Diisopropylethylamine → tert-butyl [2-methyl-4-(1-methyl-1H-pyrazol-4-yl)-1H-imidazol-1-yl]carbamate

tert-Butyl 2-ethanimidoylhydrazinecarboxylate (17.3 g, 99.9 mmol), 2-bromo-1-(1-methyl-1H-pyrazol-4-yl)ethanone (16.89 g, 83.18 mmol) and N,N-diisopropylethylamine (31.9 mL, 183 mmol) were combined in ice-cold 2-methyltetrahydrofuran (400 mL) and 1,2-dimethoxyethane (100 mL), and the reaction mixture was heated to reflux. After 2.5 hours, the reaction was cooled and washed with 50% saturated aqueous sodium chloride solution (75 mL). The aqueous layer was extracted with 2-methyltetrahydrofuran (100 mL), and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was dissolved in warm ethyl acetate (60 mL), allowed to cool to room temperature, then cooled to 5° C. for 30 minutes. The resulting solid was collected by filtration and washed with a small quantity of cold ethyl acetate, then washed with diethyl ether, to provide the product as a very pale yellow solid. Yield: 16.0 g, 57.7 mmol, 69%. LCMS m/z 278.5 (M+1). 1H NMR (500 MHz, CDCl3) δ 1.49 (br s, 9H), 2.23 (s, 3H), 3.84 (s, 3H), 6.87 (s, 1H), 7.51 (s, 1H), 7.60 (s, 1H), 8.67 (br s, 1H).

1. temperaturethe reaction was cooled
2. washwashed with 50% saturated aqueous sodium chloride solution (75 mL)
3. extractionThe aqueous layer was extracted with 2-methyltetrahydrofuran (100 mL)
4. dry with materialthe combined organic layers were dried over magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. dissolutionThe residue was dissolved in warm ethyl acetate (60 mL)
8. temperaturecooled to 5° C. for 30 minutes
9. filtrationThe resulting solid was collected by filtration
10. washwashed with a small quantity of cold ethyl acetate
11. washwashed with diethyl ether
12. customto provide the product as a very pale yellow solid

ORD record

ord-7b584e320ec94262a280a69bff15aac7

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200000B2