4-Methylmorpholine → 3-(2-Chlorophenyl)-1-(4-methylphenyl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indole-6-carboxamide

HRID 1047651Notes

Reaction equation

HRID 1047651 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([OH:19])=O)=[CH:14][CH:15]=2)[N:10]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)[CH:9]=1.[O-:27][N+:28]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][CH:31]=[C:30]([C@H:38]([NH2:40])[CH3:39])[CH:29]=1.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]([NH:40][C@@H:38]([C:30]3[CH:29]=[N+:28]([O-:27])[C:33]([C:34]([F:35])([F:36])[F:37])=[CH:32][CH:31]=3)[CH3:39])=[O:19])=[CH:14][CH:15]=2)[N:10]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)[CH:9]=1

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 59539683(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamineHCID 666614783-(2-Chlorophenyl)-1-(4-methylphenyl)-1H-indole-6-carboxylic acid

Product 1

HCID 666615193-(2-Chlorophenyl)-1-(4-methylphenyl)-N-{(1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethyl}-1H-indole-6-carboxamideYield 67.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(2-chlorophenyl)-1-(4-methylphenyl)-1H-indole-6-carboxylic acid (9.5 mg, 26.0 μmol) in N,N-dimethylformamide (0.5 mL) were added hydrochloride salt of (1R)-1-[1-oxido-6-(trifluoromethyl)pyridin-3-yl]ethanamine (7.3 mg, 30.0 μmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (12.5 mg, 65.0 μmol), 1-hydroxy-7-azabenzotriazole (2.2 mg, 16.0 μmol) and N-methylmorpholine (12.0 μL, 0.11 mmol). The mixture was stirred at ambient temperature for 30 min. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave the bistrifluoroacetate salt of the title compound (9.7 mg): HRMS [M+1] found=550.1505; 1H NMR (500 MHz, CDCl3): δ 8.50 (s, 1H); 8.08 (s, 1H); 7.67 (t, J=7.7 Hz, 3H); 7.61-7.47 (m, 4H); 7.44-7.21 (m, 6H); 6.66 (d, J=6.6 Hz, 1H); 5.31-5.23 (m, 1H); 2.44 (s, 3H); 1.64 (dd, J=20.9, 7.1 Hz, 3H).

Workup

  1. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-c32f67d45bf248f5832d4ee675907381
Source dataset
uspto-grants-2013_10
Patent number
US08569512B2

Reaction notes

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