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

HRID 714810Notes

Reaction equation

HRID 714810 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH:15]([CH3:17])[CH3:16])([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]([CH3:17])[CH3:16])[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 117840068(3S)-1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178408692-(4-((4-((3S)-3-cyano-3-isopropyl-2-oxopyrrolidin-1-yl) pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)-N-methylacetamide hydrochlorideYield 100%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A solution of (3S)-1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile (55 mg) obtained in Step A of Example 9, 2-(4-amino-1H-pyrazol-1-yl)-N-methylacetamide (38 mg) and acetic acid (13 μL) in ethanol (2 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 (NH, ethyl acetate/methanol). To a solution of the residue (83 mg) in ethanol (3 mL) was added 1M hydrochloric acid (220 μL), and the solvent was evaporated under reduced pressure. The residue was recrystallized (diisopropyl ether/ethanol) to give the title compound (87 mg).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe obtained residue was purified by silica gel column chromatography (NH, ethyl acetate/methanol)
  3. additionTo a solution of the residue (83 mg) in ethanol (3 mL) was added 1M hydrochloric acid (220 μL)
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was recrystallized (diisopropyl ether/ethanol)

Sources & evidence

ORD record
ord-be445a605af5482699947619dfd495a2
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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