Acetic Acid → 5-Methanesulfonyl-1-[3-[4-(2-nitro-phenyl)-piperazin-1-yl]-propyl]-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine

HRID 271765

Reaction equation

HRID 271765 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].[N+:28]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1)([O-:30])=[O:29].CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][CH2:25][CH2:26][N:40]3[CH2:41][CH2:42][N:37]([C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=4[N+:28]([O-:30])=[O:29])[CH2:38][CH2:39]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]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 1009491-(2-Nitrophenyl)piperazineHCID 516892Sodium BicarbonateHCID 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 101212995-Methanesulfonyl-1-[3-[4-(2-nitro-phenyl)-piperazin-1-yl]-propyl]-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridineYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 (0.060 g, 0.15 mmol) and 1-(2-nitro-phenyl)-piperazine (0.032 g, 0.157 mmol) in CH2Cl2 (0.5 mL), glacial AcOH (8.5 μL, 0.15 mmol) was added and stirred for 15 min at room temperature. NaBH(OAc)3 (0.041 g, 0.19 mmol) was added and stirred under nitrogen overnight. Saturated NaHCO3 (0.5 mL) was then added and stirred for 15 min. The layers separated and the aqueous layer was extracted with CH2Cl2 (0.5 mL). MPLC purification (silica, 2-15% MeOH/CH2Cl2) afforded the desired product as a white solid (0.063 g, 71%). TLC (silica, 12% MeOH/CH2Cl2): Rf=0.67. MS (electrospray): exact mass calculated for C27H31F3N6O4S, 592.21; m/z found, 593.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.80 (dd, J=1.6, 8.2 Hz, 1H), 7.77 (d, J=8.3 Hz, 2H), 7.70 (d, J=8.3 Hz, 2H), 7.52 (ddd, J=1.6, 7.3, 8.3 Hz, 1H), 7.19 (dd, J=1.2, 8.3 Hz, 1H), 7.09 (m, 1H), 4.59 (s, 2H), 4.17 (t, J=6.9 Hz, 2H), 3.71 (t, J=5.8 Hz, 2H), 3.13 (br t, J =4.8 Hz, 4H), 2.96 (t, J=5.6 Hz, 2H), 2.95 (s, 3H), 2.66 (br t, J=4.4 Hz, 4H), 2.51 (t, J=7.0 Hz, 2H), 2.17 (q, J=6.9 Hz, 2H).

Workup

  1. stirringstirred under nitrogen overnight
  2. stirringstirred for 15 min
  3. customThe layers separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (0.5 mL)
  5. customMPLC purification (silica, 2-15% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-0c37199c6ea947809bdd6954dd07ccc4
Source dataset
uspto-grants-2008_11
Patent number
US07452890B2

Linked notes

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