Diisopropylethylamine → HCID 57639109, Verbindung

HRID 2111948Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2111948
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:30](=[O:38])[NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21](O)=[O:22])=[CH:18][C:17]4[CH:24]=[C:25]([O:28][CH3:29])[CH:26]=[CH:27][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:39]([N:46]1[CH2:51][C@H:50]([CH3:52])[NH:49][C@H:48]([CH3:53])[CH2:47]1)[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O.Cl>[CH2:39]([N:46]1[CH2:47][C@H:48]([CH3:53])[N:49]([C:21]([C:19]2[CH2:20][N:14]3[C:13]4[CH:12]=[C:11]([C:30]([NH:31][S:32]([N:35]([CH3:37])[CH3:36])(=[O:34])=[O:33])=[O:38])[CH:10]=[CH:9][C:8]=4[C:7]([CH:1]4[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]4)=[C:15]3[C:16]3[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:17]=3[CH:18]=2)=[O:22])[C@H:50]([CH3:52])[CH2:51]1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Komponenten

8

Edukt 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12197174(3r,5s)-1-Benzyl-3,5-dimethylpiperazine2×HCID 59682115HCID 59682115, Verbindung

Produkt 1

HCID 57639109HCID 57639109, VerbindungAusbeute 14,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 313Hydrochloric AcidLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a stirred solution of 13-cyclohexyl-10-(((dimethylamino)sulfonyl)carbamoyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-6-carboxylic acid (200 mg, 0.37 mmol), (3R,5S)-1-benzyl-3,5-dimethylpiperazine (115 mg, 0.56 mmol) and diisopropylethylamine (0.26 mL) in DMF (4 mL) was added HATU (212 mg, 0.56 mmol). The reaction mixture was stirred at rt for 2 h, treated with additional (3R,5S)-1-benzyl-3,5-dimethylpiperazine (100 mg, 0.49 mmol) and stirred at 100° C. for 3 h. The reaction was cooled to rt, diluted with H2O (30 mL) and 1M HCl (aq.) (1.5 mL) and extracted with EtOAc (20 mL). The organic layer was separated, washed with brine (10 mL), dried (MsSO4), filtered and concentrated. The residue was diluted with MeOH (5 mL) and purified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer) to yield rel-6-(((2R,6S)-4-benzyl-2,6-dimethyl-1-piperazinyl)carbonyl)-13-cyclohexyl-N-((dimethylamino)sulfonyl)-3-methoxy-7H-indolo[2,1-a][2]benzazepine-10-carboxamide (38 mg, 0.052 mmol, 14%) as an orange solid. 1HNMR (300 MHz, CD3OD) δ 1.02-2.22 (m, 20H), 2.58-3.03 (m, 3H), 3.05 (s, 6H), 3.27-3.40 (m, 2H), 3.92 (s, 3H), 4.34-4.56 (m, 1H), 4.99-5.19 (m, 1H), 6.89 (s, 1H) 7.08 (d, J=2.6 Hz, 1H), 7.14 (dd, J=8.8, 2.6 Hz, 1H), 7.19-7.33 (m, 5H), 7.55 (d, J=8.4 Hz, 1H), 7.65 (d, J=8.4 Hz, 1H), 7.90 (d, J=8.4 Hz, 1H), 8.17 (s, 1H). LCMS: m/e 724 (M+H)+, ret time 3.37 min, column B, 4 minute gradient.

Aufarbeitung

  1. stirringstirred at 100° C. for 3 h
  2. temperatureThe reaction was cooled to rt
  3. extractionextracted with EtOAc (20 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. customdried (MsSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. additionThe residue was diluted with MeOH (5 mL)
  10. custompurified by preparative HPLC (H2O/CH3CN with 10 mM NH4OAc buffer)

Quellen und Nachweise

ORD-Eintrag
ord-b7386e5524ea407aba6d805564eebcb5
Quelldatensatz
uspto-grants-2009_04
Patentnummer
US07521441B2

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