成人免费xx,国产又黄又湿又刺激不卡网站,成人性视频app菠萝网站,色天天天天

Home Cart Sign in  
Chemical Structure| 66728-98-1 Chemical Structure| 66728-98-1

Structure of 66728-98-1

Chemical Structure| 66728-98-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

{[proInfo.proName]}

CAS No.: 66728-98-1

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 66728-98-1 ]

CAS No. :66728-98-1
Formula : C9H5BrClN
M.W : 242.50
SMILES Code : ClC1=NC=C(Br)C2=C1C=CC=C2
MDL No. :MFCD00234469
InChI Key :HRWILRGBDZGABZ-UHFFFAOYSA-N
Pubchem ID :459766

Safety of [ 66728-98-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 66728-98-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 0.0
Molar Refractivity 54.45
TPSA ?

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

12.89 ?2

Lipophilicity

Log Po/w (iLOGP)?

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

2.34
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

3.75
Log Po/w (WLOGP)?

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

3.65
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.

3.12
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

3.76
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

3.32

Water Solubility

Log S (ESOL):?

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

-4.32
Solubility 0.0115 mg/ml ; 0.0000476 mol/l
Class?

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

Moderately soluble
Log S (Ali)?

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

-3.71
Solubility 0.0469 mg/ml ; 0.000194 mol/l
Class?

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

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

-5.17
Solubility 0.00162 mg/ml ; 0.00000668 mol/l
Class?

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

Moderately 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

 Yes
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

 Yes
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.

-5.12 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<2.0
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)

 1.66

Application In Synthesis of [ 66728-98-1 ]

* 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 [ 66728-98-1 ]

[ 66728-98-1 ] Synthesis Path-Downstream   1~32

  • 1
  • [ 98-50-0 ]
  • [ 66728-98-1 ]
  • [4-(4-bromo-[1]isoquinolylamino)-phenyl]-arsonic acid [ No CAS ]
  • 2
  • [ 66728-98-1 ]
  • [ 141-52-6 ]
  • [ 59050-59-8 ]
YieldReaction ConditionsOperation in experiment
98% In 1,4-dioxane; for 1h;Microwave irradiation; Sealed tube; Heating; General procedure: Morpholine (10 mmol), 7-bromo-1-chloroisoquinoline (2 mmol) and 1,4-dioxane (5ml) were dissolved in 10 ml of vial tube. The vial was sealed with a crimp cap and placed in a Biotage initiator microwave cavity. The reaction mixtures were heated 1h at 120 oC. The resulting mixture was evaporated in vacuum. The product was extracted with ethyl acetate. The ethyl acetate layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. The product was purified by silica gel column chromatography using hexane : ethyl acetate = 1:1.7-Bromo-1-(4-morpholinyl)isoqinoline (2a) was obtained in 99 % yield as a brown solid; mp: 129-130; 1H NMR(CDCl3, 300 MHz) delta 8.21 (s, 1H), 8.17 (d, J = 5.7 Hz, 1H), 7.81 (s, 2H), 7.47 - 7.35 (m, 2H), 7.29 (d, J = 5.6 Hz, 1H), 7.10 (t, J = 8.7 Hz, 1H), 4.05 - 3.91 (m, 7H), 3.45 (t, 4H); 13C NMR (75 MHz, CDCl3) delta 160.3, 141.2, 136.6, 133.2, 129.0, 127.8, 122.8, 119.9, 115.9, 67.0, 51.9; MS(m/z) : 293.17 (M+1). The following compounds (2b-f) were prepared with general procedure for nucleophlic substitution of 1-chloro-4 or 7-bromoisoquinoline.
  • 3
  • [ 37616-36-7 ]
  • [ 66728-98-1 ]
  • 4-bromo-1-(2-dimethylamino-ethoxy)-isoquinoline [ No CAS ]
  • 4
  • [ 3749-21-1 ]
  • [ 66728-98-1 ]
YieldReaction ConditionsOperation in experiment
72% With trichlorophosphate; In chloroform; at 0 - 20℃; for 1.5h;Heating / reflux; 2d) 4-BROMO-1-CHLORO-ISOQUINOLINE To a solution of 4-bromoisoquinoline (52. 08 g, 0. 250 MOL) in methylene chloride (600 mL) is added m-chloroperbenzoic acid (64.47 g, 0.250 MOL). The mixture is stirred for 2.5 hours. To the mixture is added 1.5 g of m-chloroperbenzoic acid and the mixture is stirred for 30 minutes. The solution is washed with 1 N NAOH, brine, and then dried over sodium sulfate. The solvent is removed to give a white solid. The solid is crystallized from hot acetone to yield 32.22 g (57.6%) of a white SOLID. 1H, 13C NMR consistent with structure. The N-oxide (15.75 g, 0.0703 mol) is dissolved in chloroform (50 mL) and cooled in an ice bath. Phosphorus OXYCHLORIDE (20 mL) is added dropwise and then the mixure is warmed to room temperature and then heated to reflux for 1.5 hours. The mixture is allowed to cool to room temperature and is then poured over ice. The aqueous mixture is neutralized to pH 7-8 with NAHCO3 AND then extracted with chloroform. The organic phase is washed with brine, dried over sodium sulfate and the solvent is removed. The residue is purified by flash chromatography (SIO2/5% ETHYL acetate/hexanes). Collected 12.22 g (72%). M+H = 389. 'H NMR ; 5 8. 50 (s, 1H), 8.40 (d, 1H), 8.20 (d, 1H), 7.92 (t, 1H), 7.79 (t, 1H).
52% With trichlorophosphate; In dichloromethane; N,N-dimethyl-formamide; at 0 - 25℃;Inert atmosphere; General procedure: To a stirred solution of the appropriate azine N-oxides in anhydrous CH2Cl2 (0.1M) at 0 C is added POCl3 (1.2 equiv) followed by dropwise addition of DMF (0.5 equiv) under argon. The resulting reaction mixture was warmed to 25 C and stirred for several hours until the reaction is complete as indicated by TLC. Saturated aqueous sodium carbonate solution is added to the reaction mixture slowly to adjust the pH to 7~8. The resulting mixture is separated and the aqueous phase is extracted with CH2Cl2 thoroughly. The organic phase is combined and washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford the crude product, which is purified by flash column chromatography using PE/EA (80:1) as eluent.
With sodium hydrogencarbonate; trichlorophosphate; In dichloromethane; 1,2-dichloro-ethane; (b) A yellow suspension of 4-bromoisoquinoline N-oxide, P-1a, (6.9 g, 30.8 mmol. 1.0 eq) in 1,2-dichloroethane (60 mL) was treated with phosphorus oxychloride (Aldrich, 9.0 mL, 96.4 mmol, 1.8 eq) and warmed to 80 C. After 1.5 hours, the resultant green suspension was carefully poured into a cold solution of 50% saturated sodium bicarbonate (500 mL) and the aqueous layer was extracted with diethyl ether (3*300 mL). The combined organic extracts were washed with water (200 mL), brine (200 mL), dried over magnesium sulfate, and concentrated under reduced pressure to give a tan solid (6.8 g). The crude product was dissolved in a minimal amount of dichloromethane and purified by flash chromatography over silica gel using 5% ether/cyclohexane to give 4-bromo-1-chloro-isoquinoline, P-1b, as a white solid (5.7 g, 77%): HPLC Rf=15.4 min.; TLC Rf=0.4 (5% ether/cyclohexane); 1H NMR (300 MHz, DMSO-d6) delta8.68 (s, 1H), 8.42 (d, 1H, J=8.4 Hz), 8.26 (d, 1H, J=8.3 Hz), 8.15 (t, 1H, J=7.6 Hz), 8.02 (t, 1H, J=7.6 Hz); 13C NMR (75 MHz, DMSO-d6) delta150.4, 143.0, 135.8, 133.8, 130.8, 127.3, 126.8, 126.5, 119.0; MS (ESI) m/z 242/244 [M+H]+.
115 mg With trichlorophosphate; In N,N-dimethyl-formamide; toluene; at 20℃;Inert atmosphere; Cooling with ice; 4-Bromoisoquinoline (34) (200 mg, 0.961 mmol), Na2WO4·H2O (32 mg, 0.096 mmol), AcOH (5 ml) and 30% H2O2 (297 mul, 88 mmol) were added in the reaction flask and the mixture was stirred at 80 C for 3 h. After cooling 50 ml of CH2Cl2 was added and the organic phase washed with saturated NaHCO3 and water. After drying the organic phase with anhydrous Na2SO4 and removal of the solvent under vacuum, 240 mg of crude N-oxide 35 was obtained. The crude 35 was dissolved in mixture of dimethylformamide (1.5 ml) and toluene (4.5 ml) and phosphorus oxychloride (176 mul, 1.92 mmol,) was added in ice cooled reaction mixture under argon. The reaction mixture was stirred at rt for 1 h and then partitioned between EtOAc and water. The organic layer was washed with saturated NaHCO3 (twice), water, dried over anhydrous Na2SO4, and solvent removed under vacuum. The residue (270 mg) was purified by silica gel flash chromatography (2.5% EtOAc-petroleum ether) to give 115 mg (total yield 49%) of 36 as a white solid. 1H NMR (CDCl3): delta 8.48 (s, 1H); 8.35 (d, 1H, J = 8.5 Hz); 8.20 (d, 1H, J = 8.5 Hz); 7.87 (t, 1H, J = 7.6 Hz); 7.77 (t, 1H, J = 7.6 Hz).

  • 5
  • [ 19493-44-8 ]
  • [ 66728-98-1 ]
  • 6
  • [ 917-64-6 ]
  • [ 66728-98-1 ]
  • [ 104704-40-7 ]
  • 7
  • [ 66728-98-1 ]
  • [ 50-01-1 ]
  • <i>N</i>-(4-bromo-isoquinolin-1-yl)-guanidine [ No CAS ]
  • 8
  • [ 3951-95-9 ]
  • [ 66728-98-1 ]
  • 9
  • [ 66728-98-1 ]
  • [ 124-41-4 ]
  • 4-bromo-1-methoxyisoqionoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% In methanol; at 70℃; Example I 4-BROMO-1-METHOXYISOQUINOLINE A solution of 0. 5 g (2. 1 mmol) <strong>[66728-98-1]4-bromo-1-chloroisoquinoline</strong> in 10 mL (5 mmol) 0. 5 M sodium methoxide in methanol was heated to 70 C for overnight with stirring, then cooled to a4mbient temperature and diluted with 30 mL water to produce copious white precipitate. The mixture was cooled to 0 C for 60 minutes, then filtered, washed with water, and air-dried to produce 0. 44 g (1. 8 mmol, 88%) of the title compound as a white, waxy solid. 1H-NMR (300 MHz, CDC13, 6) : 8. 25 (D, J = 8 Hz, 1H), 8. 18 (s, 1H), 8. 06 (d, J= 8 Hz, 1H), 7. 78 (td, J= 1 Hz, 7 Hz, 1H), 7. 60 (td, J= 1 Hz, 7 Hz, 1H), 4. 12 (s, 3H) ; m/z : 239 [M+H] +.
  • 10
  • [ 66728-98-1 ]
  • [ 83889-38-7 ]
  • 11
  • [ 66728-98-1 ]
  • [ 104704-41-8 ]
  • 12
  • [ 66728-98-1 ]
  • [ 104704-42-9 ]
  • 13
  • [ 66728-98-1 ]
  • [ 104704-44-1 ]
  • 14
  • [ 66728-98-1 ]
  • [ 104704-48-5 ]
  • 15
  • [ 66728-98-1 ]
  • [ 104704-46-3 ]
  • 16
  • [ 66728-98-1 ]
  • 3-Methyl-3H-isoindol-1-ylamine [ No CAS ]
  • 23
  • [ 66728-98-1 ]
  • bis-(1-ethoxy-[4]isoquinolyl)-amine [ No CAS ]
  • 25
  • [ 66728-98-1 ]
  • 4-boronic acid-1-chloro-isoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% 2e) 4-Boronic ACID-1-CHLORO-ISOQUINOLINE To a-74C solution OF 4-BROMO-1-CHLORO-ISOQUINOLINE (1. 25 g, 5.2 MMOL) in anhydrous THF (30 mL) is added dropwise n-BuLi (2.5 M in hexane, 2.3 mL, 5.7 mmol) over 45 minutes. Triisopropyl borate (1.4 mL, 6.1 MMOL) IN ADDED dropwise, and the mixture is stirred AT-74C for 2 hours. Upon warming to room temperature, the reaction is quenched with 3 mL water via syringe. After concentrating to an aqueous mixture, the reaction is acidified with 1 N HCI (aqueous) to a pH of approximately 1, which produced a white solid. The solid product is collected by filtration and dried (760 mg, 71%). M+H1 = 207. 9. 'H NMR (DMSO-D6) ; No. 8.72 (bs, 2H), 8.53 (d, 1H), 8. 47 (s, 1H), 8.31 (d, 1H), 7.90 (t, 1 H), 7.80 (t, 1 H).
  • 26
  • [ 66728-98-1 ]
  • [ 62673-31-8 ]
  • [ 953053-38-8 ]
YieldReaction ConditionsOperation in experiment
tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; at 25℃; for 12h; In a 40 mL vial 490 mg (2.00 mmol) l-chloro-4-bromo-isoquinoline and 40 mg (0.034 mmol) tetrakis(triphenylphosphine)palladium(0) is added to 4 mL THF. After all solids are dissolved, 8 mL of 0.5 M (4.0 mmol) benzyl zinc bromide in THF is slowly added by <n="101"/>syringe and the resulting reaction mixture is stirred at 25C. After 12 hrs, the mixture is poured into cold solution of saturated NH4Cl and extracted with EtOAc. The organic extracts are concentrated in vacuo and the resulting residue is purified by silica chromatography using a heptane/EtOAc gradient. Pure fractions are pooled and evaporated to give 150 mg (0.50 mmol) of the title compound.
  • 27
  • [ 66728-98-1 ]
  • [ 123-30-8 ]
  • [ 1071541-73-5 ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic acid; In iso-butanol; at 100℃;Sealed tube; Example 26 Synthesis of 4-(4-bromoisoquinolin-1-ylamino)phenol hydrochloride A mixture of 4-aminophenol (225 mg, 2062 mumol) and <strong>[66728-98-1]4-bromo-1-chloroisoquinoline</strong> (500 mg, 2062 mumol) was heated in sec-butanol (15 mL) in a sealed tube at 100 C. for 2 hours. TFA (477 mul, 6186 mumol) was added and the reaction mixture was allowed to stir at 100 C. overnight. LCMS analysis showed conversion to 4-(4-bromoisoquinolin-1-ylamino)phenol hydrochloride. The dark red reaction mixture was cooled, and diethyl ether was added. The resulting precipitate was filtered and washed with diethyl ether, and the solid was dried in vacuo to provide 4-(4-bromoisoquinolin-1-ylamino)phenol hydrochloride as a purple solid.
Example 14 Synthesis of 4-(4-bromoisoquinolin-l-ylamino)phenol hydrochloride; A mixture of 4-aminophenol (225 mg, 2062 mumol) and 4-bromo-l-chloroisoquinoline (500 mg, 2062 mumol) was heated in sec-butanol (15 mL) in a sealed tube at 100 0C for 2 <n="58"/>A- 1401 -WO-PCT - 57 -hours. TFA (477 mul, 6186 mumol) was added and the reaction mixture was allowed to stir at 100 0C overnight. LCMS analysis showed conversion to 4-(4-bromoisoquinolin-l- ylamino)phenol hydrochloride. The dark red reaction mixture was cooled, and diethyl ether was added. The resulting precipitate was filtered and washed with diethyl ether, and the solid was dried in vacuo to provide 4-(4-bromoisoquinolin-l-ylamino)phenol hydrochloride as a purple solid.
  • 28
  • [ 66728-98-1 ]
  • [ 100-39-0 ]
  • [ 374555-10-9 ]
  • 29
  • [ 66728-98-1 ]
  • [ 135361-30-7 ]
  • [ 848841-53-2 ]
YieldReaction ConditionsOperation in experiment
94% 4a) 1-Chloro-[4,7']biisoquinolinyl A solution of 4-BROMO-1-CHLOROISOQUINOLINE (see Example 2d) (5.0 g, 20.7 MMOL) in 150 mL THF is cooled TO-78C. A solution of n-BuLi (1.6 M in hexanes) (15 mL, 24 MMOL) is added dropwise and the reaction temperature is maintained AT-78C--68C. The reaction mixture is kept stirring AT-78C for 30 minutes. ZNBR2 (dried under vacuum at 80C) (6.5 g, 24.9 MMOL) is dissolved in 50 mL THF and is transferred to above mixture slowly AT-78C. The solution is stirred 40 minutes AT-78C, then warmed to room temperature by removing the cooling bath. Pd (PPh3) 4 (2.4 g, 2.1 mmol is added followed by TRIFLUOROMETHANESULFONIC acid ISOQUINOLIN-7-YL ESTER- (5.7 G, 20. 7 MMOL) in 50 mL THF. The reaction mixture is heated to 60C for 30 minutes and is then concentrated. The resulting oil is dissolved in dichloromethane and washed with saturated NAHCO3. ORGANIC phase is separated, dried (MgS04) and concentrated to give a yellow solid. The solid is collected by filtration, washed with ether then hexane and dried under vacuum. 5.68 G (94%) yellow solid is obtained. m. p. 169.0-169. 6C. H NMR (400 MHz, DMSO-d6) d 9.44 (s, 1 H) ; 8.61 (d, 1 H, J=5.6 Hz); 8.45-8. 43 (m, 1H) ; 8.40 (s, 1H) ; 8.34 (s, 1H) ; 8.18 (d, 1H, J=8.1 Hz); 7.97-7. 90 (m, 5H) ppm. API-MS, m/z 291. 14 ([M+H]+, calcd. 291.06).
  • 30
  • [ 66728-98-1 ]
  • [ 848841-54-3 ]
  • [ 848841-55-4 ]
YieldReaction ConditionsOperation in experiment
97.6% 6b) 6- (1-CHLORO-ISOQUINOLIN-4-VL)-QUINAZOLINE A solution of 4-BROMO-1-CHLORO-ISOQUINOLINE (see Compound 2d) (4.74 g, 19.52 MMOL) in 300 mL THF is cooled TO-72C. A solution of n-BuLi (2.5 M in hexanes) (9.37 mL, 23.42 MMOL) IS ADDED dropwise and the reaction temperature maintained AT-70C--68C for 30 minutes. ZnBr2 (4.84 mg, 21.47 MMOL) is dissolved in 50 mL THF and is transferred to above mixture SLOWLY AT-70C. The solution is stirred 20 minutes AT-70C, then warmed to room temperature. Pd (PPH3) 4 (2.25 g, 1.95 MMOL) and 6-iodoquinazoline (5 g, 19.52 MMOL) in 4 mL THF are added to the reaction mixture dropwise in the order. Then the reaction mixture is heated to 60C for 30 minutes, then kept at room temperature overnight. The reaction mixture is quenched with NH4CI and extracted with ethyl acetate. White solid (4.0 g) is collected by filtration. The organic solution is washed with saturated NH4CI, then brine and dried over sodium sulfate. The solution is concentrated until white solid comes out from solution. The solid is collected by filtration, washed with ether and dried under vacuum. 1.53 g solid is obtained. Yield is 97.6%. H NMR (DMSO, 400 MHz) ; 8 9. 73 (s, 1H), 9.40 (s, 1H), 8. 48 7. 8. 44 (m, 1H), 8.42 (s, 1H), 8.40 (s, 1 H), 8.21 (s, 3H), 7.96-7. 9 (m, 3H). API-MS M/Z 292. 02 ([M+H] +, CALCD. 292.06).
  • 31
  • [ 66728-98-1 ]
  • [ 848841-60-1 ]
  • [ 848841-61-2 ]
YieldReaction ConditionsOperation in experiment
46% 18b) 4-BENZVLOXY-6- (1-CHLORO-ISOQUINOLIN-4-VL)-QUINAZOLINE A solution OF 4-BROMO-1-CHLORO-ISOQUINOLINE (802 mg, 3.31 MMOL} in THF (20 mL) is cooled TO-72C. A solution of n-BuLi (2.5 M in hexanes) (1.6 mL, 3.97 MMOL) is added dropwise and the reaction temperature maintained at-70C for 30 min. ZnBr2 (900 mg, 4.2 MMOL) is dissolved in THF (6 mL) and is transferred to above mixture slowly at-70 C. The solution is stirred 40 min AT-70 C, then warmed to room temperature. Pd (PPH3) 4 (400 mg, 0.36 MMOL) in THF (6 mL) and 4-benzyloxy-6-iodo-quinazoline (1.2 g, 3.31 MMOL) in THF (4 mL) are added to the reaction mixture dropwise. The solution is heated to 60 C for 30 min, then kept at rt overnight. The reaction mixture is diluted with ethyl acetate, washed with sat. NH4CI, then brine, and dried over sodium sulfate. The solution is concentrated until white solid precipitates from solution. The solid is collected by filtration, washed with ether and dried under vacuum. 600 mg OF 4-BENZYLOXY-6- (1-CHLORO-ISOQUINOLIN-4-YL)-QUINAZOLINE is obtained. Yield was 46%. MS/ESI+, M+1 = 397.96
  • 32
  • [ 66728-98-1 ]
  • [ 848841-62-3 ]
  • 1-chloro-4-(6-morpholin-4-yl-pyrazin-2-yl)-isoquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% 19b) 1-CHLORO-4- (6-MORPHOLIN-4-VL-PVRAZIN-2-YL)-ISOQUINOLINE A solution of 4-BROMO-1-CHLORO-ISOQUINOLINE (400 mg, 1.65 MMOL) in THF (20 mL) is cooled TO-72°C. A solution of n-BuLi (2.5 M in hexanes) (0.80 mL, 2 MMOL) is added dropwise and the reaction temperature maintained AT-70 °C~-68°C FOR 30min. ZnBr2 (408 mg, 1.91 MMOL) is dissolved in THF (6 mL) and is transferred to above mixture slowly at-70 °C. The solution is stirred 40 min at-70 °C, then warmed to room temperature by removing the cooling bath. Pd (PPh3) 4 (190 mg, 0.164 MMOL) in 6ML THF and 4-(6-BROMO-PYRAZIN-2-YL)- morpholine (400 mg, 1.65 MMOL) in THF (4 mL) are added to the reaction mixture dropwise, then the solution is heated to 60 °C for 30 min and then kept at rt overnight. The reaction mixture is diluted with ethyl acetate, washed with sat. NH4CI . then brine, and dried over sodium sulfate. The solution is concentrated until white solid came out from solution. The solid is collected by filtration, washed with ether and dried under vacuum. 300 mg of 1- CHLORO-4- (6-MORPHOLIN-4-YL-PYRAZIN-2-YL)-ISOQUINOLINE IS obtained. Yield was 56percent. MS/ESI+, M+1 = 327
 

Related Products

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 66728-98-1 ]

Bromides

Chemical Structure| 1245647-25-9

A118531 [1245647-25-9]

5-Bromo-1-chloro-6-methylisoquinoline

Similarity: 0.89

Chemical Structure| 1233025-78-9

A436624 [1233025-78-9]

8-Bromo-1-chloroisoquinoline

Similarity: 0.87

Chemical Structure| 215453-51-3

A183570 [215453-51-3]

7-Bromo-1-chloroisoquinoline

Similarity: 0.85

Chemical Structure| 29241-60-9

A101296 [29241-60-9]

5-Bromo-2-chloro-3-methylpyridine

Similarity: 0.82

Chemical Structure| 778611-64-6

A105216 [778611-64-6]

5-Bromo-2-chloro-4-methylpyridine

Similarity: 0.82

Chlorides

Chemical Structure| 1245647-25-9

A118531 [1245647-25-9]

5-Bromo-1-chloro-6-methylisoquinoline

Similarity: 0.89

Chemical Structure| 1233025-78-9

A436624 [1233025-78-9]

8-Bromo-1-chloroisoquinoline

Similarity: 0.87

Chemical Structure| 215453-51-3

A183570 [215453-51-3]

7-Bromo-1-chloroisoquinoline

Similarity: 0.85

Chemical Structure| 29241-60-9

A101296 [29241-60-9]

5-Bromo-2-chloro-3-methylpyridine

Similarity: 0.82

Chemical Structure| 778611-64-6

A105216 [778611-64-6]

5-Bromo-2-chloro-4-methylpyridine

Similarity: 0.82

Related Parent Nucleus of
[ 66728-98-1 ]

Isoquinolines

Chemical Structure| 1245647-25-9

A118531 [1245647-25-9]

5-Bromo-1-chloro-6-methylisoquinoline

Similarity: 0.89

Chemical Structure| 1233025-78-9

A436624 [1233025-78-9]

8-Bromo-1-chloroisoquinoline

Similarity: 0.87

Chemical Structure| 215453-51-3

A183570 [215453-51-3]

7-Bromo-1-chloroisoquinoline

Similarity: 0.85

Chemical Structure| 205055-63-6

A112852 [205055-63-6]

6-Bromo-1-chloroisoquinoline

Similarity: 0.79

Chemical Structure| 1204298-52-1

A104687 [1204298-52-1]

4-Bromo-6-methylisoquinoline

Similarity: 0.77