine as organic base]2-Chloro nicotinic acid (41.5gms; 0.263moles) was added to toluene (125ml) and thionyl chloride (19ml; 0.26moles) and dimethyl formamide (2.5ml; 0.005moles) were added and the mixture refluxed at 800C -900C till completion of reaction. The reaction mixture was concentrated under reduced pressure and the residue diluted with dioxane (55ml). Pyridine (62.5ml; 0.77moles) was added to a mixture of 3-Amino-2-chloro-4-methyl pyridine of formula (111) stirred in cyclohexane (62.5ml). The acid chloride (IV) mixture in dioxane, EPO <DP n="21"/>was added to the mixture containing (III) and stirred for 2.5 hours at 25C to 32C. TLC monitoring of the reaction mixture showed lot of impurities. The solid separating out was filtered washed with cyclohexane. Compound (V) was dissolved in acetone (300ml), refiuxed, and concentrated to 50ml. The mixture was cooled between 5 and 100C, filtered and dried.Yield: 32gms % Yield: 64.9%.
With N,N-dimethyl-aniline; In toluene; at 25 - 40℃; for 2.5h;Product distribution / selectivity; Example 11: Preparation of 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridine carboxamide (V) [utilizing toluene as solvent and N,N-dimethyl aniline as organic base during acylation]2-Chloro nicotinic acid (165.75gms; 1.057moles) was added to toluene (542gms) and thionyl chloride (56.40gms; 0.477moles) and dimethyl formamide (5.9gms; 0.080moles) were added and the mixture refluxed at 80C-90C till completion of reaction. The reaction mixture was concentrated under reduced pressure and the residue diluted with toluene (542gms). 3-Amino-2-chloro-4-methyl pyridine (125gms; 0.877moles) of formula (III) was added to the mixture containing compound of formula (IV) at ambient temperature followed by addition of N,N-dimethyl aniline (127.12gms; 1.05moles). The reaction mixture was stirred for 2.5 hours at 250C to 4O0C. After completion of reaction, the reaction mixture was cooled to ambient temperature and neutralized with 10% sodium carbonate solution to pH 7.0 to 7.5. The solid separating out was filtered, washed with toluene and dried. Yield: 220-230 gms % Yield: 89-93%. Purity: 99%
With pyridine; In 1,4-dioxane; cyclohexane; at 20℃; for 48h;Product distribution / selectivity; 2-Chloro-N-(2-chloro-4-methyl-pyridin-3-yl)-nicotinamide: The procedure is carried out as described in Hargrave J. Med. Chem. 1991, 34, 2231-2241, which is hereby incorporated by reference in its entirety. To a solution of <strong>[133627-45-9]3-amino-2-chloro-4-methylpyridine</strong> (18.2 mmol) in 6:1 cyclohexane-dioxane (6 mL), and pyridine (5.75 mL) is added a solution of 2-chloronicotinoyl chloride (12.8 mmol) in 1,4-dioxane (5 mL). The resulting mixture is stirred at ambient temperature for 48 hours and the precipitate is filtered and washed with water. The solid is taken up in ethanol (17.5 mL) and aqueous NaOH (0.1 N, 3.6 mL). The solution is then heated to reflux for 2 hours, cooled to ambient temperature and stirred overnight. The solvent is removed under vacuum and water (10 mL) is added to residue, with stirring. The mixture is cooled to 1OC and the crystalline product is filtered, washed with cold water and dried under vacuum to give the desired product, 2-chloro-N-(2-chloro-4-methyl-pyridin-3-yl)-nicotinamide.
With pyridine; In acetonitrile; at 20 - 45℃;Product distribution / selectivity; Step 3[00287] 2-Chloro-N-(2-chloro-4-methyl-pyridin-3-ylVnicotinamide: Pyridine (125 g, 1.58 mol, 1.10 equiv) was added to a solution of 2-chloro-4-methyl-pyridin-3-ylamine (204.6 g, 1.44 mol, 1.00 equiv) in acetonitrile (1500 ml) in a 2 liter 3 -necked round-bottom flask. 2- chloronicotinoyl chloride (270 g, 1.54 mol, 1.07 equiv) was added dropwise to the solution while maintaining the temperature at 20 C. The solution was allowed to react overnight while maintaining the temperature at 45 C in an oil bath. The solution was then diluted with water (2 L) and sodium carbonate was added till the pH of the solution reached 8. The solution was filtered, the filter cake was washed with water (100mLx3), and the filter cake was dissolved in tetrahydrofuran (3 L). The solution was decolorized by the addition of active carbon, and then filtered. The filtrate was then dried over sodium sulfate, concentrated in vacuo using a rotary evaporator. The product of 2-chloro-lambda/-(2-chloro-4-methyl-pyridin-3-yl) nicotinamide (32Og, purity: 94%, yield:79%) was obtained as a light red solid. The material was used in next step without further purification.

  • 2
  • [ 23056-39-5 ]
  • [ 133627-45-9 ]
YieldReaction ConditionsOperation in experiment
90.79% Example-1 : Preparation of 3-Aniino-2-chloro-4-methyl pyridine of formula (III)First method: Reduction with Iron in acetic acid.2-Chloro-3-nitro-4-methylpyridine (II; lOOOgm, 5.75moles), was dissolved in acetic acid(10 litres) and heated to 700C -8O0C. Iron (750gm, 13.42moles) was added and the temperature maintained at 700C to 8O0C. After completion of reaction, the reaction mixture was concentrated under reduced pressure. The residual mass was diluted with water (5 litres). The pH of the aqueous layer was adjusted between 8.0-8.5 by addition of aqueous sodium carbonate solution and organic layer was separated. The aqueous layer was washed with ethyl acetate (2 litres). The organic layer after optional charcoal treatment was concentrated under reduced pressure to give 3-Amino-2-chloro-4-methyl pyridine of formula (III).Yield: 750gm %Yield: 90.79% HPLC purity: 99.25%.
90.1 - 96.7% Example 12: Preparation of 3-Amino-2-chloro-4-methyl pyridine of formula (III)First method: Reduction of 2-chloro-3-nitro-4-methyl pyridine with Iron and hydrochloric acid in an aqueous medium.2-Chloro-3-nitro-4-methylpyridine (II; lOOgm, 0.579moles), was suspended in methanol (1000 ml). Hydrochloric acid (550ml; 15.06 moles ) was added to the mixture and heated to 65C. Iron (195gms, 3.49moles) was added and the temperature maintained at 65C. The reaction mixture was monitored by thin layered chromatography and after completion of reaction; the reaction mixture was cooled to ambient temperature. Ethyl acetate was EPO <DP n="24"/>added to the reaction mixture and stirred. The organic layer was separated and concentrated. 3-Amino-2-chloro-4-methyl pyridine of formula (III) thus obtained was dried.Yield: 74.4gms~79.9gms %Yield: 90.1-96.7% HPLC purity: 99%.
90.7 - 96.8% Example 10: Preparation of 3-Amino-2-chloro-4-methyl pyridine of formula (III)First method: Reduction of 2-chloro-3-nitro-4-methyl pyridine with Iron and phosphoric acid in an aqueous medium.2-Chloro-3-nitro-4-methylpyridine (II; 2000gm, 11.59moles), was suspended in water (20 litres). Orthophosphoric acid (4.545kg; 46,36 moles ) was added to the mixture and heated between 70C-80C. Iron (1813 gms, 32.45moles) was added and the temperature maintained at 700C to 800C. The reaction mixture was monitored by thin layered chromatography and after completion of reaction; the reaction mixture was cooled to ambient temperature. Ethyl acetate was added to the reaction mixture and stirred. The EPO <DP n="23"/>organic layer was separated and concentrated. Cyclohexane (3.116 kg) was added to the residue with stirring and the resulting mixture after stirring at 10-150C for 60 minutes was filtered, washed with cyclohexane and dried to give 3-Amino-2-chloro-4-methyl pyridine of formula (III). Yield: 15 OOgms to 1600gms %Yield: 90.7 to 96.8% HPLC purity: 99%.
72.60% With sodium dithionite; In methanol; water; at 70 - 80℃;Product distribution / selectivity; Example-2: Preparation of 3-Amino-2-chloro-4-methyl pyridine of formula (III) EPO <DP n="19"/>Second method: Reduction with sodium dithionite2-Chloro-3-nitro-4-methylpyridine (II; lOOgm, 0.575moles), was dissolved in methanol (1000 ml) and heated to 70C-80C. Sodium dithionite (300gm, 1.725moles) dissolved in water (1000 ml) was added gradually to the reaction mixture and the temperature maintained at 700C to 8O0C. After completion of reaction, the reaction mixture was concentrated under reduced pressure, residue extracted with ethyl acetate (1000 ml) and the separated organic layer was then concentrated under reduced pressure to give 3-Amino-2-chloro-4-methyl pyridine of formula (III). Yield: 60gm % Yield: 72.60%HPLC purity: 99.25%.

  • 3
  • [ 108-24-7 ]
  • [ 133627-45-9 ]
  • [ 76006-00-3 ]
  • 4
  • [ 3430-27-1 ]
  • [ 133627-45-9 ]
YieldReaction ConditionsOperation in experiment
83.2% First, 21.6 g of 3-amino-4-methylpyridine was added to the reaction kettle,In the cold water bath slowly dropping 72mL concentrated hydrochloric acid,Stirring to clarify after warming to 40 C, 30 ~ 60min slowly dropping 30mL 30% hydrogen peroxide, temperature control reaction 2h.After completion of the reaction, the system rhoEta = 3 was adjusted with 45% sodium hydroxide solution, extracted with trichloromethane, dried and removed to obtain the crude product. Recrystallization from petroleum ether or n-hexane gave white or pale yellow needle-like crystals of 2-chloro-3-amino-4-methylpyridine with a purity of 99.0%, a yield of 83.2%
78% Step 2[00286] 2-chloro-4-methyl-pyridin-3 -ylamine : A solution of 4-methylpyridin-3 -amine(200 g, 1.85 mol, 1.00 equiv) in concentrated hydrochloric acid (3 L) was placed in a 5 L 3- necked round-bottom flask. Hydrogen peroxide (30%) (210 g, 1.85 mol, 1.00 equiv) was added dropwise to the solution while maintaining the temperature at 20 C. The resulting solution was allowed to react overnight at ambient temperature. Saturated aqueous sodium carbonate was added to the solution, till a pH of 8 was reached. The solution was filtered, and the filter cake was washed with water (100 ml x3). The filter cake was dissolved in ethyl acetate (300OmL) and dried over sodium sulfate. The solution was filtered, and the filtrate was concentrated in vacuo <n="74"/>using a rotary evaporator. The product (204.6 g, purity: 90%, yield:78%) of 2-chloro-4-methyl- pyridin-3-ylamine was obtained as a light red solid. The material was used in next step without further purification.
With hydrogenchloride; sodium hydroxide; chlorine; In water; F) Preparation of 3-amino-2-chloro-4-methylpyridine STR16 3-Amino-4-methylpyridine (21.6g, 0.2 mole) was suspended in 75 ml of water at room temperature. The mixture was dissolved by the addition of 25 ml conc. hydrochloric acid. The solution was cooled to 20 C. and 15.6 g (0.22 mole) of chlorine gas was introduced through an inlet tube reaching below the surface of the reaction mixture over 25 minutes. The mixture was stirred under a nitrogen purge for an additional 30 minutes, then cooled to 10 C. and basified by the addition of 70 mL of a 12.5 N. sodium hydroxide solution. Additional water (100 mL) was added to maintain efficient agitation of the mixture. The precipitate was collected, washed with water and dried to give 14.5g of the title product. The aqueous phase was extracted with 3 times 100 mL of methylene chloride. The organic phases were washed with water, dried over magnesium sulfate, and concentrated to give an additional 9.4g, mp 62-64
23.9 g (84%) With hydrogenchloride; sodium hydroxide; chlorine; In water; F) Preparation of 3-Amino-2-Chloro-4-Methylpyridine STR16 3-Amino-4-methylpyridine (21.6 g, 0.2 mole) was suspended in 75 ml of water at room temperature. The mixture was dissolved by the addition of 25 ml conc. hydrochloric acid. The solution was cooled to 20 C. and 15.6 g (0.22 mole) of chlorine gas was introduced through an inlet tube reaching below the surface of the reaction mixture over 25 minutes. The mixture was stirred under a nitrogen purge for an additional 30 minutes, then cooled to 10 C. and basified by the addition of 70 mL of a 12.5 N. sodium hydroxide solution. Additional water (100 mL) was added to maintain efficient agitation of the mixture. The precipitate was collected, washed with water and dried to give 14.5 g of the title product. The aqueous phase was extracted with 3 times 100 mL of methylene chloride. The organic phases were washed with water, dried over magnesium sulfate, and concentrated to give an additional 9.4 g, mp 62-64 C. Total yield, 23.9 g (84%).
With hydrogenchloride; dihydrogen peroxide; In water; at 0 - 20℃; for 1h; 62c) 2-chloro-4-methylpyridin-3-amine A mixture of 4-methylpyridin-3-amine (0.62 g), 12N hydrogen chloride (3.8 mL) and 30% hydrogen peroxide (0.75 mL) was stirred at 0 C. to room temperature for 1 h. The mixture was neutralized with K2CO3, and the mixture was extracted with AcOEt. The organic layer was dried over MgSO4, and concentrated in vacuo to give 2-chloro-4-methylpyridin-3-amine (0.75 g) as an orange solid.MS (API+): [M+H]+ 143.1.

  • 5
  • [ 152362-01-1 ]
  • [ 133627-45-9 ]
YieldReaction ConditionsOperation in experiment
98% With sodium hypobromide; bromine; sodium hydroxide; In water; at 65 - 75℃; for 4h; Bromine (1.6 g) was added to a solution of sodium hydroxide (1.6 g) in fresh water or sea water (11.8 g) at 0-5C. 2-Chloro-4-methyl nicotinamide (1.7 g) was added to cold sodium hypobromite solution in 1.5 h. The ice bath was removed, and the reaction mixture was allowed to warm to room temperature. The resulting yellow solution was heated to 65C for 2 h, and warmed to 75C for 2 h. When the solution cooled to room temperature, the product was extracted three times with chloroform (30 mL). The combined extract was dried over anhydrous sodium sulfate, filtered, and concentrated to a solid. Recrystallization with n-hexane yielded a coarse white crystal product. The product yield using zinc powder-treated sea water as raw material was 98%, mp 70-71C. (Literature [7]: Yield 92.3%, mp 69-70C). The synthesis route of 3-amino-2-chloro-4-methylpyridine is shown in Scheme 2.
96.9% With bromine; sodium hydroxide; In water; toluene; at 0 - 60℃; 1. COMAD (10,3 g) was added to a 3-neck flask fitted with a thermocouple, a dropping funnel, and a heating and cooling system.2. Water (15 g) was added to the reactor and the suspension was agitated.3. The mixture was cooled to 0-5C.4. The NaOBr solution of vessel I was added to the COMAD suspension in vessel 2 slowly while maintaining the temperature between 0-5C.5. Afier charging was complete, the temperature of the reaction mixture was held at0-5C for 15-20 minutes. A clear yellow solution resulted; no solid or suspension was formed.6. The reactor contents were allowed to warm to 15C and were held at this temperature for 15-20 minutes.7. The reaction mixture was heated to 25C and maintained at a temperature between22-25C for 1.5 hours, or until the evolution of heat subsided.8. 10 ml of water was added to the reaction mixture which was then heated to 80C and held for 1 hour.9. The reaction mixture was then cooled to 50-60C and toluene (21.62 g) was added; the mixture was agitated for 15-20 minutes.10. The top organic layer was separated.11. Toluene (10.3 g) was added to the aqueous layer and the mixture was agitated for15-20 minutes. The agitation was stopped and the top organic layer was separated.12. The organic layers were combined and washed with water (10 g) and the water layer was decanted.13. Toluene (25.0 g) was removed via distillation under reduced pressure.14. The reactor temperature was adjusted to 55-60C and hexane (6.5 g) was added slowly with agitation over 15 minutes. The solution because cloudy and a white precipitate started to appear.15. The mixture was cooled slowly to room temperature and then to 0-5C.16. The mixture was held at 0-5C for 1 hour.17. The solid precipitate was retrieved by filtered and washed once with hexanes (6.6 g).18. The product was dried under vacuo at 25C to a constant weight.In an exemplary synthesis, the isolated yield was 8.34 g (96.9%) of off white to white crystalline product.
90.6% With sodium hydroxide; bromine; In water; at 0 - 75℃; for 3h; Example 11 Synthesis of 3-amino-2-chloro-4-methylpyridine (1) A solution of 11.7g (0.293 mole) of sodium hydroxide in 11 ML of water was stirred and cooled to 0C. bromine 14.2g (0.293 mole) was added dropwise maintaining the temperature at 0C. To a pale yellow solution was added 13.2g (0.077 mole) of 2-Chloro-4-methylnicotinamide (10) in portions at 0-5C. The ice-bath was removed and the reaction mixture warmed to 75C over one hour and maintained at 60-75C for an additional 2 hours.. The mixture was cooled overnight and the crystalline product collected by filtration to give 10g (90.6%) of the title compound [mp: 62-64C]. NMR and MS was identical to data reported by Hargrave, et al., J. Heterocyclic Chem., 34, 223 (1991).
90.6% Example 6 Synthesis of 3-amino-2-chloro-4-methylpyridine (1) A solution of 11.7g (0.293 mole) of sodium hydroxide in 11 mL of water was stirred and cooled to 0C. Bromine 14.2g (0.293 mole) was added dropwise maintaining the temperature at '0C. To a pale yellow solution was added 13.2g (0.077 mole) of 2-chloro-4-methylpyridine-3-carboxamide (9) in portions at 0-5C. The ice-bath was removed and the reaction mixture warmed to 75C over one hour and maintained at 60-75C for an additional 2 hours. The mixture was cooled overnight and the crystalline product collected by filtration to give 10g (90.6%) of the title compound [mp: 62-64C]. NMR and MS was identical to data reported by Hargrave et al., J. Heterocyclic Chem., 34, 223 (1991).
10 g (90.6%) With sodium hydroxide; bromine; In water; EXAMPLE 6 Synthesis of 3-amino-2-chloro-4-methylpyridine (1) A solution of 11.7 g (0.293 mole) of sodium hydroxide in 11 mL of water was stirred and cooled to 0 C. Bromine 14.2 g (0.293 mole) was added dropwise maintaining the temperature at 0 C. To a pale yellow solution was added 13.2 g (0.077 mole) of 2-chloro-4-methylpyridine-3-carboxamide (9) in portions at 0-5 C. The ice-bath was removed and the reaction mixture warmed to 75 C. over one hour and maintained at 60-75 C. for an additional 2 hours. The mixture was cooled overnight and the crystalline product collected by filtration to give 10 g (90.6%) of the title compound [mp: 62-64 C.]. NMR and MS was identical to data reported by Hargrave et al., J. Heterocyclic Chem., 34, 223 (1991).
41.5 g With calcium hypochlorite; calcium oxide; In water; at 10℃; To the above mixture, 61.5 g of calcium hypochlorite was added in portions,After the addition was complete, the heat was kept stirring for 30 minutes,50 mL of an aqueous solution of 40 wt% calcium oxide was further added in portions,Control temperature does not exceed 10 ,The reaction was continued for 2 to 3 hours to obtain a reaction mixture.The resulting cold reaction mixture was added dropwise to water (150 mL)Control temperature of 100 degrees or less; dropping finished,70 ~ 80 C to continue the reaction 2 hours; cooling to 5 C,With concentrated hydrochloric acid adjusted pH value of 6.5 to 7; suction filtration,The filter cake was washed with ice water; the filter cake was added to 75 mL of water,Heated to 60 to 70 C, stirred for 30 minutes,Slowly cooled to 0 ~ 5 , the precipitation of crystals, filtration,The filter cake was washed with ice water, dried in vacuo,To obtain 41.5 g of 2-chloro-3-amino-4-methylpyridine,HPLC purity was 99.9%.

  • 7
  • [ 133627-45-9 ]
  • (Z)-ethyl 3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyano-3-isopropylaminoacrylate [ No CAS ]
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  • [ 133627-45-9 ]
  • (Z)-ethyl 3-(2-chloro-4-methylpyridin-3-ylamino)-3-propylamino-2-cyanoacrylate [ No CAS ]
  • 9
  • [ 133627-45-9 ]
  • (Z)-ethyl 3-butylamino-3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyanoacrylate [ No CAS ]
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  • [ 133627-45-9 ]
  • (Z)-ethyl 3-benzylamino-3-(2-chloro-4-methylpyridin-3-ylamino)-2-cyanoacrylate [ No CAS ]
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  • [ 5832-44-0 ]
  • [ 133627-45-9 ]
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  • [ 50839-95-7 ]
  • [ 133627-45-9 ]
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  • [ 50840-02-3 ]
  • [ 133627-45-9 ]
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  • [ 142266-63-5 ]
  • [ 133627-45-9 ]
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  • [ 152362-00-0 ]
  • [ 133627-45-9 ]
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  • [ 133627-45-9 ]
  • 2-((2'-cyclopropylamino)-3'-pyridyl)-7-mrthyloxazolo<5,4-b>pyridine [ No CAS ]
  • 19
  • [ 133627-45-9 ]
  • [ 76006-11-6 ]
YieldReaction ConditionsOperation in experiment
46% With potassium acetate; sodium nitrite; In water; ethyl acetate; Step 1: 7-chloro-1H-pyrazolo[3,4-c]pyridine To a cooled (internal temperature of <13 C.) mixture of <strong>[133627-45-9]3-amino-2-chloro-4-methylpyridine</strong> (10.14 g, 71.1 mmol, Matrix) and potassium acetate (9.02 g, 92 mmol) in AcOH (200 mL) was added a solution of sodium nitrite (7.36 g, 107 mmol) in water (30 mL) dropwise while maintaining an internal temperature <13 C. The reaction was allowed to warm slowly to rt and stirred for 66 h. The mixture was concentrated under reduced pressure and the residue was basified with saturated NaHCO3. The solid was filtered and washed with water. The solid was stirred over EtOAc overnight and filtered. The filtrate was combined with the organic extracts, evaporated onto silica gel and purified by flash chromatography (Isco (120 gram)) eluting with EtOAc:hexanes (0:1?1:1) to give a white crystalline solid (4.99 g, 46%). MS m/z=153.9, 155.9 [M+H]+. Calculated for C6H4ClN3: 153.
A solution of <strong>[133627-45-9]2-chloro-4-methylpyridin-3-amine</strong> [133627-45-9] (3.0 g, 21.0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1.45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at rt for 15 min then allowed to stand at ambient temperature for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added to the mixture which was allowed to stand at rt for 3 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHC03. The insoluble solid was filtered off (dried under vacuum; batch 1) and the organic filtrate was washed with water and brine, then dried (Phase separator) and concentrated under vacuum (batch 2). The two batches were combined to give 7-chloro-1 H- pyrazolo[3,4-c]pyridine as a solid. MS (LC-MS): 153 [M+H]+, tR (HPLC conditions k): 0.9 min.
With acetic acid; sodium nitrite; In water; at 20℃; for 27h; A solution of <strong>[133627-45-9]2-chloro-4-methylpyridin-3-amine</strong> [133627-45-9] (3.0 g, 21.0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1 .45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at RT for 15 min then allowed to stand at RT for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added to the mixture which was allowed to stand at RT for 3 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHC03. The insoluble solid was filtered off (dried under vacuum; batch 1 ) and the organic filtrate was washed with water and brine, dried (Phase separator) and concentrated under vacuum (batch 2). The two batches were combined to give 7-chloro-1 H-pyrazolo[3,4-c]pyridine as a solid. MS (LC-MS): 153 [M+H]+, tR (HPLC conditions d): 0.9 min.
With acetic acid; sodium nitrite; In water; at 20℃; for 27h; A solution of <strong>[133627-45-9]2-chloro-4-methylpyridin-3-amine</strong> [133627-45-9] (3.0 g, 21.0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1.45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at RT for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added to the mixture which was allowed to stir at RT for 3h. Acetic acid was evaporated under reduced pressure and the residual aq. solution was partitioned between EtOAc and sat. aq. NaHCO3. The solid was filtered and dried under vacuum to yield batch 1 of product. The organic filtrate was washed with water and brine, then dried (phase separator) and concentrated to afford batch 2. The two batches were combined to give 7-chloro-iH-pyrazolo[3,4-c]pyridine as a solid. MS (LC/MS): 153 [M+H]+, tR (HPLC conditions d): 0.9 mm.
With acetic acid; sodium nitrite; In water; at 20℃; for 27h; A solution of <strong>[133627-45-9]2-chloro-4-methylpyridin-3-amine</strong> [133627-45-9] (3.0 g, 21 .0 mmol) in acetic acid (300 mL) was treated with a solution of sodium nitrite (1.45 g, 21.0 mmol) in water (2.5 mL). The reaction mixture was stirred at rt for 24 h. An additional solution of sodium nitrite (500 mg, 7.25 mmol) in water (1 mL) was added and the reaction mixture was stirred at RT for additional 3 h. Acetic acid was evaporated under reduced pressure and the residual aqueous solution was partitioned between EtOAc and sat. aq. NaHCO3. The insoluble solid was filtered (dried under vacuum; batch 1) and the organic filtrate was washed with water and brine, then dried (phase separator) and concentrated (batch 2). The two batches were combined to give 7-chloro-i Hpyrazolo[3,4-c]pyridine as a solid. MS (LC/MS): 153 [M+H]+, tR (HPLC conditions d): 0.9 mm.

  • 24
  • [ 133627-45-9 ]
  • [ 133627-17-5 ]
  • 25
  • [ 133627-45-9 ]
  • [ 135795-45-8 ]
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  • [ 133627-45-9 ]
  • [ 133627-18-6 ]
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  • [ 133627-45-9 ]
  • [ 133627-19-7 ]
  • 28
  • 2-(cyclopropylamino)-3-pyridinecarbonyl chloride hydrochloride [ No CAS ]
  • [ 133627-45-9 ]
  • [ 133627-47-1 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate; In acetonitrile; at 50℃; for 20h; EXAMPLE 4 Preparation of N-(2-chloro-4-methyl-3-pyridinyl)-2-(cyclopropylamino)-3-pyridinecarboxamide A solution of 2-chloro-4-methyl-3-pyridinamine (5.70 g, 0.040 mol) in 10 ml of acetonitrile was charged rapidly dropwise to a mixture of the acid chloride from Example 3, ground anhydrous potassium phosphate (8.49 g, 0.04 mol) and 40 ml of acetonitrile.The reaction mixture was heated at 50 C. for 20 hours and the reaction progress monitored by HPLC analysis.When the reaction was complete, the reaction mixture was cooled to ambient temperature and treated with 50 ml of water, giving a solution having a PH of about 4.5-5.The mixture was acidified to PH 1 by addition of dilute HCl solution and stirred for 30 min at ambient temperature.The reaction mixture was filtered to remove any insoluble material and the filtrate was basified to PH 9-10 with dilute sodium hydroxide solution and stirred for 30 minutes at ambient temperature.The mixture was then acidified to PH 7-8 by addition of dilute HCl, forming a dark oily layer on top of the solution.water was added, as this had been observed during past experiments of a similar nature to hasten crystallization.The oily layer crystallized slowly on stirring overnight.The solid product was collected and dried in a vacuum oven at 50 C. to obtain 9.37 g of the title compound.
YieldReaction ConditionsOperation in experiment
93.1% (e) Preparation of 2-chloro-3-amino-4-methylpyridine Bromine (34.7 g, 0.204 moles) was added to a stirred solution of sodium hydroxide (8.14 g. 0.224 moles) and water (205 mL) at 0 C. The product of the preceding step, 2-chloro-3-amido-4-picoline (34.7 g, 0.204 moles) was then added to the reaction mixture followed by heating to 22 C. An additional 66 mL water was then added to the reaction mixture followed by heating to 70 C. and stirring for one additional hour. The reaction mixture was cooled to ambient temperature and extracted with methylene chloride (60 mL). The methylene chloride was removed by rotary evaporation to give 24.8 g of 2-chloro-3-amino-4-methylpyridine (6). mp: 69 C. Yield: 93.1 % 1H NMR: 7.5 (d, J=4.64 Hz, 1H), 7.0 (d, J=4.28 Hz, 1H), 5.25 (s, 2H), 2.1 (s,3H) 13C-NMR: 140.0, 136.2, 135.6,131.9, 125.7, 19.0 IR(KBr): 3429, 3308, 3198, 1630, 1590, 1550, 1475, 1451, 1441, 1418, 1377, 1295, 1122, 860, 821, 656, 527 cm-1 Mass spectrum m/z: 145, 144, 142, 107, 106, 105, 80, 79, 78, 62, 54, 53, 52
90% EXAMPLE 15 2-Chloro-3-amino-4-methylpyridine In a manner similar to that described for 2-chloro-3-aminopyridine in Example 14, the title compound was prepared in 90% yield (m.p. 63-66 C., uncorrected) from 2.57 g of 2-chloro-4-methyl-3-pyridinecarboxamide, 2.28 g of NaOH, and 3.1 g of bromine.
85.2% (e) Preparation of 2-chloro-3-amino-4-methylpyridine Bromine (34.7 g, 0.204 moles) was added to a stirred solution of sodium hydroxide (8.14 g. 0.224 moles) and water (205 mL) at 0 C. The product of the preceding step, 2-chloro-3-amido-4-picoline (34.7 g, 0.204 moles) was then added to the reaction mixture followed by heating to 22 C. An additional 66 mL water was then added to the reaction mixture followed by heating to 70 C. and stirring for one additional hour. The reaction mixture was cooled to ambient temperature and extracted with methylene chloride (60 mL). The methylene chloride was removed by rotary evaporation to give 24.8 g of 2-chloro-3-amino-4-methylpyridine (6). mp: 69 C. Yield: 85.2% 1H NMR: 7.5 (d, J=4.64 Hz, 1H), 7.0 (d, J=4.28 Hz, 1H), 5.25 (s, 2H), 2.1 (s,3H) 13C-NMR: 140.0, 136.2, 135.6, 131.9, 125.7, 19.0 IR (KBr): 3429, 3308, 3198, 1630, 1590, 1550, 1475, 1451, 1441, 1418, 1377, 1295, 1122, 860, 821, 656, 527 cm-1 Mass spectrum m/z: 145, 144, 142, 107, 106, 105, 80, 79, 78, 62, 54, 53, 52
The internal temperature of the second reaction was maintained below 40 C. using a cool water bath. Fifty minutes after addition of the sulfide, TLC analysis of the second reaction mixture revealed that the desulfurization was complete. The second reaction mixture was then gently heated and a final reaction temperature of 51 C. was reached 1 hour 25 minutes after addition of sulfide. The second reaction mixture was then allowed to cool to ambient temperature overnight. Stirring was then discontinued, producing a reaction solution and a nickel residue. The reaction solution is transferred Out of the vessel via 12 gauge line using nitrogen pressure. The nickel residue was extracted three times, each time with 2.4 liters of fresh methanol, stirring for twenty minutes and then settling for one hour. The combined extracts were concentrated under reduced pressure and a maximum temperature of 65 C., producing a dark oil weighing 330 grams. The oil was taken up into 2.5 liters of toluene, filtered and concentrated again under pressure up to 65 C., producing a residue weighing 307 grams. This residue was purified by fractional distillation. The resultant pure distilled 3-amino-2-chloro-4-methylpyridine was characterized as follows: Boiling point: 140 C./10 mmHg Melting point: 66-68 C. (uncorrected) Combustion analysis: Calculated % C, H, N, Cl: 50.54, 4.95, 19.65, 24.86 Found % C, H, N, Cl 50.54, 4.90, 19.73, 24.60 NMR: 250 MHz proton spectrum; CDCl3 solvent; ppm downfield shift from TMS reference: 2.178, singlet, 3H; 4.173, hr. singlet, 2H; 6.899, doublet J=4.76 Hz; 1 H; 7.665, doublet J=4.74 Hz, 1H 68 MHz 13 C spectrum; CDCl3 solvent; ppm downfield shift (from 0.00 with 13CDCl3 reference at 76.996 ppm): 17.093, 124.49, 131.665, 136.302, 137.476, 138.099 Mass spectrum: low resolution Cl; methane; m/z, intensity: 143, 100; 145, 31.92
2nd Step Chlorination of 3-amino-4-methylpyridine The residue thus obtained from the first step is dissolved by the addition of 250 liters of 36% hydrochloric acid, then a total of 103 liters of 35% H2 O2 are added continuously at a temperature of 34-45 C. After the reaction has ended the pH is adjusted to between -1 and +1 using sodium hydroxide solution. Extraction is then carried out several times using methylene chloride. The aqueous phase remaining is then adjusted to a pH between 3.5 and 5 using sodium hydroxide solution. After the addition of 6 kg of sodium sulphite, extraction is carried out several times with methylene chloride. The combined organic phases are evaporated down and worked up. 122.6 kg=86% of theory of the 3-amino-2-chloro-4-methylpyridine are obtained. A further 8.6 kg of product are obtained by working up the mother liquors.

  • 30
  • [ 23056-39-5 ]
  • tin(IV) chloride dihydrate [ No CAS ]
  • [ 133627-45-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; acetic acid; In hydrogenchloride; water; b 3-Amino-2-chloro-4-methylpyridine 16.2 g of 2-chloro-4-methyl-3-nitropyridine was added to 470 ml of acetic acid and the resulting mixture stirred at room temperature for 15 min. A solution of 160 g of stannic chloride dihydrate in 200 ml of concentrated hydrochloric acid was then added in one portion and the resulting mixture stirred overnight at room temperature. This mixture was then diluted to 1 liter with water and 10N sodium hydroxide was added slowly with cooling until the white precipitate of tin hydrochloride dissolved. The product was extracted with methylene chloride, dried (sodium sulfate) and concentrated to give 12.8 g of a yellow oil, which solidified on standing, of almost pure 3-amino-2-chloro-4-methylpyridine suitable for use in the next reaction.
  • 31
  • 2-chloronicotinoyl chloride [ No CAS ]
  • [ 133627-45-9 ]
  • [ 133627-46-0 ]
YieldReaction ConditionsOperation in experiment
With pyridine; In 1,4-dioxane; dichloromethane; cyclohexane; c 2-Chloro-N-(2-chloro-4-methyl-3-pyridinyl)-3-pyridinecarboxamide Using a procedure analogous to that described in Example 1a, the carboxamide was prepared from 12.8 g of 3-amino-2-chloro-4-methyl pyridine, 15.8 g of 2-chloronicotinoyl chloride, 7.1 g of pyridine, 30 ml of cyclohexane and 60 ml of dioxane. After removal of the solvent, the product was dissolved in methylene chloride, washed with water and dried (sodium sulfate). After removal of the solvent, the residue was washed with ethyl acetate to give 1.2 g of the title compound, m.p. 193-194 C.
YieldReaction ConditionsOperation in experiment
ii) 3-amino-2-chloro-4-methylthiomethylpyridine prepared above in B (90.2 mg, 0.48 mmoles) was dissolved in trifluoroacetic acid (450 mul). To the resulting solution was added dimethylsulfate (57.1 mg, 0.452 mmoles) at ambient temperature and allowed to stand at ambient temperature for 68 hours, to produce an alkylation solution. A proton NMR spectrum of the alkylation solution revealed that complete alkylation had ocurred. The alkylation solution was then evaporated to dryness and the resultant residue was twice dissolved in methanol and evaporated to dryness, to produce an amber oil weighing 306.8 mg. The oil was dissolved in methanol (500 mul) and stirred in an atmosphere of nitrogen at ambient temperature while zinc dust (63 mg, 0.98 mmoles) was added portionwise over two hours. After complete addition of the zinc dust, the resultant mixture was allowed to continue stirring for 21 hours. An aliquot of the mixture was then removed for analysis by thin layer chromatography (silica gel; 3% methanol/dichloromethane as eluant) which revealed highly selective conversion to 3-amino-2-chloro-4-methylpyridine had occurred. The mixture was then filtered and the filtrate was concentrated to produce a dry residue. The residue was partitioned between ether and water (2 ml each). The layers were separated and the aqueous phase was extracted three additional times with 2 ml portions of ether. The ethereal extracts were combined and dried with anhydrous sodium sulfate, filtered and concentrated at reduced pressure to give 3-amino-2-chloro-4-methylpyridine as an oil weighing 66.6 mg. The oil solidified on standing. Product identity is confirmed by comparison of its proton NMR and TLC chromatographic properties (5% ethylacetate/dichloromethane, R =0.45; 3% methanol/dichloromethane, R =0.70) with those of an authentic sample.
  • 33
  • [ 133627-45-9 ]
  • [ 175421-33-7 ]
YieldReaction ConditionsOperation in experiment
In ethyl acetate; EXAMPLE 10 STR30 <strong>[133627-45-9]3-Amino-2-chloro-4-methylpyridine</strong> (4.3 g) was added to a solution of trichloromethyl chloformate (6.0 g) in ethyl acetate (100 ml) at 0 to 5 C. with stirring and the mixture was refluxed under heating for 6 hours. After removal of the solvent under reduced pressure, 2-chloro-4-methyl-3-pyridylisocyanate (4.9 g) was obtained.
 

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