4-Benzyloxycarbonyl-1-{methyl[1-(tert-butoxycarbonyl)-4-piperidinyl]amino}-2-piperazinone → 4-Benzyloxycarbonyl-1-{methyl[1-(4-pyridyl)-4-piperidinyl]amino}-2-piperazinone

A solution of 4-benzyloxycarbonyl-1-{methyl[1-(tert-butoxycarbonyl)-4-piperidinyl]amino}-2-piperazinone (8.49 g) in trifluoroacetic acid (20 ml) was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and a mixture of the resultant residue, 4-chloropyridine hydrochloride (4.35 g) and triethylamine (11.54 g) in ethanol (180 ml) was reacted in a sealed tube at 150° C. for 18 hours. The reaction mixture was concentrated, and the residue was made alkaline by adding a saturated aqueous solution of sodium hydrogen carbonate, and then extracted with dichloromethane. The extract was washed with water and brine, dried, and concentrated to obtain a residue, which was purified by a column chromatography on a silica gel (dichloromethane: 10% aqueous ammonia-containing methanol=20:1) to obtain the title compound (2.23 g) as a pale yellow amorphous material.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. additiona mixture of the resultant residue, 4-chloropyridine hydrochloride (4.35 g) and triethylamine (11.54 g) in ethanol (180 ml)
3. customwas reacted in a sealed tube at 150° C. for 18 hours
4. concentrationThe reaction mixture was concentrated
5. additionby adding a saturated aqueous solution of sodium hydrogen carbonate
6. extractionextracted with dichloromethane
7. washThe extract was washed with water and brine
8. customdried
9. concentrationconcentrated
10. customto obtain a residue, which
11. customwas purified by a column chromatography on a silica gel (dichloromethane: 10% aqueous ammonia-containing methanol=20:1)

ORD record

ord-1c37c03bd023437e8af48e8bd4405ae9

Source dataset

uspto-grants-2004_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06723722B1