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

HRID 605356Notes

Reaction equation

HRID 605356 reaction equation
[C:1]([C:3]1[C:4]([N:10]=[CH:11][N:12](C)C)=[N:5][C:6]([CH3:9])=[CH:7][CH:8]=1)#[N:2].[CH3:15][O:16][C:17](=[O:40])[C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:27][CH:26]=2)=[C:20](N)[CH:19]=1.CCOC(C)=O.C([O-])([O-])=O.[K+].[K+]>CC(O)=O.O>[CH3:15][O:16][C:17](=[O:40])[C:18]1[CH:19]=[CH:20][C:21]([S:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32]([O:34][C:35]([CH3:37])([CH3:36])[CH3:38])=[O:33])=[CH:27][CH:26]=2)=[C:22]([NH:2][C:1]2[C:3]3[CH:8]=[CH:7][C:6]([CH3:9])=[N:5][C:4]=3[N:10]=[CH:11][N:12]=2)[CH:23]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 59376792Methyl 3-amino-4-((4-((tert-butoxycarbonyl)amino)phenyl)thio)benzoateHCID 66808573N'-(3-Cyano-6-methyl-pyridin-2-yl)-N,N-dimethyl-formamidine

Product 1

HCID 670403334-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-methyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl esterYield 62%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of N′-(3-cyano-6-methyl-pyridin-2-yl)-N,N-dimethyl-formamidine (1.00 g, 5.3 mmol) and 3-amino-4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-benzoic acid methyl ester (prepared in Example 385C) (1.99 g, 5.3 mmol) in AcOH (20 mL) was heated at 120° C. for 30 minutes under N2. After cooling to room temperature, the reaction mixture was portioned between AcOEt (250 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) to yellow amorphous, which was solidified by the treatment of i-Pr2O. The resulting solid was collected by filtration, washed with i-Pr2O, and dried at 40° C. overnight under reduced pressure to give the title compound as pale yellow crystal (1.70 g, 62%).

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) to yellow amorphous, which
  8. filtrationThe resulting solid was collected by filtration
  9. washwashed with i-Pr2O
  10. customdried at 40° C. overnight under reduced pressure

Sources & evidence

ORD record
ord-7140ee43438d41a5a5c04c4563884bce
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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