N,N-Dimethylethylenediamine → methyl 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)ethylcarbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

HRID 2405481Notes

Reaction equation

HRID 2405481 reaction equation
Cl[C:2]([C@:4]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]1[C@@H:6]1[C@@:19]([CH3:22])([CH2:20][CH2:21]2)[C@@:18]2([CH3:23])[C@@H:9]([C@:10]3([CH3:36])[C@@H:15]([CH2:16][CH2:17]2)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)=[CH:12][CH2:11]3)[CH2:8][CH2:7]1)=[O:3].CCN(C(C)C)C(C)C.[CH3:52][N:53]([CH3:57])[CH2:54][CH2:55][NH2:56]>ClCCCl.CN(C1C=CN=CC=1)C>[CH3:52][N:53]([CH3:57])[CH2:54][CH2:55][NH:56][C:2]([C@:4]12[CH2:39][CH2:38][C@@H:37]([CH:40]([CH3:42])[CH3:41])[C@@H:5]1[C@@H:6]1[C@@:19]([CH3:22])([CH2:20][CH2:21]2)[C@@:18]2([CH3:23])[C@@H:9]([C@:10]3([CH3:36])[C@@H:15]([CH2:16][CH2:17]2)[C:14]([CH3:25])([CH3:24])[C@@H:13]([C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)[CH2:12][CH2:11]3)[CH2:8][CH2:7]1)=[O:3]

Participants

6

Reactant 3

HCID 66053N,N-DimethylethylenediamineHCID 81531DiisopropylethylamineHCID 86666171methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(chlorocarbonyl)-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 67775847methyl 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)ethylcarbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoateYield 44%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a flask containing methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(chlorocarbonyl)-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 (77 mg, 0.13 mmol) in DCE (2 mL) was added Hunig's base (0.068 mL, 0.390 mmol), DMAP (1 mg, 8.19 mmol), and N,N-dimethylethylenediamine (0.029 mL, 0.260 mmol). The mixture was stirred for two hours at rt. The reaction was quenched with 5 mL of water and was extracted with dichloromethane (3×5 mL). The combined organic layers were dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure and was purified by Biotage flash chromatography using a 0-10% MeOH in dichloromethane gradient. The fractions containing the expected product were combined and concentrated under reduced pressure to give methyl 4-((1S,3aS,5aR,5bR,7aS,9S,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)ethylcarbamoyl)-1-isopropyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate as a white foam (37 mg, 44% yield). LCMS: m/e 647.7 (M+H)+, 3.09 min (method 3).

Workup

  1. customThe reaction was quenched with 5 mL of water
  2. extractionwas extracted with dichloromethane (3×5 mL)
  3. dry with materialThe combined organic layers were dried with Na2SO4
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customwas purified by Biotage flash chromatography
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6bf93bd97f044b77a388488a255a72d6
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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