Pyridine → N-(4-Methyl-3-nitro-phenyl)-4-(4-methyl-piperazin-1-ylmethyl)-benzamide

Temperature

23 °C

Thionyl chloride (53.3 g, 448 mmol) Is added over a period of 15 min to a suspension of 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid (70.0 g, 299 mmol) in toluene (300 ml) at 0° C. At the end of the addition, the reaction mixture is heated at 23° C. over a period of 45 min. The excess of SOCl2 is removed by co-distillation with toluene under reduced pressure at 40° C. At the end of the distillation, the resulting suspension id cooled down to 0° C. and the benzoyl chloride is filtered off, washed with toluene (2×50 ml) and dried in vacuo at 45° C. overnight. Yield: 55.0 g, 79% of theory based on the di-hydrochloride salt of the benzoylchloride, white solid. The dried benzoyl chloride (55 g) is then resuspended in toluene (100 ml). A solution of 4-methyl-3-nitroaniline (22.75 g, 145 mmol) and pyridine (34.4 g, 435 mmol) in toluene (60 ml) is added dropwise at 23° C. over a period of 15 min. The resulting orange-brown reaction mixture is heated at 45° C. and is stirred for 6 hrs. The suspension is filtrated and the filtercake is washed successively with toluene (300 ml) and acetone (350 ml), and is then suspended in water (350 ml). Aqueous NaOH (30%) is added until the pH of the suspension reaches 11 and remains stable. The suspension is further stirred for 1 h at 40° C. before being filtrated. The filtercake is washed with water (5×50 ml) and dried in vacuo to give 51.3 g of the title compound (96%) as beige crystals, (98.7% area by HPLC).

1. additionAt the end of the addition
2. customThe excess of SOCl2 is removed by co-distillation with toluene under reduced pressure at 40° C
3. distillationAt the end of the distillation
4. temperaturethe resulting suspension id cooled down to 0° C.
5. filtrationthe benzoyl chloride is filtered off
6. washwashed with toluene (2×50 ml)
7. customdried in vacuo at 45° C. overnight
8. temperatureThe resulting orange-brown reaction mixture is heated at 45° C.
9. filtrationThe suspension is filtrated
10. washthe filtercake is washed successively with toluene (300 ml) and acetone (350 ml)
11. additionAqueous NaOH (30%) is added until the pH of the suspension
12. stirringThe suspension is further stirred for 1 h at 40° C.
13. filtrationbefore being filtrated
14. washThe filtercake is washed with water (5×50 ml)
15. customdried in vacuo

ORD record

ord-2776fe48f5a24e7dba7f5d2c1c5ad343

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456283B2