Ammonia → HCID 135529936, compound

To a solution of N-benzyloxycarbonyl-2-(benzotriazol-1-yl)glycine (3.59 g) in dry tetrahydrofuran (THF, 30 ml) was added oxalyl chloride (1.05 ml) at 0-5° C. under stirring and nitrogen stream. After one drop of dimethylformamide was added, the mixture was stirred for 2 hours under the same conditions. To the reaction mixture was added dropwise a mixture of 2-cyclohexycarbonyl-6-methylaniline (2.17 g) and N-methylmorpholine (2.23 g) in dry THF for 20 minutes under the same conditions. The mixture was allowed to warm to ambient temperature and stirred for 1 hour. THF was removed in vacuo to afford a residue, which was dissolved in ethyl acetate and washed with diluted aqueous sodium bicarbonate, water and brine successively. After drying over magnesium sulfate, the solvent was removed in vacuo to give an amorphous mass (5.77 g), which was dissolved in methanol (4 ml). To the solution was added 9M methanolic ammonia (22 ml) and the mixture was stirred at ambient temperature overnight. The mixture was evaporated in vacuo to give a residue, which was dissolved in ethyl acetate and washed with 1N-sodium hydroxide aqueous solution and water. The organic layer was dried over magnesium sulfate and evaporated in vacuo to give a residue, which was dissolved in acetic acid (60 ml). Ammonium acetate (4.0 g) was added to the solution and the mixture was stirred for 1.5 hour at ambient temperature. Acetic acid was removed in vacuo to give a residue, which was dissolved in ethyl acetate and washed with diluted sodium hydroxide aqueous solution and water successively. After drying over magnesium sulfate, the solvent was removed in vacuo to give a crystalline mass, which was pulverized in a mixture of diisopropyl ether and n-hexane and collected by filtration to give (3RS)-3-benzyloxycarbonylamino-5-cyclohexyl-9-methyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one (2.36 g, 58.3% yield) as a crystalline powder.

1. stirringthe mixture was stirred for 2 hours under the same conditions
2. additionTo the reaction mixture was added dropwise
3. stirringstirred for 1 hour
4. customTHF was removed in vacuo
5. customto afford a residue, which
6. washwashed with diluted aqueous sodium bicarbonate, water and brine successively
7. dry with materialAfter drying over magnesium sulfate
8. customthe solvent was removed in vacuo
9. customto give an amorphous mass (5.77 g), which
10. stirringthe mixture was stirred at ambient temperature overnight
11. customThe mixture was evaporated in vacuo
12. customto give a residue, which
13. washwashed with 1N-sodium hydroxide aqueous solution and water
14. dry with materialThe organic layer was dried over magnesium sulfate
15. customevaporated in vacuo
16. customto give a residue, which
17. stirringthe mixture was stirred for 1.5 hour at ambient temperature
18. customAcetic acid was removed in vacuo
19. customto give a residue, which
20. washwashed with diluted sodium hydroxide aqueous solution and water successively
21. dry with materialAfter drying over magnesium sulfate
22. customthe solvent was removed in vacuo
23. customto give a crystalline mass, which
24. filtrationcollected by filtration

ORD record

ord-6028edbea3954cd390e5b8970f6a7b4b

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06291452B1