2-(piperidin-4-yl)-1H-1,3-benzodiazole → 1-[1-{3-[4-(1H-Benzoimidazol-2-yl)-piperidin-1-yl]-2-hydroxy-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

HRID 967385Notes

Reaction equation

HRID 967385 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[NH:11][C:10]3[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=3[N:8]=2)[CH2:3][CH2:2]1.[O:16]1[CH2:18][CH:17]1[CH2:19][N:20]1[C:28]2[CH2:27][CH2:26][N:25]([C:29](=[O:31])[CH3:30])[CH2:24][C:23]=2[C:22]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)=[N:21]1>CCO>[NH:11]1[C:10]2[CH:12]=[CH:13][CH:14]=[CH:15][C:9]=2[N:8]=[C:7]1[CH:4]1[CH2:3][CH2:2][N:1]([CH2:18][CH:17]([OH:16])[CH2:19][N:20]2[C:28]3[CH2:27][CH2:26][N:25]([C:29](=[O:31])[CH3:30])[CH2:24][C:23]=3[C:22]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=3)=[N:21]2)[CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 7158102-(piperidin-4-yl)-1H-1,3-benzodiazoleHCID 222938171-[1-Oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

Product 1

HCID 101205671-[1-{3-[4-(1H-Benzoimidazol-2-yl)-piperidin-1-yl]-2-hydroxy-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanoneYield 36%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 83 mg (0.41 mmol) of 2-piperidin-4-yl-1H-benzoimidazole was dissolved in 4 mL EtOH and treated with 100 mg (0.27 mmol) of 1-[1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone. The solution was heated to 60° C. overnight. The solvent was then removed by rotary evaporation and the crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc) to afford 55 mg (36%) of a white solid. MS (electrospray): exact mass calculated for C30H33F3N6O2, 566.26. m/z found, 567.3 [M+H]+. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers):10.66 (br s, 0.5H), 10.57 (br s, 0.5H), 7.73 (bd, J=8.41 Hz, 1H), 7.72-7.63 (m, 3H), 7.60 (bd, J=8.41 Hz, 1H), 7.39-7.32 (m, 1H), 7.23-7.13 (m, 2H), 7.02 (br s, 1), 4.86 and 4.75 (A and B of AB quartet, J=15.85 Hz, 1.25H), 4.64 (br s, 1H), 4.21-4.06 (m, 2H), 4.06-3.81 (m, 2H), 3.80-3.63 (m, 1H), 3.80-3.69 (m, 1H), 3.00-2.68 (m, 5H), 2.44-2.36 (m, 2H), 2.39-2.23 (m, 2H), 2.19 (s, 1.6H), 2.15 (s, 1.4H), 2.13-2.00 (m, 4H), 2.00-1.80 (m, 2H).

Workup

  1. customThe solvent was then removed by rotary evaporation
  2. customthe crude product was purified by column chromatography (silica, 0-10% MeOH/EtOAc)

Sources & evidence

ORD record
ord-842505519df64f42a9276b165d7d6cf3
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

Loading…