Diisopropylethylamine → N-{(3RS,4SR)-4-(4-Chloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-4-methoxy-N-methyl-3-trifluoromethyl-benzamide

HRID 1951085Notes

Reaction equation

HRID 1951085 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][NH:11][CH2:10][CH:9]2[N:13]([CH3:28])[C:14](=[O:27])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([C:23]([F:26])([F:25])[F:24])[CH:16]=2)=[CH:4][CH:3]=1.[CH3:29][C:30]1([C:33]([N:35]2[CH2:40][CH2:39][CH:38]([C:41](O)=[O:42])[CH2:37][CH2:36]2)=[O:34])[CH2:32][CH2:31]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][N:11]([C:41]([CH:38]3[CH2:37][CH2:36][N:35]([C:33]([C:30]4([CH3:29])[CH2:32][CH2:31]4)=[O:34])[CH2:40][CH2:39]3)=[O:42])[CH2:10][CH:9]2[N:13]([CH3:28])[C:14](=[O:27])[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([C:23]([F:24])([F:25])[F:26])[CH:16]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 594381681-(1-Methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acidHCID 67025659N-[(3RS,4SR)-4-(4-Chloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide

Product 1

HCID 67025670N-{(3RS,4SR)-4-(4-Chloro-phenyl)-1-[1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carbonyl]-pyrrolidin-3-yl}-4-methoxy-N-methyl-3-trifluoromethyl-benzamideYield 72%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of N-[(3RS,4SR)-4-(4-chloro-phenyl)-pyrrolidin-3-yl]-4-methoxy-N-methyl-3-trifluoromethyl-benzamide (200 mg, 0.484 mmol) in DMF (2 mL) was added 1-(1-methyl-cyclopropanecarbonyl)-piperidine-4-carboxylic acid (113 mg, 0.533 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (221 mg, 0.581 mmol) and N,N-diisopropyl ethyl amine (498 μl, 2.90 mmol). The solution was stirred for 3 h at ambient temperature. After diluting with ethyl acetate (15 mL) the solution was washed twice with water (15 mL) and brine (10 mL). The aqueous layers were extracted with ethyl acetate (15 mL) and dried over sodium sulfate. Purification by chromatography (SiO2, heptane:ethyl acetate:methanol=50:50:0 to 0:90:10) afforded the title compound (210 mg, 72%) as a light brown oil. MS m/e: 606.2 [M]+.

Workup

  1. washwas washed twice with water (15 mL) and brine (10 mL)
  2. extractionThe aqueous layers were extracted with ethyl acetate (15 mL)
  3. dry with materialdried over sodium sulfate
  4. customPurification by chromatography (SiO2, heptane:ethyl acetate:methanol=50:50:0 to 0:90:10)

Sources & evidence

ORD record
ord-dd5ccdde0ccd466ebf909cb833a2d469
Source dataset
uspto-grants-2013_03
Patent number
US08404679B2

Reaction notes

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