Water → 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-1,4-diazepan-1-yl]carbonyl}amino)propyl]benzoic acid monoacetic acid

Tert-butyl 4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3,7-dioxo-4-(2,4,6-trimethoxybenzyl)-1,4-diazepan-1-yl]carbonyl}amino) propyl]-2-nitrobenzoate (9.5 g) was dissolved in 4N solution of hydrochloric acid in an ethyl acetate (170 ml), and the mixture stirred at room temperature for 16 hours. Next, sandy zinc (9g) was added to the reaction solution, and the mixture was stirred at 40° C. for 20 hours. Water was added to the reaction solution to wash it, then the organic layer was dried over anhydrous magnesium sulfate and concentrated in vacuo. Then 20% hydrous isopropyl alcohol (60 ml) was added to the obtained residue, and the resultant mixture was heated to dissolve the residue at 50° C., and acetic acid (30 ml) and water (90 ml) were added to the solution. The mixture was cooled down to room temperature, and stirred for 2 hours. The precipitated crystals were collected by filtration and dried to obtain a crude product of the title compound (6.2 g) as a colorless crystal. The obtained crude product (6g) was heated to dissolve at 55° C. in 20% hydrous isopropyl alcohol (40 ml), then acetic acid (20 ml) was added to the solution, and the mixture was stirred at that temperature for 1 hour 30 minutes. After water was added to the solution, the resulting mixture was gradually cooled down to room temperature and then stirred for 3 hours. The precipitated crystals were collected by filtration and dried to obtain the title compound (5.6 g) as a colorless crystal.

1. stirringthe mixture was stirred at 40° C. for 20 hours
2. washto wash it
3. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
4. concentrationconcentrated in vacuo
5. additionThen 20% hydrous isopropyl alcohol (60 ml) was added to the obtained residue
6. temperaturethe resultant mixture was heated
7. dissolutionto dissolve the residue at 50° C.
8. additionacetic acid (30 ml) and water (90 ml) were added to the solution
9. temperatureThe mixture was cooled down to room temperature
10. stirringstirred for 2 hours
11. filtrationThe precipitated crystals were collected by filtration
12. customdried

ORD-Eintrag

ord-6fa8ba682b9a4b6d824769bef2dccd42

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08049006B2