4-Methylmorpholine → (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

HRID 85710Notes

Reaction equation

HRID 85710 reaction equation
[OH:1][C@H:2]1[C@H:7]([OH:8])[C@@H:6]([OH:9])[CH:5]([OH:10])[O:4][C@@H:3]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12].[O:21]=[S:22]1(=[O:69])[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][NH:30][C@:31]23[CH2:65][CH2:64][C@@H:63]([C:66]([CH3:68])=[CH2:67])[C@@H:32]2[C@@H:33]2[C@@:46]([CH3:49])([CH2:47][CH2:48]3)[C@@:45]3([CH3:50])[C@@H:36]([C@:37]4([CH3:62])[C@@H:42]([CH2:43][CH2:44]3)[C:41]([CH3:52])([CH3:51])[C:40]([C:53]3[CH:61]=[CH:60][C:56]([C:57](O)=[O:58])=[CH:55][CH:54]=3)=[CH:39][CH2:38]4)[CH2:35][CH2:34]2)[CH2:24][CH2:23]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1>O1CCOCC1>[O:69]=[S:22]1(=[O:21])[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][NH:30][C@:31]23[CH2:65][CH2:64][C@@H:63]([C:66]([CH3:68])=[CH2:67])[C@@H:32]2[C@@H:33]2[C@@:46]([CH3:49])([CH2:47][CH2:48]3)[C@@:45]3([CH3:50])[C@@H:36]([C@:37]4([CH3:62])[C@@H:42]([CH2:43][CH2:44]3)[C:41]([CH3:52])([CH3:51])[C:40]([C:53]3[CH:54]=[CH:55][C:56]([C:57]([O:10][C@H:5]5[O:4][C@H:3]([C:11]([O:13][CH2:14][C:15]6[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=6)=[O:12])[C@@H:2]([OH:1])[C@H:7]([OH:8])[C@H:6]5[OH:9])=[O:58])=[CH:60][CH:61]=3)=[CH:39][CH2:38]4)[CH2:35][CH2:34]2)[CH2:24][CH2:23]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14602688Benzyl D-GlucuronateHCID 60152109BMS-955176

Product 1

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-carboxylateYield 14.4%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of (2S,3S,4S,5R)-benzyl 3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxylate (61.7 mg, 0.217 mmol), 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)benzoic acid (100 mg, 0.145 mmol), HATU (88 mg, 0.232 mmol) and N-methylmorpholine (0.048 mL, 0.434 mmol) in dioxane (3 mL) was stirred overnight at room temperature. The reaction mixture was filtered, the clear solution was purified by prep HPLC with acetonitrile/water/ammonium acetate to provide the desired product as white solid (20 mg, 14%). LCMS: m/e 957.7 (M+H)+, 2.36 min (method 6). 1H NMR (500 MHz, Acetic) δ 8.05 (d, J=8.2 Hz, 2H), 7.58-7.14 (m, 7H), 5.95 (d, J=7.6 Hz, 1H), 5.38 (d, J=4.6 Hz, 1H), 5.26 (s, 2H), 4.84 (s, 1H), 4.74 (s, 1H), 4.30 (d, J=9.5 Hz, 1H), 4.05-3.78 (m, 3H), 3.46 (d, J=11.9 Hz, 1H), 3.38-3.22 (m, 6H), 3.20-3.11 (m, 3H), 3.07 (br. s., 2H), 2.95 (dt, J=10.8, 5.5 Hz, 1H), 2.42-1.01 (m, 22H), 1.77 (s, 3H), 1.30 (s, 3H), 1.15 (s, 3H), 1.12 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe clear solution was purified by prep HPLC with acetonitrile/water/ammonium acetate

Sources & evidence

ORD record
ord-ef9c1f726d7d43768280b8061ee0fa8f
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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