Triethylamine → (2S,3S,4S,5R,6R)-6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)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)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid
Reaction equation
[O:1]=[S:2]1(=[O:68])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:64][CH2:63][C@@H:62]([C:65]([CH3:67])=[CH2:66])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:61])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]3[CH:60]=[CH:59][C:36]([C:37]([O:39][C@H:40]5[O:45][C@H:44]([C:46]([O:48]CC6C=CC=CC=6)=[O:47])[C@@H:43]([OH:56])[C@H:42]([OH:57])[C@H:41]5[OH:58])=[O:38])=[CH:35][CH:34]=3)=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1.C([SiH](C)C)(C)(C)C.C(N(CC)CC)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>ClC(Cl)C.C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[O:68]=[S:2]1(=[O:1])[CH2:3][CH2:4][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:64][CH2:63][C@@H:62]([C:65]([CH3:67])=[CH2:66])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[C@@H:16]([C@:17]4([CH3:61])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:31])([CH3:32])[C:20]([C:33]3[CH:60]=[CH:59][C:36]([C:37]([O:39][C@H:40]5[O:45][C@H:44]([C:46]([OH:48])=[O:47])[C@@H:43]([OH:56])[C@H:42]([OH:57])[C@H:41]5[OH:58])=[O:38])=[CH:35][CH:34]=3)=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:6][CH2:7]1Participants
Reactant 4
HCID 8471Triethylamine
HCID 2724141Tetrabutylammonium Fluoride
HCID 5072427tert-Butyldimethylsilane
HCID 86676633(2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)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)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylateProduct 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 60 °C
Procedure
A mixture of (2S,3S,4S,5R,6R)-benzyl 6-((4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)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)benzoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate (8 mg, 8.36 mmol), tert-butyldimethylsilane (1.943 mg, 0.017 mmol), palladium acetate (3.75 mg, 0.017 mmol) and triethylamine (5.82 μl, 0.042 mmol) in dichloroethane (1 mL) was heated up at 60° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered and the filtrates were concentrated to provide the residue. To this residue in THF (1.0 mL) was added TBAF (10.93 mg, 0.042 mmol), the reaction mixture was stirred for 1 hours. The reaction mixture was then purified by prep. HPLC to provide the desired product as a colorless oil (4 mg, 52%). LCMS: m/e 867.69 (M+H)+, 2.42 min (method 10). 1H NMR (500 MHz, Acetic) δ 8.06 (d, J=8.2 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 5.96 (d, J=7.9 Hz, 1H), 5.37 (d, J=4.4 Hz, 1H), 4.84 (s, 1H), 4.74 (s, 1H), 4.40-4.16 (m, 1H), 4.02-3.76 (m, 3H), 3.46 (d, J=12.3 Hz, 1H), 3.37-3.22 (m, 6H), 3.20-3.11 (m, 3H), 3.07 (br. s., 2H), 3.00-2.82 (m, 1H), 2.37-1.03 (m, 22H), 1.76 (s, 3H), 1.29 (s, 3H), 1.14 (s, 3H), 1.10 (s, 3H), 1.02 (s, 3H), 0.99 (s, 3H).
Workup
- temperatureThe reaction mixture was cooled to room temperature
- filtrationfiltered
- concentrationthe filtrates were concentrated
- customto provide the residue
- customThe reaction mixture was then purified by prep
Sources & evidence
- ORD record
- ord-051becbae45c414caf8a2ccb979a8349
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08846647B2
Linked notes
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