Trifluoroacetic acid → HCID 71596821, compound

HRID 405069Notes

Reaction equation

HRID 405069 reaction equation
[CH3:1][N:2]([CH3:55])[CH:3]([C:49]1[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=1)[CH2:4][NH:5][CH2:6][C@:7]12[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:8]1[C@@H:9]1[C@@:22]([CH3:25])([CH2:23][CH2:24]2)[C@@:21]2([CH3:26])[C@@H:12]([C@:13]3([CH3:42])[C@@H:18]([CH2:19][CH2:20]2)[C:17]([CH3:28])([CH3:27])[C:16]([C:29]2[CH:41]=[CH:40][C:32]([C:33]([O:35]C(C)(C)C)=[O:34])=[CH:31][CH:30]=2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:55][N:2]([CH3:1])[CH:3]([C:49]1[CH:50]=[N:51][CH:52]=[CH:53][CH:54]=1)[CH2:4][NH:5][CH2:6][C@:7]12[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:8]1[C@@H:9]1[C@@:22]([CH3:25])([CH2:23][CH2:24]2)[C@@:21]2([CH3:26])[C@@H:12]([C@:13]3([CH3:42])[C@@H:18]([CH2:19][CH2:20]2)[C:17]([CH3:27])([CH3:28])[C:16]([C:29]2[CH:30]=[CH:31][C:32]([C:33]([OH:35])=[O:34])=[CH:40][CH:41]=2)=[CH:15][CH2:14]3)[CH2:11][CH2:10]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86676408HCID 86676408, compound

Product 1

HCID 71596821HCID 71596821, compoundYield 13.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(dimethylamino)-2-(pyridin-3-yl)ethylamino)methyl)-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 (125 mg, 0.167 mmol) in DCM (1 ml) was added TFA (0.4 ml, 5.19 mmol). The mixture was stirred at rt for 4.5 h then was concentrated under reduced pressure. The residue was dissolved in dioxane and MeOH and was purified by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure. Impurities were still present so the residue was purified again by prep HPLC. The fractions containing the expected product were combined and concentrated under reduced pressure to give the title compound as an off-white solid (16 mg, 13.8%). LCMS: m/e 692.5 (M+H)+, 2.30 min (method 6). 1H NMR (500 MHz, Acetic Acid) δ ppm 8.83-8.98 (m, 2H), 8.27-8.42 (m, 1H), 7.99-8.11 (m, 2H), 7.71-7.84 (m, 1H), 7.27-7.35 (m, 2H), 5.33-5.42 (m, 1H), 5.22-5.30 (m, 1H), 4.79 (d, J=14.34 Hz, 1H), 4.67 (d, J=12.82 Hz, 1H), 4.21-4.38 (m, 2H), 3.34-3.52 (m, 1H), 2.97-3.15 (m, 1H), 2.83 (br. s., 3H), 2.82 (br. s., 3H), 2.43-2.58 (m, 1H), 0.88-2.23 (m, 40H).

Workup

  1. concentrationthen was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in dioxane
  3. customMeOH and was purified by prep HPLC
  4. additionThe fractions containing the expected product
  5. concentrationconcentrated under reduced pressure
  6. customwas purified again by prep HPLC
  7. additionThe fractions containing the expected product
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4a603e1c11d44b759bc7721d4fddfeac
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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