Sodium Hydroxide → BMS-955176

HRID 85618Notes

Reaction equation

HRID 85618 reaction equation
[O:1]=[S:2]1(=[O:50])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[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([CH3:43])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]3[CH:42]=[CH:41][C:36]([C:37]([O:39]C)=[O:38])=[CH:35][CH:34]=3)=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1.[OH-].[Na+]>O1CCOCC1>[O:50]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[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([CH3:43])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]3[CH:42]=[CH:41][C:36]([C:37]([OH:39])=[O:38])=[CH:35][CH:34]=3)=[CH:19][CH2:18]4)[CH2:15][CH2:14]2)[CH2:4][CH2:3]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68357879methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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)benzoate

Product 1

HCID 60152109BMS-955176Yield 40.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
78 °C

Procedure

A mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-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)benzoate (500 mg, 0.709 mmol) and aqueous sodium hydroxide 10N (1.42 mL, 14.2 mmol) in dioxane (10 mL) was heated at 78° C. for 3 h. The reaction was filtered and the resulting clear solution was purified by prep HPLC to provide the title compound as white solid (200 mg, 39%). LCMS: m/e 691.59 (M+H)+, 2.53 min (method 10). 1H NMR (500 MHz, Acetic acid d4) δ ppm 8.04 (d, J=8.24 Hz, 2H), 7.30 (d, J=8.24 Hz, 2H), 5.45-5.34 (m, 1H), 4.85 (s, 1H), 4.74 (s, 1H), 3.55-3.40 (m, 1H), 3.39-3.22 (m, 6H), 3.22-3.11 (m, 4H), 3.11-3.03 (m, 1H), 3.04-2.94 (m, 1H), 2.36-1.18 (m, 22H), 1.76 (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 was filtered
  2. customthe resulting clear solution was purified by prep HPLC

Sources & evidence

ORD record
ord-7abbf91257724ea78ef93b7526e78bb2
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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