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

HRID 870223Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 870223
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([CH:22]2[C:31]3[C:26](=[C:27]([Cl:33])[CH:28]=[C:29]([Cl:32])[CH:30]=3)[CH2:25][N:24]([CH3:34])[CH2:23]2)[CH:17]=1)=[O:14].[OH:35][C@H:36]([C@@H:47]([OH:58])[C:48]([O:50]N1C(=O)CCC1=O)=O)[C:37]([O:39]N1C(=O)CCC1=O)=O.[CH2:59]([N:61]([CH2:64][CH3:65])[CH2:62][CH3:63])C>CN(C=O)C>[Cl:32][C:29]1[CH:30]=[C:31]2[C:26](=[C:27]([Cl:33])[CH:28]=1)[CH2:25][N:24]([CH3:34])[CH2:23][CH:22]2[C:18]1[CH:17]=[C:16]([NH:15][C:13](=[O:14])[CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:37](=[O:39])[C@H:36]([OH:35])[C@@H:47]([OH:58])[C:48]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13](=[O:14])[NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([CH:63]3[C:31]4[C:65](=[C:27]([Cl:33])[CH:28]=[C:29]([Cl:32])[CH:30]=4)[CH2:64][N:61]([CH3:59])[CH2:62]3)[CH:17]=2)=[O:50])[CH:21]=[CH:20][CH:19]=1

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 124912Disuccinimidyl tartarateHCID 708720803-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)-N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)propanamide2×

Produkt 1

HCID 86699383(2R,3R)-N1,N4-bis(2-(2-(2-(3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamino)-3-oxopropoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamideAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
35 °C

Versuchsvorschrift

To 3-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)-N-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenyl)propanamide (intermediate 179.7) (270 mg, 0.53 mmol, 2.00 equiv) in anhydrous DMF (5.0 mL) was added (2R,3R)-bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxysuccinate (prepared from (2R,3R)-tartaric acid as described in example 168) (91.0 mg, 0.26 mmol, 1.00 equiv) and triethylamine (0.3 mL) and the resulting solution was stirred for 2 h at 35° C. The resulting mixture was then concentrated under vacuum. The residue was purified by Prep-HPLC, to give 170 mg (56%) of a TFA salt of (2R,3R)—N1,N4-bis(2-(2-(2-(3-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylamino)-3-oxopropoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide as an off-white solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.92 (s, 1H), 7.65 (s, 2H), 7.54 (d, J=1.5 Hz, 2H), 7.36-7.46 (m, 4H), 7.02 (dd, J=7.5, 1.2 Hz, 2H), 6.90 (s, 2H), 4.83-4.75 (m, 2H), 4.65-4.60 (m, 2H), 4.53 (s, 1H), 4.46 (m, 3H), 3.88-3.80 (m, 6H), 3.64-3.51 (m, 22H), 3.41-3.35 (m, 4H), 3.16 (s, 6H), 2.64 (t, J=6.0 Hz, 4H). MS (m/z): 1136 [M+H]+.

Aufarbeitung

  1. concentrationThe resulting mixture was then concentrated under vacuum
  2. customThe residue was purified by Prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-4c0ec49726d6439a8aa55f18827e0672
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08969377B2

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