Triethylamine → 2,2'-oxybis(N-(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)

HRID 870228Notes

Reaction equation

HRID 870228 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]([CH3:35])[CH2:24]2)[CH:18]=1)(=[O:16])=[O:15].[CH2:36]([N:38]([CH2:41][CH3:42])[CH2:39][CH3:40])C.[O:43]([CH2:55][C:56]([O:58]N1C(=O)CCC1=O)=O)[CH2:44][C:45]([O:47]N1C(=O)CCC1=O)=O>CN(C=O)C>[O:43]([CH2:55][C:56]([NH:1][CH2:2][CH2:3][O:58][CH2:56][CH2:55][O:43][CH2:44][CH2:45][O:47][CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:40]2[C:32]3[C:42](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=3)[CH2:41][N:38]([CH3:36])[CH2:39]2)[CH:18]=1)(=[O:16])=[O:15])=[O:58])[CH2:44][C:45]([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]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]([CH3:35])[CH2:24]2)[CH:18]=1)(=[O:16])=[O:15])=[O:47]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 51340992Bis(2,5-dioxopyrrolidin-1-yl) 2,2'-oxydiacetate2×HCID 67458308N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2×

Product 1

HCID 866723532,2'-oxybis(N-(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)acetamide)Yield 86.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 50-mL round-bottom flask, was placed a solution of N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (compound 28) (150 mg, 0.28 mmol, 1.00 equiv) in DMF (5 mL), triethylamine (56 mg, 0.55 mmol, 2.01 equiv) and bis(2,5-dioxopyrrolidin-1-yl) 2,2′-oxydiacetate (intermediate 178.1) (44 mg, 0.14 mmol, 0.49 equiv). The resulting solution was stirred overnight at room temperature, at which time the mixture was concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC with the following conditions: Column, C18 silica gel; mobile phase, methanol/water=0.05/100 increasing to methanol/water=90/100 within 19 min; Detector, UV 254 nm. This resulted in 72.4 mg (44%) of the title compound as a white solid. 1H-NMR (300 MHz, CD3OD, ppm): δ 7.79 (d, J=7.2 Hz, 2H), 7.71 (s, 2H), 7.49˜7.58 (m, 4H), 7.36˜7.37 (m, 2H), 6.82 (s, 2H), 4.39˜4.44 (m, 2H), 4.06 (s, 4H), 3.80 (d, J=16.2 Hz, 2H), 3.65 (d, J=16.2 Hz, 2H), 3.55˜3.61 (m, 16H), 3.43˜3.52 (m, 12H), 3.02˜3.08 (m, 6H), 2.65˜2.70 (m, 2H), 2.49 (s, 6H). MS (m/z): 1190 [M+H]+

Workup

  1. customInto a 50-mL round-bottom flask, was placed
  2. concentrationwas concentrated under vacuum
  3. customThe crude product (150 mg) was purified by preparative HPLC with the following conditions
  4. waitmobile phase, methanol/water=0.05/100 increasing to methanol/water=90/100 within 19 min

Sources & evidence

ORD record
ord-47e2e84e06d648469fc5f7a2e22c7b2f
Source dataset
uspto-grants-2015_03
Patent number
US08969377B2

Reaction notes

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