Iodoethane → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(ethyl(2-methoxy-2-oxoethyl)amino)ethylcarbamoyl)-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)benzoate

HRID 2405490Notes

Reaction equation

HRID 2405490 reaction equation
[CH3:1][O:2][C:3](=[O:50])[CH2:4][NH:5][CH2:6][CH2:7][NH:8][C:9]([C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][CH:34]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:10].I[CH2:52][CH3:53].C(=O)([O-])[O-].[K+].[K+]>C(#N)C.O1CCOCC1>[CH2:52]([N:5]([CH2:4][C:3]([O:2][CH3:1])=[O:50])[CH2:6][CH2:7][NH:8][C:9]([C@:11]12[CH2:46][CH2:45][C@@H:44]([C:47]([CH3:49])=[CH2:48])[C@@H:12]1[C@@H:13]1[C@@:26]([CH3:29])([CH2:27][CH2:28]2)[C@@:25]2([CH3:30])[C@@H:16]([C@:17]3([CH3:43])[C@@H:22]([CH2:23][CH2:24]2)[C:21]([CH3:32])([CH3:31])[C:20]([C:33]2[CH:34]=[CH:35][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:41][CH:42]=2)=[CH:19][CH2:18]3)[CH2:15][CH2:14]1)=[O:10])[CH3:53]

Participants

6

Reactant 3

HCID 6340IodoethaneHCID 11430Potassium CarbonateHCID 67775719methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(2-methoxy-2-oxoethylamino)ethylcarbamoyl)-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)benzoate

Product 1

HCID 67775678methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(ethyl(2-methoxy-2-oxoethyl)amino)ethylcarbamoyl)-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)benzoate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(2-methoxy-2-oxoethylamino)ethylcarbamoyl)-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)benzoate (50 mg, 0.071 mmol), iodoethane (0.047 mL, 0.571 mmol) and potassium carbonate (19.72 mg, 0.143 mmol) in acetonitrile (2.0 mL) and dioxane (2.0 mL) was heated up for 8 hours. LCMS indicated the formation of desired product and consumption of starting material. The reaction mixture was quenched with distilled water, extracted with DCM (3×3 mL). All the extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure to provide the crude intermediate methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(ethyl(2-methoxy-2-oxoethyl)amino)ethylcarbamoyl)-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)benzoate. To this intermediate in dioxane (1 mL) was added 1N sodium hydroxide (0.224 mL, 0.224 mmol). The reaction mixture was heated up at 78° C. for 3 hours until LCMS indicated the consumption of starting material. The reaction mixture was filtered and the clear solution was purified by prep HPLC to provide the title compound as a white solid (29 mg, 59%). LCMS: m/e 687.40 (M+H)+, 2.11 min (method 1). 1H NMR (500 MHz, Acetic Acid-d4) δ ppm 8.03 (d, J=8.24 Hz, 2H), 7.30 (d, J=8.24 Hz, 2H), 5.37 (d, J=4.58 Hz, 1H), 4.78 (s, 1H), 4.65 (s, 1H), 4.02 (s, 2H), 3.85-3.63 (m, 2H), 3.58-3.37 (m, 4H), 3.22-3.01 (m, 1H), 2.69-2.43 (m, 1H), 1.73 (s, 3H), 2.30-1.20 (m, 24H), 1.08 (s, 3H), 1.07 (s., 3H), 1.06 (s., 3H), 1.01 (s, 3H), 0.99 (s, 3H).

Workup

  1. temperaturewas heated up for 8 hours
  2. customthe formation of desired product and consumption of starting material
  3. customThe reaction mixture was quenched with distilled water
  4. extractionextracted with DCM (3×3 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-35a772a6aaa74bdf92e3a793a7931973
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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