Tetrahydro-4H-pyran-4-one → 1'-ethyl-6'-(pyridin-4-yl)-2,3,5,6-tetrahydro-1'H-spiro[pyran-4,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one

HRID 2363964Notes

Reaction equation

[CH2:1]([NH:3][C:4]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=2)[S:6][C:5]=1[C:15]([NH2:17])=[O:16])[CH3:2].[O:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH2:1]([N:3]1[C:4]2[CH:8]=[C:7]([C:9]3[CH:14]=[CH:13][N:12]=[CH:11][CH:10]=3)[S:6][C:5]=2[C:15](=[O:16])[NH:17][C:21]21[CH2:22][CH2:23][O:18][CH2:19][CH2:20]2)[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-(ethylamino)-5-(pyridin-4-yl)thiophene-2-carboxamide (0.100 g, 0.400 mmol), tetrahydro-4H-pyran-4-one (1.0 mL), p-toluenesulfonic acid monohydrate (0.0095 g, 0.050 mmol) and acetic acid (2.0 mL) was stirred for 3 h at 100° C. in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (150 mL). Extraction with ethyl acetate/THF (4:1, 100 mL, 50 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure gave an oil. This oil was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol), then triturated with ethyl acetate, and the precipitate was collected by filtration to afford the title compound (0.0715 g, 54%) as a yellow solid:

Workup

extractionExtraction with ethyl acetate/THF (4:1, 100 mL, 50 mL)
dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
customgave an oil
customThis oil was purified by column chromatography (Combiflash, 12 g silica gel, dichloromethane to 90:10 dichloromethane/methanol)
customtriturated with ethyl acetate
filtrationthe precipitate was collected by filtration

Sources & evidence

ORD record: ord-c54590fccf56456aac325bc460a72873
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691828B2

Reaction notes

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