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| 74124-79-1 Chemical Structure| 74124-79-1

Structure of N,N'-Disuccinimidyl carbonate
CAS No.: 74124-79-1

Chemical Structure| 74124-79-1

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

{[proInfo.proName]}

CAS No.: 74124-79-1

,{[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

Product Citations

Chandra, Shambhu Deo ; Gunasekera, Shanal ; Noichl, Benjamin Philipp ; Patrick, Brian O ; Perrin, David M ;

Abstract: We report a streamlined synthesis of (2S,3R,4R)-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.

Purchased from AmBeed: ; ; ;

Alternative Products

Product Details of [ 74124-79-1 ]

CAS No. :74124-79-1
Formula : C9H8N2O7
M.W : 256.17
SMILES Code : O=C(ON1C(CCC1=O)=O)ON2C(CCC2=O)=O
MDL No. :MFCD00009767
InChI Key :PFYXSUNOLOJMDX-UHFFFAOYSA-N
Pubchem ID :676246

Safety of [ 74124-79-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P310-P305+P351+P338

Computational Chemistry of [ 74124-79-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 0
Fraction Csp3 0.44
Num. rotatable bonds 4
Num. H-bond acceptors 7.0
Num. H-bond donors 0.0
Molar Refractivity 58.33
TPSA ?

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

110.29 ?2

Lipophilicity

Log Po/w (iLOGP)?

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

1.19
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

-1.25
Log Po/w (WLOGP)?

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

-1.49
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.

-0.58
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

-1.18
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.66

Water Solubility

Log S (ESOL):?

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

-0.38
Solubility 108.0 mg/ml ; 0.42 mol/l
Class?

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

Very soluble
Log S (Ali)?

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

-0.57
Solubility 68.9 mg/ml ; 0.269 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

0.24
Solubility 444.0 mg/ml ; 1.73 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

 No
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.

-8.75 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

 0.0
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<0.0
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)

 2.4

Application In Synthesis of [ 74124-79-1 ]

* 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 [ 74124-79-1 ]

[ 74124-79-1 ] Synthesis Path-Downstream   1~33

  • 1
  • [ 74124-79-1 ]
  • [ 143726-85-6 ]
  • [ 936633-33-9 ]
  • 2
  • [ 74124-79-1 ]
  • [ 3513-81-3 ]
  • [ 74-88-4 ]
  • [ 160232-88-2 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In acetonitrile; A. N-hydroxysuccinimidyl-1-methoxypropane-3-carbonate A solution of 355 mg of <strong>[3513-81-3]2-methylene-1,3-propanediol</strong> in acetonitrile (30 mL) was added sequentially, at ambient temperature, 65 mg of sodium hydride and 0.25 mL iodomethane. The mixture was stirred for 12 h and concentrated in vacuo. The residue was then taken up in 15 mL of acetonitrile and treated sequentially, at ambient temperature under an atmosphere of nitrogen, with 1.3 g of N,N-disuccinimidyl carbonate and 1.6 mL of triethylamine. After stirring for 14 h, the reaction mixture was concentrated in vacuo and the residue was diluted CH2 Cl2, washed with saturated sodium bicarbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with EtOAc as eluant to give 95 mg of the title compound. (1 H)-NMR (CDCl3) consistent with structure.
With triethylamine; In acetonitrile; A. N-hydroxysuccinimidyl-1-methoxypropane-3-carbonate A solution of 355 mg of <strong>[3513-81-3]2-methylene-1,3-propanediol</strong> in acetonitrile (30 mL) was added sequentially, at ambient temperature, 65 mg of sodium hydride and 0.25 mL iodomethane. The mixture was stirred for 12 h and concentrated in vacuo. The residue was then taken up in 15 mL of acetonitrile and treated sequentially, at ambient temperature under an atmosphere of nitrogen, with 1.3 g of N,N-disuccinimidyl carbonate and 1.6 mL of triethylamine. After stirring for 14 h, the reaction mixture was concentrated in vacuo and the residue was diluted CH2 Cl2, washed with saturated sodium bicarbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with EtOAc as eluant to give 95 mg of the title compound. (1 H)-NMR (CDCl3) consistent with structure.
  • 3
  • [ 74124-79-1 ]
  • [ 302348-51-2 ]
  • [ 1255209-41-6 ]
  • 4
  • [ 129488-10-4 ]
  • [ 74124-79-1 ]
  • [ 1094503-56-6 ]
  • [ 1094506-60-1 ]
  • [ 1094506-63-4 ]
YieldReaction ConditionsOperation in experiment
Into a three-necked flask equipped with a magnetic stirrer and placed under N2 is introduced tert-butyl (2S)-2-[(3,4-dichlorophenyl)(hydroxy)methyl]piperidine-1-carboxylate (1.9 g, 5.2 mmol) dissolved in acetonitrile (30 mL). N,N'-Disuccinimyl carbamate (2.05 g, 8 mmol) and triethylamine (2.19 mL, 15.6 mmol) are then added and the reaction medium is stirred for 4 hours at RT. After concentrating the reaction medium by evaporation under RP, the residue thus obtained is taken up in saturated aqueous sodium hydrogen carbonate solution and the aqueous phase is extracted with EtOAc (3.x.30 mL). The organic phase is washed with aqueous NaCl solution, dried over MgSO4 and concentrated by evaporation under RP. The residue obtained is diluted in DCM (15 mL). This solution is then added dropwise to solution, prepared beforehand and placed in a one-necked flask, of <strong>[129488-10-4]5-amino-N-tert-butoxycarbonyl-1H-indazole</strong> (1.45 g, 6.2 mmol), DCM (40 mL) and triethylamine (1.1 mL, 7.8 mmol). The reaction medium is stirred at RT overnight. 40 mL of DCM and 30 mL of saturated aqueous sodium hydrogen carbonate solution are then added. After separation of the phases by settling, the organic phase is washed with aqueous NaCl solution, dried over MgSO4, filtered and concentrated by evaporation under RP. The residue is purified by chromatography on silica gel eluted with a 3/1 cyclohexane/EtOAc mixture. tert-Butyl (2S)-2-[(S)-(3,4-dichlorophenyl)[(1-(tert-butoxycarbonyl)-1H-indazol-5-yl)carbamoyl]oxy}methyl]piperidine-1-carboxylate (0.215 g) is thus obtained the form of a colourless lacquer and tert-butyl (2S)-2-[(R)-(3,4-dichlorophenyl)[(1-(tert-butoxycarbonyl)-1H-indazol-5-yl)carbamoyl]oxy}methyl]piperidine-1-carboxylate (0.434 g) is obtained in the form of a white foam. (M-H)-=617.
  • 5
  • [ 129488-10-4 ]
  • [ 74124-79-1 ]
  • [ 1094503-74-8 ]
  • [ 1094506-77-0 ]
YieldReaction ConditionsOperation in experiment
Into a one-necked flask equipped with a magnetic stirrer is introduced tert-butyl (2S)-2-[3-(ethoxycarbonyl)phenyl](hydroxy)methyl}piperidine-1-carboxylate (4.7 g, 12.8 mmol) dissolved in acetonitrile (85 mL) with N,N'-disuccinimidyl carbonate (13.1 g, 51 mmol). Triethylamine (8.95 mL, 64 mmol) is then added and the reaction medium is stirred for 4 hours at a temperature in the region of 20° C. The reaction medium is concentrated to dryness and the evaporation residue is taken up in saturated aqueous sodium hydrogen carbonate solution (50 mL) and extracted with twice 40 mL of EtOAc. A persistent insoluble material is removed by filtration of the organic phases through a sinter funnel. The filtrate is dried over MgSO4, filtered and concentrated to dryness under RP to give the activated intermediate. Into a second one-necked flask equipped with a magnetic stirrer is introduced tert-butyl 5-amino-indazole-1-carboxylate (3 g, 12.8 mmol) with DCM (125 mL) and triethylamine (2.7 mL, 19.1 mmol). Into this solution is poured the activated intermediate dissolved in DCM (40 mL) over about 10 minutes. The reaction medium is stirred in the region of 20° C. for 16 hours. The medium is hydrolysed with saturated aqueous sodium hydrogen carbonate solution (80 mL), the phases are separated by settling and the aqueous phase is re-extracted with DCM (30 mL). The combined organic extracts are dried over MgSO4, filtered and concentrated to dryness under RP. The garnet-coloured oil isolated is chromatographed on 420 g of silica gel 60, particle size 15-40 mum, contained in a column 5 cm in diameter, eluting with a 7/3v/v cyclohexane/EtOAc mixture, under an excess pressure of 0.6 bar of argon. The evaporation of the fractions gives 1.53 g of tert-butyl 5-[([(2S)-1-(tert-butoxycarbonyl)piperid-2-yl][3-(ethoxycarbonyl)phenyl]methoxy}carbonyl)amino]-1H-indazole-1-carboxylate in the form of a white-coloured foam. (M-H)-=621. 1H NMR (DMSO, 400 MHz): 70percent-30percent mixture of isomers, delta (ppm) from 0.98 to 2.00 (m, 27H); 2.98 (m, 1H); 3.90 (broad m, 1H); 4.33 (q, J=7.5 Hz, 2H); 4.50 (broad m, 1H); 6.09 (d, J=10.0 Hz, 0.7H); 6.23 (broad d, J=9.0 Hz, 0.3H); 7.50 (t, J=7.5 Hz, 0.7H); 7.58 (m, 1.3H); 7.68 (broad d, J=7.5 Hz, 0.7H); 7.75 (broad d, J=7.5 Hz, 0.3H); from 7.85 to 8.00 (m, 3H); 8.04 (broad s, 0.7H); 8.08 (broad s, 0.3H); 8.32 (s, 0.7H); 8.34 (s, 0.3H); 9.82 (broad m, 0.3H); 10.1 (s, 0.7H).
  • 6
  • [ 635713-68-7 ]
  • [ 635713-07-4 ]
  • [ 74124-79-1 ]
  • [ 1384431-99-5 ]
  • 7
  • [ 4138-26-5 ]
  • [ 74124-79-1 ]
  • N-(3-(1H-imidazol-1-yl)propyl)-2-((4-fluorobenzyl)amino)-1,3-thiazole-5-carboxamide [ No CAS ]
  • N1-(4-fluorobenzyl)-N1-(5-[3-(1H-imidazol-1-yl)propyl]carbamoyl}-1,3-thiazol-2-yl)piperidine-1,3-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Example 6B (0.018 g, 0.05 mmol) was dissolved in acetonitrile (0.5 ml), and treated with potassium carbonate (0.021 g, 0.15 mmol) and 1 -(2-chloroethyl)pyrrolidine (0.017 g, 0.1 mmol). The reaction mixture was heated via microwave at 180 °C for 30 minutes, concentrated in vacuo, and submitted to reverse-phase HPLC (as described in Example 6C) to provide the title compound.
  • 8
  • [ 88675-24-5 ]
  • [ 74124-79-1 ]
  • N-(3-(1H-imidazol-1-yl)propyl)-2-((4-fluorobenzyl)amino)-1,3-thiazole-5-carboxamide [ No CAS ]
  • 2-[(4-fluorobenzyl)(tetrahydrofuran-3-ylcarbamoyl)amino]-N-[3-(1H-imidazol-1-yl)propyl]-1,3-thiazole-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: Example 6B (0.018 g, 0.05 mmol) was dissolved in acetonitrile (0.5 ml), and treated with potassium carbonate (0.021 g, 0.15 mmol) and 1 -(2-chloroethyl)pyrrolidine (0.017 g, 0.1 mmol). The reaction mixture was heated via microwave at 180 °C for 30 minutes, concentrated in vacuo, and submitted to reverse-phase HPLC (as described in Example 6C) to provide the title compound.
  • 9
  • crizotinib [ No CAS ]
  • [ 74124-79-1 ]
  • [ 908112-43-6 ]
  • (1r,4r)-4-((2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)amino)cyclohexyl 4-(4-(6-amino-5-(1-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
14.1 mg A solution of 4-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro H-indazol-l-yl)-2-(((lr,4r)-4- hydroxycyclohexyl)amino)benzamide (46.4 mg, 0.10 mmol), disuccinimidyl carbonate (38.4 mg, 0.15 mmol) and triethylamine (0.10 mL) in DMF (2.0 mL) was stirred at room temperature for 4 hrs. After 3-(l-(2,6-dichloro-3-fluorophenyl)ethoxy)-5-(l-(piperidin-4-yl)-lH-pyrazol-4-yl)pyridin-2-a mine (crizotinib) (90 mg, 0.20 mmol) was added, the reaction mixture was continually stirred at room temperature for overnight. Solvent was evaporated under reduced pressure to give a residue, which was purified by ISCO over silica gel to afford (lr,4r)-4-((2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-lH-ind azol- 1 -yl)phenyl)amino)cyclohexyl 4-(4-(6-amino-5-(l-(2,6-dichloro-3-fluorophenyl)ethoxy)pyridin-3-yl)- lH-pyrazol-l-yl)piper idine-l-carboxylate (14.1 mg) as a white solid. 1H NMR (400 MHz, Methanol-^) delta 7.84 (d, / = 0.8 Hz, 1H), 7.66 (d, /= 8.4 Hz, 1H), 7.58 - 7.47 (m, 2H), 7.41 (dd, /= 9.0, 4.8 Hz, 1H), 7.24 - 7.15 (m, 1H), 7.06 (d, /= 1.7 Hz, 1H), 6.82 (d, /= 2.1 Hz, 1H), 6.65 (dd, /= 8.5, 2.1 Hz, 1H), 6.26 (q, / = 6.6 Hz, 1H), 4.63-4.59 (m, 2H), 4.33-4.28 (m, 1H), 4.16 (d, / = 13.6 Hz, 2H), 3.48 - 3.38 (m, 1H), 3.00-2.86 (m, 6H), 2.40 (s, 2H), 2.12 - 1.74 (m, 11H), 1.59- 1.34 (m, 4H), 1.01 (s, 6H). ESMS calculated for C45H47CI2F4N9O5: 939.3; found: 940.7 (M + H)+.
  • 10
  • [ 74124-79-1 ]
  • [ 908112-43-6 ]
  • [ 57260-71-6 ]
  • 1-tert-butyl 4-((1r,4r)-4-((2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl)phenyl)amino)cyclohexyl) piperazine-1,4-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% A solution of 4-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-lH-indazol-l-yl)-2-(((lr,4r)-4- hydroxycyclohexyl)amino)benzamide (557 mg, 1.2 mmol), disuccinimidyl carbonate (460 mg, 1.8 mmol) and triethylamine (0.40 mL) in DMF (10 mL) was stirred at room temperature for overnight. ie/t-Butyl piperazine- 1-carboxylate (452 mg, 2.40 mmol) was added and the reaction mixture was continually stirred at room temperature for 4 hrs. Solvent was evaporated under reduced pressure to give a residue, which was purified by ISCO over silica gel to afford 1-tert-butyl 4-((lr,4r)-4-((2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-lH- indazol-l-yl)phenyl)amino)cyclohexyl) piperazine- 1,4-dicarboxylate (469 mg, 58%) as a white solid. 1H NMR (400 MHz, Chloroform-J) delta 8.19 (d, /= 7.3 Hz, 1H), 7.50 (d, /= 8.4 Hz, 1H), 6.77 (d, / = 2.0 Hz, 1H), 6.61 (dd, / = 8.4, 2.0 Hz, 1H), 5.68 (s, 2H), 4.74 (s, 1H), 3.44-3.40 (m, 9 H), 2.85 (s, 2H), 2.49 (s, 2H), 2.15-2.08 (m, 4H), 1.57-1.51 (m, 4H), 1.47 (s, 9H), 1.14 (s, 6H). ESMS calculated for C33H43F3N6O6: 676.3; found: 677.5 (M + H)+.
  • 11
  • [ 74124-79-1 ]
  • [ 5331-43-1 ]
  • [ 5497-76-7 ]
  • C18H25N3O5 [ No CAS ]
  • 12
  • [ 74124-79-1 ]
  • [ 870-46-2 ]
  • [ 5497-76-7 ]
  • C15H27N3O5 [ No CAS ]
  • 13
  • [ 747412-49-3 ]
  • [ 74124-79-1 ]
  • N-ε-4-methyltrityl-L-lysine [ No CAS ]
  • [ 75286-49-6 ]
  • [ 60-24-2 ]
  • 5-carboxy-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate [ No CAS ]
  • C108H153N23O19S2 [ No CAS ]
  • C108H153N23O19S2 [ No CAS ]
  • 14
  • [ 747412-49-3 ]
  • [ 74124-79-1 ]
  • C84H130N15O15PolS3 [ No CAS ]
  • [ 75286-49-6 ]
  • [ 60-24-2 ]
  • C77H121N19O14S2 [ No CAS ]
  • C77H121N19O14S2 [ No CAS ]
  • 15
  • [ 74124-79-1 ]
  • [ 71082-51-4 ]
  • 2,5-dioxopyrrolidin-1-yl 7-(trifluoromethyl)quinoline-3-carboxylate [ No CAS ]
  • 16
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-2-cyclopentyl-5-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-[4-(1-cyclopentyl-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% To a solution of Intermediate 9, 60 mg (0.22 minol), and 4-dimethylaminopyridine, 32 mg (0.26 minol), in tetrahydrofuran, 25 mL, was added N,N-disuccinimidyl carbonate, 67.9 mg, (0.26 minol). The reaction was stirred for 1 hour then triethylamine, 0.092 mL (0.66 minol), and 2,3-dihydro-IH-pyrrolo[3,4-c]pyridine hydrochloride (6000-50-6), 41.3 mg (0.26 minol), was added and the reaction was left to stir at room temperature for 18 hours. Water was added and the mixture was extracted with dichloromethane. The combined organics were dried over solid sodium sulfate and concentrated under vacuum. Purification by flash chromatography on silica gel 60 (eluent: ethyl acetate-heptane 0:1, 1:1, 1:0 and methanol-ethyl acetate 1:9) gave thedesired product, 62.8 mg (68percent).1H NMR (300 MHz, CDCI3): 6 [ppm] = 1.16 (d, 3H), 1.57-2.00 (m, 8H), 2.46 (d, IH), 2.64 (dd, IH), 3.27 (m, IH), 4.90 (d, 4H), 5.21 (m, IH), 6.40 (s, IH), 7.30 (d, IH), 7.52 (d, 2H), 7.76 (d, 2H), 8.58 (d, IH), 8.63 (s, IH).UPLC-MS (Method 4): R 1.93 min., 100percent. MS (ESIpos): mz[M+H]418.
  • 17
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-5-methyl-2-(2,2,2-trifluoroethyl)-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-{4-[4-methyl-6-oxo-1-(2,2,2-trifluoroethyl)-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
20% A solution of 100mg of Intermediate 11(0.35 minol, 1.00 eq) in DMF (10 mL) was treated with108 mg of N,N?-disuccinimidyl carbonate (0.42 minol, 1.20 eq) and 51.4 mg of 4-dimethylaminopyridine (0.42 minol, 1.20 eq) and was left over night at room temperature. Asuspension of 81 .2 mg of 2,3-dihydro-1 H-pyrrolo[3,4-c]pyridine dihydrochloride (0.42 minol, 1 .20eq) and 667 pL of triethylamine (4.78 minol, 3.60 eq) in DMF (5 mL) was added. The reactionmixture was left for 3 days at room temperature. The mixture was poured into water. The aqueous phase was three times extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2504 and the solved was removed under reduced pressure. The residue was purified by preparative reverse phase HPLC to yield the desired productExample 11(30 mg, 20percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.09 (d, 3H), 2.40-2.47 (m, IH), 2.79-2.87 (m, IH),3.42-3.54 (m, IH), 4.26-4.38 (m, IH), 4.37-4.37 (m, IH), 4.80-4.83 (m, 4H), 7.41 -7.47 (m, I H), 7.65 - 7.72 (m, 2H), 7.72 - 7.79 (m, 2H), 8.50 (d, I H), 8.61 (s, I H), 8.66 (s, I H).U PLC-MS (Method 2): R= 0.81 min; MS (ESipos): mz [M÷H] 432.
  • 18
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-5-methyl-2-(tetrahydro-2H-pyran-4-yl)-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-{4-[4-methyl-6-oxo-1-(tetrahydro-2H-pyran-4-yl)-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
11% A solution of 177 mg of Intermediate 14 (0.31 minol, 50percent purity 1.00 eq) in DMF (19 mL) wastreated with 94.7 mg of N,N?-disuccinimidyl carbonate (0.37 minol, 1.20 eq) and 45.2 mg, of 4-dimethylaminopyridine (0.37 minol, 1.20 eq). The mixture was left over night at room temperature. A suspension of 71.4 mg of 2,3-dihydro-IH-pyrrolo[3,4-c]pyridine dihydrochloride (0.37 minol, 1.20 eq) and 155 pL of triethylamine (1.11 minol, 3.60 eq) on DMF (3 mL) wasadded. The reaction mixture was stirred 3 days at room temperature. The mixture was poured into water and extracted three times with ethyl acetate. The combined organic layers were washed with brine and dried over Na2SO4. The aqueous and the organic phase were evaporated under reduced pressure. Both residues were purified by preparative HPLC to yield in total 15.0mg of the desired product Example 21(0.03 minol, 11percent).1H-NMR (400MHz, DMSO-d6): oe [ppm]= 1.05 (d, 3H), 1.49- 1.61 (m, 2H), 1.80- 1.93 (m, IH),2.02 - 2.16 (m, I H), 2.29 - 2.37 (m, I H), 2.68 - 2.76 (m, I H), 3.88 - 3.99 (m, 2H), 4.70 - 4.80 (m,IH), 4.91 (d, 4H), 7.64 - 7.71 (m, 3H), 7.74 - 7.79 (m, 2H), 8.64 (d, IH), 8.72 (s, IH), 8.76 (s,I H). Three protons are not visible.U PLC-MS (Method 2): R 0.71 min; MS (ESIpos): mz [M÷H] 434.
  • 19
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-5-methyl-2-phenyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-[4-(4-methyl-6-oxo-1-phenyl-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% A solution of 100 mg of Intermediate 23(0.36 minol, 1.00 eq) in DMF (11 mL) was treated with110 mg of N,N?-disuccinimidyl carbonate (0.43 minol, 1.20 eq) and 53.4 mg of 4-dimethylaminopyrdine (0.44 minol, 1.20 eq). The mixture was stirred over night at roomtemperature. A solution of 82.9 mg of 2,3-dihydro-1 H-pyrrolo[3,4-c]pyridine dihydrochloride (0.43minol, 1 .20 eq) and 2.99 mL of triethylamine (21.47 minol, 30 eq) in DMF (2 mL) was added. The mixture was stirred over night. THE was removed from under reduced pressure. The remaining solution was poured into water. The solid was removed by filtration, the filtrate was taken to dryness and the residue was purified by preparative reverse phase HPLC to yield 35.0mg of the desired product (21percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.07 (d, 3H), 2.17 (s, 6H), 2.22-2.36 (m, IH), 2.40-2.48 (m, 2H), 2.64 - 2.70 (m, I H), 3.37 - 3.44 (m, I H), 3.59 - 3.75 (m, I H), 3.91 - 4.08 (m, I H),4.83 (d, 4H), 7.44 (d, IH), 7.63 - 7.71 (m, 2H), 7.71 - 7.79 (m, 2H), 8.50 (d, IH), 8.65 (s, IH),8.61 (s, IH).UPLC-MS (Method 1): R0.83 min; MS (ESIpos): mz[M+H]426.
  • 20
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-2-[2-(dimethylamino)ethyl]-5-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-(4-{1-[2-(dimethylamino)ethyl]-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl}phenyl)-1,3- dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
13% A solution of 100mg of Intermediate 24 (0.36 minol, 1.00 eq) in DMF (11 mL) was treated with112 mg of N,N?-disuccinimidyl carbonate (0.44 minol, 1.20 eq) and 53.4 mg of 4-dimethylaminopyrdine (0.44 minol, 1.20 eq). The mixture was stirred over night at roomtemperature. A solution of 84.4 mg of 2,3-dihydro-1 H-pyrrolo[3,4-c]pyridine dihydrochloride (0.44minol, 1 .20 eq) and 3.05 mL of triethylamine (21.87 minol, 30 eq) in DMF (2 mL) was added. The mixture was stirred over night. THE was removed from under reduced pressure. The remaining solution was poured into water. The solid was removed by filtration, the filtrate was taken to dryness and the residue was purified by preparative reverse phase HPLC to yield 20.0mg of the desired product (13percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.07 (d, 3H), 2.17 (s, 6H), 2.22-2.36 (m, IH), 2.40-2.48 (m, 2H), 2.64 - 2.70 (m, I H), 3.37 - 3.44 (m, I H), 3.59 - 3.75 (m, I H), 3.91 - 4.08 (m, I H),4.83 (d, 4H), 7.44 (d, IH), 7.63 - 7.71 (m, 2H), 7.71 - 7.79 (m, 2H), 8.50 (d, IH), 8.65 (s, IH),8.61 (s, IH).UPLC-MS (Method 1): R0.47 min; MS (ESIpos): mz[M+2H]421
  • 21
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-2-[4-(difluoromethoxy)benzyl]-5-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-(4-{1-[4-(difluoromethoxy)benzyl]-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl}phenyl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
12% A solution of 200 mg of Intermediate 25 (0.56 minol, 1.00 eq) in DMF (8 mL) was treated with171 mg of N,N?-disuccinimidyl carbonate (0.67 minol, 1.20 eq) and 82.0 mg of 4- dimethylaminopyrdine (0.67 minol, 1.20 eq). The mixture was stirred for 3 days at room temperature. A suspension of 129 mg of 2,3-dihydro-IH-pyrrolo[3,4-c]pyridine dihydrochloride (0.67 minol, 1.20 eq) and 279 pL of triethylamine (2.00 minol, 3.6 eq) in DMF (2 mL) was added. The mixture was stirred over night. The resulting suspension was filtered, the solid was removedand the filtrate was taken to dryness. The residue was purified by reverse phase preparative HPLC to yield 34.0mg of the desired product (12percent).1H-NMR (400MHz, DMSO-d6): oe [ppm]= 1.04 (d, 3H), 2.30 -2.40 (m, IH), 2.75 -2.86 (m, IH),3.38-3.48 (m, IH), 4.78 -4.87 (m, 5H), 4.99 (s, IH), 7.00- 7.22 (m, 3H), 7.34 -7.40 (m, 2H),7.44 (d, I H), 7.62 - 7.68 (m, 2H), 7.69 - 7.75 (m, 2H), 8.50 (d, I H), 8.63 (d, 2H).UPLC-MS (Method 2): Rt0.92 min; MS (ESIpos): mz [M÷H] 506.
  • 22
  • [ 158425-42-4 ]
  • [ 74124-79-1 ]
  • [ 6000-50-6 ]
  • N-[4-(4-oxo-3,4-dihydrophthalazin-1-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.5% A solution of 100.0 mg of 4-(4-aminophenyl)-2-methylphthalazin-1(2H)-one (by S. Demirayak etal. in Eur. J. Med. Chem. 2004, 39, 1089?1095, 0.42 minol, 1.00 eq) in DMF (12 mL) wastreated with 129.6mg of N,N?-disuccinimidyl carbonate (0.51 minol, 1.20 eq) and 61.8mg of 4-dimethylaminopyridine (0.51 minol, 1.20 eq). The mixture was left of night at room temperature.A suspension of 97.7 mg of 2,3-dihydro-1 H-pyrrolo[3,4-c]pyridine dihydrochloride (0.51 minol,1.20 eq) and 1.76 mL of triethylamine (12.79 minol, 30 eq) in DMF (2 mL) was added and themixture was again stirred over night. The suspension was filtered, the filtrate was taken to dryness and the residue was purified by preparative reverse phase HPLC to obtain 2.5 mg of the desired material (1.5percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 4.86 (d, 4H), 7.39 - 7.60 (m, 3H), 7.76 (d, 3H), 7.83 -8.00 (m, 2H), 8.24-8.40 (m, IH), 8.52 (d, IH), 8.67 (s, IH), 8.63 (s, IH), 12.80 (s, IH).UPLC-MS (Method 2): R0.80 min; MS (ESIpos): mz [M÷H] 384.
  • 23
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-5-methyl-2-[2-(morpholin-4-yl)ethyl]-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-(4-{4-methyl-1-[2-(morpholin-4-yl)ethyl]-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl}phenyl)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
11% A solution of 150 mg of Intermediate 34 (0.47 minol, 1.00 eq) in DMF (5 mL) was treated with145 mg of N,N?-disuccinimidyl carbonate (0.57 minol, 1.20 eq) and 181 mg of 4-dimethylaminopyrdine (0.57 minol, 1.20 eq). The mixture was stirred over night at roomtemperature. A suspension of 109 mg of 2,3-dihhydro-IH-pyrrolo[3,4-c]pyridine dihydrochloride(0.57 minol, 1.20 eq) and 2.00 mL of triethylamine in DMF (2 mL) was added. The mixture was stirred for 3 days. The solid was removed by filtration, the filtrate was taken to dryness and the residue was purified by preparative reverse phase HPLC to yield 24.2 mg of the desired product(11percent).1H-NMR(400MHz, DMSO-d6): oe [ppm]= 1.09-1.13 (m, 3H), 2.30 (dd, IH), 2.35 -2.45 (m, 4H),2.65-2.75 (m, IH), 3.36-3.43 (m, 4H), 3.50 (t, 4H), 3.59-3.68 (m, IH), 4.12 (dt, IH), 4.82 (d,4H), 7.44 (d, I H), 7.64 - 7.69 (m, 2H), 7.71 - 7.77 (m, I H), 8.50 (d, I H), 8.63 (d, 2H).UPLC-MS (Method 2): R = 0.49 min; MS (ESIpos): mz [M÷H] 463.
  • 24
  • [ 74124-79-1 ]
  • [ 6000-50-6 ]
  • [ 43191-77-1 ]
  • N-[4-(1,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% A solution of 108 mg of Intermediate 4 (0.50 minol, 1.00 eq) in THE (18 mL) was treated with154 mg N,N?-disuccinimidyl carbonate (0.60 minol, 1.20 eq) and 73.3 mg of 4-dimethylaminopyrindine. The reaction mixture was stirred at room temperature over night. Asuspension of 116mg 2,3-dihydro-IH-pyrrolo[3,4-c]pyridine dihydrochloride (0.6 minol, 1.20 eq)and 251 pL of triethylamine (1.80 minol, 3.60 eq) was added. The reaction mixture was stirred at room temperature and additionally 250 pL triethylamine were added. After stirring for 3 days the precipitate was filtered off and discarded. The filtrate was taken to dryness. The remaining residue was purified by preparative reverse phase HPLC to provide 150 mg of the desiredproduct Example 4 (83percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.07 (d, 3H), 2.30 (dd, IH), 2.65-2.75 (m, IH), 3.32(s, 3H), 4.83 (d, 4H), 7.41 -7.46 (m, IH), 7.64-7.69 (m, 2H), 7.71 -7.76 (m, 2H), 8.14 (s, IH),8.50 (d, I H), 8.62 (d, 2H). One proton under the water protons.LC-MS (Method 2): R = 0.62 min; MS (ESIpos): mz = 364 [M÷H]
  • 25
  • [ 74124-79-1 ]
  • 6-(6-aminopyridin-3-yl)-2,5-dimethyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-[5-(1,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)pyridin-2-yl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% To a solution of Intermediate 83 45 mg (0.21 minol) in acetonitrile, 6mL, was added N,Ndisuccinimidyl carbonate, 63.38 mg (0.25 minol). The reaction was stirred at room temperature for 18 hours in a sealed tube. To a suspension of 2,3-dihydro-IH-pyrrolo[3,4-c]pyridinehydrochloride, 32 mg (0.21 minol) in acetonitrile, I mL, was added triethylamine, 0.057 mL (0.41 minol), the slurry was transferred to the tube and the reaction was left to stir at room temperature for 18 hours. The reaction mixture was diluted with water and extracted with ethyl acetate. The combined organics were dried over solid sodium sulfate and concentrated under vacuum.Purification by MDAP (Eluent: Acetonitrile: 0.1percent NH4OH 5:90, 40:60) gave 102.4, 15.9 mg (21percent) as a white solid.1H NMR (300 MHz, CDCI3): 6 [ppm] = 1.23 (d, 3H), 2.50 (d, IH), 2.70 (dd, IH), 3.27 (m, IH),3.47 (s, 3H), 4.92 (d, 4H), 7.32 (m, IH), 8.14 (m, IH), 8.22 (m, IH), 8.58-8.64 (m, 3H).UPLC-MS (Method 4): R= 1.31min., 99percent ES (ESIpos) [M÷H] 365.
  • 26
  • [ 74124-79-1 ]
  • (5S)-6-(4-aminophenyl)-2,5-dimethyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-{4-[(4S)-1,4-dimethyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
83% A solution of 500 mg of Intermediate 6 (2.30 minol, 1.00 eq) in THE (60 mL) was treated with707 mg of N,N?-disuccinimidyl carbonate (2.76 minol, 1.20 eq) and 338 mg of 4-dimethylaminopyridine (2.76 minol, 1.20 eq). The mixture was stirred for 3 days at roomtemperature. A suspension of 533 mg 2,3-dihydro-IH-pyrrolo[3,4-c] pyrimidine dihydrochloride(2.76 minol, 1.20 eq) and 1.16 mL of triethylamine (8.29 minol, 3.60 eq) in DMF (3 mL) wasadded. Additionally 5 mL of DMF were added to the mixture and it was stirred again over night at room temperature. The precipitate was filtered off and discarded. The filtrate was poured into water. The resulting suspension was stirred over night, the precipitate collected by filtration, washed with water and dried to provide the desired product Example 5 (732 mg, 83percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.07 (d, 3H), 2.30 (dd, IH), 2.70 (dd, IH), 3.35-3.45 (m, I H), 4.82 (d, 4H), 7.44 (d, I H), 7.63 - 7.70 (m, 2H), 7.71 - 7.76 (m, 2H), 8.50 (d, I H), 8.62 (d,I H). The methyl group is under the water protons.LC-MS (Method 2): R = 0.60 min; MS (ESIpos): mz = 364 [M÷H].Optical rotation (Method 5): [a] = + 35750 (c = 1.00, DMSO).
  • 27
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-5-isopropyl-2-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-[4-(4-isopropyl-1-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% To a solution of 6-(4-aminophenyl)-5-isopropyl-2-methyl-4, 5-dihydropyridazin-3(2H )-one Intermediate 91, 50 mg (0.20 minol) and 4-dimethylaminopyridine, 30 mg (0.25 minol) in tetrahydrofuran, 5 mL, N,N-disuccinimidyl carbonate, 63 mg (0.25 minol) was added. After 2 hours at room temperature 2,3-dihydro-1 H-pyrollo[3,4-c]pyridine dihydrochloride, 59 mg (6000- 50-6, 0.31 minol) and triethylamine, 0.29 mL, (2.04 minol) dissolved in N,N dimethylformide (3mL) were added and the mixture was stirred for a further 16 hours. The reaction mixture was diluted with a saturated solution of aminonium chloride and extracted with ethyl acetate. The combined organic layers were dried over solid sodium sulfate, filtered and concentrated undervacuum. The crude compound was purified by reverse phase chromatography (BIOTAGE SP4, 30 g Biotage cartridge) using acetonitrile and water containing 10min aminonium bicarbonate pH 10 buffer (3:97 to 100:0) to give Example 78, 31 mg (42percent) as a colourless solid.1H NMR (400 MHz, CDCI3): 6 [ppm] = 0.89 (m, 6H), 1.96 (m, IH), 2.56 (dd, IH), 2.70 (d, IH),3.04 (m, IH), 3.41 (s, 3H), 4.89 (d, 4H), 6.44 (s, IH), 7.33 (m, IH), 7.51 (d, 2H), 7.73 (d, 2H),8.59 (m, IH), 8.65 (m, IH).UPLC (Method 3): R = 0.61 min., 95percent. MS (ESIpos): mz = [M÷H] 392.
  • 28
  • [ 74124-79-1 ]
  • [ 6000-50-6 ]
  • [ 36725-28-7 ]
  • N-[4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% A solution of 406 mg of Intermediate 7 (2.00 minol, 1.00 eq) in THE (30 mL) was treated with615 mg of N,N?-disuccinimidyl carbonate (2.40 minol, 1.20 eq) and 293 mg of 4-dimethylaminopyridine (2.40 minol, 1 .20 eq). The mixture was stirred for three days at roomtemperature. A suspension of 463 mg of 2,3-dihydro-IH-pyrrolo[3,4-c]pyridine dihydrochloride(2.40 minol, 1.20 eq) and 1.00 mL of triethylamine (7.2Ominol, 3.60 eq) in DMF (2 mL) was added and the resulting suspension as again stirred over night. The mixture was poured into water, the precipitate was collected by filtration and was washed with water to provide after trituration with ethanol 440 mg of the desired product (63percent).1H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.07 (d, 3H), 2.17-2.26 (m, IH), 2.62-2.71 (m, IH),3.35-3.42 (m, IH), 4.82 (d, 4H), 7.41 -7.46 (m, IH), 7.61 -7.74 (m, 4H), 8.50 (d, IH), 8.61 (d,2H), 10.85 (s, IH).LC-MS (Method 1): R = 0.57 min; MS (ESIpos): mz = 350 [M÷H].
  • 29
  • [ 74124-79-1 ]
  • 6-(4-aminophenyl)-2-isopropyl-5-methyl-4,5-dihydropyridazin-3(2H)-one [ No CAS ]
  • [ 6000-50-6 ]
  • N-[4-(1-isopropyl-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl]-1,3-dihydro-2H-pyrrolo[3,4-c]pyridine-2-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% A solution of 100mg of Intermediate 22 (0.41 minol, 1.00 eq) in DMF (12 mL)was treated with125 mg of N,N?-disuccinimidyl carbonate (0.49 minol, 1.20 eq) and 59.7 mg of 4-dimethylaminopyrdine (0.49 minol, 1.20 eq). The mixture was stirred over night at roomtemperature. A solution of 94.4 mg of 2,3-dihydro-I H-pyrrolo[3,4-c]pyridine dihydrochloride (0.49minol, 1 .20 eq) and 1.70 mL of triethylamine (12.37 minol, 30 eq) in DMF (2 mL) was added.The mixture was stirred over night. THE was removed from under reduced pressure. The remaining solution was poured into water. The solid was removed by filtration, the filtrate was taken to dryness and the residue was purified by preparative reverse phase HPLC to yield 40.3 mg of the desired product (25percent).H-NMR (400MHz, DMSO-d6): oe [ppm] = 1.04 (d, 3H), 1.15 (d, 3H), 1.24 (d, 3H), 2.29 (dd, IH),2.68 (dd, IH), 3.21 - 3.42 (m, IH), 4.83 (d, 4H), 4.90 (quin, IH), 7.44 (d, IH), 7.60 - 7.72 (m,2H), 7.72 - 7.83 (m, 2H), 8.50 (d, I H), 8.62 (d, 2H).UPLC-MS (Method 1): RO.78 min; MS (ESIpos): mz [M÷2H] 393.
  • 30
  • [ 74124-79-1 ]
  • [ 72040-64-3 ]
  • [ 89889-52-1 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 2.25h; To a suspension of compound 9 (1 eq., 520 mg, 1.45 mmol) in DMF (25.5 mL) weresubsequently added N,N-disuccinimidyl carbonate (2.5 eq., 931 mg, 3.64 mmol) and TEA(2 eq., 294 mg, 0.404 mL, 2.91 mmol). After 15 minutes the precipitate solubilized, stirringcontinued for 2h at room temperature. lOx volume of Et20 was then added and theobtained precipitate was filtered to yield the crude product, which was recrystallized froma minimum amount of ACN to yield compound 10 as a white solid. The structure of 10 wasconfirmed by ESI-MS analysis (Method 1).ESI-MS m/z: 455.5 [M+H]
  • 31
  • [ 747412-49-3 ]
  • [ 74124-79-1 ]
  • C110H159N18O16PolS3 [ No CAS ]
  • [ 75286-49-6 ]
  • [ 60-24-2 ]
  • 5-carboxy-2-(6-(dimethylamino)-3-(dimethyliminio)-3H-xanthen-9-yl)benzoate [ No CAS ]
  • C108H153N23O19S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
25 pmol of NH2-Fx-r-Fx-r-Fx-r-K(Mtt) on resin was reacted with S-trityl-2- mercaptoproprionic acid (4 eq), PyBOP (4 eq), and DIPEA (8 eq) in 1 mL DMF. The peptide was washed (2 x DMF/MeOH/DCM) and deprotected with trifluoroacetic (0146) acid:triisopropylsilane:DCM (5:3:92, 2 x 15 minutes). The peptide washed and equilibrated in acetonitrile:water (5: 1 ). Cysteamine (20 eq) was dissolved in 1 mL acetonitrile:water (5: 1 ) and added to the reaction mixture followed by iodine (10 eq). The reaction was stirred for 30 minutes. The peptide was washed (2 x DMF:MeOH:DCM) and reacted with 5- Carboxytetramethylrhodamine (2 eq), HBTU (2 eq), and DIPEA (4 eq) in 0.5 mL DMF for 2 hours. The peptide was washed, cleaved from resin using trifluoroacetic (0147) acid:triisopropylsilane:water (95:2.5:2.5) and precipitated in ether at -20°C for 1 hour. The precipitate was purified by HPLC and lyophilized. 5-(2,4-Dihydroxy-5-isopropylphenyl)-N-ethyl- 4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide (Luminespib, 3 eq, Adooq Bioscience, Irvine CA) was reacted with Nu,Nu'-Disuccinimidyl carbonate (3 eq, Sigma-Aldrich) and 4- (Dimethylamino)pyridine (12 eq, Sigma-Aldrich) in 0.4 mL DMF for 1 hour. The peptide was dissolved in 0.1 mL DMF and added to the reaction mixture and the solution was left stirring overnight. The peptide was precipitated in ether and purified by HPLC. The earlier eluting isomer was purified and tested due to its higher relative abundance. The solution was frozen in dry ice as the compound eluted from the column and lyophilized. The peptide was identified by ESI mass spectrometry, expected m/z = 2140.12, found m/z = 2140.12. The peptide was quantified using the 5-Carboxytetramethylrhodamine absorbance at 547 nm with an extinction coefficient of 92000 M"1cm"1.
  • 32
  • [ 747412-49-3 ]
  • [ 74124-79-1 ]
  • C84H131N16O15PolS3 [ No CAS ]
  • [ 75286-49-6 ]
  • [ 60-24-2 ]
  • C77H121N19O14S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
25 muetaetaomicronIota of NH2-Fx-r-Fx-r-Fx-r on resin was reacted with S-trityl-2- mercaptoproprionic acid (4 eq), PyBOP (4 eq), and DIPEA (8 eq) in 1 mL DMF. The peptide was washed (2 x DMF/MeOH/DCM), cleaved from resin using trifluoroacetic (0139) acid:triisopropylsilane:water (95:2.5:2.5) and precipitated in ether at -20°C for 1 hour. The precipitate was purified by RP-HPLC, dried under vacuum and dissolved in 0.5 mL (0140) acetonitrile:water (5:1). 2-mercpatoethanol (20 eq, Sigma-Aldrich) was added to the reaction mixture followed by iodine (10 eq) and the reaction was stirred for 30 minutes. The peptide was purified by HPLC and lyophilized. 5-(2,4-Dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4- (morpholinomethyl)phenyl)isoxazole-3-carboxamide (Luminespib, 3 eq, Adooq Bioscience, Irvine CA) was reacted with Nu,Nu'-Disuccinimidyl carbonate (3 eq, Sigma-Aldrich) and 4- (Dimethylamino)pyridine (12 eq, Sigma-Aldrich) in 0.4 mL DMF for 1 hour. The peptide was dissolved in 0.1 mL DMF and added to the reaction mixture and the solution was left stirring overnight. The peptide was precipitated in ether and purified by HPLC. Two isomers were identified during HPLC purification, likely due to attachment to either of the two resorcinol hydroxyls. The earlier eluting isomer was purified and tested due to its higher relative abundance. The solution was frozen in dry ice as the compound eluted from the column and lyophilized. The peptide was identified by ESI mass spectrometry, expected m/z = 1599.88, found m/z = 1599.88. The peptide was quantified via absorbance spectrophotometry using a SpectraMax M5 spectrophotometer. The absorbance profile of Compound 5 was found to be shifted as compared to Luminespib itself, therefore the peptide was quantified by cleavage in 25 mM TCEP in PBS pH 7.4 for 10 minutes, then measuring free Luminespib absorbance at 305 nm with an extinction coefficient of 8520 M"1cm"1. TCEP was not found to affect the extinction coefficient of Luminespib.
  • 33
  • [ 74124-79-1 ]
  • [ 35661-51-9 ]
  • C20H17N3O6 [ No CAS ]
 

Related Products

Historical Records

Categories