Acetic Acid → N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1800727Notes

Reaction equation

HRID 1800727 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([CH3:34])=[C:19]([NH:21][C:22]3[N:27]=[C:26]([S:28][C:29]#[N:30])[C:25]([N+:31]([O-])=O)=[CH:24][N:23]=3)[CH:20]=2)=[O:13])[CH:9]=[CH:10][CH:11]=1)([CH3:5])[CH3:4])#[N:2].C(O)C.C(O)(=O)C>CN1CCCC1=O.[C].[Pd]>[NH2:30][C:29]1[S:28][C:26]2[N:27]=[C:22]([NH:21][C:19]3[CH:20]=[C:15]([NH:14][C:12](=[O:13])[C:8]4[CH:9]=[CH:10][CH:11]=[C:6]([C:3]([C:1]#[N:2])([CH3:5])[CH3:4])[CH:7]=4)[CH:16]=[CH:17][C:18]=3[CH3:34])[N:23]=[CH:24][C:25]=2[N:31]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 702EthanolHCID 866460892-{[5-({[3-(1-Cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenyl]amino}-5-nitropyrimidin-4-yl thiocyanate

Product 1

HCID 86646090N-{3-[(2-amino[1,3]thiazolo[5,4-d]pyrimidin-5-yl)amino]-4-methylphenyl}-3-(1-cyano-1-methylethyl)benzamideYield 58.1%

Reagents, catalysts & solvents 2

HCID 178418390HCID 178418390, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 2-{[5-({[3-(1-cyano-1-methylethyl)phenyl]carbonyl}amino)-2-methylphenyl]amino}-5-nitropyrimidin-4-yl thiocyanate (1.09 mmol, 515 mg) in 1-methylpyrrolidin-2-one (9 mL)/ethanol (6 mL) were added 10% palladium-carbon (120 mg) and acetic acid (0.5 mL), and the mixture was stirred at room temperature under a hydrogen atmosphere (3.0 atm) for 19 hr. The insoluble material was filtered off, saturated aqueous sodium hydrogen carbonate solution (30 mL) was added, and the mixture was extracted with ethyl acetate (30 mL, 20 ml). The combined organic layer was washed with saturated brine (10 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→10/90), and the fractions containing the object product were concentrated under reduced pressure. The obtained residue was recrystallized from ethyl acetate and hexane to give the title compound (281 mg, 58%) as purple crystals.

Workup

  1. filtrationThe insoluble material was filtered off
  2. additionsaturated aqueous sodium hydrogen carbonate solution (30 mL) was added
  3. extractionthe mixture was extracted with ethyl acetate (30 mL, 20 ml)
  4. washThe combined organic layer was washed with saturated brine (10 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe insoluble material was filtered off
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=40/60→10/90)
  9. additionthe fractions containing the object product
  10. concentrationwere concentrated under reduced pressure
  11. customThe obtained residue was recrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-2b9755ef6a254c9291065bdd90c0dfa3
Source dataset
uspto-grants-2013_01
Patent number
US08344135B2

Reaction notes

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