1,8-Diazabicyclo(5.4.0)undec-7-ene → (4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-amine

温度

70 °C

1,8-Diazabicyclo[5.4.0]undec-7-ene (0.084 mL, 0.534 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(2,4-difluoro-5-{[(2,2,2-trifluoroethyl)amino]methyl}phenyl)-6-(fluoromethyl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C27) (0.4064 g, 0.7650 mmol) in methanol (30 mL). The resulting solution was heated to 70° C. until complete consumption of starting material. The reaction mixture was concentrated under reduced pressure to yield product as an orange oily residue. Purification via silica gel chromatography (Gradient: 0% to 20% methanol in dichloromethane) afforded the product as a white solid. Yield: 0.273 g (84%). LCMS m/z 428 [M+H+]. 1H NMR (400 MHz, CD3OD) δ 7.38 (t, J=8.8 Hz, 1H), 6.98 (dd, J=12.2, 9.7 Hz, 1H), 4.42-4.48 (m, 1H), 4.30-4.37 (m, 1H), 4.09 (dd, J=11.2, 2.0 Hz, 1H), 3.86-3.90 (m, 3H), 3.72 (d, J=11.2 Hz, 1H), 3.13-3.18 (m, 2H), 2.90-2.97 (m, 2H), 2.70 (dd, J=12.4, 2.6 Hz, 1H), 1.76-1.87 (m, 1H), 1.52 (ddd, J=13.1, 4.0, 2.3 Hz, 1H).

1. concentrationThe reaction mixture was concentrated under reduced pressure
2. customto yield product as an orange oily residue
3. customPurification via silica gel chromatography (Gradient: 0% to 20% methanol in dichloromethane)

ORDレコード

ord-f34e5a9401564c408a9646650244e3c0

出典データセット

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08822456B2