Sodium triacetoxyborohydride → N-(2-Aminophenyl)-4-{1-[(3-ethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzamide

HRID 222401Notes

Reaction equation

HRID 222401 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[CH:29]=[CH:28][C:10]([C:11]([NH:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[NH:20]C(=O)OC(C)(C)C)=[O:12])=[CH:9][CH:8]=2)[CH2:3][CH2:2]1.[CH2:30]([C:32]1[C:36]([CH:37]=O)=[CH:35][NH:34][N:33]=1)[CH3:31].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[NH2:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[NH:13][C:11](=[O:12])[C:10]1[CH:28]=[CH:29][C:7]([CH:4]2[CH2:3][CH2:2][N:1]([CH2:37][C:36]3[C:32]([CH2:30][CH3:31])=[N:33][NH:34][CH:35]=3)[CH2:6][CH2:5]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 59830875Tert-butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamateHCID 1784380373-Ethyl-1H-pyrazole-4-carbaldehyde

Product 1

HCID 178438036N-(2-Aminophenyl)-4-{1-[(3-ethyl-1H-pyrazol-4-yl)methyl]piperidin-4-yl}benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

tert-Butyl 2-[(4-piperidin-4-ylbenzoyl)amino]phenylcarbamate (prepared as described in Method 1 below; 395 mg, 1.0 mmol) and 3-ethyl-1H-pyrazole-4-carbaldehyde (149 mg, 1.2 mmol) were stirred at ambient temperature in dichloromethane (10 ml) for 1 hour. Sodium triacetoxyborohydride (297 mg, 1.4 mmol) was added and the mixture stirred at ambient temperature for 24 hours. The resulting solution was absorbed onto an SCX-2 column which was washed with methanol (2 column volumes) and then the product eluted with a 2M solution of ammonia in methanol (2 column volumes) to give the product as a white foam. This was purified by chromatography on silica eluting with 10% methanol in dichloromethane. The residue was dissolved in dichloromethane (4 ml) and trifluoroacetic acid (1 ml) was added and the mixture stirred for 3 hours at ambient temperature. The resulting solution was absorbed onto an SCX-2 column which was washed with methanol (2 column volumes) and then the product eluted with a 2M solution of ammonia in methanol (2 column volumes) to give the title compound (232 mg, 75%). NMR Spectrum: (DMSO d6) δ 1.18 (t, 3H), 1.65 (m, 2H), 1.77 (m, 2H), 2.00 (m, 2H), 2.57 (m, 3H), 2.95 (m, 2H), 3.34 (s, 2H), 4.86 (br s, 2H), 6.60 (m, 1H), 6.78 (d, 1H), 6.97 (m, 1H), 7.17 (d, 1H), 7.29 (br s, 1H), 7.37 (d, 2H), 7.91 (d, 2H), 9.55 (s, 1H), 12.39 (s, 1H); Mass Spectrum: M+H+404.

Workup

  1. customThe resulting solution was absorbed onto an SCX-2 column which
  2. washwas washed with methanol (2 column volumes)
  3. washthe product eluted with a 2M solution of ammonia in methanol (2 column volumes)

Sources & evidence

ORD record
ord-793c407d576f417fa3138fa67246d411
Source dataset
uspto-grants-2012_06
Patent number
US08207202B2

Reaction notes

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