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

HRID 45708

Reaction equation

HRID 45708 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].[OH:33][CH:34]([CH:45]([OH:56])[C:46]([O:48]N1C(=O)CCC1=O)=O)[C:35]([O:37]N1C(=O)CCC1=O)=O.[CH2:57]([N:59]([CH2:62][CH3:63])[CH2:60][CH3:61])C>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:35](=[O:37])[CH:34]([OH:33])[CH:45]([OH:56])[C:46]([NH:1][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:61]3[C:29]4[C:63](=[C:25]([Cl:31])[CH:26]=[C:27]([Cl:30])[CH:28]=4)[CH2:62][N:59]([CH3:57])[CH2:60]3)[CH:15]=2)(=[O:13])=[O:12])=[O:48])(=[O:13])=[O:12])[CH:19]=[CH:18][CH:17]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrateHCID 67458027N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide

Product 1

HCID 86672357N1,N4-bis(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask was placed a solution of N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (300 mg, 0.60 mmol, 1.00 equiv) in DMF (5 mL), bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxysuccinate (92.5 mg, 0.27 mmol, 0.45 equiv) and triethylamine (TEA; 1.0 g, 9.88 mmol, 16.55 equiv). The resulting solution was stirred overnight at room temperature and then concentrated under vacuum. The crude product (300 mg) 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 (20% CH3CN up to 40% in 5 min, up to 100% in 2 min); Detector, uv 220&254 nm. This resulted in 192.4 mg (28%) of a TFA salt of the title compound as a white solid. 1H-NMR (300 MHz, DMSO, ppm) δ 7.92 (d, J=7.8 Hz, 2H), 7.82 (m, 2H), 7.67 (t, J=7.8 Hz, 2H), 7.57 (m, 2H), 7.55 (d, J=6.9 Hz, 2H), 6.86 (m, 2H), 4.84 (s, 2H), 4.79 (s, 2H), 4.54 (d, 2H), 4.48 (s, 2H), 3.92 (m, 2H), 3.53 (m, 22H), 3.18 (s, 6H), 3.07 (t, J=5.4 Hz, 4H). MS (m/z): 1119 [M+H]+.

Workup

  1. customInto a 50-mL round-bottom flask was placed
  2. concentrationconcentrated under vacuum
  3. customThe crude product (300 mg) was purified by Prep-HPLC with the following conditions
  4. waitmobile phase, Water with 0.05% TFA and CH3CN (20% CH3CN up to 40% in 5 min
  5. waitup to 100% in 2 min)

Sources & evidence

ORD record
ord-b1273d715c564a00a80f3ca83c102e68
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Linked notes

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