Nitric Acid → 4-(2-Amino-3-nitro-pyridin-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

Temperatur

0 °C

Following the procedure of Recl. Trav. Chim. Pays-Bas 88(11): 1263 (1969), 4-Chloro-pyridin-2-ylamine (A) (6.8 g, 67 mmol) was carefully dissolved in H2SO4 (45.2 ml) at 0° C. Nitric acid (2.3 ml) was added, maintaining the temperature at 0° C. The solution was stirred at 5° C. for 2 days. After it was judged complete by TLC (40% ethyl acetate/hexane), the mixture was carefully made basic with the addition of solid Na2CO3. The mixture was then extracted with ethyl acetate several times. The ethyl acetate was dried over magnesium sulfate and the solvents were removed under vacuum. The resulting crude was dissolved in DMSO (25 ml) with t-butyl-1-piperazine carboxylate (14.3 g, 75 mmol) and DIEA (10.3 g, 80 mmol). This mixture was heated to 50° C. for 3 hours before it was judged complete by MS. The mixture was purified by HPLC Method E to yield the title product 5 (2.8 g (13%), 8.6 mmol). 1H NMR (DMSO-d6): δ 7.82 (d, J=5.8 Hz, 1H), 6.98 (bs, 2H), 6.31 (d, J=5.8 Hz, 1H), 3.41 (m, 4H), 3.13 (m, 4H), 1.41 (s, 9H). MS (ESI-POS): [M+H]+=324.

1. extractionThe mixture was then extracted with ethyl acetate several times
2. dry with materialThe ethyl acetate was dried over magnesium sulfate
3. customthe solvents were removed under vacuum
4. temperatureThis mixture was heated to 50° C. for 3 hours before it
5. customThe mixture was purified by HPLC Method E

ORD-Eintrag

ord-5b4c7ddf50b94af585985b3af63181bc

Quelldatensatz

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07534796B2