Water → HCID 117840290, compound

HRID 714835Notes

Reaction equation

HRID 714835 reaction equation
Cl.Cl.[NH2:3][CH2:4][C:5]([N:8]1[CH:12]=[C:11]([NH:13][C:14]2[N:19]=[C:18]([N:20]3[CH2:24][CH2:23][C@:22]([CH:27]4[CH2:29][CH2:28]4)([C:25]#[N:26])[C:21]3=[O:30])[CH:17]=[CH:16][N:15]=2)[CH:10]=[N:9]1)([CH3:7])[CH3:6].C(N(CC)CC)C.[CH3:38][O:39][CH2:40][C:41]([Cl:43])=[O:42].O>O1CCCC1>[ClH:43].[C:25]([C@@:22]1([CH:27]2[CH2:28][CH2:29]2)[CH2:23][CH2:24][N:20]([C:18]2[CH:17]=[CH:16][N:15]=[C:14]([NH:13][C:11]3[CH:10]=[N:9][N:8]([C:5]([CH3:7])([CH3:6])[CH2:4][NH:3][C:41](=[O:42])[CH2:40][O:39][CH3:38])[CH:12]=3)[N:19]=2)[C:21]1=[O:30])#[N:26]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 96623Methoxyacetyl chlorideHCID 117840151HCID 117840151, compound

Product 1

HCID 117840290HCID 117840290, compoundYield 75.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (3S)-1-(2-((1-(1-amino-2-methylpropan-2-yl)-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3-cyclopropyl-2-oxopyrrolidine-3-carbonitrile dihydrochloride (100 mg) obtained in Example 115 in tetrahydrofuran (5 mL) were added successively dropwise triethylamine (0.15 mL) and methoxyacetyl chloride (26 mg) at 0° C. under nitrogen atmosphere, and the mixture was stirred at room temperature for 5 hr. To the reaction mixture was added water, 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 (ethyl acetate/methanol). To a solution of the residue (89 mg) in ethanol (5.0 mL) was added 1 M hydrochloric acid (0.20 mL), and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the residue was recrystallized (diisopropyl ether/ethyl acetate) to give the title compound (81 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe obtained organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/methanol)
  6. additionTo a solution of the residue (89 mg) in ethanol (5.0 mL) was added 1 M hydrochloric acid (0.20 mL)
  7. stirringthe mixture was stirred at room temperature for 5 min
  8. customThe solvent was evaporated under reduced pressure
  9. customthe residue was recrystallized (diisopropyl ether/ethyl acetate)

Sources & evidence

ORD record
ord-7b444c3c906e4ed2af493da41a531700
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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