N,N-Dimethylaniline → 7-Benzyl-4-chloro-5,6,7,8-tetrahydro-2-(methoxymethyl)pyrido[3,4-d]pyrimidine

HRID 2219915Notes

Reaction equation

[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](=O)[NH:13][C:12]([CH2:19][O:20][CH3:21])=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:24])=O.CN(C)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>ClCCCl>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([Cl:24])=[N:13][C:12]([CH2:19][O:20][CH3:21])=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 7-benzyl-5,6,7,8-tetrahydro-2-(methoxymethyl)pyrido[3,4-d]pyrimidin-4(3H)-one (2.01 g, 7.04 mmol), phosphorus oxychloride (5.16 mL, 56.35 mmol) and N,N-dimethylaniline (0.89 mL, 7.04 mmol) in 1,2-dichloroethane was heated to 80° C. for two h. The mixture was allowed to cool to r.t. and poured over crushed ice (100 mL). The mixture was made basic (pH=˜8) by the addition of saturated aqueous sodium bicarbonate and extracted with ethyl acetate (200 mL). The organic layer was dried over magnesium sulfate and concentrated to leave a dark oil which was purified by silica gel chromatography (ethyl acetate/hexane gradient) to yield 1.76 g (82%) of the title compound as a brown oil.

Workup

temperatureto cool to r.t.
additionpoured
extractionextracted with ethyl acetate (200 mL)
dry with materialThe organic layer was dried over magnesium sulfate
concentrationconcentrated
customto leave a dark oil which
customwas purified by silica gel chromatography (ethyl acetate/hexane gradient)

Sources & evidence

ORD record: ord-557c21b78473421ea7ad1135f241eb39
Source dataset: uspto-grants-2008_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07414131B2

Reaction notes

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