Phosphorus oxychloride → N-(4-Chloro-6-(4-fluorophenyl)pyrido[3,2-d]pyrimidin-2-yl)acetamide

HRID 1517461Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:12]=[C:13]([NH:19][C:20](=[O:22])[CH3:21])[NH:14][C:15](=O)[C:16]=3[N:17]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:34]>O1CCOCC1>[Cl:34][C:15]1[C:16]2[N:17]=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[CH:9]=[CH:10][C:11]=2[N:12]=[C:13]([NH:19][C:20](=[O:22])[CH3:21])[N:14]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a suspension of N-[6-(4-fluoro-phenyl)-4-oxo-3,4-dihydro-pyrido[3,2-d]pyrimidin-2-yl]-acetamide (0.77 g, 2.58 mmol) and DIEA (1.34 mL, 7.74 mmol) in dioxane (25 mL) was added POCl3 (0.73 mL, 7.74 mmol). The mixture was heated to 80° C. for 30 minutes. After the removal of solvent, the residue was dissolved in ethyl acetate (200 mL) and the solution was filtered through a short column with silica gel. The column was additionally washed with ethyl acetate. The filtrate and washings were combined and concentrated. The precipitate formed was isolated by filtration to give the pure title compound as a brown solid (0.43 g, yield 43%) which was characterised as follows: MS (m/z) 317.0 [M+H]+.

Workup

customAfter the removal of solvent
dissolutionthe residue was dissolved in ethyl acetate (200 mL)
filtrationthe solution was filtered through a short column with silica gel
washThe column was additionally washed with ethyl acetate
concentrationconcentrated
customThe precipitate formed
customwas isolated by filtration

Sources & evidence

ORD record: ord-06f7b2309fec4d1487012e95de5d0852
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232278B2

Reaction notes

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