Triethylamine → 2,2'-oxybis(N-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)acetamide)

HRID 1470180

Reaktionsgleichung

Reaktionsgleichung von HRID 1470180
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]2[C:29]3[C:24](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=3)[CH2:23][N:22]([CH3:32])[CH2:21]2)[CH:15]=1)(=[O:13])=[O:12].[CH2:33]([N:35]([CH2:38][CH3:39])[CH2:36][CH3:37])C.[O:40]([CH2:52][C:53]([O:55]N1C(=O)CCC1=O)=O)[CH2:41][C:42]([O:44]N1C(=O)CCC1=O)=O>CN(C=O)C>[O:40]([CH2:41][C:42]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:37]2[C:29]3[C:39](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=3)[CH2:38][N:35]([CH3:33])[CH2:36]2)[CH:15]=1)(=[O:13])=[O:12])=[O:44])[CH2:52][C:53]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][NH:10][S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]2[C:29]3[C:24](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=3)[CH2:23][N:22]([CH3:32])[CH2:21]2)[CH:15]=1)(=[O:13])=[O:12])=[O:55]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 51340992Bis(2,5-dioxopyrrolidin-1-yl) 2,2'-oxydiacetate2×HCID 67458027N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

Produkt 1

HCID 866723552,2'-oxybis(N-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)acetamide)Ausbeute 27 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (150 mg, 0.30 mmol) in DMF (2 mL) was added triethylamine (60 mg, 0.59 mmol) and bis(2,5-dioxopyrrolidin-1-yl) 2,2′-oxydiacetate (intermediate 178.1) (49 mg, 0.15 mmol) and the resulting solution was stirred overnight. After removal of the solvent, the crude product (150 mg) was purified by Flash-Prep-HPLC (C18 silica gel; methanol/water=0.05/100 increasing to methanol/water=90/100 within 25 min) to give 44.4 mg (27%) of the title compound as a TFA salt. 1H-NMR (300 MHz, CD3CD, ppm): 7.79˜7.76 (m, 2H), 7.70 (s, 2H), 7.57-7.50 (m, 4H), 7.36 (d, J=Hz, 2H), 4.89-4.41 (m, 2H), 4.06 (m, 4H), 3.81-3.62 (m, 5H), 3.59-3.42 (m, 11H), 3.33-3.31 (m, 8H), 3.07-3.01 (m, 6H), 2.71-2.64 (m, 2H), 2.48 (s, 6H). LCMS (ES, m/z): 1103[M+H]+.

Aufarbeitung

  1. customAfter removal of the solvent
  2. customthe crude product (150 mg) was purified by Flash-Prep-HPLC (C18 silica gel

Quellen und Nachweise

ORD-Eintrag
ord-f72bc56e61d94ca4aecb732f3705b943
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09006281B2

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