Sodium Carbonate → 8-(2,6-Difluorophenyl)-4-(2-methylphenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one

HRID 30087Notes

Reaction equation

HRID 30087 reaction equation
[C:1](=O)([O-])[O-].[Na+].[Na+].Cl[C:8]1[C:9]2[CH:19]=[CH:18][C:17](=[O:20])[N:16]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])[C:10]=2[N:11]=[C:12]([S:14][CH3:15])[N:13]=1.F[C:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1COCC1>[F:28][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([F:27])[C:21]=1[N:16]1[C:10]2[N:11]=[C:12]([S:14][CH3:15])[N:13]=[C:8]([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=3[CH3:1])[C:9]=2[CH:19]=[CH:18][C:17]1=[O:20]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 119515134-Chloro-2-methylsulfanyl-8-(2,6-difluorophenyl)-8H-pyrido[2,3-d]pyrimidin-7-one

Product 1

HCID 597893358-(2,6-Difluorophenyl)-4-(2-methylphenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-oneYield 63%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

THF (10 mL) and 2M sodium carbonate (2 mL) were added to a mixture of 4-chloro-8-(2,6-difluorophenyl)-2-(methylthio)pyrido[2,3-d]pyrimidin-7(8H)-one (0.34 g, 1.0 mmol, solid-supported tetrakis(triphenylphosphine)palladium(0) (0.39 g, 0.1 mmol) and 4-fluorobenzeneboronic acid (0.21 g, 1.5 mmol). The mixture was irradiated with microwave at about 150° C. for about 20 min, then filtered and the filtrate evaporated. The crude product was redissolved in ethyl acetate (10 mL) and water (10 mL). The layers were separated and the organic layer was dried over magnesium sulphate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel with cyclohexane containing ethyl acetate (0 to 50%) to give the title compound (0.25 g, 63%). LC-MS m/z 396 (M+H)+, 3.55 min (ret time).

Workup

  1. customThe mixture was irradiated with microwave at about 150° C. for about 20 min
  2. filtrationfiltered
  3. customthe filtrate evaporated
  4. dissolutionThe crude product was redissolved in ethyl acetate (10 mL)
  5. customThe layers were separated
  6. dry with materialthe organic layer was dried over magnesium sulphate
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by flash chromatography on silica gel with cyclohexane
  10. additioncontaining ethyl acetate (0 to 50%)

Sources & evidence

ORD record
ord-d91e773741974fb5b4f0fe96cc26679b
Source dataset
uspto-grants-2008_09
Patent number
US07423042B2

Reaction notes

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