Tetrahydrofuran → HCID 12043694, compound

HRID 2301950Notes

Reaction equation

HRID 2301950 reaction equation
[F:1][C:2]([F:20])([F:19])[C:3]1(C(O)=O)[CH:7]=[CH:6][N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=2)[NH:4]1.S(Cl)(Cl)=O.[NH:25]1[C:33]2[C:28](=[CH:29][C:30]([C:34]3[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=3[S:40]([NH:43]C(C)(C)C)(=[O:42])=[O:41])=[CH:31][CH:32]=2)[CH2:27][CH2:26]1.[H-].[Na+].C1C[O:53][CH2:52]C1>C(#N)C>[C:14]([C:10]1[CH:9]=[C:8]([N:5]2[C:6]([C:52]([N:25]3[C:33]4[C:28](=[CH:29][C:30]([C:34]5[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=5[S:40]([NH2:43])(=[O:42])=[O:41])=[CH:31][CH:32]=4)[CH2:27][CH2:26]3)=[O:53])=[CH:7][C:3]([C:2]([F:1])([F:19])[F:20])=[N:4]2)[CH:13]=[CH:12][CH:11]=1)#[N:15]

Participants

7

Reactant 5

HCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 24758Sodium hydrideHCID 12043691HCID 12043691, compoundHCID 68805857HCID 68805857, compound

Product 1

HCID 12043694HCID 12043694, compoundYield 92%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To the solution of 3-(trifluoromethyl)-1-(3-cyanophenyl)-1H-pyrazolecarboxylic acid (0.2 g, 0.6 mmol) in dry acetonitrile (10 mL) was added thionyl chloride (0.37 g, 1.8 mmol). The reaction mixture was warmed up to 50° C. for 1 h. The solvent and excess thionyl chloride were removed under reduced pressure and dried on a vacuum pump over 18 h. This residue was dissolved in THF and treated with a mixture of 2-(2,3-dihydro-1H-indol-5-yl)-N-(1,1-dimethylethyl)benzenesulfonamide from Example 1 (0.3 g, 0.8 mmol) in THF (5 mL) and NaH (72 mg, 1.6 mmol). The reaction mixture was allowed to stir at ambient temperature for 0.5 h, then quenched with water and extracted with EtOAc (3×). Ethyl acetate extracts were dried over sodium sulfate and concentrated. The crude residue was purified by flash chromatography (hexane/EtOAc, 1:3) to afford the title product (0.38 g, 92%). LRMS (ES+): 593.2 (M+H)+.

Workup

  1. customThe solvent and excess thionyl chloride were removed under reduced pressure
  2. customdried on a vacuum pump over 18 h
  3. dissolutionThis residue was dissolved in THF
  4. customquenched with water
  5. extractionextracted with EtOAc (3×)
  6. dry with materialEthyl acetate extracts were dried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude residue was purified by flash chromatography (hexane/EtOAc, 1:3)

Sources & evidence

ORD record
ord-76aec682de874bc099c0fd4357e64a84
Source dataset
uspto-grants-2002_08
Patent number
US06429205B1

Reaction notes

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