Sodium hydride → 1-(3-chloro-1-phenyl-propyl)-1H-indazole-4-carbonitrile

HRID 250203Notes

Reaction equation

HRID 250203 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:6]=1[CH:7]=[N:8][NH:9]2)#[N:4].[Cl:14][CH2:15][CH2:16][CH:17](OS(C)(=O)=O)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN1CCCC1=O>[Cl:14][CH2:15][CH2:16][CH:17]([N:9]1[C:10]2[CH:11]=[CH:12][CH:13]=[C:5]([C:3]#[N:4])[C:6]=2[CH:7]=[N:8]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 247293471H-Indazole-4-carbonitrileHCID 57985877Methanesulfonic acid 3-chloro-1-phenyl-propyl ester

Product 1

HCID 580884451-(3-chloro-1-phenyl-propyl)-1H-indazole-4-carbonitrileYield 36.8%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

Sodium hydride (0.092 g, 60% in oil) was added to a solution of 4-cyanoindazole (0.300 g) in N-methylpyrrolidinone (5 mL) and the reaction mixture was stirred at room temperature for 30 minutes. Methanesulfonic acid 3-chloro-1-phenyl-propyl ester (0.573 g) was added followed by 3 ml more of N-methylpyrrolidinone. The reaction mixture was stirred for an additional 6 hours at room temperature. The reaction mixture was partitioned between water and ethyl acetate, and the organic layer was washed with water, then with brine, and dried (MgSO4). Evaporation to dryness gave a residue which was purified by column chromatography on silica gel using ethyl acetate-hexane (1:9) to give 1-(3-chloro-1-phenyl-propyl)-1H-indazole-4-carbonitrile (0.228 g) as a foam, (M+H=297).

Workup

  1. stirringThe reaction mixture was stirred for an additional 6 hours at room temperature
  2. customThe reaction mixture was partitioned between water and ethyl acetate
  3. washthe organic layer was washed with water
  4. dry with materialwith brine, and dried (MgSO4)
  5. customEvaporation to dryness
  6. customgave a residue which
  7. customwas purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-70e31736f1c04e8aadfd794e87fa6569
Source dataset
uspto-grants-2011_01
Patent number
US07863305B2

Reaction notes

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