2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Base Information

• Chemical Name: 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester
• CAS No.: 820993-06-4
• Molecular Formula: C₃₂H₄₇F₂N₃O₇
• Molecular Weight: 623.738
• Mol file: 820993-06-4.mol

Synonyms:2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Chemical Property of 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

Chemical Property:

Purity/Quality:

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

Useful:

Technology Process of 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

There total 7 articles about 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 67.0%

3-amino-5,5-difluoro-2-hydroxy-pentanoic acid methyl ester (262437-58-1) + N-{[1-(tert-butoxycarbonyl)-2-cyclohexyl-2,3-dihydro-1H-indol-2-yl]carbonyl}-L-leucine (820251-14-7) → 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (820993-06-4)

Guidance literature:

With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20 ℃; for 12h;

DOI:10.1021/jm049435d

Reference yield:

L-Leucine benzyl ester (1738-69-8) → 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (820993-06-4)

Guidance literature:

Multi-step reaction with 3 steps

1: HATU; DIEA / CH₂Cl₂ / 12 h

2: 57 mg / H₂ / Pd/C / methanol / 1 h / 1551.44 Torr

3: 67 percent / HOBt; DIEA; EDC / CH₂Cl₂ / 12 h / 20 °C

With hydrogen; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; palladium on activated charcoal; In methanol; dichloromethane;

DOI:10.1021/jm049435d

Reference yield:

rac-3-bromocyclohexene (1521-51-3,113667-32-6) → 2-cyclohexyl-2-{1-[3,3-difluoro-1-(hydroxy-methoxycarbonyl-methyl)-propylcarbamoyl]-3-methyl-butylcarbamoyl}-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (820993-06-4)

Guidance literature:

Multi-step reaction with 5 steps

1.1: KHMDS / tetrahydrofuran; toluene / 0.5 h / -78 - -30 °C

1.2: 70 percent / tetrahydrofuran; toluene / -78 - 20 °C

2.1: 95 percent / aq. NaOH / tetrahydrofuran / 72 h / 90 °C

3.1: HATU; DIEA / CH₂Cl₂ / 12 h

4.1: 57 mg / H₂ / Pd/C / methanol / 1 h / 1551.44 Torr

5.1: 67 percent / HOBt; DIEA; EDC / CH₂Cl₂ / 12 h / 20 °C

With sodium hydroxide; hydrogen; potassium hexamethylsilazane; benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; palladium on activated charcoal; In tetrahydrofuran; methanol; dichloromethane; toluene;

DOI:10.1021/jm049435d

upstream raw materials:

3-amino-5,5-difluoro-2-hydroxy-pentanoic acid methyl ester

N-{[1-(tert-butoxycarbonyl)-2-cyclohexyl-2,3-dihydro-1H-indol-2-yl]carbonyl}-L-leucine

L-Leucine benzyl ester

rac-3-bromocyclohexene