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

HRID 349004Notes

Reaction equation

HRID 349004 reaction equation
[CH2:1]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([OH:16])=O)[CH:12]=2)[N:7]([CH3:17])[CH:6]=1)[CH2:2][CH2:3][CH3:4].[NH2:18][C@@H:19]([CH2:33][C:34]1[CH:39]=[C:38]([F:40])[CH:37]=[C:36]([F:41])[CH:35]=1)[C@H:20]([OH:32])[CH2:21][NH:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH3:31])[CH:25]=1>C(Cl)Cl.O1CCCC1>[CH2:1]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]([NH:18][C@@H:19]([CH2:33][C:34]3[CH:35]=[C:36]([F:41])[CH:37]=[C:38]([F:40])[CH:39]=3)[C@H:20]([OH:32])[CH2:21][NH:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([CH2:30][CH3:31])[CH:25]=3)=[O:16])[CH:12]=2)[N:7]([CH3:17])[CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 2

HCID 210857263-Butyl-1-methyl-1H-indole-5-carboxylic acidHCID 57487282(2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol

Product 1

HCID 575126263-Butyl-N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-1-methyl-1H-indole-5-carboxamideYield 31.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a mixture of 3-Butyl-1-methyl-1H-indole-5-carboxylic acid (0.15 g) in methylene chloride (5 mL) and tetrahydrofuran (10 mL) was added 1,1-carbonyldiimidazole (0.105 g). The mixture was stirred at 40° C. at which time (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (0.2 g) in methylene chloride (5 mL) was added. The mixture was stirred at 40° C. for 18 h then poured into methylene chloride (50 mL). The mixture was washed with water then brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Column chromatography on silica gel (100 mL) using 85:10:5 (methylene chloride: hexanes: methanol) as eluent to give 0.102 g of the title compound: MS (ESI+) for C33H39F2N3O2 m/z 547.9 (M+H)+.

Workup

  1. additionwas added
  2. washThe mixture was washed with water
  3. dry with materialbrine, dried over anhydrous sodium sulfate
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-777ae8f0684c4642be12d3e778e3fc44
Source dataset
uspto-grants-2007_02
Patent number
US07176242B2

Reaction notes

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