2-(Piperidin-4-yl)-5-(trifluoromethyl)-1,3-benzothiazole → 1-[1-{2-Hydroxy-3-[4-(5-trifluoromethyl-benzothiazol-2-yl)-piperidin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

HRID 967380Notes

Reaction equation

HRID 967380 reaction equation
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[S:8][C:9]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:10]=3[N:11]=2)[CH2:3][CH2:2]1.[O:20]1[CH2:22][CH:21]1[CH2:23][N:24]1[C:32]2[CH2:31][CH2:30][N:29]([C:33](=[O:35])[CH3:34])[CH2:28][C:27]=2[C:26]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=2)=[N:25]1>CCO>[OH:20][CH:21]([CH2:22][N:1]1[CH2:6][CH2:5][CH:4]([C:7]2[S:8][C:9]3[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:10]=3[N:11]=2)[CH2:3][CH2:2]1)[CH2:23][N:24]1[C:32]2[CH2:31][CH2:30][N:29]([C:33](=[O:35])[CH3:34])[CH2:28][C:27]=2[C:26]([C:36]2[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=2)=[N:25]1

Participants

4

Reactant 2

HCID 71319932-(Piperidin-4-yl)-5-(trifluoromethyl)-1,3-benzothiazoleHCID 222938171-[1-Oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone

Product 1

HCID 102332671-[1-{2-Hydroxy-3-[4-(5-trifluoromethyl-benzothiazol-2-yl)-piperidin-1-yl]-propyl}-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanoneYield 80%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 63 mg (0.22 mmol) 2-piperidin-4-yl-5-trifluoromethyl-benzothiazole was dissolved in 4 mL EtOH and treated with 40 mg (0.11 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 57 mg (80%) of a white solid. MS (electrospray): exact mass calculated for C31H31F6N5O2S, 651.21. m/z found, 652.2 [M+H]+. 1H NMR (CDCl3, 400 MHz, a mixture of amide rotamers): 8.24 (s, 1H), 7.97 (d, J=8.41 Hz, 1H), 7.78 (d, J=8.41 Hz, 1H), 7.70 (m, 2H), 7.65 (d, J=8.41 Hz, 1H), 7.60 (dd, J=8.41, 1.37 Hz, 1H), 4.88 and 4.76 (A and B of AB quartet, J=15.85 Hz, 1H), 4.66 (br s, 1H), 4.25-4.15 (m, 2H), 4.08-3.99 (m, 1.5H), 3.91-3.83 (m, 0.5H), 3.82-3.68 (m, 1H), 3.16 (tt, J=11.35, 3.52 Hz, 1H), 3.12-3.06 (m, 1H), 3.02-2.97 (m, 1H), 2.9-2.87 (m, 1.4H), 2.87-2.75 (m, 0.6H), 2.55-2.43 (m, 3H), 2.27-2.17 (m, 3H), 2.21 (s, 1.5H), 2.17 (s, 1.5H), 2.04-1.87 (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-fc7690f5b38b4cf7be4002d755e2d212
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

Loading…