Methanol → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[(4-carboxyphenyl)sulfonylamino]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]benzoic acid

HRID 405096Notes

Reaction equation

HRID 405096 reaction equation
C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([CH3:56])([CH3:55])[C@H:16]3[C@:29]([CH3:32])([CH2:30][CH:31]=2)[C@@H:28]2[C@:19]([CH3:54])([C@@:20]4([CH3:53])[C@H:25]([CH2:26][CH2:27]2)[C@H:24]2[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:23]2([CH2:39][NH:40][S:41]([C:44]2[CH:52]=[CH:51][C:47]([C:48]([OH:50])=[O:49])=[CH:46][CH:45]=2)(=[O:43])=[O:42])[CH2:22][CH2:21]4)[CH2:18][CH2:17]3)=[CH:10][CH:9]=1)=[O:7])(C)(C)C.CO>O1CCOCC1.O>[C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([CH3:56])([CH3:55])[C@H:16]3[C@:29]([CH3:32])([CH2:30][CH:31]=2)[C@@H:28]2[C@:19]([CH3:54])([C@@:20]4([CH3:53])[C@H:25]([CH2:26][CH2:27]2)[C@H:24]2[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:23]2([CH2:39][NH:40][S:41]([C:44]2[CH:52]=[CH:51][C:47]([C:48]([OH:50])=[O:49])=[CH:46][CH:45]=2)(=[O:42])=[O:43])[CH2:22][CH2:21]4)[CH2:18][CH2:17]3)=[CH:10][CH:9]=1)([OH:7])=[O:5]

Participants

5

Reactant 2

HCID 887MethanolHCID 866764184-(N-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(tert-butoxycarbonyl)phenyl)-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-3a-yl)methyl)sulfamoyl)benzoic acid

Product 1

HCID 715972344-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[(4-carboxyphenyl)sulfonylamino]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]benzoic acidYield 19%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

4-(N—(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(tert-butoxycarbonyl)phenyl)-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-3a-yl)methyl)sulfamoyl)benzoic acid (10 mg, 0.013 mmol) from Step 1 was dissolved in dioxane (1 ml) and MeOH (5 ml) sodium hydroxide (10.20 mg, 0.255 mmol) (powder) was added followed by 5 drops of water. The resulting suspension was stirred at 70° C. for 6 h. After the reaction was completed, all volatile material was removed in vacuo. The residue was re-dissolved in MeOH and purified by prep. HPLC to afford 4-(N—(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-carboxyphenyl)-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-3a-yl)methyl)sulfamoyl)benzoic acid as a white solid (1.8 mg, 18.4%). LCMS: m/e 728.2 (MH+), 2.11 min (method 3). 1H NMR (400 MHz, MeOD) δ ppm 8.24 (m, J=8.5 Hz, 2H), 8.01 (m, J=8.5 Hz, 2H), 7.94 (m, J=8.3 Hz, 2H), 7.24 (m, J=8.3 Hz, 2H), 5.31 (d, J=4.3 Hz, 1H), 4.70 (d, J=2.3 Hz, 1H), 4.59 (s, 1H), 3.05 (s, 1H), 2.62 (d, J=13.1 Hz, 1H), 2.37 (br. s., 1H), 2.11 (m, 1H), 1.76-2.01 (m, 4H), 1.65-1.76 (m, 6H), 1.53-1.65 (m, 4H), 1.44 (br. s., 5H), 1.31 (d, J=2.8 Hz, 6H), 1.03 (s, 6H), 1.01 (s, 3H), 0.99 (s, 3H), 0.96 (s, 3H).

Workup

  1. customall volatile material was removed in vacuo
  2. dissolutionThe residue was re-dissolved in MeOH
  3. custompurified by prep

Sources & evidence

ORD record
ord-e556972301da49f186231e6366a0599e
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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