Methanesulfonyl chloride → (4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(5-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)methanone

HRID 58493Notes

Reaction equation

HRID 58493 reaction equation
Cl.[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:21]4[CH2:22][NH:23][CH2:24][CH2:25][C:20]=4[NH:19][N:18]=3)=[O:16])[CH2:11][CH2:10]2)=[C:5]([C:26]([F:29])([F:28])[F:27])[CH:4]=1.C(N(C(C)C)CC)(C)C.[CH3:39][S:40](Cl)(=[O:42])=[O:41]>CN(C=O)C>[F:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH2:14][CH2:13][N:12]([C:15]([C:17]3[C:21]4[CH2:22][N:23]([S:40]([CH3:39])(=[O:42])=[O:41])[CH2:24][CH2:25][C:20]=4[NH:19][N:18]=3)=[O:16])[CH2:11][CH2:10]2)=[C:5]([C:26]([F:29])([F:27])[F:28])[CH:4]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 118483361HCID 118483361, compound

Product 1

HCID 118483447(4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(5-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)methanoneYield 10%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4-(4-fluoro-2-(trifluoromethyl)phenyl) piperidin-1-yl)(4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)methanone hydrochloride (38 mg, 0.088 mmol) and diisopropylethylamine (35 μL, 0.20 mmol) in DMF (2.0 mL) was added methanesulfonyl chloride (9 L, 0.12 mmol). The mixture was stirred for 16 h at ambient temperature. The solvent was removed under reduced pressure and the residue diluted with H2O (10 mL) and extracted with ethyl acetate (3×10 mL). The combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure. The obtained solids were chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 100% (10% CH30H in CH2Cl2 with 0.01% NH4OH) in CH2Cl2) and freeze dried to give (4-(4-fluoro-2-(trifluoromethyl)phenyl)piperidin-1-yl)(5-(methylsulfonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)methanone as a white solid (4 mg, 10%): 1H NMR (300 MHz, DMSO-d6) δ 13.05 (s, 1H), 7.73-7.69 (m, 1H), 7.57-7.46 (m, 2H), 5.28-5.24 (m, 1H), 4.70-4.65 (m, 1H), 4.38-4.33 (m, 2H), 3.51-3.45 (m, 2H), 3.22-3.10 (m, 2H), 2.94 (s, 3H), 2.84-2.70 (m, 3H), 1.73 (br s, 4H); ESI MS m/z 475 [M+H]+.

Workup

  1. customThe solvent was removed under reduced pressure
  2. additionthe residue diluted with H2O (10 mL)
  3. extractionextracted with ethyl acetate (3×10 mL)
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained solids were chromatographed over silica gel (Isco CombiFlash Rf unit, 12 g Redisep column, 0% to 100% (10% CH30H in CH2Cl2 with 0.01% NH4OH) in CH2Cl2) and freeze
  7. customdried

Sources & evidence

ORD record
ord-bc0d26957c2c4712a35fc16d29a79eea
Source dataset
uspto-grants-2016_09
Patent number
US09434727B2

Reaction notes

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