Trifluoroacetic acid → N-(2-Aminophenyl)-4-{1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzamide

HRID 222405Notes

Reaction equation

HRID 222405 reaction equation
[CH3:1][N:2]1[C:6]([CH3:7])=[C:5]([CH2:8][N:9]2[CH2:14][CH2:13][CH:12]([C:15]3[CH:37]=[CH:36][C:18]([C:19]([NH:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[NH:28]C(=O)OC(C)(C)C)=[O:20])=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)[CH:4]=[N:3]1.FC(F)(F)C(O)=O>ClCCl>[NH2:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[NH:21][C:19](=[O:20])[C:18]1[CH:17]=[CH:16][C:15]([CH:12]2[CH2:11][CH2:10][N:9]([CH2:8][C:5]3[CH:4]=[N:3][N:2]([CH3:1])[C:6]=3[CH3:7])[CH2:14][CH2:13]2)=[CH:37][CH:36]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59830880tert-Butyl {2-[(4-{1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzoyl)amino]phenyl}carbamate

Product 1

HCID 16225172N-(2-Aminophenyl)-4-{1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzamideYield 73.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl {2-[(4-{1-[(1,5-dimethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzoyl)amino]phenyl}carbamate (prepared as described in Method 7; 308 mg, 0.61 mmol) was taken up in dichloromethane (2 ml) and trifluoroacetic acid (1 ml) added. The reaction mixture was stirred at ambient temperature for 1 hour before being poured onto an SCX-3 cartridge (5 g). The cartridge was washed with dichloromethane (50 ml) and methanol (50 ml), before eluting the product with a 2M solution of ammonia in methanol (50 ml). The ammoniacal fraction was evaporated to afford a white solid (182 mg) that was purified by reverse phase preparative HPLC to afford the title compound (134 mg, 55%); NMR Spectrum: (DMSO d6) δ 1.70 (m, 4H), 2.01 (m, 2H), 2.22 (s, 3H), 2.57 (m, 1H), 2.95 (m, 2H), 3.28 (s, 2H), 3.71 (s, 3H), 4.86 (s, 2H), 6.60 (m, 1H), 6.78 (m, 1H), 6.97 (m, 1H), 7.17 (m, 1H), 7.23 (s, 1H), 7.37 (d, 2H), 7.90 (d, 2H), 9.55 (s, 1H); Mass Spectrum: M+H+404.

Workup

  1. additionbefore being poured onto an SCX-3 cartridge (5 g)
  2. washThe cartridge was washed with dichloromethane (50 ml) and methanol (50 ml)
  3. washbefore eluting the product with a 2M solution of ammonia in methanol (50 ml)
  4. customThe ammoniacal fraction was evaporated

Sources & evidence

ORD record
ord-3a7d8f2578b949f58dd4609eec9d22b0
Source dataset
uspto-grants-2012_06
Patent number
US08207202B2

Reaction notes

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