Trifluoroacetic acid → HCID 24905347, compound

Anisole (0.051 ml, 0.47 mmol) and trifluoroacetic acid (1.0 ml) were added to a dichloromethane (3.2 ml) solution of 5-{2-amino-6-[2-(5-tert-butoxycarbonylaminopentylcarbamoyl)ethylsulfanyl]pyrimidin-4-yl}-2,4-dimethyl benzoic acid tert-butyl ester (111 mg, 0.19 mmol) obtained in Step 2 above. The reaction solution was stirred for 6 hours while gradually warming from 0° C. up to room temperature. The reaction solution was concentrated under reduced pressure, and then benzene (1.5 ml) was added to the residue. The resulting solution was concentrated under reduced pressure. This treatment was repeated three times, and then the obtained pale yellow oily material was dissolved in N,N-dimethylformamide (94.5 ml). N-Hydroxybenzotriazole (128 mg, 0.95 mmol), diisopropylethylamine (0.33 ml, 1.9 mmol), and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (362 mg, 1.9 mmol) were sequentially added to the solution. The resulting reaction solution was reacted at room temperature for 14 hours, and then concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (100 ml), and sequentially washed twice with water (50 ml), and with a saturated aqueous sodium bicarbonate solution (50 ml), water (50 ml), and a saturated aqueous sodium chloride solution (50 ml). The washed ethyl acetate solution was dried over anhydrous sodium sulfate (10 g). After filtration, the filtrate was concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography with diol-silica gel (developing solvent: ethyl acetate to ethyl acetate:methanol=20:1) and amino-silica gel (ethyl acetate to ethyl acetate:methanol=15:1) to yield 4-amino-20,22-dimethyl-7-thia-3,5,11,17-tetraazatricyclo[17.3.1.12,6]tetracosa-1(22),2(24),3,5,19(23),20-hexaene-10,18-dione (Compound 1) (36 mg) as a white solid material.

1. temperaturewhile gradually warming from 0° C. up to room temperature
2. concentrationThe reaction solution was concentrated under reduced pressure
3. additionbenzene (1.5 ml) was added to the residue
4. concentrationThe resulting solution was concentrated under reduced pressure
5. dissolutionthe obtained pale yellow oily material was dissolved in N,N-dimethylformamide (94.5 ml)
6. customThe resulting reaction solution
7. customwas reacted at room temperature for 14 hours
8. concentrationconcentrated under reduced pressure
9. additionThe resulting residue was diluted with ethyl acetate (100 ml)
10. washsequentially washed twice with water (50 ml)
11. dry with materialThe washed ethyl acetate solution was dried over anhydrous sodium sulfate (10 g)
12. filtrationAfter filtration
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe resulting crude product was purified by silica gel column chromatography with diol-silica gel (developing solvent: ethyl acetate to ethyl acetate:methanol=20:1) and amino-silica gel (ethyl acetate to ethyl acetate:methanol=15:1)

ORD record

ord-43551275fd794d38a35d8bfa04c864c1

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08362236B2