1,1'-Carbonyldiimidazole → 3-acetyl-1-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1H-indole-6-carboxamide

HRID 14224Notes

Reaction equation

HRID 14224 reaction equation
[C:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([OH:15])=O)=[CH:10][CH:11]=2)[N:6]([CH2:16][CH2:17][CH2:18][CH3:19])[CH:5]=1)(=[O:3])[CH3:2].C(N1C=CN=C1)(N1C=CN=C1)=O.[NH2:32][C@@H:33]([CH2:47][C:48]1[CH:53]=[C:52]([F:54])[CH:51]=[C:50]([F:55])[CH:49]=1)[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH3:45])[CH:39]=1>ClCCl>[C:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([NH:32][C@@H:33]([CH2:47][C:48]3[CH:49]=[C:50]([F:55])[CH:51]=[C:52]([F:54])[CH:53]=3)[C@H:34]([OH:46])[CH2:35][NH:36][CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([CH2:44][CH3:45])[CH:39]=3)=[O:15])=[CH:10][CH:11]=2)[N:6]([CH2:16][CH2:17][CH2:18][CH3:19])[CH:5]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 210857003-acetyl-1-butyl-1H-indole-6-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 575082453-acetyl-1-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1H-indole-6-carboxamideYield 77.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-Acetyl-1-butyl-1H-indole-6-carboxylic acid (0.322 g) was dissolved in dichloromethane (15 mL). 1,1′-Carbonyldiimidazole was added (0.171 g). The mixture was stirred for 2 h and then a mixture of (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.250 g) in dichloromethane (15 mL) was added. After stirring overnight, the mixture was partitioned between dichloromethane, water, and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was chromatographed on silica gel using MeOH/dichloromethane (4/96) to give 3-acetyl-1-butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1H-indole-6-carboxamide (0.335 g). MS (ESI+) for C34H39F2N3O3+H1 m/z 576.30 (M+H)+.

Workup

  1. additionwas added
  2. stirringAfter stirring overnight
  3. customthe mixture was partitioned between dichloromethane, water, and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-3e55af888bed43239d72fd09885e2e11
Source dataset
uspto-grants-2010_06
Patent number
US07727997B2

Reaction notes

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