Triethylamine → 3-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid cyclopropylmethyl-amide

HRID 2224656Notes

Reaction equation

HRID 2224656 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]([C:15]3[C:23]4[C:18](=[CH:19][C:20]([C:24](O)=[O:25])=[CH:21][CH:22]=4)[NH:17][CH:16]=3)=[O:14])=[C:11]([CH3:27])[O:10][N:9]=2)=[CH:4][CH:3]=1.CN(C)CCCN=C=NCC.O[N:40]1[C:44]2[CH:45]=[CH:46][CH:47]=CC=2N=N1.CCN(CC)CC.C1(N)CC1>CN(C=O)C>[CH:45]1([CH2:44][NH:40][C:24]([C:20]2[CH:19]=[C:18]3[C:23]([C:15]([C:13]([C:12]4[C:8]([C:5]5[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=5)=[N:9][O:10][C:11]=4[CH3:27])=[O:14])=[CH:16][NH:17]3)=[CH:22][CH:21]=2)=[O:25])[CH2:47][CH2:46]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 69828CyclopropylamineHCID 757711-HydroxybenzotriazoleHCID 691119953-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid

Product 1

HCID 161183293-[3-(4-Fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid cyclopropylmethyl-amideYield 72%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 62 mg (0.17 mmol) 3-[3-(4-fluoro-phenyl)-5-methyl-isoxazole-4-carbonyl]-1H-indole-6-carboxylic acid, 41 mg (0.21 mmol) N-(3-dimethylaminopropyl)-N′-ethyl carbodiimide, 23 mg (0.17 mmol) 1-hydroxy benzotriazole, 59 uL (0.43 mmol) Et3N and 0.26 mmol cyclopropylamine in DMF (1 mL) was reacted at room temperature overnight. After evaporation the mixture was subjected to preparative HPLC purification on reversed phase eluting with an acetonitrile/water (0.05% NEt3) gradient to afford 51 mg of the title compound in 72% yield as a white solid. (m/e): 418.1 (MH+; 100%).

Workup

  1. customAfter evaporation the mixture
  2. customwas subjected to preparative HPLC purification on reversed phase
  3. washeluting with an acetonitrile/water (0.05% NEt3) gradient

Sources & evidence

ORD record
ord-d74bef7e6baf42ceab5e482f5b0bbeb3
Source dataset
uspto-grants-2008_05
Patent number
US07378435B2

Reaction notes

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