Water → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(4,5-dimethylthiazol-2-ylamino)-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 85674

Reaktionsgleichung

Reaktionsgleichung von HRID 85674
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:34]([C:37]([CH3:39])=[CH2:38])[CH2:35][CH2:36][C@:5]1([NH:40][C:41]([NH2:43])=[S:42])[CH2:4][CH2:3]2.C(N(CC)C(C)C)(C)C.Br[CH:54]([CH3:58])[C:55](=O)[CH3:56].O>CN(C=O)C>[CH3:58][C:54]1[N:43]=[C:41]([NH:40][C@:5]23[CH2:36][CH2:35][C@@H:34]([C:37]([CH3:39])=[CH2:38])[C@@H:6]2[C@@H:7]2[C@@:2]([CH3:1])([CH2:3][CH2:4]3)[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:33])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]3[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8]2)[S:42][C:55]=1[CH3:56]

Komponenten

6

Edukt 4

HCID 962WaterHCID 131422-Butanone, 3-bromo-HCID 81531DiisopropylethylamineHCID 86676618methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-thioureido-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

Produkt 1

HCID 86676617methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(4,5-dimethylthiazol-2-ylamino)-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 70,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-thioureido-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 (150 mg, 0.249 mmol) in DMF (5 mL) was added N,N-diisopropylethylamine (0.173 mL, 0.995 mmol) and 3-bromobutan-2-one (56.4 mg, 0.373 mmol). The reaction mixture was stirred at rt. After 18 h, the reaction mixture was poured into a separatory funnel containing H2O (10 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to white solid. The material was redissolved in DCM (5 mL) and MeOH was added to effect precipitation. The mixture was concentrated to remove most of DCM and the resulting white precipitate was filtered, washed with cold MeOH, and dried in a vacuum oven to give methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(4,5-dimethylthiazol-2-ylamino)-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 (121 mg, 0.175 mmol, 70.5% yield) as a white solid. LCMS: m/e 655.3 (M+H)+, 2.72 min (method 2). 1H NMR (500 MHz, CHLOROFORM-d) δ 7.95 (d, J=8.2 Hz, 2H), 7.21 (d, J=8.2 Hz, 2H), 5.31 (d, J=4.6 Hz, 1H), 4.76 (br. s., 1H), 4.65 (s, 1H), 3.93 (s, 3H), 2.43 (d, J=10.4 Hz, 1H), 2.21 (s, 3H), 2.15 (s, 3H), 2.11 (d, J=6.7 Hz, 1H), 2.07-1.96 (m, 1H), 1.80-1.65 (m, 6H), 1.57-1.36 (m, 8H), 1.35-1.27 (m, 2H), 1.23 (d, J=10.1 Hz, 1H), 1.17-1.11 (m, 1H), 1.09 (s, 3H), 1.03 (s, 3H), 1.00 (s, 3H), 0.94 (s, 6H).

Aufarbeitung

  1. additionthe reaction mixture was poured into a separatory funnel
  2. extractionextracted with EtOAc (50 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to white solid
  7. dissolutionThe material was redissolved in DCM (5 mL)
  8. additionMeOH was added to effect precipitation
  9. concentrationThe mixture was concentrated
  10. customto remove most of DCM
  11. filtrationthe resulting white precipitate was filtered
  12. washwashed with cold MeOH
  13. customdried in a vacuum oven

Quellen und Nachweise

ORD-Eintrag
ord-1dbed69d820349eab3d3c85a577bfe8a
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846647B2

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