Diisopropylamine → 4-(4-Bromo-2-fluorophenylamino)-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid

温度

-78 °C

To a solution of i-Pr2NH (0.39 mL, 2.80 mmol) in THF (4 mL) at 0° C. was added n-BuLi (1.1 mL, 2.80 mmol, 2.5 M solution in hexanes). After stirring 15 minutes, the mixture was cooled to −78° C. 4-Bromo-2-fluorophenylamine (0.38 g, 2.0 mmol) was added. After vigorous stirring for 10 minutes, a mixture of the 4-chloro-1-methyl-6-oxo-1,6-dihydropyridine-3-carboxylic acid (0.15 g, 0.80 mmol) in THF (5 mL) was added. The dry-ice bath was removed after 30 minutes, and the reaction mixture was stirred for 17 hours at room temperature. The reaction mixture was treated with a 10% aqueous HCl solution (15 mL), extracted with EtOAc, dried (MgSO4), and concentrated. Trituration with methylene chloride gave 0.21 g (77%) desired product. MS APCI (−) m/z 339, 341 (M−, Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.53 (s, 1H), 7.69 (dd, 1H), 7.46 (m, 2H), 3.41 (s, 3H).

1. stirringAfter vigorous stirring for 10 minutes
2. additionwas added
3. customThe dry-ice bath was removed after 30 minutes
4. stirringthe reaction mixture was stirred for 17 hours at room temperature
5. additionThe reaction mixture was treated with a 10% aqueous HCl solution (15 mL)
6. extractionextracted with EtOAc
7. dry with materialdried (MgSO4)
8. concentrationconcentrated

ORDレコード

ord-ec408b18ac434e6ebb840af48f8d37fa

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08101611B2