5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine → HCID 10211493, compound

HRID 1371002Notes

Reaction equation

HRID 1371002 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][CH:25]3[CH2:27][O:26]3)[N:12]=[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)[C:7]=2[CH2:6]1)(=[O:4])=[O:3].[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([CH:33]=[CH:34][N:35]2[CH:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)=[CH:31][CH:30]=1>CCO>[Cl:28][C:29]1[CH:37]=[C:36]2[C:32]([CH:33]=[CH:34][N:35]2[CH:38]2[CH2:43][CH2:42][N:41]([CH2:27][CH:25]([OH:26])[CH2:24][N:11]3[C:8]4[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][C:7]=4[C:13]([C:14]4[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:21])[F:22])=[CH:16][CH:15]=4)=[N:12]3)[CH2:40][CH2:39]2)=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 120720315-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridineHCID 22293645HCID 22293645, compound

Product 1

HCID 10211493HCID 10211493, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 86 mg (0.21 mmol) of 5-methanesulfonyl-1-oxiranylmethyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine in 4 mL of EtOH was added 50 mg (0.39 mmol) of 6-chloro-1-piperidin-4-yl-1H-indole. 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, gradient elution from 0-5% 2 N NH3/MeOH in CH2Cl2) to afford 64 mg (48%) of a white solid. MS (electrospray), exact mass calculated for C30H33ClF3N5O3S: 635.19; m/z found, 636.2 [M+H]+. HPLC (reverse phase conditions 10-90%), tR=4.88 min. 1H NMR (CDCl3, 400 MHz): 7.72 and 7.67 (A and B of AB quartet, J=8.80 Hz, 4H), 7.52 (d, J=8.41, 1H), 7.34 (s, 1H), 7.18 (d, J=3.33 Hz,1H), 7.07 (dd, J=8.41, 1.76 Hz, 1H), 6.50 (d, J=3.33 Hz, 1H), 4.59 and 4.54 (A and B of AB quartet, J=14.48 Hz, 2H), 4.24 (dd, J=13.69, 2.39 Hz, 1H), 4.21-4.14 (m, 2H), 4.05 (dd, J=13.69, 6.46 Hz, 1H), 3.69 (m, 2H), 3.15 (brd, J=11.54 Hz, 1H), 3.11-2.91 (m, 3H), 2.60-2.48 (m, 3H), 2.28 (dt, J=11.74, 2.15 Hz, 1H), 2.13-1.93 (m, 4H).

Workup

  1. customThe solvent was then removed by rotary evaporation
  2. customthe crude product was purified by column chromatography (silica, gradient elution from 0-5% 2 N NH3/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-accccf88732047f990c15ea79a4af082
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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