Hydrochloric Acid → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1R,5 S)-3,6-diazabicyclo[3.1.1]heptan-3-yl)ethyl)amino)-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

HRID 338645Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 338645
[CH3:1][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([NH:36][CH2:37][CH2:38][N:39]2[CH2:44][C@@H:43]5[CH2:45][C@@H:41]([N:42]5C(OC(C)(C)C)=O)[CH2:40]2)[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].C(O)(C(F)(F)F)=O.Cl.CCOCC>C(Cl)Cl.ClCCCl>[C@H:41]12[CH2:45][C@H:43]([NH:42]1)[CH2:44][N:39]([CH2:38][CH2:37][NH:36][C@:20]13[CH2:32][CH2:31][C@@H:30]([C:33]([CH3:35])=[CH2:34])[C@@H:21]1[C@@H:22]1[C@@:17]([CH3:53])([CH2:18][CH2:19]3)[C@@:16]3([CH3:54])[C@@H:25]([C@:26]4([CH3:29])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:55])([CH3:56])[C:11]([C:8]3[CH:9]=[CH:10][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:6][CH:7]=3)=[CH:28][CH2:27]4)[CH2:24][CH2:23]1)[CH2:40]2

Komponenten

7

Edukt 4

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 86701808(1R,5S)-tert-butyl 3-(2-(((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]chrysen-3a-yl)amino)ethyl)-3,6-diazabicyclo[3.1.1]heptane-6-carboxylate

Produkt 1

HCID 86701807methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-((1R,5 S)-3,6-diazabicyclo[3.1.1]heptan-3-yl)ethyl)amino)-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)benzoateAusbeute 87 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of (1R,5S)-tert-butyl 3-(2-(((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]chrysen-3a-yl)amino)ethyl)-3,6-diazabicyclo[3.1.1]heptane-6-carboxylate (123 mg, 0.160 mmol) in DCM (3 mL) was added TFA (0.5 mL, 6.49 mmol) and the mixture was stirred at rt for 1 h. The resulting brown reaction mixture was diluted with DCE (3 mL) and concentrated to a light brown foam. The material was dissolved in DCM (2 mL) and DCE (2 mL) and treated with 2N HCl in Et2O (0.5 mL, 1.0 mmol). The resulting slurry was concentrated and dried under vacuum to give the title compound (108.1 mg, 0.139 mmol, 87% yield) as light grey solid. LC/MS: m/e 668.5 (M+H)+, 2.28 min (method 3). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.89 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.6 Hz, 2H), 5.27 (d, J=4.4 Hz, 1H), 4.85 (s, 1H), 4.71 (s, 1H), 4.39 (d, J=5.4 Hz, 2H), 3.88 (s, 3H), 3.76 (br. s., 1H), 3.59 (br. s., 1H), 3.48 (q, J=7.1 Hz, 3H), 3.40-3.33 (m, 2H), 3.07-2.91 (m, 2H), 2.37 (d, J=10.3 Hz, 1H), 2.25-1.89 (m, 7H), 1.83 (d, J=12.0 Hz, 1H), 1.77 (br. s., 1H), 1.73-1.71 (m, 3H), 1.67 (br. s., 1H), 1.65-1.58 (m, 2H), 1.57-1.38 (m, 8H), 1.37-1.29 (m, 1H), 1.27-1.22 (m, 1H), 1.13 (s, 3H), 1.08 (s, 3H), 1.00 (s, 3H), 0.92 (s, 3H), 0.91 (s, 3H).

Aufarbeitung

  1. concentrationconcentrated to a light brown foam
  2. dissolutionThe material was dissolved in DCM (2 mL)
  3. concentrationThe resulting slurry was concentrated
  4. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-5aeb2d559a62465c8ee0d3f2167032a8
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889854B2

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