Trifluoroacetic anhydride → (S)-2-fluoro-5-(1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyridine 1-oxide

To a solution of (S)—N-(6-fluoropyridin-3-yl)-1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamide (200 mg, 0.44 mmol) and urea-hydrogen peroxide (125 mg, 1.33 mmol) in DCM (10 mL) at 0° C. was added trifluoroacetic anhydride (280 mg, 1.33 mmol). The resulting mixture was allowed to stir at RT overnight. The reaction mixture was concentrated under reduced pressure to afford an oily residue that was diluted with saturated sodium bicarbonate solution (10 mL), and the product was extracted with EtOAc (2×25 mL). The combined organic layer was dried over anhydrous sodium sulfate. Removal of EtOAc under reduced pressure gave an oily residue that was purified by reverse phase HPLC to afford 10 mg of (S)-2-fluoro-5-(1-(4-(5-isopropyl-1H-pyrazol-3-ylamino)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-2-yl)pyrrolidine-2-carboxamido)pyridine 1-oxide. 1HNMR (400 MHz, CD3OD) δ (ppm): 1.20 (d, 6H), 2.02-2.18 (m, 4H), 2.21-2.36 (m, 2H), 2.75-2.93 (m, 5H), 3.60-3.70 (m, 1H), 3.77-3.84 (m, 1H), 4.77 (dd, 1H), 6.21 (s, 1H), 7.36-7.41 (m, 1H), 7.50 (s, 1H), 8.81-8.89 (m, 1H). The other enantiomer was obtained using chiral (R) starting material.

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customto afford an oily residue that
3. extractionthe product was extracted with EtOAc (2×25 mL)
4. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
5. customRemoval of EtOAc under reduced pressure
6. customgave an oily residue that
7. customwas purified by reverse phase HPLC

ORD 기록

ord-1c4150f5359542f68a4ab25af6ca9c03

출처 데이터셋

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09422267B2