Diisopropylethylamine → 5-Bromo-4-[4-(5-methyl-isoxazol-3-ylmethyl)-piperazin-1-yl]-3-nitro-pyridin-2-ylamine

Temperature

45 °C

A solution of 4-(5-methyl-isoxazol-3-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (0.200 g, 0.71 mmol) in dichloromethane (6 ml) and TFA (8 ml) was stirred at room temperature for 2 h then concentrated in vacuo, and the resulting residue was dried in vacuo. This material (supposedly 0.70 mmol) was dissolved in isopropanol (13 ml) and to this solution 2-amino-5-bromo-4-chloro-3-nitropyridine (0.157 g, 0.63 mmol) was added followed by diisopropylethylamine (0.65 ml, 3.70 mmol). The reaction mixture was stirred at 45° C. for 20 h, then allowed to cool to room temperature and diluted with isopropanol (5 ml). The resulting orange solid was collected by filtration, washed with isopropanol (2×5 ml), diethyl ether (3×5 ml), and dried (0.170 g, 60%); 1H-NMR (500 MHz, DMSO-d6) 2.38 (s, 3H, isoxazole 5-CH3), 2.53 (br s, 4H, piperazine N(CH2)2), 3.05 (br s, 4H, piperazine N(CH2)2), 3.55 (s, 2H, NCH2 isoxazole), 6.21 (s, 1H, isoxazole 4-H), 6.97 (s, 2H, NH2), 8.16 (s, 1H, pyridine 6-H);

1. concentrationthen concentrated in vacuo
2. customthe resulting residue was dried in vacuo
3. additionwas added
4. temperatureto cool to room temperature
5. filtrationThe resulting orange solid was collected by filtration
6. washwashed with isopropanol (2×5 ml), diethyl ether (3×5 ml)
7. customdried (0.170 g, 60%)

ORD record

ord-fd92bc2e87a14bfca6ad08282a5f2a63

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088761B2