Triethylamine → N1,N4-bis(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethyl)-2,3-dihydroxysuccinamide

HRID 45710

Reaktionsgleichung

Reaktionsgleichung von HRID 45710
[NH2:1][CH2:2][CH2:3][NH:4][S:5]([C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]2[C:23]3[C:18](=[C:19]([Cl:25])[CH:20]=[C:21]([Cl:24])[CH:22]=3)[CH2:17][N:16]([CH3:26])[CH2:15]2)[CH:9]=1)(=[O:7])=[O:6].[OH:27][CH:28]([CH:39]([OH:50])[C:40]([O:42]N1C(=O)CCC1=O)=O)[C:29]([O:31]N1C(=O)CCC1=O)=O.[CH2:51]([N:53]([CH2:56][CH3:57])[CH2:54][CH3:55])C>CN(C=O)C>[Cl:24][C:21]1[CH:22]=[C:23]2[C:18](=[C:19]([Cl:25])[CH:20]=1)[CH2:17][N:16]([CH3:26])[CH2:15][CH:14]2[C:10]1[CH:9]=[C:8]([S:5]([NH:4][CH2:3][CH2:2][NH:1][C:29](=[O:31])[CH:28]([OH:27])[CH:39]([OH:50])[C:40]([NH:1][CH2:2][CH2:3][NH:4][S:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH:55]3[C:23]4[C:57](=[C:19]([Cl:25])[CH:20]=[C:21]([Cl:24])[CH:22]=4)[CH2:56][N:53]([CH3:51])[CH2:54]3)[CH:9]=2)(=[O:6])=[O:7])=[O:42])(=[O:7])=[O:6])[CH:13]=[CH:12][CH:11]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2×HCID 67457253N-(2-aminoethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

Produkt 1

HCID 46843103N1,N4-bis(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethyl)-2,3-dihydroxysuccinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-aminoethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (250 mg, 0.60 mmol, 1.00 equiv) in DMF (5 mL), bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxysuccinate (Intermediate 168.1) (92 mg, 0.27 mmol, 0.44 equiv) and triethylamine (280 mg, 2.77 mmol, 4.55 equiv) and the resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum, the residue diluted with 100 mL of ethyl acetate and then washed with 2×10 mL of water. The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product was purified by Prep-HPLC with the following conditions: Column, SunFire Prep C18, 5 um, 19*150 mm; mobile phase, Water with 0.05% TFA and CH3CN (25% CH3CN up to 35% in 5 min, up to 100% in 2.5 min); Detector, uv 220&254 nm. This resulted in 88.4 mg (15%) of a TFA salt of N1,N4-bis(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethyl)-2,3-dihydroxysuccinamide as a white solid. 1H-NMR (400 MHz, CD3OD, ppm) δ 7.67 (d, J=7.6 Hz, 2H), 7.61 (s, 2H), 7.44 (t, J=7.6 Hz, 2H), 7.37 (d, J=7.6 Hz, 2H), 7.25 (d, J=2 Hz, 2H), 6.72 (s, 2H), 4.33 (t, J=6.4 Hz, 2H), 4.30 (s, 2H), 3.64 (m, 4H), 3.21 (s, 4H), 2.98 (m, 2H), 2.90 (m, 4H), 2.65 (m, 2H), 2.42 (s, 6H). MS (m/z): 943 [M+H]+.

Aufarbeitung

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionthe residue diluted with 100 mL of ethyl acetate
  5. washwashed with 2×10 mL of water
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. concentrationconcentrated under vacuum
  8. customThe crude product was purified by Prep-HPLC with the following conditions
  9. waitmobile phase, Water with 0.05% TFA and CH3CN (25% CH3CN up to 35% in 5 min
  10. waitup to 100% in 2.5 min)

Quellen und Nachweise

ORD-Eintrag
ord-6464e404dd7e41859df57003cd4b6cc5
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541448B2

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