Dichloromethane → 2-(Chloromethyl)-7,8-dihydro-3H-pyrano[4,3-D]pyrimidin-4(5H)-one

HRID 1752231Notes

Reaction equation

CO[C:3]([CH:5]1[C:10](=O)[CH2:9][CH2:8][O:7][CH2:6]1)=[O:4].C(N(CC)CC)C.[Cl:19][CH2:20][C:21]([NH2:23])=[NH:22].C(Cl)Cl>CO>[Cl:19][CH2:20][C:21]1[NH:23][C:3](=[O:4])[C:5]2[CH2:6][O:7][CH2:8][CH2:9][C:10]=2[N:22]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of crude 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester (1780 g, 11 mol) and triethylamine (830 g, 8.2 mol) in MeOH (3560 mL) was cooled to 0° C. under N2. A solution of 2-chloro-acetamidine (567 g, 4.4 mol) in 890 mL of MeOH was added dropwise over 50 minutes. The reaction mixture was stirred at 0° C. for 30 minutes and then at about 20° C. for 16 hours. LCMS at 215 nm and TLC (DCM:MeOH=10:1) analysis showed that most of 4-oxo-tetrahydro-pyran-3-carboxylic acid methyl ester was consumed. The mixture was then filtered and concentrated to give black oil, which was subsequently purified by flash column chromatography on silica gel and eluted with DCM to give yellow solid/oil mixture, which was further triturated with MTBE (˜1200 mL) and H2O:CH3CN:EA=1:1:2 (˜600 mL) to give the title compound as a white solid (318 g). MS m/z 201.2 (M+H). CHN analysis: calculated (results). C, 47.89 (47.95), H, 4.52 (4.401), N, 13.96 (13.76).

Workup

waitat about 20° C. for 16 hours
customwas consumed
filtrationThe mixture was then filtered
concentrationconcentrated
customto give black oil, which
customwas subsequently purified by flash column chromatography on silica gel
washeluted with DCM
customto give yellow solid/oil mixture, which
customwas further triturated with MTBE (˜1200 mL) and H2O

Sources & evidence

ORD record: ord-1caf66085ae24f51a07807c21821501e
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163003B2

Reaction notes

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