1-butyl-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxylic acid → 1-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxamide

HRID 14179Notes

Reaction equation

HRID 14179 reaction equation
[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([C:17]3[O:18][CH:19]=[CH:20][N:21]=3)[CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4].[NH2:22][C@@H:23]([CH2:37][C:38]1[CH:43]=[C:42]([F:44])[CH:41]=[C:40]([F:45])[CH:39]=1)[C@H:24]([OH:36])[CH2:25][NH:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][CH3:35])[CH:29]=1>C(Cl)Cl>[CH2:1]([N:5]1[C:13]2[C:8](=[C:9]([C:17]3[O:18][CH:19]=[CH:20][N:21]=3)[CH:10]=[C:11]([C:14]([NH:22][C@@H:23]([CH2:37][C:38]3[CH:39]=[C:40]([F:45])[CH:41]=[C:42]([F:44])[CH:43]=3)[C@H:24]([OH:36])[CH2:25][NH:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([CH2:34][CH3:35])[CH:29]=3)=[O:16])[CH:12]=2)[CH:7]=[CH:6]1)[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 210851691-butyl-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 575129651-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxamideYield 23.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a mixture of 1-butyl-4-(1,3-oxazol-2-yl)-1H-indole-6-carboxylic acid (0.2 g) in methylene chloride (20 mL) was added 1,1-carbonyldiimidazole (0.114 g). The mixture was stirred at room temperature for 1 h at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.265 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 reduced pressure. Column chromatography on silica gel (100 mL) using 65% methylene chloride, 30% hexanes, and 5% methanol as eluent to give 0.0985 g of the title compound: MS (ESI+) for C35H38F2N4O3 m/z 601.99 (M+H)+.

Workup

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

Sources & evidence

ORD record
ord-cff34015ba624ba5a241ee4299a9abc9
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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