Sulfolane → Methyl 6-bromo-1-isopropyl-3-methyl-1H-indazole-4-carboxylate

온도

100 °C

To a stirred solution of methyl 6-bromo-3-formyl-1-isopropyl-1H-indazole-4-carboxylate (4.5 g, 13.84 mmol) in DMF (31.5 mL) was added p-toluenesulfonic acid monohydrate (0.342 g, 1.8 mmol), p-toluenesulfonyl hydrazide (3.35 g, 18.0 mmol) followed by sulfolane (31.5 mL), and the reaction mixture was stirred at 100° C. for 1 h. The reaction mixture was cooled to room temperature and sodium cyanoborohydride (3.489 g, 55.0 mmol) was added portion wise over a period of 25 min. The resulting reaction mixture was stirred at 100° C. for 2 h and then at RT for 6 h. The reaction mixture was diluted with water and extracted with ethyl acetate (4×300 mL). The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4, filtered, and concentrated. The crude residue (4.4 g) was purified by silica gel chromatography (eluent: 0-5% ethyl acetate: pet ether) to afford the title compound as an off white solid (2.95 g, 68%). 1H NMR (CDCl3, 400 MHz): δ 1.559 (d, J=6.8 Hz, 6H), 2.674 (s, 3H), 3.976 (s, 3H), 4.667-4.767 (m, 1H), 7.715 (d, J=1.6 Hz, 1H), 7.761 (d, J=1.6 Hz, 1H). LCMS (ES+): 98.63%, 313.06 [M+H] ion present.

1. temperatureThe reaction mixture was cooled to room temperature
2. customThe resulting reaction mixture
3. stirringwas stirred at 100° C. for 2 h
4. waitat RT for 6 h
5. extractionextracted with ethyl acetate (4×300 mL)
6. washThe combined organic layers were washed with water, brine
7. dry with materialdried over anhydrous Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude residue (4.4 g) was purified by silica gel chromatography (eluent: 0-5% ethyl acetate: pet ether)

ORD 기록

ord-16207fc8a6a043859eea413827a9a0ef

출처 데이터셋

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09018382B2