Triethylamine → 1-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}piperidine-4-carboxamide

HRID 426079Notes

Reaction equation

HRID 426079 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])CCC1.N1CC(N2CCC(C(N)=O)CC2)C1.C(N(CC)CC)C.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[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:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=1)[CH2:18][CH2:17][N:15]1[CH2:14][CH:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:5]([NH2:1])=[O:6])[CH2:8][CH2:9]2)[CH2:16]1)=[O:34]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 5003444Sodium cyanoborohydrideHCID 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 236589541-Azetidin-3-ylpiperidine-4-carboxamide

Product 1

HCID 236615481-{1-[(3S)-4-[[3-Bromo-5-(trifluoromethyl)benzoyl](methyl)amino]-3-(4-fluorophenyl)butyl]azetidin-3-yl}piperidine-4-carboxamideYield 17.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

3-Bromo-N-[(2S)-2-(4-fluorophenyl)-4-oxobutyl]-N-methyl-5-(trifluoromethyl)benzamide (see method 1; 1.00 g, 2.24 mmol) and 1-azetidin-3-ylpiperidine-4-carboxamide (see method 4; 0.49 g, 2.69 mmol) and triethylamine (1.24 mL, 9.0 mmol) were dissolved in methylene chloride (30 mL) together with methanol (5 mL). To the resultant solution was added sodium cyanoborohydride (0.21 g, 3.36 mmol) and the mixture was stirred at RT for 20 min. The solvent was removed by evaporation and the residue was partitioned between methylene chloride and saturated aqueous NaHCO3. The organic phase was filtered through a phase separator and the solvent was removed by evaporation. The product was purified by chromatography on silica gel (ammonia saturated methanol/methylene chloride, 1-20% methanol). There was obtained 0.24 g (17%) of the title compound. 1H NMR (500 MHz, CDCl3): δ 1.4-3.8 (cm, 23H), 5.7 (b, 1H), 5.8 (b, 1H), 6.8-7.4 (cm, 6H), 7.7 (s, 1H); LCMS: m/z 614 (M+1)+.

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was partitioned between methylene chloride and saturated aqueous NaHCO3
  3. filtrationThe organic phase was filtered through a phase separator
  4. customthe solvent was removed by evaporation
  5. customThe product was purified by chromatography on silica gel (ammonia saturated methanol/methylene chloride, 1-20% methanol)

Sources & evidence

ORD record
ord-e736d21716bc447787b10d96386f3a93
Source dataset
uspto-grants-2012_01
Patent number
US08106208B2

Reaction notes

Loading…