Chloroform → Methyl 1H-indazole-7-carboxylate hydrochloride

To a solution of the ester (17.5 g, 106 mmol) in chloroform (300 mL) was added acetic anhydride (22.6 mL, 239 mmol, 2.3 eq) while maintaining the temperature below 40° C. The reaction mixture was maintained at room temperature for 1 h when potassium acetate (3.00 g, 30.6 mmol, 0.3 eq) and isoamyl nitrite (30.6 mL, 228 mmol, 2.2 eqiv) was added. The reaction mixture was heated at reflux for 24 h and was allowed to cool to room temperature. The reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate, dried over sodium sulfate, and concentrated. Methanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue and the mixture was maintained for 18 h at rt. The volatiles were removed under reduced pressure and the residue was triturated with ethyl acetate (100 mL). The product was isolated by filteration, washed with ethyl acetate (20 mL), and dried to provide 15.3 g (68%) of methyl 1H-indazole-7-carboxylate hydrochloride. 1H NMR (500 MHz, DMSO-d6) δ 13.3 (bs, 1H), 8.26 (d, 1H), 8.12 (d, 1H), 8.25 (dd, 1H), 7.27 (t, 1H), 3.97 (s, 3H); MS (APCI) m/z 177 (M++1).

1. temperaturewhile maintaining the temperature below 40° C
2. additionwas added
3. temperatureThe reaction mixture was heated
4. temperatureat reflux for 24 h
5. washThe reaction mixture was washed with a saturated, aqueous solution of sodium bicarbonate
6. dry with materialdried over sodium sulfate
7. concentrationconcentrated
8. additionMethanol (100 mL) and 6 N hydrochloric acid (100 mL) were added to the residue
9. temperaturethe mixture was maintained for 18 h at rt
10. customThe volatiles were removed under reduced pressure
11. customthe residue was triturated with ethyl acetate (100 mL)
12. customThe product was isolated by filteration
13. washwashed with ethyl acetate (20 mL)
14. customdried

ORDレコード

ord-c88f9e02632d43d3a5eaac76b3144ada

出典データセット

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08252811B2