Diisopropylethylamine → 3-((2-(3-Chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)dimethylammonio)-propane-1-sulfonate

HRID 83828Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 83828
[NH2:1][CH2:2][CH2:3][N+:4]([CH3:13])([CH3:12])[CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:10])=[O:9].[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([F:50])[C:23]=1[CH2:24][S:25][C:26]1[N:27]([C:43]2[CH:48]=[CH:47][C:46]([F:49])=[CH:45][CH:44]=2)[C:28]([C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([O:41][CH3:42])[CH:35]=2)([CH3:33])[CH3:32])=[CH:29][N:30]=1)[C:18](O)=[O:19].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Cl:14][C:15]1[CH:16]=[C:17]([CH:21]=[C:22]([F:50])[C:23]=1[CH2:24][S:25][C:26]1[N:27]([C:43]2[CH:44]=[CH:45][C:46]([F:49])=[CH:47][CH:48]=2)[C:28]([C:31]([C:34]2[CH:39]=[CH:38][C:37]([Cl:40])=[C:36]([O:41][CH3:42])[CH:35]=2)([CH3:33])[CH3:32])=[CH:29][N:30]=1)[C:18]([NH:1][CH2:2][CH2:3][N+:4]([CH3:12])([CH3:13])[CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:9])=[O:10])=[O:19]

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 56969970HCID 56969970, VerbindungHCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid

Produkt 1

HCID 532523893-((2-(3-Chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzamido)ethyl)dimethylammonio)-propane-1-sulfonateAusbeute 63,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of tert-butyl 2-(dimethylamino)ethylcarbamate (1.8 g, 7.98 mmol) and 1,3-sultone (1.07 g, 8.77 mmol) in toluene was heated 4 h at 60° C. to form a white solid. After cooling to room temperature, the solids were collected by filtration and rinsed with hexanes (2×30 mL). The solids were dissolved in DCM (5 mL) and charged dropwise with TFA (5 mL). After 30 min, the reaction mixture was concentrated under reduced pressure to yield 3-((2-aminoethyl)-dimethylammonio)propane-1-sulfonate as a white solid (2.15 g). This quartarnary amine (82 mg, 0.266 mmol) was added to a solution of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)-propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (100 mg, 0.1776 mmol) in DMF (1 mL) followed by DIPEA (137 mg, 1.06 mmol) and HATU (74.2 mg, 0.195 mmol). After 20 min, the reaction was determined to be complete by LC-MS. The product mixture was concentrated and purified by HPLC (MeCN/H2O, 10-99%) to yield the title compound as a white solid (85 mg). 1H NMR (400 MHz, MeOD) δ 8.96 (t, J=5.3 Hz, 1H), 7.88 (s, 1H), 7.79 (s, 1H), 7.60 (dd, J=10.0, 1.6 Hz, 1H), 7.28-7.18 (m, 1H), 6.98 (d, J=8.6 Hz, 1H), 6.95 (d, J=8.6 Hz, 1H) 6.57-6.52 (m, 2H), 6.51-6.45 (m, 2H), 4.18 (s, 2H), 3.89 (t, J=5.5 Hz, 2H), 3.75 (s, 3H), 3.68-3.56 (m, 4H), 3.23 (s, 6H), 2.87 (t, J=6.7 Hz, 2H), 2.25 (dt, J=14.2, 7.1 Hz, 2H), 1.60 (s, 6H). LC-MS: 655.3 [M]+.

Aufarbeitung

  1. concentrationThe product mixture was concentrated
  2. custompurified by HPLC (MeCN/H2O, 10-99%)

Quellen und Nachweise

ORD-Eintrag
ord-98a04988be164e5aa8d78ebde04ca9b9
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846739B2

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