Acetic Acid → HCID 10167304, compound

HRID 1371003Notes

Reaction equation

HRID 1371003 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.[NH:29]1[CH2:34][CH2:33][CH:32]([N:35]2[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=3[N:37]=[N:36]2)[CH2:31][CH2:30]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.CCN(CC)CC>[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][C:8]2[N:11]([CH2:24][CH2:25][CH2:26][N:29]3[CH2:30][CH2:31][CH:32]([N:35]4[C:39]5[CH:40]=[CH:41][CH:42]=[CH:43][C:38]=5[N:37]=[N:36]4)[CH2:33][CH2:34]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

8

Reactant 5

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 27793801-(Piperidin-4-yl)-1H-benzotriazole--hydrogen chloride (1/1)HCID 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 10167304HCID 10167304, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

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 (0.084 g, 0.21 mmol) in CH2Cl2 (0.5 mL) were added 1-piperidin4-yl-1H-benzotriazole hydrochloride (Maybridge Chemicals, 0.050 g, 0.21 mmol), Et3N (0.1 mL) and glacial AcOH (12 L, 0.21 mmol) in that order and stirred for 20 min. NaBH(OAc)3 (0.058 g, 0.27 mmol) was added and stirred under nitrogen overnight. Saturated NaHCO3 (1 mL) was added and stirred for 30 min. The layers were separated and the aqueous layer was extracted with CH2Cl2 (3 mL). The combined organic extracts were washed with brine (3 mL), dried over Na2SO4, and removed under reduced pressure. MPLC of the crude afforded the desired compound as a white solid (0.098 g, 80 %). TLC (silica, 12% MeOH/CH2Cl2): Rf=0.44. MS (electrospray): exact mass calculated for C28H32F3N7O2S, 587.23; m/z found 588.2 [M+H]+. 1H NMR (400 MHz, CDCl3): 8.00 (d, J=8.4 Hz, 1H), 7.66 (d, J=8.2 Hz, 2H), 7.59 (d, J=8.2 Hz, 2H), 7.50 (d, J=8.4 Hz, 1H), 7.41 (dt, J=0.9, 7.6 Hz, 1H), 7.30 (dt, J=0.9, 7.6 Hz, 1H), 4.59 (brt, J=11.2 Hz, 1H), 4.50 (s, 2H), 4.10 (t, J=6.7 Hz, 2H), 3.63 (t, J=5.8 Hz, 2H), 3.00 (br d, J=12.0 Hz, 2H), 2.89 (t, J5.8 Hz, 2H), 2.86 (s, 3H), 2.38-2.27 (m, 4H), 2.17-1.99 (m, 6H).

Workup

  1. stirringstirred under nitrogen overnight
  2. stirringstirred for 30 min
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with CH2Cl2 (3 mL)
  5. washThe combined organic extracts were washed with brine (3 mL)
  6. dry with materialdried over Na2SO4
  7. customremoved under reduced pressure

Sources & evidence

ORD record
ord-83f688555c394963aad585b4458fd254
Source dataset
uspto-grants-2003_06
Patent number
US06583155B2

Reaction notes

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