Acetic Acid → 2-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl) pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-methylacetamide hydrochloride

HRID 714850Notes

Reaction equation

HRID 714850 reaction equation
[Cl:1][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]([CH2:25][C:26]([NH:28][CH3:29])=[O:27])[CH:24]=1.C(O)(=O)C>C(O)C>[ClH:1].[C:13]([C@@:10]1([CH:15]2[CH2:17][CH2:16]2)[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH2:25][C:26]([NH:28][CH3:29])=[O:27])[CH:24]=3)[N:7]=2)[C:9]1=[O:18])#[N:14]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 280651732-(4-amino-1H-pyrazol-1-yl)-N-methylacetamideHCID 117840203(3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178410592-(4-((4-((3S)-3-cyano-3-cyclopropyl-2-oxopyrrolidin-1-yl) pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-methylacetamide hydrochlorideYield 58.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile (130 mg) obtained in Step E of Example 103, 2-(4-amino-1H-pyrazol-1-yl)-N-methylacetamide (84 mg) and acetic acid (31 μL) in ethanol (3.0 mL) was stirred in a microwave reactor at 150° C. for 1 hr, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate). To a solution of the residue (190 mg) in ethanol (5.0 mL) was added 1 M hydrochloric acid (0.50 mL), and the solvent was evaporated under reduced pressure. The residue was recrystallized (diisopropyl ether/ethanol) to give the title compound (120 mg).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  3. additionTo a solution of the residue (190 mg) in ethanol (5.0 mL) was added 1 M hydrochloric acid (0.50 mL)
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was recrystallized (diisopropyl ether/ethanol)

Sources & evidence

ORD record
ord-b4e4b1f89b0f4c95989df54cb1f0767b
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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