Potassium Phosphate, Tribasic → [1-(2-{5-[6-(4-{2-[1-(2 S)-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester

HRID 72008Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 72008
[CH3:1][O:2][C:3](=[O:47])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[NH:38][C:39]([CH:42]6[CH2:46][CH2:45][CH2:44][NH:43]6)=[N:40][CH:41]=5)=[CH:33][CH:32]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[CH3:48][O:49][C:50]([NH:52][C@@H:53]([C:57]1[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1)[C:54](O)=[O:55])=[O:51].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:47])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[NH:17][C:18]([C:21]2[CH:30]=[CH:29][C:28]3[C:23](=[CH:24][CH:25]=[C:26]([C:31]4[CH:36]=[CH:35][C:34]([C:37]5[NH:38][C:39]([C@@H:42]6[CH2:46][CH2:45][CH2:44][N:43]6[C:54](=[O:55])[CH:53]([NH:52][C:50]([O:49][CH3:48])=[O:51])[C:57]6[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=6)=[N:40][CH:41]=5)=[CH:33][CH:32]=4)[CH:27]=3)[CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

Komponenten

6

Edukt 4

HCID 62657Potassium Phosphate, TribasicHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 14264559(s)-2-((Methoxycarbonyl)amino)-2-phenylacetic acidHCID 66620477{2-Methyl-1-[2-(5-{6-[4-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester

Produkt 1

HCID 66620205[1-(2-{5-[6-(4-{2-[1-(2 S)-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl esterAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

To a slurry of {2-Methyl-1-[2-(5-{6-[4-(2-pyrrolidin-2-yl-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carbonyl]-propyl}-carbamic acid methyl ester (0.045 g, 0.06 mmol) and (5)-methoxycarbonylamino-phenyl-acetic acid (0.02 g, 0.09 mmol, 1.5 equiv.) in CH2Cl2 (0.6 mL) was added HATU (0.03 g, 0.08, 1.25 equiv.) and K3PO4 (0.05 g, 0.22 mmol, 3 equiv.). The reaction mixture was stirred at room temperature for 18 hours and diluted with CH2Cl2. The salts were filtered and the filtrate was concentrated. The crude oil was purified by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% formic acid)) and lyophilized to provide [1-(2-{5-[6-(4-{2-[1-(2S)-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-phenyl)-naphthalen-2-yl]-1H-imidazol-2-yl}-pyrrolidine-1-carbonyl)-2-methyl-propyl]-carbamic acid methyl ester (0.03 g, 65%) as a white powder. LCMS-ESI+: calc'd for C47H50N8O6: 822.4 (M+). Found: 823.5 (M+H+). 1H-NMR: 400 MHz, (CDCl3) δ: (Mixture of rotomers) 7.64-8.03 (m, 9H), 7.20-7.40 (m, 6H), 7.17 (s, 2H), 6.14 (m, 1H), 5.53 (dd, 2H), 5.25-5.33 (m, 2H), 4.33 (t, 1H), 3.85 (m, 1H), 3.73 (m, 1H), 3.68 (s, 3H), 3.66 (s, 3H), 3.27 (m, 1H), 2.86-2.96 (m, 3H), 2.35 (m, 1H), 1.94-2.23 (m, 6H), 0.87-0.90 (m, 6H).

Aufarbeitung

  1. filtrationThe salts were filtered
  2. concentrationthe filtrate was concentrated
  3. customThe crude oil was purified by preparative HPLC (Gemini, 15→40% MeCN in H2O (0.1% formic acid))

Quellen und Nachweise

ORD-Eintrag
ord-1004f03a67a44821985a34fb90f3e4a0
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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