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 1479442Notes

Reaction equation

HRID 1479442 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.C(O[N:48]1[C:52](=[O:53])[CH2:51][CH2:50][C:49]1=[O:54])(=O)CCC([O-])=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:49](=[O:54])[CH2:50][CH2:51][C:52]([NH:48][CH2:2][CH2:3][O:4][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:53])(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 67458027N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2×HCID 86672349(2,5-Dioxopyrrolidin-1-yl) succinate

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-074774b3bf0347aaa190a07710cb8bea
Source dataset
uspto-grants-2016_08
Patent number
US09408840B2

Reaction notes

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