Isopropylamine → Ethyl 2-chloro-4-isopropylcarbamoyl-thiazole-5-carboxylate

Temperature

45 °C

To a stirred solution of 2-chloro-5 (ethoxycarbonyl)-1,3-thiazole-4-carboxylic acid (Intermediate 7, 1.0 g, 4.2 mmol) in dry dichloromethane (20 mL) was added oxalyl chloride (0.73 mL, 8.4 mmol) and 2 drops of dry dimethylformamide. The reaction mixture was refluxed to 45° C. for 1½ h. The reaction mixture was cooled to room temperature, and then evaporated to dryness under reduced pressure. The residue was dissolved in dry dichloromethane (20 mL) and cooled to 0° C., then 2,6-lutidine (0.493 mL, 4.237 mmol) was added followed by addition of isopropyl amine (0.360 mL, 4.237 mmol). After completion of the reaction, the reaction mixture was concentrated to dryness and the residue was extracted with ethyl acetate (2×50 mL). The organic layer was washed with 1 N hydrochloric acid (1×50 mL), then dried over anhydrous sodium sulfate and concentrated under vacuum to afford 1.13 g (96%) of the title compound as a thick syrup. NMR: 1.26 (d, 6H), 1.38 (t, 3H), 4.24 (m, 1H), 4.40 (q, 2H), 7.51 (br s, 1H).

1. temperatureThe reaction mixture was cooled to room temperature
2. customevaporated to dryness under reduced pressure
3. dissolutionThe residue was dissolved in dry dichloromethane (20 mL)
4. temperaturecooled to 0° C.
5. customAfter completion of the reaction
6. concentrationthe reaction mixture was concentrated to dryness
7. extractionthe residue was extracted with ethyl acetate (2×50 mL)
8. washThe organic layer was washed with 1 N hydrochloric acid (1×50 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. concentrationconcentrated under vacuum

ORD record

ord-29dd26eb4b8c4878a1d4423ed0bd60ba

Source dataset

uspto-grants-2010_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07674801B2