Water → 6-Trifluoromethyl-pyridine-2-carboxylic acid [3-(4-cyclohexylcarbamoyl-piperidin-1-ylmethyl)-phenyl]-amide
Reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[N:8]=[C:7]([C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=1.[CH:14]1([NH:20][C:21]([CH:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[C:32]([NH2:36])[CH:31]=3)[CH2:25][CH2:24]2)=[O:22])[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.O=P(Cl)(Cl)Cl.O>CN(C=O)C>[CH:14]1([NH:20][C:21]([CH:23]2[CH2:24][CH2:25][N:26]([CH2:29][C:30]3[CH:31]=[C:32]([NH:36][C:9]([C:7]4[CH:6]=[CH:5][CH:4]=[C:3]([C:2]([F:1])([F:13])[F:12])[N:8]=4)=[O:11])[CH:33]=[CH:34][CH:35]=3)[CH2:27][CH2:28]2)=[O:22])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 6-trifluoromethylpyridine-2-carboxylic acid (19.1 mg, 0.1 mmol) in DMF (0.5 mL) is treated successively with a solution of 1-(3-Amino-benzyl)-piperidine-4-carboxylic acid cyclohexylamide BB-1 (36.3 mg, 0.1 mmol) in DMF (0.5 mL) and with POCl3 (0.01 mL, 0.11 mmol) at RT. The resulting solution is stirred at RT for 30 min and heated at 80° C. for 1 h. The reaction mixture is treated with water (0.2 mL) and evaporated under HV. The title compound is obtained by prep. HPLC F as a colorless powder: LC-MS B: tR=1.21 min; [M+H]+=440.1. 1H-NMR (CDCl3): δ 1-1.3 (m, 6H), 1.5-2.1 (m, 12H), 2.3-2.4 (m, 1H), 3.0-3.1 (m, 2H), 3.4-3.5 (m, 1H) 5.4 (s broad, 1H), 7.16 (d, J=7, 1H), 7.37 (t, J=7, 1H), 7.67 (s, 1H), 7.79 (d, J=7.5, 1H), 7.90 (d, J=7.5, 1H), 8.15 (t, J=8, 1H), 8.53 (d, J=8, 1H) 9.81 (s, 1H).
Workup
- temperatureheated at 80° C. for 1 h
- customevaporated under HV
Sources & evidence
- ORD record
- ord-9d738eb754ad4b51820c974e0f484de7
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09428456B2
Reaction notes
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