4-Methylmorpholine → 4-(4-Fluorophenyl)-1-methyl-N-{(1R) 1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indole-6-carboxamide

HRID 1047647Notes

Reaction equation

HRID 1047647 reaction equation
[Na].[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]([C:18](O)=[O:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][N:13]3[CH3:21])=[CH:5][CH:4]=1.[O-:22][N+:23]1[C:28]([C:29]([F:32])([F:31])[F:30])=[CH:27][CH:26]=[C:25]([C@H:33]([NH2:35])[CH3:34])[CH:24]=1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1>CN(C)C=O>[F:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:17]=[C:16]([C:18]([NH:35][C@@H:33]([C:25]3[CH:24]=[N+:23]([O-:22])[C:28]([C:29]([F:30])([F:31])[F:32])=[CH:27][CH:26]=3)[CH3:34])=[O:19])[CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][N:13]3[CH3:21])=[CH:5][CH:4]=1

Participants

8

Reactant 6

HCID 79724-MethylmorpholineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5360545SodiumHCID 59539683(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamineHCID 666613264-(4-fluorophenyl)-1-methyl-1H-indole-6-carboxylic acid

Product 1

HCID 666614144-(4-Fluorophenyl)-1-methyl-N-{(1R) 1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indole-6-carboxamideYield 86.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of sodium salt of 4-(4-fluorophenyl)-1-methyl-1H-indole-6-carboxylic acid (25.0 mg, 56.0 μmol), hydrochloride salt of (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (16.4 mg, 67.0 μmol) and N-methylmorpholine (30.9 μL, 0.28 mmol) in N,N-dimethylformamide (0.56 mL) were added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (18.9 mg, 98.0 μmol), 1-hydroxy-7-azabenzotriazole (3.8 mg, 28.1 μmol). The mixture was stirred at ambient temperature. After 18 h, the mixture was concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% NH4OH) gave the title compound (22.1 mg): HRMS [M+1] found=458.1491; 1H NMR (400 MHz, DMSO): δ 8.90 (d, J=7.3 Hz, 1H); 8.53 (s, 1H); 8.06 (s, 1H); 7.94 (d, J=8.4 Hz, 1H); 7.74 (dd, =8.4, 5.5 Hz, 2H); 7.69 (s, 1H); 7.59 (d, J=3.1 Hz, 1H); 7.55 (d, J=8.4 Hz, 1H); 7.40-7.31 (m, 2H); 6.56 (d, J=3.1 Hz, 1H); 5.27-5.18 (m, 1H); 3.90 (s, 3H); 1.56 (d, J=7.1 Hz, 3H).

Workup

  1. concentrationthe mixture was concentrated
  2. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% NH4OH)

Sources & evidence

ORD record
ord-b936fa4b012148ca9d2ee0a54cec2eba
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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