Potassium Carbonate → N-[2-({(3R)-1-[1-(4-cyanophenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

HRID 564364Notes

Reaction equation

HRID 564364 reaction equation
[O:1]=[C:2]([NH:17][C@@H:18]1[CH2:22][CH2:21][N:20]([CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH2:19]1)[CH2:3][NH:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].F[C:36]1[CH:43]=[CH:42][C:39]([C:40]#[N:41])=[CH:38][CH:37]=1.[NH4+].[OH-]>CS(C)=O.CCOC(C)=O.CO>[C:40]([C:39]1[CH:42]=[CH:43][C:36]([N:26]2[CH2:25][CH2:24][CH:23]([N:20]3[CH2:21][CH2:22][C@@H:18]([NH:17][C:2](=[O:1])[CH2:3][NH:4][C:5](=[O:16])[C:6]4[CH:11]=[CH:10][CH:9]=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:7]=4)[CH2:19]3)[CH2:28][CH2:27]2)=[CH:37][CH:38]=1)#[N:41]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 145174-FluorobenzonitrileHCID 14923Ammonium HydroxideHCID 67004975N-(2-oxo-2-{[(3R)-1-piperidin-4-ylpyrrolidin-3-yl]amino}ethyl)-3-(trifluoromethyl)benzamide

Product 1

HCID 67004396N-[2-({(3R)-1-[1-(4-cyanophenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamideYield 75%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of N-(2-oxo-2-{[(3R)-1-piperidin-4-ylpyrrolidin-3-yl]amino}ethyl)-3-(trifluoromethyl)benzamide (33 mg, 0.083 mmol) in DMSO (3 mL) was added K2CO3 (17.2 mg, 0.124 mmol) followed by 4-fluorobenzonitrile (10 mg, 0.83 mmol). The mixture was heated to 120° C. for 16 hours. The crude mixture was subjected to column chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3R)-1-[1-(4-cyanophenyl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (0.031 g, 75%) as a white solid. 1H-NMR (CDCl3) δ: 1.48-1.70 (m, 3H), 1.82-1.96 (m, 2H), 2.20-2.42 (m, 3H), 2.58-2.76 (m, 2H), 2.84-3.00 (m, 3H), 3.70-3.82 (m, 2H), 4.08 (d, J=4.8 Hz, 2H), 4.38-4.51 (m, 1H), 6.45 (d, J=7.5 Hz, 1H), 6.82 (d, J=9.0 Hz, 2H), 7.18-7.27 (m, 1H), 7.44 (d, J=8.7 Hz, 2H), 7.54 (t, J=7.8 Hz, 1H), 7.74 (d, J=8.7 Hz, 1H), 7.96 (d, J=7.8 Hz, 1H), 8.07 (s, 1H). MS m/z: 500 (M+1).

Sources & evidence

ORD record
ord-305c52ebd5d645bdb73aefb08c1ae60b
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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