Trimethyl orthoformate → HCID 11569806, compound

The compound (124.0 mg) obtained in Example 77-5 was dissolved in methanol (1.5 ml). The reaction solution was added with the compound (45.2 mg) obtained in Example 14-7 and trimethyl orthoformate (0.2 ml) and the whole was stirred at room temperature for 2 hours. The reaction solution was cooled to 0° C. and added with sodium borohydride (27.8 mg) and the whole was stirred at room temperature for 10 minutes. The reaction solution was added with a saturated aqueous ammonium chloride solution and the whole was stirred at room temperature for 20 minutes. The reaction solution was added with distilled water and subjected to extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. After the drying agent was filtrated out, the resultant was concentrated under reduced pressure and the resultant residue was dissolved in methanol (2 ml). The reaction solution was added with 2-imidazole carboxaldehyde (53.9 mg) and sodium cyanoborohydride (59.3 mg) and solution was adjusted to pH 5 with acetic acid. The whole was stirred at room temperature for 15 hours. The reaction solution was added with a 1 mol/l sodium hydroxide aqueous solution and the whole was subjected to extraction with chloroform. The organic layer was washed with a saturated saline solution and dried with anhydrous sodium sulfate. After the drying agent was filtrated out, the resultant was concentrated under reduced pressure. The resultant residue was purified through silica gel column chromatography (chloroform/ethyl acetate) and treated with hydrochloric acid, thereby obtaining a hydrochloride (42.3 mg) of the subject compound as a pale-pink solid.

1. temperatureThe reaction solution was cooled to 0° C.
2. stirringthe whole was stirred at room temperature for 10 minutes
3. stirringthe whole was stirred at room temperature for 20 minutes
4. extractionsubjected to extraction with chloroform
5. washThe organic layer was washed with a saturated saline solution
6. dry with materialdried with anhydrous sodium sulfate
7. filtrationAfter the drying agent was filtrated out
8. concentrationthe resultant was concentrated under reduced pressure
9. dissolutionthe resultant residue was dissolved in methanol (2 ml)
10. additionThe reaction solution was added with 2-imidazole carboxaldehyde (53.9 mg) and sodium cyanoborohydride (59.3 mg) and solution
11. stirringThe whole was stirred at room temperature for 15 hours
12. additionThe reaction solution was added with a 1 mol/l sodium hydroxide aqueous solution
13. extractionthe whole was subjected to extraction with chloroform
14. washThe organic layer was washed with a saturated saline solution
15. dry with materialdried with anhydrous sodium sulfate
16. filtrationAfter the drying agent was filtrated out
17. concentrationthe resultant was concentrated under reduced pressure
18. customThe resultant residue was purified through silica gel column chromatography (chloroform/ethyl acetate)
19. additiontreated with hydrochloric acid

ORD record

ord-045f3fe826d24b569fb0ee0a890445d2

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932281B2