2,2-Dimethylsuccinic anhydride → HCID 50924228, compound

HRID 2179770Notes

Reaction equation

HRID 2179770 reaction equation
[CH3:1][C:2]1([CH3:47])[C@H:5]([C:6]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[O:7])[CH2:4][C@@H:3]1[NH:14][C:15]([C@:17]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:18]1[C@@H:19]1[C@@:32]([CH3:35])([CH2:33][CH2:34]2)[C@@:31]2([CH3:36])[C@@H:22]([C@:23]3([CH3:40])[C@@H:28]([CH2:29][CH2:30]2)[C:27]([CH3:38])([CH3:37])[C@@H:26]([OH:39])[CH2:25][CH2:24]3)[CH2:21][CH2:20]1)=[O:16].[CH3:48][C:49]1([CH3:56])[CH2:54][C:53](=[O:55])[O:52][C:50]1=[O:51]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1.CCOC(C)=O>[CH3:1][C:2]1([CH3:47])[C@H:5]([C:6]([N:8]2[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]2)=[O:7])[CH2:4][C@@H:3]1[NH:14][C:15]([C@:17]12[CH2:43][CH2:42][C@@H:41]([C:44]([CH3:46])=[CH2:45])[C@@H:18]1[C@@H:19]1[C@@:32]([CH3:35])([CH2:33][CH2:34]2)[C@@:31]2([CH3:36])[C@@H:22]([C@:23]3([CH3:40])[C@@H:28]([CH2:29][CH2:30]2)[C:27]([CH3:37])([CH3:38])[C@@H:26]([O:39][C:53](=[O:55])[CH2:54][C:49]([CH3:56])([CH3:48])[C:50]([OH:52])=[O:51])[CH2:25][CH2:24]3)[CH2:21][CH2:20]1)=[O:16]

Participants

6

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 50924074HCID 50924074, compound

Product 1

HCID 50924228HCID 50924228, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-N-((1S,3R)-2,2-dimethyl-3-(piperidine-1-carbonyl)cyclobutyl)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxamide (Example 11, 0.110 g, 1.697 mmol) 2,2-Dimethylsuccinic anhydride (0.2 ml, 1.697 mmol) and DMAP (0.044 g, 0.338 mmol) in pyridine (5 ml) were added at room temperature then the reaction mixture was refluxed for about 16 hours. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with EtOAc, washed with water, 1N HCl, water, brine and dried with Na2SO4, the solvent was evaporated and purified by silica gel column (100-200 mesh, elution 15% EtOAc in hexane) to afford the title compound as an off white solid. Wt: 0.080 g: Yield: 61%; 1H NMR (300 MHz, CDCl3): δ 6.01 (d, 1H, J=8.4 Hz), 4.72 (s, 1H), 4.58 (s, 1H), 4.53-4.43 (m, 1H), 4.16-4.08 (m, 1H), 3.71-3.62 (m, 2H), 3.54-3.35 (m, 3H), 3.18-3.06 (m, 1H), 2.93-2.87 (m, 1H), 2.66 (d, 1H, J=15.9 Hz), 2.56 (d, 1H, J=15.9 Hz), 2.50-2.27 (m, 2H), 1.99-1.88 (m, 2H), 1.80-1.00 (m, 46H), 0.94, 0.92, 0.83 (s, 12H); Mass: [M+1]+ 777 (100%), [M+Na]+ 799 (80%); IR (KBr, cm−1): 3411, 2944, 2867, 1733, 1730, 1625, 1467, 1445, 1368, 1253, 1220, 1192, 1022, 977, 884, 767; M.R: 139.5° C.-141.5° C.; HPLC: 96.7%.

Workup

  1. temperaturethe reaction mixture was refluxed for about 16 hours
  2. customAfter completion of the reaction (monitored by TLC)
  3. washwashed with water, 1N HCl, water, brine
  4. dry with materialdried with Na2SO4
  5. customthe solvent was evaporated
  6. custompurified by silica gel column (100-200 mesh, elution 15% EtOAc in hexane)

Sources & evidence

ORD record
ord-9eb782cf899d40dd9a7567b046fe441f
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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