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

HRID 1470177Notes

Reaction equation

HRID 1470177 reaction equation
[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]=[C:41]1[CH2:45][CH2:44][C:43](=[O:46])[N:42]1[CH:47](CC([O-])=O)[C:48]([O-:50])=O>CN(C=O)C>[Cl:30][C:27]1[CH:28]=[C:29]2[C:24](=[C:25]([Cl:31])[CH:26]=1)[CH2:23][N:22]([CH3:32])[CH2:21][CH:20]2[C:16]1[CH:15]=[C:14]([S:11]([NH:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:41](=[O:40])[CH2:45][CH2:44][C:43]([NH:42][CH2:47][CH2:48][O:50][CH2:5][CH2:6][O:7][CH2:8][CH2:9][NH:10][S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([CH:37]3[C:29]4[C:39](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=4)[CH2:38][N:35]([CH3:33])[CH2:36]3)[CH:15]=2)(=[O:13])=[O:12])=[O:46])(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 17801052(2,5-Dioxopyrrolidin-1-yl)succinateHCID 67458027N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2×

Product 1

HCID 86672354N1,N4-bis(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)succinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (intermediate 168.2) (150 mg, 0.30 mmol, 1.00 equiv) in DMF (2 mL) was added triethylamine (60 mg, 0.59 mmol, 1.98 equiv) and intermediate 177.1 (47 mg, 0.15 mmol, 0.50 equiv) and the resulting solution was stirred overnight. The mixture was then concentrated under vacuum and the crude product (150 mg) was purified by Flash-Prep-HPLC with the following conditions: column, C18 silica gel; mobile phase, methanol/water=0.05/100 increasing to methanol/water=90/100 within 25 min; Detector, UV 254 nm. This resulted in 53.1 mg (33%) of N1,N4-bis(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)succinamide as a white solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.77-7.80 (m, 2H), 7.71 (s, 2H), 7.48-7.57 (m, 4H), 7.36-7.37 (m, 2H), 6.82 (s, 2H), 4.39-4.44 (m, 2H), 3.79 (d, J=15.9 Hz, 2H), 3.66 (d, J=16.2 Hz, 2H), 3.45-3.57 (m, 16H), 3.35-3.37 (m, 4H), 3.03-3.08 (m, 6H), 2.65-2.71 (m, 2H), 2.49-2.50 (m, 10H). MS (m/z): 1089 [M+H]+

Workup

  1. concentrationThe mixture was then concentrated under vacuum
  2. customthe crude product (150 mg) was purified by Flash-Prep-HPLC with the following conditions
  3. waitmobile phase, methanol/water=0.05/100 increasing to methanol/water=90/100 within 25 min
  4. customThis resulted in 53.1 mg (33%) of N1,N4-bis(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)succinamide as a white solid

Sources & evidence

ORD record
ord-c92699db55c246d287e8011813d072c8
Source dataset
uspto-grants-2015_04
Patent number
US09006281B2

Reaction notes

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