Chlorotrimethylsilane → HCID 178470311, compound

HRID 1801943Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of ethyl 2-(2-carbamoyl-5-chlorophenylamino)-2-oxoacetate (545 mg, 2.02 mmol) and TEA (11 mL, 80 mmol) in DCE (20 mL) was added trimethylsilyl chloride (3.8 mL, 30 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 saturated aq NaHCO3 and DCM (100 mL). The separated aqueous phase was extracted with DCM (2×100 mL) and the combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 10-60% EtOAc/hexanes to afford ethyl 7-chloro-4-hydroxyquinazoline-2-carboxylate as a solid (321 mg, 63%). 1H NMR (300 MHz, DMSO-d6) δ 1.36 (t, J=7.06 Hz, 3 H), 4.39 (q, J=7.10 Hz, 2 H), 7.60-7.74 (m, 1 H), 7.85-7.98 (m, 1 H), 8.11-8.23 (m, 1 H), 12.82 (br s, 1 H).

Workup

concentrationThe mixture was concentrated under reduced pressure
customthe residue was partitioned between saturated aq NaHCO3 and DCM (100 mL)
extractionThe separated aqueous phase was extracted with DCM (2×100 mL)
dry with materialthe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe residue was purified by silica gel chromatography
washeluting with 10-60% EtOAc/hexanes

Sources & evidence

ORD record: ord-17a29638ef0642ba91a27aa8e362e9e8
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08349851B2

Reaction notes

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