Sodium Sulfate → 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

HRID 2055796Notes

Reaction equation

HRID 2055796 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][CH2:25][CH:26]=O)[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:34]=[CH:33][CH:32]=[C:31]([N+:35]([O-:37])=[O:36])[C:30]=1[N:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.S([O-])([O-])(=O)=O.[Na+].[Na+].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[Cl:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([N+:35]([O-:37])=[O:36])[C:30]=1[N:38]1[CH2:43][CH2:42][N:41]([CH2:26][CH2:25][CH2:24][N:11]2[C:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][C:7]=3[C:13]([C:14]3[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=3)=[N:12]2)[CH2:40][CH2:39]1

Participants

6

Reactant 4

HCID 24436Sodium SulfateHCID 27714081-(2-Chloro-6-nitrophenyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 222938973-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde

Product 1

HCID 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]pyridineYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde (0.5 g, 1.25 mmol) and 1-(2-chloro-6-nitrophenyl)-piperazine (0.301 g, 1.25 mmol) in CH2Cl2 (6 mL) was added sodium sulfate (0.354 g, 2.50 mmol) and sodium triacetoxyborohydride (0.396 g, 1.87 mmol). The mixture was allowed to stir at room temperature overnight. The mixture was diluted with CH2Cl2 and washed with water. The CH2Cl2 layer was dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was purified by column chromatography (silica, 10% acetone/CH2Cl2) to afford 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 (0.380 g, 49%). MS (electrospray): exact mass calculated for C27H30CIF3N6O4S, 626.2; m/z found, 627.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.73 (d, J=8.2 Hz, 2H), 7.66 (d, J=8.2 Hz, 2H), 7.54 (dd, J=8.2, 1.2 Hz, 1H), 7.49 (dd, J=8.2,1.2 Hz, 1H), 7.10 (t, J=8.2 Hz, 1H), 4.58 (s, 2H), 4.13 (t, J=6.5 Hz, 2H), 3.71 (t, J=5.9 Hz, 2H), 3.01-3.11 (m, 4H), 2.95 (t, J=5.9 Hz, 2H), 2.92 (s, 3H), 2.42-2.53 (m, 4H), 2.40 (t, J=6.5 Hz, 2H), 2.12 (q, J=6.5 Hz, 2H).

Workup

  1. washwashed with water
  2. dry with materialThe CH2Cl2 layer was dried over Na2SO4
  3. customthe solvent was removed under reduced pressure
  4. customThe residue was purified by column chromatography (silica, 10% acetone/CH2Cl2)

Sources & evidence

ORD record
ord-8cc48a9b71e34233adf3ea38b2586dc2
Source dataset
uspto-grants-2008_02
Patent number
US07332494B2

Reaction notes

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