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

HRID 1752534Notes

Reaction equation

HRID 1752534 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.C(OCC)(=O)C.C([O-])([O-])=O.[K+].[K+]>C(O)(=O)C>[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

6

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 1

HCID 176Acetic AcidSolvent

Procedure

A suspension of N′-(3-cyano-6-isopropyl-pyridin-2-yl)-N,N-dimethyl-formamidine (2.00 g, 9.3 mmol) and the product from Example 1C (3.46 g, 9.3 mmol) in Acetic acid (40 mL) was heated at 120° C. for 20 minutes under N2. After cooling to room temperature, the reaction mixture was portioned between ethyl acetate (150 mL) and H2 (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 a pale brown oil. The oily residue was separated by silica gel column chromatography (ethyl acetate/n-hexane=5/1) gave yellow crystal. Further purification by washing with cold ethyl acetate (15 mL) gave the title compound as slightly yellow crystal (3.27 g, 65% yield).

Workup

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

Sources & evidence

ORD record
ord-2d22bc73d20a4b589b03cbd2ae3a2aae
Source dataset
uspto-grants-2015_10
Patent number
US09163017B2

Reaction notes

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