Tetrahydrofuran → 2-(6-{[Bis-(3-morpholin-4-yl-propyl)-amino]-methyl}-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide

To a mixture of 0.150 g (0.23 mmole) of 2-(5-{[bis-(3-morpholin-4-yl-propyl)-amino]-methyl}-2-nitro-phenylamino)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (VI.49a), 20 mL of tetrahydrofuran, and 20 mL of saturated ammonium chloride solution was added 0.089 g (1.38 mg-atom) of zinc powder. After 5 minutes the mixture was filtered and the filtrate partitioned between 50 mL of saturated ammonium chloride and 50 mL of tetrahydrofuran. The tetrahydrofuran layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was stirred for 3 hours with 30 mL of acetic acid and 0.178 g (1.2 mmole) of triethyl orthoformate. The mixture was concentrated under reduced pressure, diluted with 100 mL of dichloromethane and washed with saturated sodium bicarbonate solution, then brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with dichloromethane-methanol-ammonium hydroxide (92:8:1) to give 0.075 g of 2-(6-{[bis-(3-morpholin-4-yl-propyl)-amino]-methyl}-benzoimidazol-1-yl)-4-(3-chloro-phenyl)-thiazole-5-carboxylic acid amide (I.49) as a light pink solid. MH+/Z=638.

1. filtrationAfter 5 minutes the mixture was filtered
2. customthe filtrate partitioned between 50 mL of saturated ammonium chloride and 50 mL of tetrahydrofuran
3. dry with materialThe tetrahydrofuran layer was dried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. concentrationThe mixture was concentrated under reduced pressure
7. additiondiluted with 100 mL of dichloromethane
8. washwashed with saturated sodium bicarbonate solution
9. dry with materialbrine, dried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by silica gel chromatography
12. washeluting with dichloromethane-methanol-ammonium hydroxide (92:8:1)

ORD 기록

ord-e5ddf3802b72457e8b25a4e5ea1450d1

출처 데이터셋

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08044213B2