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

HRID 588712Notes

Reaction equation

CO[C:3]([CH:5]1[C:10](=O)[CH2:9][CH2:8][O:7][CH2:6]1)=[O:4].CCN(CC)CC.[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 NEt3 (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-65d4dcb4f9a74aecab55bb51d722a0f1
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227982B2

Reaction notes

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