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

HRID 1470152

Reaction equation

HRID 1470152 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]2[C:32]3[C:27](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=3)[CH2:26][N:25]([CH2:35][CH3:36])[CH2:24]2)[CH:18]=1)(=[O:16])=[O:15].[OH:37][CH:38]([CH:49]([OH:60])[C:50]([O:52]N1C(=O)CCC1=O)=O)[C:39]([O:41]N1C(=O)CCC1=O)=O.[CH2:61]([N:63]([CH2:66][CH3:67])[CH2:64][CH3:65])[CH3:62]>CN(C=O)C>[Cl:33][C:30]1[CH:31]=[C:32]2[C:27](=[C:28]([Cl:34])[CH:29]=1)[CH2:26][N:25]([CH2:35][CH3:36])[CH2:24][CH:23]2[C:19]1[CH:18]=[C:17]([S:14]([NH:13][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:39](=[O:41])[CH:38]([OH:37])[CH:49]([OH:60])[C:50]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][NH:13][S:14]([C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:62]3[C:32]4[C:65](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=4)[CH2:64][N:63]([CH2:66][CH3:67])[CH2:61]3)[CH:18]=2)(=[O:16])=[O:15])=[O:52])(=[O:16])=[O:15])[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2×HCID 70872092N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

Product 1

HCID 46844150N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL 3-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (100 mg, 0.18 mmol, 1.00 equiv) in DMF (3 mL), bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxysuccinate (Intermediate 168.1) (25 mg, 0.07 mmol, 0.45 equiv) and triethylamine (75 mg, 4.50 equiv). The resulting solution was stirred overnight at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The crude product was purified by Flash-Prep-HPLC with water:methanol (1:10-1:100). This resulted in 12.1 mg (5%) of N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide as yellow oil. 1H-NMR (300 MHz, DMSO, ppm): δ 7.70-7.60 (m, 8H), 7.53-7.49 (m, 6H), 6.88 (s, 2H), 5.61-5.59 (m, 2H), 4.38 (m, 2H), 4.24-4.22 (m, 2H), 3.78-3.72 (m, 2H), 3.58-3.48 (m, 2H), 3.43 (m, 7H), 3.43-3.40 (m, 11H), 3.27-3.20 (m, 5H), 2.91-2.87 (m, 6H), 2.76-2.70 (m, 2H), 2.61-2.55 (m, 3H), 1.04-0.99 (m, 6H). MS (m/z): 1235 [M+H]+.

Workup

  1. customInto a 50-mL 3-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. customThe crude product was purified by Flash-Prep-HPLC with water:methanol (1:10-1:100)
  5. customThis resulted in 12.1 mg (5%) of N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-ethyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide as yellow oil

Sources & evidence

ORD record
ord-e9a8e14710c54b1c915fc976240c57a6
Source dataset
uspto-grants-2015_04
Patent number
US09006281B2

Linked notes

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