Acetic Acid → (3S)-3-cyclopropyl-1-(2-((1-(1-(hydroxymethyl)cyclobutyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrile

HRID 714839Notes

Reaction equation

HRID 714839 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH:15]3[CH2:17][CH2:16]3)([C:13]#[N:14])[C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][N:23]([C:25]2([CH2:29][OH:30])[CH2:28][CH2:27][CH2:26]2)[CH:24]=1.C(O)(=O)C>CC(O)C>[CH:15]1([C@:10]2([C:13]#[N:14])[CH2:11][CH2:12][N:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]4[CH:21]=[N:22][N:23]([C:25]5([CH2:29][OH:30])[CH2:28][CH2:27][CH2:26]5)[CH:24]=4)[N:7]=3)[C:9]2=[O:18])[CH2:17][CH2:16]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 916187111-(4-Amino-1h-pyrazol-1-yl)cyclobutanemethanolHCID 117840203(3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 117840631(3S)-3-cyclopropyl-1-(2-((1-(1-(hydroxymethyl)cyclobutyl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-2-oxopyrrolidine-3-carbonitrileYield 62.6%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (150 mg) obtained in Step E of Example 103, (1-(4-amino-1H-pyrazol-1-yl)cyclobutyl)methanol (95 mg) obtained in Step C of Example 127 and acetic acid (34 mg) in propan-2-ol (4.0 mL) was stirred in a microwave reactor at 160° C. for 1 hr. The reaction mixture was concentrated under reduced pressure, the residue was poured into saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The obtained organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate), and recrystallized (diisopropyl ether/ethyl acetate) to give the title compound (140 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionthe residue was poured into saturated aqueous sodium hydrogen carbonate solution
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe obtained organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (NH, hexane/ethyl acetate)
  8. customrecrystallized (diisopropyl ether/ethyl acetate)

Sources & evidence

ORD record
ord-8b70d8274fae48da85f295c428aa2b74
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

Loading…