Water → N-[2-({(3R)-1-[1-(4-methoxyphenyl)-2-oxopiperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 564385Notes

Reaction equation

HRID 564385 reaction equation
O.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]=[CH:12][C:11]2=[O:16])=[CH:6][CH:5]=1.[O:17]=[C:18]([NH:33][C@@H:34]1[CH2:38][CH2:37][NH:36][CH2:35]1)[CH2:19][NH:20][C:21](=[O:32])[C:22]1[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=1.[NH4+].[OH-]>CCOC(C)=O.CO>[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:36]3[CH2:37][CH2:38][C@@H:34]([NH:33][C:18](=[O:17])[CH2:19][NH:20][C:21](=[O:32])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:29])([F:31])[F:30])[CH:23]=4)[CH2:35]3)[CH2:12][C:11]2=[O:16])=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14923Ammonium HydroxideHCID 59556069(R)-N-(2-oxo-2-(pyrrolidin-3-ylamino)ethyl)-3-(trifluoromethyl)benzamideHCID 670050131-(4-methoxyphenyl)-5,6-dihydropyridin-2(1H)-one

Product 1

HCID 57814063N-[2-({(3R)-1-[1-(4-methoxyphenyl)-2-oxopiperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 53.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A slurry of water (19 μL, 0.10 mmol), 1-(4-methoxyphenyl)-5,6-dihydropyridin-2(1H)-one (42 mg, 0.207 mmol) and N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (130 mg, 0.41 mmol) was heated to 90° C. overnight. The crude mixture was subjected to flash chromatography (1% NH4OH, 15% MeOH, EtOAc) to yield the title compound as a white solid (57 mg, 53%). 1H-NMR (CD3OD) δ: 1.70-1.82 (m, 1H), 1.83-2.00 (m, 1H), 2.15-2.37 (m, 2H); 2.40-2.58 (m, 1H), 2.56-2.81 (m, 4H), 2.83-3.00 (m, 2H), 3.29-3.33 (m, 2H), 3.60-3.71 (m, 2H), 3.79 (s, 3H), 4.04 (s, 2H), 4.38-4.47 (m, 1H), 6.94 (d, J=8.7 Hz, 2H), 7.16 (d, J=8.7 Hz, 2H), 7.69 (t, J=7.8 Hz, 1H), 7.86 (d, J=7.8 Hz, 1H), 8.14 (d, J=7.8 Hz, 1H), 8.22 (s, 1H). MS m/z: 519 (M+1).

Sources & evidence

ORD record
ord-dc9f1c36093e4635aea256a2c3d10220
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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