Triethylamine → 1-Butyl-4-cyano-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-1H-indole-6-carboxamide

HRID 14182

Reaction equation

HRID 14182 reaction equation
[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([C:17]#[N:18])[CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[NH2:26][C@@H:27]([CH2:41][C:42]1[CH:47]=[C:46]([F:48])[CH:45]=[C:44]([F:49])[CH:43]=1)[C@H:28]([OH:40])[CH2:29][NH:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][CH3:39])[CH:33]=1>C(Cl)Cl>[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([C:17]#[N:18])[CH:10]=[C:11]([C:14]([NH:26][C@@H:27]([CH2:41][C:42]3[CH:43]=[C:44]([F:49])[CH:45]=[C:46]([F:48])[CH:47]=3)[C@H:28]([OH:40])[CH2:29][NH:30][CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38][CH3:39])[CH:33]=3)=[O:16])[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 210851701-butyl-4-cyano-1H-indole-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 210851731-Butyl-4-cyano-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl)-1H-indole-6-carboxamideYield 70.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of 1-butyl-4-cyano-1H-indole-6-carboxylic acid (0.29 g) in methylene chloride (10 mL) was added 1,1-carbonyldiimidazole (0.194 g) and triethylamine (0.267 g). The mixture was stirred at room temperature for 45 minutes at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.5 g) dissolved in methylene chloride (10 mL) was added. The mixture was stirred at room temperature for 18 h then poured into methylene chloride (50 mL), washed with water followed by brine, dried over anhydrous magnesium sulfate and concentrated under vacuum. Column chromatography on silica gel (100 mL) using 5% methanol in methylene chloride as eluent to give 0.47 g of the title compound: MS (ESI+) for C33H36F2N4O2 m/z 559.0 (M+H)+.

Workup

  1. additionwas added
  2. washwashed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-3bba66f0bde4413690c93677c302aaa5
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Linked notes

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