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 338641Notes

Reaction equation

HRID 338641 reaction equation
[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

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 86701803HCID 86701803, compound

Product 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)benzoateYield 81.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-2882f57787114b05928c858700f9b1dd
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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