Dichloromethane → (4-(3,4-Difluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl) methanone hydrochloride salt

HRID 58445Notes

Reaction equation

HRID 58445 reaction equation
[F:1][C:2]1[C:3]([C:32]([F:35])([F:34])[F:33])=[C:4]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]4[CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][C:19]=4[NH:20][N:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C(O)(C(F)(F)F)=O.C(Cl)[Cl:44]>>[ClH:44].[F:1][C:2]1[C:3]([C:32]([F:33])([F:34])[F:35])=[C:4]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:18]4[CH2:24][NH:23][CH2:22][C:19]=4[NH:20][N:21]=3)=[O:16])[CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 118483349HCID 118483349, compound

Product 1

HCID 118483352(4-(3,4-Difluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl) methanone hydrochloride saltYield 66%

Procedure

To a mixture of tert-butyl 3-(4-(3,4-difluoro-2-(trifluoro-methyl)phenyl) piperidine-1-carbonyl)-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxylate (37, 0.132 g, 0.26 mmol) and CH2Cl2 (1 mL) was added TFA (1 mL). The mixture stirred at ambient temperature for 2 h and was concentrated under reduced pressure. The residue was dissolved in CH2Cl2 and the solution was washed with saturated NaHCO3, dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (0-20% CH3OH in CH2Cl2) to give (4-(3,4-difluoro-2-(trifluoromethyl)phenyl) piperidin-1-yl)(1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazol-3-yl) methanone (38) as a white solid (0.070 g, 66%): 1H NMR (500 MHz, CDCl3) δ7.36-7.31 (m, 1H), 7.12 (m, 1H), 4.82 (br, 1H), 4.38 (br, 1H), 4.11 (s, 2H), 4.09 (s, 2H), 3.24 (m, 2H), 2.89 (br, 1H), 1.93-1.68 (m, 4H); MS (ESI+) m/z 401 [M+H]+.

Workup

  1. concentrationwas concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in CH2Cl2
  3. washthe solution was washed with saturated NaHCO3
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was chromatographed over silica gel (0-20% CH3OH in CH2Cl2)

Sources & evidence

ORD record
ord-7c25596684e348df819c38b77935641c
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

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