Sodium hydride → 2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile

HRID 1875409Notes

Reaction equation

HRID 1875409 reaction equation
[CH3:1][C:2]1([CH3:16])[CH2:10][C:9]2[NH:8][N:7]=[C:6]([C:11]([F:14])([F:13])[F:12])[C:5]=2[C:4](=[O:15])[CH2:3]1.[H-].[Na+].[OH:19][CH:20]([CH2:32][OH:33])[CH2:21][NH:22][C:23]1[CH:30]=[C:29](F)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26].[NH4+].[Cl-]>CC(N(C)C)=O>[OH:19][CH:20]([CH2:32][OH:33])[CH2:21][NH:22][C:23]1[CH:30]=[C:29]([N:8]2[C:9]3[CH2:10][C:2]([CH3:16])([CH3:1])[CH2:3][C:4](=[O:15])[C:5]=3[C:6]([C:11]([F:14])([F:13])[F:12])=[N:7]2)[CH:28]=[CH:27][C:24]=1[C:25]#[N:26]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 441904636,6-Dimethyl-3-(trifluoromethyl)-1,5,6,7-tetrahydro-4H-indazol-4-oneHCID 669527352-(2,3-Dihydroxy-propylamino)-4-fluorobenzonitrile

Product 1

HCID 669529362-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrileYield 97.2%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of 6,6-Dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one (0.961 g, 4.14 mmol, 1 eq) and NaH (99 mg, 4.14 mmol, 1 eq) in dimethyl acetamide (20 mL) was added slowly 2-(2,3-Dihydroxy-propylamino)-4-fluoro-benzonitrile (0.87 g, 4.14 mmol, 1 eq). Then the reaction mixture was stirred at 150° C. overnight, cooled, poured into saturated NH4Cl aq. solution (100 mL), extracted by EtOAc (3×150 mL), dried over Na2SO4, filtered, concentrated. The crude product was purified by flash silica gel chromatography, eluted by EtOAc to give 2-(2,3-Dihydroxy-propylamino)-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.7 g, 97% yield). LCMS (m/z): M+H=423.

Workup

  1. temperaturecooled
  2. extractionextracted by EtOAc (3×150 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by flash silica gel chromatography
  7. washeluted by EtOAc

Sources & evidence

ORD record
ord-640d19367093466cba1844c2dedd4039
Source dataset
uspto-grants-2012_11
Patent number
US08309548B2

Reaction notes

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