Acetonitrile → [5-(1H-Pyrazol-4-yl)-thiophen-3-yl]-(2-pyridin-2-yl-pyrrolidin-1-yl)-methanone

HRID 2068658Notes

Reaction equation

[NH:1]1[CH:5]=[C:4]([C:6]2[S:10][CH:9]=[C:8]([C:11]([OH:13])=O)[CH:7]=2)[CH:3]=[N:2]1.[NH:14]1[CH2:18][CH2:17][CH2:16][CH:15]1[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=1.C(#N)C>S(Cl)(Cl)=O>[NH:2]1[CH:3]=[C:4]([C:6]2[S:10][CH:9]=[C:8]([C:11]([N:14]3[CH2:18][CH2:17][CH2:16][CH:15]3[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[O:13])[CH:7]=2)[CH:5]=[N:1]1

Participants

Conditions

Temperature: 60 °C

Procedure

5-(1H-Pyrazol-4-yl)-thiophene-3-carboxylic acid (0.075 g, 0.39 mmol) was suspended in thionyl chloride (1 mL) and the mixture heated at 60° C. for 1 hour. The mixture was cooled and concentrated by evaporation, azeotroping with toluene (×3). 2-Pyrrolidin-2-yl-pyridine (0.173 g, 1.17 mmol) and acetonitrile (1.5 mL) were added and the reaction mixture stirred for 30 minutes and then the solvent was removed by evaporation. The crude material was purified by HPLC, eluting with 5%-95% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were evaporated, azeotroping with methanol (×3), to give the title compound as a foam (0.025 g). LCMS m/z 325.18 [M+H]+ R.T.=5.07 min (Analytical Method 2).

Workup

temperatureThe mixture was cooled
concentrationconcentrated by evaporation
customazeotroping with toluene (×3)
customthe solvent was removed by evaporation
customThe crude material was purified by HPLC
washeluting with 5%-95% acetonitrile in water (0.1% formic acid) over 20 minutes
additionThe fractions containing the desired product
customwere evaporated
customazeotroping with methanol (×3)

Sources & evidence

ORD record: ord-9c176ed8043e44babcc0c5a61c7d426f
Source dataset: uspto-grants-2012_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08299063B2

Reaction notes

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