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

HRID 45724

Reaction equation

HRID 45724 reaction equation
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]2[C:26]3[C:21](=[C:22]([Cl:28])[CH:23]=[C:24]([Cl:27])[CH:25]=3)[CH2:20][N:19]([CH3:29])[CH2:18]2)[CH:12]=1)(=[O:10])=[O:9].[OH:30][CH:31]([CH:42]([OH:53])[C:43]([O:45]N1C(=O)CCC1=O)=O)[C:32]([O:34]N1C(=O)CCC1=O)=O.[CH2:54]([N:56]([CH2:59][CH3:60])[CH2:57][CH3:58])C>CN(C=O)C>[Cl:27][C:24]1[CH:25]=[C:26]2[C:21](=[C:22]([Cl:28])[CH:23]=1)[CH2:20][N:19]([CH3:29])[CH2:18][CH:17]2[C:13]1[CH:12]=[C:11]([S:8]([NH:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:32](=[O:34])[CH:31]([OH:30])[CH:42]([OH:53])[C:43]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:58]3[C:26]4[C:60](=[C:22]([Cl:28])[CH:23]=[C:24]([Cl:27])[CH:25]=4)[CH2:59][N:56]([CH3:54])[CH2:57]3)[CH:12]=2)(=[O:10])=[O:9])=[O:45])(=[O:10])=[O:9])[CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2×HCID 67460236N-(2-(2-aminoethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2×

Product 1

HCID 86672346N1,N4-bis(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethyl)-2,3-dihydroxysuccinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-(2-aminoethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (intermediate 176.1) (60 mg, 0.13 mmol, 1.00 equiv) in DMF (3 mL), bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxybutanedioate (intermediate 168.1) (21 mg, 0.06 mmol, 0.47 equiv) and triethylamine (50 mg, 0.49 mmol, 3.77 equiv). The resulting solution was stirred overnight at room temperature at which time the mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with acetonitrile:water (0.05% CF3COOH) (10%-100%). This resulted in 21 mg (13%) of a TFA salt of N1,N4-bis(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethyl)-2,3-dihydroxysuccinamide as a white solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.92 (d, J=7.8 Hz, 2H), 7.81 (m, 2H), 7.67 (t, J=7.8 Hz, 2H), 7.57 (m, 2H), 7.55 (d, J=6.9 Hz, 2H), 6.85 (m, 2H), 4.78 (s, 2H), 4.77 (s, 2H), 4.54 (d, J=40.2 Hz, 2H), 4.48 (s, 2H), 3.92 (m, 2H), 3.53 (m, 10H), 3.18 (s, 6H), 3.07 (t, J=5.4 Hz, 4H). MS (m/z): 517 [½M+1]+.

Workup

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationwas concentrated under vacuum
  4. customThe crude product was purified by Prep-HPLC with acetonitrile

Sources & evidence

ORD record
ord-cfcfd86f4ca8452487789d729b129fa2
Source dataset
uspto-grants-2013_09
Patent number
US08541448B2

Linked notes

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