2,3-Dichloropyridine → 6-(3-Chloropyridin-2-yl)-N-(4-fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine

HRID 535350Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[CH2:18][NH:17][CH2:16][CH2:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[CH:4][CH:3]=1.Cl[C:20]1[C:25]([Cl:26])=[CH:24][CH:23]=[CH:22][N:21]=1.C(N(CC)C(C)C)(C)C>O1CCOCC1.CN(C)C(=O)C>[Cl:26][C:25]1[C:20]([N:17]2[CH2:16][CH2:15][C:11]3[N:12]=[CH:13][N:14]=[C:9]([NH:8][C:5]4[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=4)[C:10]=3[CH2:18]2)=[N:21][CH:22]=[CH:23][CH:24]=1

Participants

Conditions

Temperature: 150 °C

Procedure

N-(4-Fluorophenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-amine (0.47 g, 1.92 mmol) was dissolved in a mixture of dioxane/N,N-dimethylacetamide (4:1) (3 mL). To the mixture was added 2,3-dichloropyridine (420 mg, 2.86 mmol) and N,N-diisopropylethylamine (0.38 mL, 2.2 mmol). The mixture was heated at 150° C. in a Personal Chemistry microwave for 16 h. The solvents were removed under vacuum and the residue was dissolved in ethyl acetate and washed with sat. NaHCO3 and brine. The organic layer was dried over Na2SO4, filtered and evaporated to give a brown residue. The residue was purified by silica gel chromatography using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as an off-white powder (200 mg, 30%).

Workup

customThe solvents were removed under vacuum
dissolutionthe residue was dissolved in ethyl acetate
washwashed with sat. NaHCO3 and brine
dry with materialThe organic layer was dried over Na2SO4
filtrationfiltered
customevaporated
customto give a brown residue
customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record: ord-188aa263ffb94706a59bfa1145200613
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08859545B2

Reaction notes

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