Triethylamine → methyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3 a-((2-((1S,4S)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-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

HRID 338641ノート

反応式

HRID 338641 の反応式
[C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][N:2]2[CH2:8][CH2:9][NH:10][C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1.C(N(CC)CC)C.[CH3:57][S:58](Cl)(=[O:60])=[O:59]>C(Cl)Cl>[CH3:29][C@:26]12[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:43])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:31])([CH3:32])[C:20]([C:33]3[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=3)=[CH:19][CH2:18]4)[CH2:15][CH2:14][C@@H:13]1[C@H:12]1[C@H:44]([C:47]([CH3:49])=[CH2:48])[CH2:45][CH2:46][C@:11]1([NH:10][CH2:9][CH2:8][N:2]1[CH2:3][C@@H:4]3[CH2:7][C@H:1]1[CH2:6][N:5]3[S:58]([CH3:57])(=[O:60])=[O:59])[CH2:28][CH2:27]2

参加物

5

反応物 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86701803HCID 86701803、化合物

生成物 1

HCID 89886428methyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3 a-((2-((1S,4S)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-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収率 81.8%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1S,4S)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)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 (75.2 mg, 0.113 mmol) and triethyl amine (0.078 mL, 0.563 mmol) in DCM (3 mL) was added methanesulfonyl chloride (10.67 μl, 0.135 mmol). The reaction mixture was stirred at rt. After 1.5 h, the reaction mixture was diluted with DCM (25 mL) and washed with H2O (2 mL). The aqueous layer was extracted with DCM (15 mL). The combined organic layer was washed with brine, dried over MgSO4, filtered and concentrated to give methyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-((1S,4S)-5-(methylsulfonyl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)ethyl)amino)-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 as a light brown solid (69.0 mg, 78% yield). LC/MS: m/e 746.8 (M+H)+, 246 min (method 3). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.88 (d, J=8.1 Hz, 2H), 7.15 (d, J=8.1 Hz, 2H), 5.25 (d, J=4.6 Hz, 1H), 4.71 (s, 1H), 4.57 (s, 1H), 4.26 (s, 1H), 3.86 (s, 3H), 3.69 (br. s., 1H), 3.58 (d, J=9.5 Hz, 1H), 3.19 (dd, J=9.4, 1.8 Hz, 1H), 2.97 (dd, J=9.8, 2.0 Hz, 1H), 2.85 (s, 3H), 2.80 (dd, J=8.3, 4.2 Hz, 2H), 2.65 (d, J=9.8 Hz, 1H), 2.61-2.44 (m, 2H), 2.07 (dd, J=17.1, 6.4 Hz, 2H), 1.95-1.68 (m, 6H), 1.66 (s, 3H), 1.65-1.37 (m, 9H), 1.31-1.06 (m, 7H), 1.04 (s, 3H), 0.96 (s, 3H), 0.94 (s, 3H), 0.89 (s, 6H).

後処理

  1. washwashed with H2O (2 mL)
  2. extractionThe aqueous layer was extracted with DCM (15 mL)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-2882f57787114b05928c858700f9b1dd
出典データセット
uspto-grants-2014_11
特許番号
US08889854B2

反応ノート

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