Diethyl Carbonate → 2-{3-Phenyl-4-[(pyridin-2-ylmethyl)-amino]-thieno[2,3-b]pyridin-6-yl}-malonic acid diethyl ester

HRID 215993Notes

Reaction equation

[CH2:1]([O:3][C:4](=[O:29])[CH2:5][C:6]1[N:11]=[C:10]2[S:12][CH:13]=[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:9]2=[C:8]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH:7]=1)[CH3:2].[C:30](=O)([O:34]CC)[O:31][CH2:32][CH3:33].[H-].[Na+]>C1COCC1.O>[CH2:1]([O:3][C:4](=[O:29])[CH:5]([C:6]1[N:11]=[C:10]2[S:12][CH:13]=[C:14]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:9]2=[C:8]([NH:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH:7]=1)[C:30]([O:31][CH2:32][CH3:33])=[O:34])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

{3-Phenyl-4-[(pyridin-2-ylmethyl)-amino]-thieno[2,3-b]pyridin-6-yl}-acetic acid ethyl ester (180 mg, 0.45 mmol) was dissolved in dry THF (10 ml) under nitrogen. Diethyl Carbonate (0.27 ml, 2.23 mmol) was added and the mixture cooled to 0° C. Sodium Hydride (36 mg, 0.89 mmol) was added and the mixture stirred at 0° C. for a further 10 min, then at room temperature for 20 min, then brought to reflux for 45 min. On cooling, the reaction was diluted with water (100 ml) and extracted with DCM (3×50 ml), the extracts combined, dried over magnesium sulphate and concentrated. The residue was purified on silica, eluting (Ethyl Acetate/DCM), 0-20%) to give 2-{3-Phenyl-4-[(pyridin-2-ylmethyl)-amino]-thieno[2,3-b]pyridin-6-yl}-malonic acid diethyl ester as a yellow solid. Yield=96 mg (45%).

Workup

waitat room temperature for 20 min
temperatureto reflux for 45 min
temperatureOn cooling
extractionextracted with DCM (3×50 ml)
dry with materialdried over magnesium sulphate
concentrationconcentrated
customThe residue was purified on silica
washeluting (Ethyl Acetate/DCM), 0-20%)

Sources & evidence

ORD record: ord-be379132baeb41daae63c7c2d3a121b5
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08193215B2

Reaction notes

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