Trifluoroacetic acid → HCID 71596818, compound

HRID 405065Notes

Reaction equation

HRID 405065 reaction equation
C([O:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[C:15]([CH3:59])([CH3:58])[C@H:16]3[C@:29]([CH3:32])([CH2:30][CH:31]=2)[C@@H:28]2[C@:19]([CH3:57])([C@@:20]4([CH3:56])[C@H:25]([CH2:26][CH2:27]2)[C@H:24]2[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:23]2([CH2:39][NH:40][CH2:41][CH2:42][N:43]2[CH2:48][CH2:47][N:46](C(OC(C)(C)C)=O)[CH2:45][CH2:44]2)[CH2:22][CH2:21]4)[CH2:18][CH2:17]3)=[CH:10][CH:9]=1)=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH3:56][C@:20]12[C@@:19]3([CH3:57])[C@@H:28]([C@:29]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:58])([CH3:59])[C:14]([C:11]3[CH:12]=[CH:13][C:8]([C:6]([OH:7])=[O:5])=[CH:9][CH:10]=3)=[CH:31][CH2:30]4)[CH2:27][CH2:26][C@@H:25]1[C@H:24]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:23]1([CH2:39][NH:40][CH2:41][CH2:42][N:43]1[CH2:44][CH2:45][NH:46][CH2:47][CH2:48]1)[CH2:22][CH2:21]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86676406HCID 86676406, compound

Product 1

HCID 71596818HCID 71596818, compoundYield 16.43%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-(2-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-9-(4-(tert-butoxycarbonyl)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]chrysen-3a-yl)methylamino)ethyl)piperazine-1-carboxylate (136 mg, 0.167 mmol) in DCM (1 ml) was added TFA (0.4 ml, 5.19 mmol). The mixture was stirred at rt for 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. HPLC showed some impurities were still present, so the reaction was repurified by prep. HPLC. The fractions were concentrated under reduced pressure to give the title compound as a white solid (18 mg, 0.027 mmol, 16.43% yield). LCMS: m/e 656.6 (M+H)+, 2.24 min (method 6). 1H NMR (500 MHz, Acetic) δ ppm 8.03 (d, J=8.24 Hz, 2H),7.30 (d, J=8.24 Hz, 2H), 5.37 (d, J=4.58 Hz, 1H), 4.79 (s, 1H), 4.68 (s, 1H), 3.50-3.67 (m, 6H), 3.40 (d, J=12.82 Hz, 1H), 3.22-3.29 (m, 6H), 2.99 (d, J=13.12 Hz, 1H), 2.49-2.58 (m, 1H), 1.76 (s, 3H), 1.19 (s, 3H), 1.16-2.23 (m, 22H), 1.10 (s, 3H), 1.08 (s, 3H), 1.02 (s, 3H), 1.00 (s, 3H).

Workup

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

Sources & evidence

ORD record
ord-516667716d1d4258bcde7172e67bc494
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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