Acetic Acid → 3-Chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenylamine

HRID 734130Notes

Reaction equation

HRID 734130 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-])=O)[C:3]=1[N:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][N:20]2[C:28]3[CH2:27][CH2:26][N:25]([S:29]([CH3:32])(=[O:31])=[O:30])[CH2:24][C:23]=3[C:22]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][CH:34]=3)=[N:21]2)[CH2:13][CH2:12]1.C(O)(=O)C>CCO.[Zn]>[Cl:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][N:20]3[C:28]4[CH2:27][CH2:26][N:25]([S:29]([CH3:32])(=[O:30])=[O:31])[CH2:24][C:23]=4[C:22]([C:33]4[CH:34]=[CH:35][C:36]([C:39]([F:40])([F:41])[F:42])=[CH:37][CH:38]=4)=[N:21]3)[CH2:13][CH2:12]2)=[C:4]([NH2:8])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 179754011-{3-[4-(2-chloro-6-nitro-phenyl)-piperazin-1-yl]-propyl}-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 102107373-Chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenylamineYield 100.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of 1-{3-[4-(2-chloro-6-nitro-phenyl)-piperazin-1-yl]-propyl}-5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (0.153 g, 0.244 mmol) in EtOH (2.44 mL) was added zinc dust (0.80 mg, 1.22 mmol) and slow addition of acetic acid (0.70 mL). After 15 min the yellow solution became colorless and the access zinc dust was filtered through a plug of celite. The filtrate was concentrated and the residue was purified by column chromatography (silica, 0-10% MeOH/CH2Cl2) to afford 3-chloro-2-(4-{3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propyl}-piperazin-1-yl)-phenylamine (0.146 g, 100%). MS (electrospray): exact mass calculated for C27H32ClF3N6O2S, 596.2; m/z found, 597.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.73 (d, J=8.2 Hz, 2H), 7.66 (d, J=8.2 Hz, 2H), 6.88 (t, J=8.2 Hz, 1H), 6.63 (t, J=7.6 Hz, 2H), 4.55 (s, 2H), 4.36 (s, 2H), 4.15 (t, J=6.5 Hz, 2H), 3.60-3.70 (m, 4H), 2.97 (t, J=5.3 Hz, 2H), 2.90 (s, 3H), 2.83 (d, J=10.8 Hz, 2H), 2.74 (d, J=11.5 Hz, 2H), 2.37 (t, J=6.6 Hz, 2H), 2.11-2.20 (m, 4H).

Workup

  1. filtrationthe access zinc dust was filtered through a plug of celite
  2. concentrationThe filtrate was concentrated
  3. customthe residue was purified by column chromatography (silica, 0-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-43e26df3e5034912904dff8a662ad0b3
Source dataset
uspto-grants-2009_09
Patent number
US07589202B2

Reaction notes

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