Water → 1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carbonitrile

HRID 1928641Notes

Reaction equation

[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([C:22]([NH2:24])=O)[CH:19]=[N:18]2)=[CH:13][CH:12]=1.S(Cl)(Cl)=O.O.C(=O)(O)[O-].[Na+]>CN(C)C=O>[CH3:1][C@@H:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[CH:21]=[C:20]([C:22]#[N:24])[CH:19]=[N:18]2)=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1-(4-{3-[(2R)-2-methylpyrrolidin-1-yl]propoxy}phenyl)-1H-pyrazole-4-carboxamide obtained in Example 2-(2) (0.466 g) in N,N-dimethylformamide (5.0 mL), thionyl chloride (1.0 mL) was added dropwise under ice cooling and stirred at 0° C. for 30 minutes. The reaction mixture was adjusted to pH 8 by addition of water and saturated aqueous sodium bicarbonate, and then extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=1:1), and the resulting crystal was washed with hexane:diisopropyl ether (1:1) to give the titled compound (0.253 g) as a colorless solid.

Workup

extractionextracted with ethyl acetate
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (eluting solvent: n-hexane:ethyl acetate=1:1)
washthe resulting crystal was washed with hexane:diisopropyl ether (1:1)

Sources & evidence

ORD record: ord-d4d2e667b20b4285ad11a17ff4f87a0e
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183387B2

Reaction notes

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