Acetic Acid → 1-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}-N,N-dimethylpiperidine-4-carboxamide diformate

HRID 426078Notes

Reaction equation

HRID 426078 reaction equation
[N:1]1([C:5]([CH:7]2[CH2:12][CH2:11][N:10]([CH:13]3[CH2:16][N:15]([CH2:17][CH2:18][C@@H:19]([C:36]4[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=4)[CH2:20][N:21]([CH3:35])[C:22](=[O:34])[C:23]4[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([Br:33])[CH:24]=4)[CH2:14]3)[CH2:9][CH2:8]2)=[O:6])[CH2:4]C[CH2:2]1.N1CC(N2CCC(C(N(C)C)=O)CC2)C1.[C:58]([OH:61])(=[O:60])C>CO>[CH:58]([OH:61])=[O:60].[CH:58]([OH:61])=[O:60].[Br:33][C:25]1[CH:24]=[C:23]([CH:28]=[C:27]([C:29]([F:31])([F:30])[F:32])[CH:26]=1)[C:22]([N:21]([CH3:35])[CH2:20][C@H:19]([C:36]1[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=1)[CH2:18][CH2:17][N:15]1[CH2:14][CH:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:5]([N:1]([CH3:2])[CH3:4])=[O:6])[CH2:8][CH2:9]2)[CH2:16]1)=[O:34]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 23582759N-[(2S)-4-{3-[4-(Azetidin-1-ylcarbonyl)piperidin-1-yl]azetidin-1-yl}-2-(4-fluorophenyl)butyl]-3-bromo-N-methyl-5-(trifluoromethyl)benzamideHCID 236587821-azetidin-3-yl-N,N-dimethylpiperidine-4-carboxamide

Product 1

HCID 866165021-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}-N,N-dimethylpiperidine-4-carboxamide diformateYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 3-bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see method 1; 0.178 g, 0.40 mmol), 1-azetidin-3-yl-N,N-dimethylpiperidine-4-carboxamide (see method 3; 0.084 g, 0.40 mmol), acetic acid (0.3 mL), (polystyrylmethyl)trimethylammonium cyanoborohydride (0.098 g, 0.52 mmol) and methanol was stirred at RT for 6 h. The resin was filtered off and washed with methanol. The solvent of the filtrate was removed by evaporation and the product was purified by reversed phase chromatography (C8) using acetonitrile and aqueous ammonium formate/formic acid solution (0.1 M N4CO2H, 0.1 M HCO2H, pH 4) as eluent. There was obtained 0.23 g (77%) of the title compound. 1H NMR (500 MHz, CD3OD): δ 1.6-2.0 (cm, 6H), 2.6-4.2 (cm, 24H), 7.0-8.0 (cm, 6H), 8.4 (s, 1H); LCMS: m/z 642 (M+1)+.

Workup

  1. filtrationThe resin was filtered off
  2. washwashed with methanol
  3. customThe solvent of the filtrate was removed by evaporation
  4. customthe product was purified by reversed phase chromatography (C8)

Sources & evidence

ORD record
ord-1d5c64a5a0634719ab58055bd2f82efe
Source dataset
uspto-grants-2012_01
Patent number
US08106208B2

Reaction notes

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