反应 #172779

ord-7ad31e7b3c954cfbbaa5f54c0a27434c

反应方程式

C=C(C)[C@@H]1CC[C@]2(NC(=O)CN3CCC(F)(F)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4,4-difluoropiperidin-1-yl)acetamido)-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)benzoic acid
C=C(C)[C@@H]1CC[C@]2(N)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
methyl 4-((1R,3aS,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)benzoate
→
C=C(C)[C@@H]1CC[C@]2(NC(=O)CN3CCC(F)(F)C3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
title compound
收率 38.0%
C=C(C)[C@@H]1CC[C@]2(NC(=O)CN3CCC(F)(F)C3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(3,3-difluoropyrrolidin-1-yl)acetamido)-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)benzoic acid
收率 38.0%

反应物

C=C(C)[C@@H]1CC[C@]2(NC(=O)CN3CCC(F)(F)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)O)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4,4-difluoropiperidin-1-yl)acetamido)-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)benzoic acid
C=C(C)[C@@H]1CC[C@]2(N)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(c6ccc(C(=O)OC)cc6)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
methyl 4-((1R,3aS,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)benzoate
—
3,3-difluoropyrrolidine, HCl

试剂

无

反应条件

详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    其他m/e 677.5 (M+H)+, 2.26 min (method 6)

实验过程

The title compound was prepared in 38% yield from methyl 4-((1R,3aS,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)benzoate following the same procedure as described for the preparation of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4,4-difluoropiperidin-1-yl)acetamido)-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)benzoic acid, except and 3,3-difluoropyrrolidine, HCl was used instead of 4,4-difluoropiperidine, HCl in Step 2. LCMS: m/e 677.5 (M+H)+, 2.26 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=7.92 (d, J=8.2 Hz, 2H), 7.40 (s, 1H), 7.20 (d, J=8.2 Hz, 2H), 5.29 (dd, J=1.7, 6.3 Hz, 1H), 4.75 (d, J=1.2 Hz, 1H), 4.65 (s, 1H), 3.59-3.44 (m, 2H), 3.43-3.36 (m, 1H), 3.31-3.20 (m, 2H), 2.63-2.55 (m, 1H), 2.55-2.47 (m, 3H), 2.47-2.39 (m, 1H), 2.13 (dd, J=6.4, 17.1 Hz, 1H), 1.94-1.83 (m, 1H), 1.81-1.76 (m, 2H), 1.76-1.73 (m, 1H), 1.72 (s, 3H), 1.70-1.65 (m, 1H), 1.57-1.46 (m, 6H), 1.46-1.40 (m, 2H), 1.39-1.31 (m, 2H), 1.26 (dd, J=2.7, 10.7 Hz, 1H), 1.19-1.10 (m, 2H), 1.09 (s, 3H), 1.03 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H).

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: US08846647B2uspto-grants-2014_09