2,2-Dimethylsuccinic anhydride → HCID 66860742, compound

HRID 2179812Notes

Reaction equation

HRID 2179812 reaction equation
[CH3:1][C:2]1([CH3:9])[CH2:7][C:6](=[O:8])[O:5][C:3]1=[O:4].[CH2:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:23][C@H:22]([NH:24][C:25]([C@:27]34[CH2:53][CH2:52][C@@H:51]([C:54]([CH3:56])=[CH2:55])[C@@H:28]3[C@@H:29]3[C@@:42]([CH3:45])([CH2:43][CH2:44]4)[C@@:41]4([CH3:46])[C@@H:32]([C@:33]5([CH3:50])[C@@H:38]([CH2:39][CH2:40]4)[C:37]([CH3:48])([CH3:47])[C@@H:36]([OH:49])[CH2:35][CH2:34]5)[CH2:31][CH2:30]3)=[O:26])[C:21]2([CH3:58])[CH3:57])=[O:19])[CH2:14][CH2:13]1)[CH3:11]>CN(C1C=CN=CC=1)C.N1C=CC=CC=1.CCOC(C)=O>[CH2:10]([N:12]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:20]2[CH2:23][C@H:22]([NH:24][C:25]([C@:27]34[CH2:53][CH2:52][C@@H:51]([C:54]([CH3:56])=[CH2:55])[C@@H:28]3[C@@H:29]3[C@@:42]([CH3:45])([CH2:43][CH2:44]4)[C@@:41]4([CH3:46])[C@@H:32]([C@:33]5([CH3:50])[C@@H:38]([CH2:39][CH2:40]4)[C:37]([CH3:47])([CH3:48])[C@@H:36]([O:49][C:6](=[O:8])[CH2:7][C:2]([CH3:9])([CH3:1])[C:3]([OH:5])=[O:4])[CH2:35][CH2:34]5)[CH2:31][CH2:30]3)=[O:26])[C:21]2([CH3:57])[CH3:58])=[O:19])[CH2:14][CH2:13]1)[CH3:11]

Participants

6

Reactant 2

HCID 870672,2-Dimethylsuccinic anhydrideHCID 66858286HCID 66858286, compound

Product 1

HCID 66860742HCID 66860742, compoundYield 60.8%

Reagents, catalysts & solvents 3

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

Procedure

2,2-Dimethylsuccinic anhydride (238 mg) was added to a stirred solution of (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-N-((1S,3R)-3-(4-ethylpiperazine-1-carbonyl)-2,2-dimethylcyclobutyl)-9-hydroxy-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysene-3a-carboxamide (Example 67, 125 mg) and DMAP (45 mg) in dry pyridine (10 mL) at room temperature. After addition, the reaction mixture was refluxed for 14 hours. After completion of the reaction (monitored by TLC), it was diluted with EtOAc, the organic layer was washed with aqueous 1N HCl, then washed with water and brine, and dried with Na2SO4. The solvent was evaporated and purified by silica gel column (100-200, elution 35% EtOAc in hexane) to afford 90 mg of title compound (60.8% yield) as an off white solid with 81.67% HPLC purity. 1H-NMR (300 MHz, CDCl3): δ 5.92 (d, J=7.8 Hz, 1H), 4.73 (s, 1H), 4.58 (s, 1H), 4.52-4.44 (m, 1H), 4.19-4.09 (m, 1H), 3.90 (m, 2H), 3.7 (m, 2H), 3.15-3.04 (m, 1H), 2.87-2.82 (m, 6H), 2.60 (m, 3H), 2.5-2.3 (m, 3H), 2.00-1.91 (m, 3H), 1.75-1.10 (m, 36H), 0.947, 0.914, 0.900 (s, 18H); Mass: [M+1]+ 806 (100%); IR (KBr, cm−1): 3394, 2957, 2873, 1724, 1623, 1455, 1374, 1367, 1244, 1188, 1146, 980, 883, 765; M.R: 63.8° C.-122.5° C.

Workup

  1. additionAfter addition
  2. temperaturethe reaction mixture was refluxed for 14 hours
  3. customAfter completion of the reaction (monitored by TLC), it
  4. washthe organic layer was washed with aqueous 1N HCl
  5. washwashed with water and brine
  6. dry with materialdried with Na2SO4
  7. customThe solvent was evaporated
  8. custompurified by silica gel column (100-200, elution 35% EtOAc in hexane)

Sources & evidence

ORD record
ord-8272c76231954ed0bc610d29eafff559
Source dataset
uspto-grants-2015_06
Patent number
US09067966B2

Reaction notes

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