Sodium hydride → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (3-amino-5-bromo-pyrazin-2-yl)-amide

To a mixture of 5-bromo-pyrazine-2,3-diamine (250 mg, 1.32 mmol) in 1:1 DMF/DCM (8 mL) was added NaH (159 mg, 3.97 mmol, 60% dispersion in mineral oil) slowly. After stirring at room temperature for 1 h, the resulting mixture was cooled to 0° C. Solid 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carbonyl chloride (373 mg, 1.59 mmol, prepared as described in Example 1, STEP C) was added slowly. The resulting mixture was warmed to room temperature and then stirred for 18 h. The resulting mixture was treated with 50 mL of EtOAc and washed with aqueous saturated NH4Cl (20 mL), H2O (2×10 mL) and brine (10 mL). After drying with Na2SO4, the resulting solution was concentrated in vacuo and the residue was purified by flash chromatography on silica gel (0:100-20:80 EtOAc/hexanes) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (3-amino-5-bromo-pyrazin-2-yl)-amide as a light brown solid. 1H-NMR (400 MHz, CDCl3) δ: 8.88 (s, 1H), 8.12 (s, 1H), 5.34 (br. s., 2H), 4.14 (s, 3H), 1.42 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calculated For C13H16BrClN6O: 387.0 (M+H). Measured: 387.0.

1. temperaturethe resulting mixture was cooled to 0° C
2. temperatureThe resulting mixture was warmed to room temperature
3. stirringstirred for 18 h
4. washwashed with aqueous saturated NH4Cl (20 mL), H2O (2×10 mL) and brine (10 mL)
5. dry with materialAfter drying with Na2SO4
6. concentrationthe resulting solution was concentrated in vacuo
7. customthe residue was purified by flash chromatography on silica gel (0:100-20:80 EtOAc/hexanes)

ORD record

ord-c432ed495de7448394e7be1abd6964e7

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409915B2