BMS-955176 → 4-((1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropyl-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)benzoic acid

HRID 85653Notes

Reaction equation

HRID 85653 reaction equation
[O:1]=[S:2]1(=[O:49])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[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([CH3:42])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]3[CH:41]=[CH:40][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.[H][H]>CO.C(OCC)(=O)C.[Pd]>[O:49]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C@:11]23[CH2:45][CH2:44][C@@H:43]([CH:46]([CH3:47])[CH3:48])[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([CH3:42])[C@@H:22]([CH2:23][CH2:24]3)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]3[CH:41]=[CH:40][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

6

Reactant 2

HCID 60152109BMS-955176HCID 178418361HCID 178418361, compound

Product 1

HCID 683578764-((1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxido-4-thiomorpholinyl)ethyl)amino)-1-isopropyl-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)benzoic acidYield 28%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 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)benzoic acid (100 mg, 0.145 mmol) and 10% Pd/C (90 mg, 0.087 mmol) in methanol (5 mL) and ethyl acetate (5 mL) was loaded onto a PARR shaker reactor and treated with hydrogen for 25 hours under 40 psi at room temperature. The reaction mixture was filtered through a celite pad to remove the catalyst. The filtrate was purified by HPLC to provide the title compound as a white solid (5.6 mg, 28%). LCMS: m/e 693.46 (M+H)+, 2.46 min (method 10). 1H NMR (500 MHz, Acetic acid d4) δ ppm 8.04 (d, J=8.2 Hz, 2H), 7.31 (d, J=8.2 Hz, 2H), 5.39 (d, J=4.6 Hz, 1H), 3.50-3.36 (m, 1H), 3.36-3.21 (m, 6H), 3.21-2.98 (m, 5H), 2.31-1.29 (m, 24H), 1.29 (s, 3H), 1.13 (s, 6H), 1.03 (s, 3H), 1.01 (s, 3H), 0.94 (d, J=6.7 Hz, 3H), 0.86 (d, J=6.7 Hz, 3H).

Workup

  1. customwas loaded onto a PARR shaker reactor
  2. filtrationThe reaction mixture was filtered through a celite pad
  3. customto remove the catalyst
  4. customThe filtrate was purified by HPLC

Sources & evidence

ORD record
ord-dd51a677e7c94478b4a4e4001517b4d3
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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