2-Thiophenecarboxylic acid, tetrahydro-3-oxo-, methyl ester → 2-(3-chlorophenyl)-6,7-dihydro-1H-thieno[3,2-d]pyrimidin-4-one

HRID 1509025Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](=[NH:7])[NH2:6].O=[C:12]1[CH2:16][CH2:15][S:14][CH:13]1[C:17](OC)=[O:18].C[O-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[N:6]=[C:17]([OH:18])[C:13]3[S:14][CH2:15][CH2:16][C:12]=3[N:7]=2)[CH:8]=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 3-chlorobenzimidamide (4.8 g, 31.2 mmol) in ethanol (150 mL) was added methyl 3-oxotetrahydrothiophene-2-carboxylate (5.0 g, 31.2 mmol) and sodium methoxide (1.7 g, 31.2 mmol). The mixture was stirred at 85° C. for 16 h. The mixture was concentrated after which ethanol (10 mL) was added and the suspension was chilled to 0° C. HCl (2 M, 50 mL) was added and the suspension was filtered and washed with water. The solid was purified by column chromatography (silica, dichloromethane/methanol) to afford the title compound (1.9 g, 23%) as a brown solid. MW=264.73. 1H NMR (DMSO-d6, 500 MHz) δ 12.85 (s, 1H), 8.13 (s, 1H), 8.07-8.01 (m, 1H), 7.63-7.59 (m, 1H), 7.56-7.51 (m, 1H), 3.41-3.24 (m, 4H); APCI MS m/z 265 [M+H]+.

Workup

concentrationThe mixture was concentrated after which ethanol (10 mL)
additionwas added
temperaturethe suspension was chilled to 0° C
additionHCl (2 M, 50 mL) was added
filtrationthe suspension was filtered
washwashed with water
customThe solid was purified by column chromatography (silica, dichloromethane/methanol)

Sources & evidence

ORD record: ord-15b29c97f3454a0483e41fe64af6a2cc
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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