1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → tert-butyl 3-(4-(3,5-bis(trifluoromethyl)phenyl)piperidine-1-carbonyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate

HRID 58458Notes

Reaction equation

HRID 58458 reaction equation
Cl.[F:2][C:3]([F:21])([F:20])[C:4]1[CH:5]=[C:6]([CH:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.[C:22]([O:26][C:27]([N:29]1[CH2:34][CH2:33][C:32]2[NH:35][N:36]=[C:37]([C:38](O)=[O:39])[C:31]=2[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C(N(C(C)C)CC)(C)C.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C.O>[F:21][C:3]([F:2])([F:20])[C:4]1[CH:5]=[C:6]([CH:14]2[CH2:19][CH2:18][N:17]([C:38]([C:37]3[C:31]4[CH2:30][N:29]([C:27]([O:26][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:28])[CH2:34][CH2:33][C:32]=4[NH:35][N:36]=3)=[O:39])[CH2:16][CH2:15]2)[CH:7]=[C:8]([C:10]([F:12])([F:13])[F:11])[CH:9]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 450739294-(3,5-Bis(trifluoromethyl)phenyl)piperidine HydrochlorideHCID 509864325-[(tert-butoxy)carbonyl]-1H,4H,5H,6H,7H-pyrazolo[4,3-c]pyridine-3-carboxylic acid

Product 1

HCID 118483360tert-butyl 3-(4-(3,5-bis(trifluoromethyl)phenyl)piperidine-1-carbonyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylateYield 86.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 4-(3,5-bis(trifluoromethyl)phenyl)piperidine hydrochloride (20, 100 mg, 0.30 mmol), 5-(tert-butoxycarbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine-3-carboxylic acid (81 mg, 0.30 mmol), and diisopropylethylamine (0.18 mL, 0.90 mmol) in DMF (5.6 mL) was added EDCI (69 mg, 0.36 mmol) and HOBt (49 mg, 0.36 mmol). The resulting solution was stirred at ambient temperature for 18 h. The reaction mixture was diluted with H2O (30 mL). The resulting precipitate was collected by filtration to yield tert-butyl 3-(4-(3,5-bis(trifluoromethyl)phenyl)piperidine-1-carbonyl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate (53) as a white solid (142 mg, 86%): 1H NMR (300 MHz, DMSO-d6) δ 12.95 (s, 1H), 8.03-7.97 (m, 2H), 7.95-7.90 (m, 1H), 5.31-5.13 (m, 1H), 4.76-4.58 (m, 1H), 4.52-4.39 (m, 2H), 3.64-3.53 (m, 2H), 3.20-3.03 (m, 2H), 2.87-2.61 (m, 3H), 1.97-1.81 (m, 2H), 1.78-1.58 (m, 2H), 1.41 (s, 9H); ESI MS m/z 547 [M+H]+.

Workup

  1. filtrationThe resulting precipitate was collected by filtration

Sources & evidence

ORD record
ord-d7e63a3893ac48b7adc8d1fc0367b974
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

Loading…