Water → HCID 117840438, compound

HRID 714873Notes

Reaction equation

HRID 714873 reaction equation
CN.[C:3](N1C=CN=C1)([N:5]1C=CN=[CH:6]1)=[O:4].[CH2:15]([C@:17]1([C:42]#[N:43])[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]3[CH:34]=[CH:33][C:32]([N:35]4[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]4)=[CH:31][CH:30]=3)[N:23]=2)[C:18]1=[O:41])[CH3:16].O>O1CCCC1>[C:42]([C@@:17]1([CH2:15][CH3:16])[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[CH:26][N:25]=[C:24]([NH:28][C:29]3[CH:30]=[CH:31][C:32]([N:35]4[CH2:40][CH2:39][N:38]([C:3]([NH:5][CH3:6])=[O:4])[CH2:37][CH2:36]4)=[CH:33][CH:34]=3)[N:23]=2)[C:18]1=[O:41])#[N:43]

Participants

6

Reactant 4

HCID 962WaterHCID 6329MethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 89863359HCID 89863359, compound

Product 1

HCID 117840438HCID 117840438, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 2 M methylamine in tetrahydrofuran (0.28 mL) were added 1,1′-carbonyldiimidazole (91 mg) and tetrahydrofuran (3.0 mL) in an ice bath, and the mixture was stirred at the same temperature for 10 min. To the reaction mixture was added (3R)-3-ethyl-2-oxo-1-(2-((4-(piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)pyrrolidine-3-carbonitrile (200 mg) obtained in Example 220, and the mixture was stirred at 70° C. for 2 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 (hexane/ethyl acetate). To a solution of the obtained purified product (290 mg) in ethanol (3 mL) was added 1 M hydrochloric acid (0.64 mL), and the mixture was stirred at room temperature for 5 min. The solvent was evaporated under reduced pressure, and the residue was recrystallized (ethanol/diisopropyl ether) to give the title compound (220 mg)

Workup

  1. stirringthe mixture was stirred at 70° C. for 2 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe obtained organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
  7. customTo a solution of the obtained purified product (290 mg) in ethanol (3 mL)
  8. additionwas added 1 M hydrochloric acid (0.64 mL)
  9. stirringthe mixture was stirred at room temperature for 5 min
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was recrystallized (ethanol/diisopropyl ether)

Sources & evidence

ORD record
ord-e79389619e0249e3b27b0d587d447272
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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