Trifluoroacetic acid → 4-(2-amino-5-bromo-3-nitropyridin-4-yl)-N-phenylpiperazine-1-carboxamide

Temperatur

0 °C

A solution of tert-butyl 4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazine-1-carboxylate (250 mg, 0.62 mmol) in CH2Cl2 (2.5 mL) at 0° C. was treated with TFA (2.5 mL) and stirred at 0° C. for 1.5 h. After this time, the solvents were evaporated in vacuo and the excess TFA removed by azeotroping with toluene (3×10 ml). The residue was suspended in CHCl3 (2.5 mL) and treated with DIPEA (5 eq, 3.11 mmol, 0.54 mL) and phenyl isocyanate (1.05 eq, 0.65 mmol, 0.07 mL). The reaction was warmed to room temperature and stirred for 12 h. The formed precipitate was filtered off and dried to give the product as a yellow solid (221 mg, 84% for two steps); 1H-NMR (500 MHz, DMSO-d6) 3.07 (br s, 4H, piperazine N(CH2)2), 3.58 (br s, 4H, piperazine N(CH2)2), 6.94 (tt, J=7.4, 1.1 Hz, 1H, phenyl H-4), 7.03 (br s, 2H, NH2), 7.24 (dd, J=8.5, 7.5 Hz, 2H, phenyl H-3 & H-5), 7.45 (dd, J=8.5, 1.1 Hz, 2H, phenyl H-2 & H-6), 8.21 (s, 1H, pyridine H-6), 8.59 (br s, 1H, NH);

1. customAfter this time, the solvents were evaporated in vacuo
2. customthe excess TFA removed
3. customby azeotroping with toluene (3×10 ml)
4. temperatureThe reaction was warmed to room temperature
5. stirringstirred for 12 h
6. filtrationThe formed precipitate was filtered off
7. customdried

ORD-Eintrag

ord-ff26065cbc9a42de9f4a3ee48294feca

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08088761B2