反応 #155605

反応方程式

Methylamine

N-[(4aR,6R,8aS)-8a-(5-cyano-2-fluorophenyl)-6-(4-methyl-1,3-oxazol-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide

→

product

3-[(4aR,6R,8aS)-2-amino-6-(4-methyl-1,3-oxazol-2-yl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-4-fluorobenzonitrile

溶媒

ethanol

反応条件

後処理

1. 1
   濃縮The reaction mixture was concentrated under reduced pressure
2. 2
   その他to give a yellow oily residue
3. 3
   その他Purification via silica gel chromatography (Gradient: 0% to 20% methanol in dichloromethane)

実験手順

Methylamine (8 M in ethanol, 7.1 mL, 57.1 mmol) was added to a solution of N-[(4aR,6R,8aS)-8a-(5-cyano-2-fluorophenyl)-6-(4-methyl-1,3-oxazol-2-yl)-4,4a,5,6,8,8a-hexahydropyrano[3,4-d][1,3]thiazin-2-yl]benzamide (C41) (0.227 g, 0.48 mmol) in ethanol (12 mL). The resulting solution was allowed to stir at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure to give a yellow oily residue. Purification via silica gel chromatography (Gradient: 0% to 20% methanol in dichloromethane) afforded the product as an off-white solid. Yield: 144 mg, 81%. LCMS m/z 374.1 [M+H+]. 1H NMR (400 MHz, CD3OH) δ 7.77 (ddd, J=8.5, 4.5, 2.2 Hz, 1H), 7.68 (dd, J=7.2, 2.3 Hz, 1H), 7.61 (q, J=2.3 Hz, 1H), 7.35 (dd, J=12.1, 8.6 Hz, 1H), 4.82 (dd, J=11.9, 2.5 Hz, 1H), 4.25 (dd, J=11.2, 2.2 Hz, 1H), 3.79 (d, J=11.2 Hz, 1H), 3.06-3.13 (m, 1H), 2.89 (dd, J=12.7, 4.1 Hz, 1H), 2.78 (dd, J=12.7, 2.9 Hz, 1H), 2.33-2.43 (m, 1H), 2.15 (d, J=1.4 Hz, 3H), 1.87-1.91 (m, 1H).

出典