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

HRID 605358Notes

Reaction equation

HRID 605358 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([N:11]=[CH:12][N:13](C)C)[C:8]([C:16]#[N:17])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20](=[O:43])[C:21]1[CH:26]=[CH:25][C:24]([S:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:30][CH:29]=2)=[C:23](N)[CH:22]=1.CCOC(C)=O.C([O-])([O-])=O.[K+].[K+]>CC(O)=O.O>[CH3:18][O:19][C:20](=[O:43])[C:21]1[CH:22]=[CH:23][C:24]([S:27][C:28]2[CH:33]=[CH:32][C:31]([NH:34][C:35]([O:37][C:38]([CH3:40])([CH3:39])[CH3:41])=[O:36])=[CH:30][CH:29]=2)=[C:25]([NH:17][C:16]2[C:8]3[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[N:10][C:9]=3[N:11]=[CH:12][N:13]=2)[CH:26]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 59376792Methyl 3-amino-4-((4-((tert-butoxycarbonyl)amino)phenyl)thio)benzoateHCID 66808575N'-(6-tert-Butyl-3-cyano-pyridin-2-yl)-N,N-dimethyl-formamidine

Product 1

HCID 670407204-(4-tert-Butoxycarbonylamino-phenylsulfanyl)-3-(7-tert-butyl-pyrido[2,3-d]pyrimidin-4-ylamino)-benzoic acid methyl esterYield 47.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of N′-(6-tert-butyl-3-cyano-pyridin-2-yl)-N,N-dimethyl-formamidine (0.46 g, 2.0 mmol) and 3-amino-4-(4-tert-butoxycarbonylamino-phenylsulfanyl)-benzoic acid methyl ester [prepared in Example 385C] (0.75 g, 2.0 mmol) in AcOH (10 mL) was heated at 120° C. for 30 minutes under N2. After cooling to room temperature, the reaction mixture was portioned between AcOEt and H2O, 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 (CH2Cl2/MeOH=98/2) to give the title compound as off-white powder (0.53 g, 47%).

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 (CH2Cl2/MeOH=98/2)

Sources & evidence

ORD record
ord-d7e114dc6ace4eb3be9a9c1cff04318c
Source dataset
uspto-grants-2011_03
Patent number
US07910595B2

Reaction notes

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