反应详情

温度

120 °C

In a 15 mL medium pressure flask was added (R)-benzyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)cyclohex-3-enecarboxylate (70 mg, 0.112 mmol), phosphoric acid, potassium salt (119 mg, 0.561 mmol), (1S,4S)-5-(2-chloroethyl)-2-thia-5-azabicyclo[2.2.1]heptane 2,2-dioxide (70.6 mg, 0.337 mmol) and potassium iodide (55.9 mg, 0.337 mmol). The solid mixture was dried at 50° C. vacuum oven for 15 mins and filled with N2 (g). Acetonitrile (3 mL) was added and the mixture was heated at 120° C. After 22 h, the resulting creamy reaction was cooled to rt and filtered. The light yellow paste obtained was washed with DCM (25 mL). The liquid filtrate was concentrated to give crude product as a light brown solid which was purified by reverse phase HPLC using prep-HPLC method 15 to give the title compound (67.2 mg, 0.062 mmol, 55.5% yield) as a white solid. LC/MS: m/e 797.6 (M+H)+, 4.68 min (method 8). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.42-7.32 (m, 5H), 5.35 (br. s., 1H), 5.18 (d, J=4.4 Hz, 1H), 5.14 (s, 2H), 4.78 (s, 1H), 4.70 (s, 1H), 4.18 (br. s., 1H), 3.58 (br. s., 1H), 3.37 (dd, J=13.4, 2.7 Hz, 1H), 3.32-3.22 (m, 2H), 3.21-3.15 (m, 1H), 3.07 (d, J=13.0 Hz, 1H), 3.00 (dd, J=13.2, 3.2 Hz, 1H), 2.93-2.74 (m, 2H), 2.67-2.54 (m, 2H), 2.45-2.29 (m, 8H), 2.27-2.11 (m, 4H), 2.07-1.88 (m, 6H), 1.80-1.73 (m, 1H), 1.70 (s, 3H), 1.67 (br. s., 1H), 1.60-1.42 (m, 8H), 1.38 (d, J=10.8 Hz, 2H), 1.31 (br. s., 1H), 1.10 (s, 3H), 1.04 (s, 3H), 0.94 (s, 3H), 0.93 (s, 3H), 0.87 (s, 3H). 13C NMR (101 MHz, CHLOROFORM-d) δ 175.7, 148.1, 147.2, 139.3, 136.2, 128.5, 128.1, 128.0, 122.6, 121.0, 111.4, 77.2, 70.5, 66.1, 61.5, 60.7, 56.2, 53.0, 52.7, 49.3, 49.2, 48.8, 44.8, 42.1, 41.7, 40.83-40.72, 40.7, 39.0, 37.5, 36.9, 36.1, 33.8, 32.8, 31.6, 29.6, 28.3, 27.7 (br. s., 1C), 27.70-27.57, 25.9, 25.8, 25.2, 21.5, 20.9, 19.6, 19.4, 16.4, 16.1, 14.5.

1. customThe solid mixture was dried at 50° C. vacuum oven for 15 mins
2. additionfilled with N2 (g)
3. additionAcetonitrile (3 mL) was added
4. customthe resulting creamy reaction
5. temperaturewas cooled to rt
6. filtrationfiltered
7. customThe light yellow paste obtained
8. washwas washed with DCM (25 mL)
9. concentrationThe liquid filtrate was concentrated
10. customto give crude product as a light brown solid which
11. customwas purified by reverse phase