Ozone → (7s)-n-Methoxy-7-{[(5-methoxy-2-methyl-1h-indol-3-yl)acetyl]amino}-n-methyl-7-(5-phenyl-1h-imidazol-2-yl)heptanamide

HRID 251748

Reaktionsgleichung

Reaktionsgleichung von HRID 251748
C[CH2:2][N:3]=[C:4]=[N:5][CH2:6][CH2:7][CH2:8]N(C)C.Cl.[CH:13]1[CH:14]=[CH:15][C:16]2N(O)N=[N:19][C:17]=2C=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]2[C:31](=[CH:32][CH:33]=1)[NH:30][C:29]([CH3:34])=[C:28]2[CH2:35][C:36]([OH:38])=O.[O:39]=[O+][O-].CC[N:44]([CH:48]([CH3:50])C)[CH:45](C)C.CN(C(ON1N=N[C:61]2[CH:62]=[CH:63][CH:64]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:75][O:76]NC.Cl>CN(C=O)C>[CH3:75][O:76][N:44]([CH3:45])[C:48](=[O:39])[CH2:50][CH2:13][CH2:14][CH2:15][CH2:16][C@H:17]([NH:19][C:36](=[O:38])[CH2:35][C:28]1[C:27]2[C:31](=[CH:32][CH:33]=[C:25]([O:24][CH3:23])[CH:26]=2)[NH:30][C:29]=1[CH3:34])[C:4]1[NH:5][C:6]([C:7]2[CH:8]=[CH:61][CH:62]=[CH:63][CH:64]=2)=[CH:2][N:3]=1

Komponenten

9

Edukt 7

HCID 24823OzoneHCID 757711-HydroxybenzotriazoleHCID 761515-Methoxy-2-methylindole-3-acetic acidHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Produkt 1

HCID 87331719(7s)-n-Methoxy-7-{[(5-methoxy-2-methyl-1h-indol-3-yl)acetyl]amino}-n-methyl-7-(5-phenyl-1h-imidazol-2-yl)heptanamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

A solution of EDC.HCl (1.2 eq.), HOBt (1.2 eq.) and (5-methoxy-2-methyl-1H-indol-3-yl)acetic acid (1.2 eq.) in DMF was stirred for 1 hr at RT and was then added to a solution of the amine (QQ2) (1 eq.) and DIPEA (2 eq.) in DMF. The mixture was stirred overnight then more HATU (2 eq.) was added followed after 1 h by CH3ON(CH3)H.HCl (2 eq.). After stirring for a further 12 hours the crude was purified by preparative RP-HPLC, using H2O (0.1% TFA) and MeCN (+0.1% TFA) as eluents (column: C18). The desired fractions were lyophilized to afford the titled compound as a white solid. The compound was then extracted from sat. aq. NaHCO3 solution to obtain the free base. 1H NMR (400 MHz, DMSO-d6) δ: 10.62 (1H, s), 8.62 (1H, d, J=6.3 Hz), 8.03 (1H, s), 7.77 (2H, d, J=7.6 Hz), 7.52 (2H, t, J=7.6 Hz), 7.48-7.39 (1H, m), 7.10 (1H, d, J=8.6 Hz), 6.96 (1H, s), 6.64-6.56 (2H, m), 5.06-4.96 (1H, m), 3.69 (3H, s), 3.62 (3H, s), 3.60-3.45 (2H, m), 3.06 (3H, s), 2.35-2.26 (2H, m), 2.36-2.26 (5H, m), 1.50-1.18 (6H, m). MS (ES) C30H37N5O4 requires: 531, found: 532 (M+H)+.

Aufarbeitung

  1. stirringAfter stirring for a further 12 hours the crude
  2. customwas purified by preparative RP-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-15c17959f69b4ffea81f9436f9c7522a
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07863294B2

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