Benzaldehyde → HCID 86729875, compound

Temperature

70 °C

To a mixture of N-[4-(trans-2-aminocyclopropyl)phenyl]-Nα-[(benzyloxy)carbonyl]-L-phenylalaninamide hydrochloride (100 mg) described in a document (J. Am. Chem. Soc. 2010, 132, 6827.), sodium hydrogen carbonate (27.0 mg), and methanol (2.00 mL) was added benzaldehyde (0.022 mL), and the mixture was stirred at 70° C. for 1 hr. The reaction mixture was cooled in an ice bath, sodium borohydride (12.2 mg) was added and the mixture was stirred at 0° C. for 1.5 hr. The reaction mixture was diluted with dehydrated THF (4.00 mL), and cooled in an ice bath, and sodium borohydride (8.12 mg) was added. The ice bath was removed, and the mixture was stirred at room temperature overnight. The reaction mixture was diluted with methanol (2.00 mL) and dehydrated THF (2.00 mL), and cooled in an ice bath, sodium borohydride (8.12 mg) was added, and the mixture was stirred at 0° C. for 3 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate, and the mixture was concentrated under reduced pressure. To the residue was added water, and the mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate), and the fractions containing the object product were combined and concentrated. The residue was dissolved in methanol (5.00 mL), 10% hydrochloric acid methanol solution (1.00 mL) was added, and the mixture was concentrated under reduced pressure to give the title compound (82.3 mg).

1. temperatureThe reaction mixture was cooled in an ice bath
2. stirringthe mixture was stirred at 0° C. for 1.5 hr
3. temperaturecooled in an ice bath
4. customThe ice bath was removed
5. stirringthe mixture was stirred at room temperature overnight
6. additionThe reaction mixture was diluted with methanol (2.00 mL) and dehydrated THF (2.00 mL)
7. temperaturecooled in an ice bath
8. additionsodium borohydride (8.12 mg) was added
9. stirringthe mixture was stirred at 0° C. for 3 hr
10. additionTo the reaction mixture was added saturated aqueous sodium hydrogen carbonate
11. concentrationthe mixture was concentrated under reduced pressure
12. additionTo the residue was added water
13. extractionthe mixture was extracted twice with ethyl acetate
14. washwashed with saturated brine
15. dry with materialdried over anhydrous magnesium sulfate
16. concentrationconcentrated under reduced pressure
17. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate)
18. additionthe fractions containing the object product
19. concentrationconcentrated
20. dissolutionThe residue was dissolved in methanol (5.00 mL)
21. addition10% hydrochloric acid methanol solution (1.00 mL) was added
22. concentrationthe mixture was concentrated under reduced pressure

ORD record

ord-11a61d5b088d4241939df9ef70a697ce

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09278931B2