Sodium Bicarbonate → 4-[2-(2-Fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyrido[3,4-d]pyrimidine

HRID 1629915Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16](B(O)O)[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1.Cl[C:22]1[C:23]2[CH:31]=[CH:30][N:29]=[CH:28][C:24]=2[N:25]=[CH:26][N:27]=1.C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:17]=[C:16]([C:22]2[C:23]3[CH:31]=[CH:30][N:29]=[CH:28][C:24]=3[N:25]=[CH:26][N:27]=2)[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[N:9]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A slurry of 268 mg (1.00 mmol) 2-(2-fluoro-phenyl)-[1,8]naphthyridine-4-boronic acid, 166 mg (1.00 mmol) 4-chloropyrido[3,4-d]pyrimidine, 101 mg (1.20 mmol) sodium bicarbonate and 4.5 mg (0.020 mmol) palladium(II)acetate in a mixture of 4 ml dimethylacetamide and 4 ml ethanol was heated to 80° C. and stirred at this temperature for 18 hours. The reaction mixture was cooled to room temperature and partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate and evaporated. The residue was chromatographed on a silica gel column with dichloromethane/ethyl acetate as eluent yielding 4-[2-(2-fluoro-phenyl)-[1,8]naphthyridin-4-yl]-pyrido[3,4-d]pyrimidine as colourless crystals; HPLC/MS: 1.91 min, [M+H] 354.

Workup

temperatureThe reaction mixture was cooled to room temperature
custompartitioned between water and dichloromethane
dry with materialThe organic phase was dried over sodium sulfate
customevaporated
customThe residue was chromatographed on a silica gel column with dichloromethane/ethyl acetate as eluent

Sources & evidence

ORD record: ord-200130e464c64d089780da9a8f172427
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791113B2

Reaction notes

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