Morpholine → HCID 10430787, compound

Phenyl N-(4-(1-(methylamino)carbonyl-1H-5-indolyloxy)-2-pyridyl)-N-(phenoxycarbonyl)carbamate (20 g, 38 mmol) synthesized in Production example 5-2 was dissolved in N,N-dimethylformamide (190 ml); morpholine (13.3 mg, 153 mmol) was added thereto; and the reaction system was stirred at room temperature for 9 hours. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in ethyl acetate and a small amount of tetrahydrofuran; this suspension was filtrated with silica gel; and ethyl acetate and three different ratio of solvent mixtures of ethyl acetate:methanol=20:1, 10:1, and 5:1 were eluted through the gel. The filtrate was concentrated under reduced pressure. The residue was dissolved in diethyl ether (40 ml); hexane (200 ml) was added thereto; and precipitated insoluble syrupy portion was removed from the solution; and the resultant solution was concentrated again under reduced pressure. The residue was dissolved in ethyl acetate (300 ml) and was allowed to stand at room temperature. After the crystals were precipitated, the crystals were filtered off, washed with ethyl acetate, and dried to yield the crude crystals of the title compound (10.3 g). 9 g of this crude crystals was suspended in a mixture of tetrahydrofuran (3 ml) and N,N-dimethylformamide (3 ml each); this suspension was diluted with ethanol (60 ml); and the crystals were filtered off, washed with ethanol and dried to yield the title compound as colorless crystals (7.70 g, 19 mmol).

1. customThe reaction mixture was partitioned between ethyl acetate and water
2. washand the organic layer was washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. concentrationconcentrated under reduced pressure
5. dissolutionThe obtained residue was dissolved in ethyl acetate
6. filtrationthis suspension was filtrated with silica gel
7. washand ethyl acetate and three different ratio of solvent mixtures of ethyl acetate:methanol=20:1, 10:1, and 5:1 were eluted through the gel
8. concentrationThe filtrate was concentrated under reduced pressure
9. dissolutionThe residue was dissolved in diethyl ether (40 ml)
10. additionhexane (200 ml) was added
11. customand precipitated insoluble syrupy portion
12. customwas removed from the solution
13. concentrationand the resultant solution was concentrated again under reduced pressure
14. dissolutionThe residue was dissolved in ethyl acetate (300 ml)
15. customto stand at room temperature
16. customAfter the crystals were precipitated
17. filtrationthe crystals were filtered off
18. washwashed with ethyl acetate
19. customdried

ORD record

ord-e8283cdb4ef24428a611ab7d7792f842

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07468380B2