Acetonitrile → 6-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido(4,3-d)pyrimidine

HRID 657724Notes

Reaction equation

[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][NH:14][C:15](=O)[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:21])=O.C(#N)C>CN(C=O)C>[CH2:1]([N:8]1[CH2:18][CH2:17][C:11]2[N:12]=[CH:13][N:14]=[C:15]([Cl:21])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 6-benzyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4(3H)-one (5.0 g, 0.02 mol), phosphoryl chloride (3.30 mL, 0.035 mol) and acetonitrile (80 mL) and DMF (catalytic amount) was heated at 70° C. for 1 hour. The mixture was concentrated in vacuo and the remaining black residue was taken up in dichloromethane (250 mL) and poured over ice. The mixture was carefully neutralized with the addition of solid sodium bicarbonate. The organic layer was separated and dried over sodium sulfate and concentrated in vacuo. The mixture was purified by silica gel column with EtOAc/hexane (0-100%) to yield the title compound as a yellow oil (3 g, 57.8%). LC-MS: 260 [M+1]+; 1H NMR (400 MHz, DMSO-d6): δ 8.80 (s, 1H), 7.40-7.24 (m, 5H), 3.76 (s, 2H), 3.57 (s, 2H), 2.92 (t, 2H), 2.80 (t, 2H).

Workup

concentrationThe mixture was concentrated in vacuo
additionpoured over ice
additionThe mixture was carefully neutralized with the addition of solid sodium bicarbonate
customThe organic layer was separated
dry with materialdried over sodium sulfate
concentrationconcentrated in vacuo
customThe mixture was purified by silica gel column with EtOAc/hexane (0-100%)

Sources & evidence

ORD record: ord-7a2d76255a594b1ab4f6dbdfd69f8e80
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08076345B2

Reaction notes

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