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 1470162Notes

Reaction equation

HRID 1470162 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 [1/2M+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-2a515bca55124b6880d3e8774a685a14
Source dataset
uspto-grants-2015_04
Patent number
US09006281B2

Reaction notes

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