Ethyl Acetate → 4-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester

HRID 605332Notes

Reaction equation

HRID 605332 reaction equation
[C:1]([C:3]1[C:4]([N:12]=[CH:13][N:14](C)C)=[N:5][C:6]([CH:9]([CH3:11])[CH3:10])=[CH:7][CH:8]=1)#[N:2].[CH3:17][O:18][C:19](=[O:42])[C:20]1[CH:25]=[CH:24][C:23]([S:26][C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[CH:29][CH:28]=2)=[C:22](N)[CH:21]=1.CCOC(C)=O.C([O-])([O-])=O.[K+].[K+]>CC(O)=O.O>[CH3:17][O:18][C:19](=[O:42])[C:20]1[CH:21]=[CH:22][C:23]([S:26][C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])=[CH:29][CH:28]=2)=[C:24]([NH:2][C:1]2[C:3]3[CH:8]=[CH:7][C:6]([CH:9]([CH3:10])[CH3:11])=[N:5][C:4]=3[N:12]=[CH:13][N:14]=2)[CH:25]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 59376792Methyl 3-amino-4-((4-((tert-butoxycarbonyl)amino)phenyl)thio)benzoateHCID 66808369(E)-N'-(3-cyano-6-isopropylpyridin-2-yl)-N,N-dimethylformimidamide

Product 1

HCID 593768814-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-isopropyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine (2.00 g, 9.3 mmol) and 3-amino-4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-benzoic acid methyl ester (3.46 g, 9.3 mmol) in AcOH (40 mL) was heated at 120° C. for 20 minutes under N2. After cooling to room temperature, the reaction mixture was portioned between AcOEt (150 mL) and H2O (200 mL), and then made basic to pH 9 with K2CO3 under stirring. The organic layer was separated, washed with 10% NaHCO3, H2O and brine, dried over MgSO4, and evaporated to give pale brown oil. The oily residue was separated by silica gel column chromatography (AcOEt/n-hexane=5/1) to give yellow crystal. Further purification by washing with cold AcOEt (15 mL) gave the title compound as slightly yellow crystal (3.27 g, 65%).

Workup

  1. temperatureAfter cooling to room temperature
  2. customThe organic layer was separated
  3. washwashed with 10% NaHCO3, H2O and brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customto give pale brown oil
  7. customThe oily residue was separated by silica gel column chromatography (AcOEt/n-hexane=5/1)
  8. customto give yellow crystal
  9. customFurther purification
  10. washby washing with cold AcOEt (15 mL)

Sources & evidence

ORD record
ord-de1f332c2fbe494b8dbb9ec414efe8bc
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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