2,2-Dimethylsuccinic anhydride → HCID 89440573, compound

HRID 405706Notes

Reaction equation

[O:1]=[S:2]1(=[O:41])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[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([CH3:34])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C@@H:20]([OH:33])[CH2:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1.[CH3:42][C:43]1([CH3:50])[CH2:47][C:46](=[O:48])[O:45][C:44]1=[O:49]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[O:41]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:12]2[C@@H:13]2[C@@:26]([CH3:29])([CH2:27][CH2:28]3)[C@@:25]3([CH3:30])[CH:16]([C@:17]4([CH3:34])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C@@H:20]([O:33][C:44](=[O:49])[C:43]([CH3:50])([CH3:42])[CH2:47][C:46]([OH:48])=[O:45])[CH2:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-ol (100 mg, 0.170 mmol), 3,3-dimethyldihydrofuran-2,5-dione (436 mg, 3.4 mmol) and DMAP (208 mg, 1.7 mmol) in pyridine (1 mL) was heated up at 150° C. for 37 h. The reaction mixture was filtered and purified by prep. HPLC to provide the title compounds 4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-3,3-dimethyl-4-oxobutanoic acid, example 1, as a white solid (17 mg, 13%). LCMS: m/e 717.51 (M+H)+, 2.39 min (method 1). 1H NMR (500 MHz, Acetic) δ 4.83 (s, 1H), 4.75 (s, 1H), 4.51 (dd, J=10.8, 5.6 Hz, 1H), 3.41-3.11 (m, 11H), 3.10-2.99 (m, 1H), 2.82 (td, J=10.8, 5.5 Hz, 1H), 2.75-2.63 (m, 2H), 2.27-1.04 (m, 24H), 1.76 (s, 3H), 1.31 (s, 6H), 1.19 (s, 3H), 1.13 (s, 3H), 0.95 (s, 3H), 0.92 (s, 3H), 0.92 (s, 3H) and 4-(((1R,3aS,5aR,5bR,7aR,9S,11aR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)oxy)-2,2-dimethyl-4-oxobutanoic acid, example 2, as a white solid (60 mg, 47%). LCMS: m/e 717.51 (M+H)+, 2.44 min (method 1). 1H NMR (500 MHz, Acetic) δ 4.82 (s, 1H), 4.72 (s, 1H), 4.57 (dd, J=10.2, 6.0 Hz, 1H), 3.44 (d, J=12.5 Hz, 1H), 3.35-3.20 (m, 6H), 3.19-3.09 (m, 3H), 3.05 (d, J=4.6 Hz, 2H), 2.97-2.85 (m, 1H), 2.81-2.58 (m, 2H), 2.32-2.13 (m, 2H), 1.79-1.05 (m, 22H), 1.75 (s, 3H), 1.33 (s, 3H), 1.31 (s, 3H), 1.23 (s, 3H), 1.11 (s, 3H), 0.96 (s, 3H), 0.90 (s, 3H), 0.89 (s, 3H).

Workup

filtrationThe reaction mixture was filtered
custompurified by prep

Sources & evidence

ORD record: ord-6f83a6b7e1c641e1aad41c435c552dc3
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754069B2

Reaction notes

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