Sodium Hydroxide → 2-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[3-(1,1-dioxo-1,4-thiazinan-4-yl)propylamino]methyl]-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]spiro[3.3]hept-2-ene-6,6-dicarboxylic acid

HRID 1401019Notes

Reaction equation

HRID 1401019 reaction equation
[O:1]=[S:2]1(=[O:61])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][NH:11][CH2:12][C@:13]23[CH2:57][CH2:56][C@@H:55]([C:58]([CH3:60])=[CH2:59])[C@@H:14]2[C@@H:15]2[C@@:28]([CH3:31])([CH2:29][CH2:30]3)[C@@:27]3([CH3:32])[C@@H:18]([C@:19]4([CH3:54])[C@@H:24]([CH2:25][CH2:26]3)[C:23]([CH3:34])([CH3:33])[C:22]([C:35]3[CH2:53][C:37]5([CH2:40][C:39]([C:47]([O:49]C(C)C)=[O:48])([C:41]([O:43]C(C)C)=[O:42])[CH2:38]5)[CH:36]=3)=[CH:21][CH2:20]4)[CH2:17][CH2:16]2)[CH2:4][CH2:3]1.[OH-].[Na+]>O1CCOCC1.CO>[O:61]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][NH:11][CH2:12][C@:13]23[CH2:57][CH2:56][C@@H:55]([C:58]([CH3:60])=[CH2:59])[C@@H:14]2[C@@H:15]2[C@@:28]([CH3:31])([CH2:29][CH2:30]3)[C@@:27]3([CH3:32])[C@@H:18]([C@:19]4([CH3:54])[C@@H:24]([CH2:25][CH2:26]3)[C:23]([CH3:34])([CH3:33])[C:22]([C:35]3[CH2:53][C:37]5([CH2:38][C:39]([C:41]([OH:43])=[O:42])([C:47]([OH:49])=[O:48])[CH2:40]5)[CH:36]=3)=[CH:21][CH2:20]4)[CH2:17][CH2:16]2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 86692375diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((3-(1,1-dioxidothiomorpholino)propyl)amino)methyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate

Product 1

HCID 865754482-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[3-(1,1-dioxo-1,4-thiazinan-4-yl)propylamino]methyl]-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]spiro[3.3]hept-2-ene-6,6-dicarboxylic acidYield 2.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((3-(1,1-dioxidothiomorpholino)propyl)amino)methyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate (90 mg, 0.104 mmol) in dioxane (3 mL) and MeOH (2 mL) was added 1N NaOH (2 mL, 2 mmol). The mixture was stirred at 50° C. for 12 h. The crude product was purified by preparative HPLC using method 14. The fractions containing the expected product were combined and concentrated to give 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((3-(1,1-dioxidothiomorpholino)propyl)amino)methyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylic acid as a white solid (2 mg, 2.46%). MS: m/e 779.5 (M+H)+, 2.31 min (method 2). 1H NMR (400 MHz, DMSO-d6) δ 6.02 (s, 1H), 5.48 (d, J=4.5 Hz, 1H), 4.71 (s, 1H), 4.60 (s, 1H), 3.12 (d, J=4.8 Hz, 5H), 3.01 (br. s., 4H), 2.91 (br. s., 5H), 2.72-2.64 (m, 1H), 2.57-2.49 (m 6H), 2.17-1.96 (m, 2H), 1.82 (d, J=5.8 Hz, 5H), 1.67 (m, 8H), 1.53-1.17 (m, 12H), 1.13 (s, 3H), 1.05 (m, 6H), 0.97 (s, 3H), 0.78 (s, 3H).

Workup

  1. customThe crude product was purified by preparative HPLC
  2. additionThe fractions containing the expected product
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-d0f094e43db74f9893eb70dec043cf3c
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Reaction notes

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