Sodium Hydroxide → HCID 54764028, compound

HRID 2405475Notes

Reaction equation

HRID 2405475 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH3:56])([CH3:55])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:54])([C@@:17]4([CH3:53])[C@H:22]([CH2:23][CH2:24]2)[C@H:21]2[C@H:30]([C:33]([CH3:35])=[CH2:34])[CH2:31][CH2:32][C@:20]2([C:36]([NH:38][CH2:39][CH2:40][C:41]([N:43]2[CH2:48][CH2:47][CH:46]([C:49]([O:51]C)=[O:50])[CH2:45][CH2:44]2)=[O:42])=[O:37])[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].[OH-].[Na+]>O1CCOCC1.Cl>[C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2[C:12]([CH3:56])([CH3:55])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:54])([C@@:17]4([CH3:53])[C@H:22]([CH2:23][CH2:24]2)[C@H:21]2[C@H:30]([C:33]([CH3:35])=[CH2:34])[CH2:31][CH2:32][C@:20]2([C:36]([NH:38][CH2:39][CH2:40][C:41]([N:43]2[CH2:44][CH2:45][CH:46]([C:49]([OH:51])=[O:50])[CH2:47][CH2:48]2)=[O:42])=[O:37])[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:9][CH:10]=1)([OH:4])=[O:2]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 67775712HCID 67775712, compound

Product 1

HCID 54764028HCID 54764028, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of methyl 1-(3-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(methoxycarbonyl)phenyl)-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]chrysene-3a-carboxamido)propanoyl)piperidine-4-carboxylate (0.058 g, 0.075 mmol) in 1,4-dioxane (2 mL) was added NaOH (1N) (0.377 mL, 0.377 mmol). The mixture was heated to 85° C. for 15 h then was cooled to rt. The mixture was diluted with 5 mL of 1N HCl and was extracted with dichloromethane (4×5 mL). The combined organic layers were dried with Na2SO4, the drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by Biotage flash chromatography using a 0-10% MeOH in dichloromethane gradient with 0.1% HOAc added to the mixture. The compound was further purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to give the title compound (41.5 mg, 0.056 mmol, 74.3% yield) as a white solid. LCMS: m/e 739.4 (M−H)−, 2.37 min (method 4). 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=6.10 Hz, 1H), 4.79 (s, 1H), 4.64 (s, 1H), 4.43-4.53 (m, 1H), 3.95-4.02 (m, 1H), 3.46-3.70 (m, 2H), 3.18-3.27 (m, 1H), 3.13 (qd, J=11.04, 4.12 Hz, 1H), 2.65-2.97 (m, 4H), 2.47-2.57 (m, 1H), 1.74 (s, 3H), 1.07 (s, 3H), 1.06 (s, 3H), 1.05 (s, 3H), 1.03-2.24 (m, 25H), 1.00 (s, 3H), 0.99 (s, 3H).

Workup

  1. temperaturethen was cooled to rt
  2. extractionwas extracted with dichloromethane (4×5 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. customThe residue was purified by Biotage flash chromatography
  7. additionadded to the mixture
  8. customThe compound was further purified by prep HPLC
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c9a214a43de0464082b9044640c5f856
Source dataset
uspto-grants-2014_08
Patent number
US08802661B2

Reaction notes

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