Chlorotrimethylsilane → HCID 178470309, compound

HRID 625783Notes

Reaction equation

[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[C:5]=1[NH:11][C:12](=O)[C:13]([O:15][CH2:16][CH3:17])=[O:14])(=[O:3])[NH2:2].[Si](Cl)(C)(C)C>ClCCCl>[OH:3][C:1]1[C:4]2[C:5](=[C:6]([CH3:10])[CH:7]=[CH:8][CH:9]=2)[N:11]=[C:12]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[N:2]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl 2-(2-carbamoyl-6-methylphenylamino)-2-oxoacetate (490 mg, 1.96 mmol) and TEA (10.4 mL, 75 mmol) in DCE (20 mL) was added TMS-Cl (3.6 mL, 29 mmol) and the solution was stirred at 80° C. for 16 h. The mixture was concentrated under reduced pressure and the residue was partitioned between DCM (100 mL) and saturated aq NaHCO3. The separated aqueous phase was extracted with DCM (2×100 mL) and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography eluting with 10-40% EtOAc/hexanes to afford ethyl 4-hydroxy-8-methylquinazoline-2-carboxylate as a solid (330 mg, 72%). 1H NMR (300 MHz, DMSO-d6) δ 1.36 (t, J=7.2 Hz, 3H), 2.58 (s, 3H), 4.39 (q, J=7.2 Hz, 2H), 7.46-7.64 (m, 1H), 7.64 (m, 1H), 8.02 (m, 1H), 12.62 (br s, 1H).

Workup

concentrationThe mixture was concentrated under reduced pressure
customthe residue was partitioned between DCM (100 mL) and saturated aq NaHCO3
extractionThe separated aqueous phase was extracted with DCM (2×100 mL)
dry with materialthe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluting with 10-40% EtOAc/hexanes

Sources & evidence

ORD record: ord-437851dc9e2d46f895c377d234125944
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09308207B2

Reaction notes

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