Diisopropylethylamine → 1-(2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)-4-aza-1-azoniabicyclo-[2.2.2]octane chloride hydrochloride

HRID 83827Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 83827
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)[C:5](O)=[O:6].[ClH:38].[Cl-].[NH2:40][CH2:41][CH2:42][N+:43]12[CH2:50][CH2:49][N:46]([CH2:47][CH2:48]1)[CH2:45][CH2:44]2.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=O)C>[ClH:1].[Cl-:38].[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)[C:5]([NH:40][CH2:41][CH2:42][N+:43]12[CH2:50][CH2:49][N:46]([CH2:45][CH2:44]1)[CH2:47][CH2:48]2)=[O:6]

Komponenten

6

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 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acidHCID 672347361-(2-Aminoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride hydrochloride

Produkt 1

HCID 867022211-(2-(3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)-4-aza-1-azoniabicyclo-[2.2.2]octane chloride hydrochlorideAusbeute 80,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a suspension of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (0.11 g, 0.19 mmol), 1-(2-aminoethyl)-4-aza-1-azoniabicyclo[2.2.2]octane chloride hydrochloride (0.066 g, 2.5 mmol), and HATU (0.088 g, 0.23 mmol) in DMF (0.7 mL) was added DIPEA (0.2 mL, 1.16 mmol). The reaction was stirred for 2 h and purified by HPLC (MeCN/H2O, 10-99%, 0.05% TFA modifier). The product fractions were concentrated and then dissolved in THF (2 mL) and 2N solution of HCl in ether (2 mL). The mixture was filtered to afford the title compound (59 mg) as a white solid. 1H-NMR (DMSO-d6, 400 MHz) δ 9.67 (s, 1H), 7.84 (s, 1H), 7.84-7.76 (m, 2H), 7.27 (d, J=8.2 Hz, 1H), 7.01-6.97 (m, 2H), 6.50-6.43 (m, 4H), 4.22 (s, 2H), 3.86-3.71 (m, 10H), 3.67 (s, 3H), 3.53-3.49 (m, 6H), 1.49 (s, 6H); MS (ES): 700 [M]+.

Aufarbeitung

  1. custompurified by HPLC (MeCN/H2O, 10-99%, 0.05% TFA modifier)
  2. concentrationThe product fractions were concentrated
  3. dissolutiondissolved in THF (2 mL)
  4. filtrationThe mixture was filtered

Quellen und Nachweise

ORD-Eintrag
ord-e6d6ec48b23b44bc8639a36d1c43f0e4
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846739B2

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