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

HRID 714809Notes

Reaction equation

HRID 714809 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]([NH2:28])=[O:27])[CH:24]=1.C(O)(=O)C.C(=O)([O-])O.[Na+]>C(O)C.O.C(#N)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]([NH2:28])=[O:27])[CH:24]=3)[N:7]=2)[C:9]1=[O:18])#[N:14]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 283739472-(4-amino-1H-pyrazol-1-yl)acetamideHCID 117840068(3S)-1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178409332-(4-((4-((3S)-3-cyano-3-isopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)acetamide hydrochlorideYield 15.5%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 18373917Acetonitrile--water (1/1)Solvent

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)acetamide (35 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). The obtained crude product was subjected to HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% ammonium formate)), to the obtained fraction was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. To a solution of the residue (17 mg) in ethanol (3 mL) was added 1M hydrochloric acid (57 μL), and the solvent was evaporated under reduced pressure. The residue was recrystallized (diisopropyl ether/ethanol) to give the title compound (13 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. customThe obtained crude product
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialThe extract was dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. additionTo a solution of the residue (17 mg) in ethanol (3 mL) was added 1M hydrochloric acid (57 μL)
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was recrystallized (diisopropyl ether/ethanol)

Sources & evidence

ORD record
ord-795a6e3b13504a21b6eb67e4e45f4338
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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