Dimethylamine → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4-(dimethylcarbamoyl)piperidin-1-yl)ethylamino)-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)benzoic acid

HRID 85662Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 85662
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[C:12]([CH3:51])([CH3:50])[C@H:13]3[C@:26]([CH3:29])([CH2:27][CH:28]=2)[C@@H:25]2[C@:16]([CH3:49])([C@@:17]4([CH3:48])[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][CH2:43][CH:42]([C:45](O)=[O:46])[CH2:41][CH2:40]2)[CH2:19][CH2:18]4)[CH2:15][CH2:14]3)=[CH:7][CH:6]=1)=[O:4].[CH3:52][NH:53][CH3:54].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.CN(C)C(=O)CN[C@]12CC[C@@H](C(C)=C)[C@@H]1[C@@H]1[C@@](C)(CC2)[C@@]2(C)[C@@H]([C@]3(C)[C@@H](CC2)C(C)(C)C(C2C=CC(C(O)=O)=CC=2)=CC3)CC1>C(Cl)Cl.C(OCC)(=O)C>[CH3:52][N:53]([CH3:54])[C:45]([CH:42]1[CH2:43][CH2:44][N:39]([CH2:38][CH2:37][NH:36][C@:20]23[CH2:32][CH2:31][C@@H:30]([C:33]([CH3:35])=[CH2:34])[C@@H:21]2[C@@H:22]2[C@@:17]([CH3:48])([CH2:18][CH2:19]3)[C@@:16]3([CH3:49])[C@@H:25]([C@:26]4([CH3:29])[C@@H:13]([CH2:14][CH2:15]3)[C:12]([CH3:50])([CH3:51])[C:11]([C:8]3[CH:7]=[CH:6][C:5]([C:3]([OH:2])=[O:4])=[CH:10][CH:9]=3)=[CH:28][CH2:27]4)[CH2:24][CH2:23]2)[CH2:40][CH2:41]1)=[O:46]

Komponenten

8

Edukt 5

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68358209HCID 68358209, VerbindungHCID 866765934-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)-2-oxoethylamino)-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)benzoic acid

Produkt 1

HCID 867628044-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4-(dimethylcarbamoyl)piperidin-1-yl)ethylamino)-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)benzoic acid

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a solution of methyl 1-(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-ylamino)ethyl)piperidine-4-carboxylate (40 mg) in dioxane (1 mL) was added lithium hydroxide (2.7 mg, 0.112 mmol) in water (1 mL). A white precipitate was observed. The mixture was stirred at 25° C. for 3 hours. The desired product was observed at m/e 699.7 (M+H)+, 2.703 min, method 10. The reaction mixture was neutralized with 1 N HCl to pH-4 and diluted with methlylene chloride (10 mL). The organic layer was then collected, dried over sodium sulfate and filtered. After removal of solvent, the crude product was obtained as an oil (40 mg, ˜100%) which was used without further purification. Step 2. To a solution of 1-(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)piperidine-4-carboxylic acid (40 mg, 0.057 mmol) in CH2Cl2 (5 ml) at rt was added dimethylamine (7.6 mg, 0.17 mmol) and HATU (65 mg, 0.18 mmol) followed by DIEA (29 mg, 0.23 mmol). The mixture was stirred for 3 hour at rt. The resulted mixture was diluted with ethyl acetate and washed with water. The organic layer was dried over sodium sulfate. The crude product was obtained after removal of solvent as a white solid (40 mg, ˜100%) which was used without further purification Step 3. 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(4-(dimethylcarbamoyl)piperidin-1-yl)ethylamino)-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)benzoic acid was prepared following step 2 of the method described above for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(dimethylamino)-2-oxoethylamino)-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)benzoic acid. The product was isolated as a white solid (9 mg, 23.0%). LCMS: m/e 712.64 (M+H)+, 2.265 min (method 11). 1H NMR (400 MHz, METHANOL-d4) δ 7.95 (d, J=8.3 Hz, 2H), 7.25 (d, J=8.3 Hz, 2H), 5.33 (d, J=4.5 Hz, 1H), 4.87 (s, 1H), 4.74 (s, 1H), 3.65-3.38 (m, 6H), 3.16 (s, 3H), 3.05 (m, 2H), 2.96 (s, 3H), 2.75 (m, 1H), 2.23-1.85 (m, 11H), 1.82-1.74 (m, 6H), 1.70-1.48 (m, 9H), 1.44-1.28 (m, 3H), 1.22 (m, 4H), 1.13 (s, 3H), 1.08 (s, 3H), 1.00 (s, 3H), 0.98 (s, 3H),

Aufarbeitung

  1. customwas used without further purification
  2. washwashed with water
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. customThe crude product was obtained
  5. customafter removal of solvent as a white solid (40 mg, ˜100%) which
  6. customwas used without further purification Step 3

Quellen und Nachweise

ORD-Eintrag
ord-fa18351b66a14282ae5f58ab135f2eac
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846647B2

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