Diisopropylethylamine → N1,N3-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)benzene-1,3-disulfonamide

HRID 1470189Notes

Reaction equation

HRID 1470189 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].C[CH2:37][N:38]([CH:42]([CH3:44])C)[CH:39]([CH3:41])C.[C:45]1([S:55](Cl)(=[O:57])=[O:56])[CH:50]=[CH:49][CH:48]=[C:47]([S:51](Cl)(=[O:53])=[O:52])[CH:46]=1>C(Cl)Cl>[Cl:33][C:30]1[CH:31]=[C:32]2[C:27](=[C:28]([Cl:34])[CH:29]=1)[CH2:26][N:25]([CH3:35])[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][S:55]([C:45]2[CH:50]=[CH:49][CH:48]=[C:47]([S:51]([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]3[CH:22]=[CH:21][CH:20]=[C:19]([CH:44]4[C:32]5[C:41](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=5)[CH2:39][N:38]([CH3:37])[CH2:42]4)[CH:18]=3)(=[O:16])=[O:15])(=[O:53])=[O:52])[CH:46]=2)(=[O:57])=[O:56])(=[O:16])=[O:15])[CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 962401,3-Benzenedisulfonyl dichlorideHCID 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 86672364N1,N3-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)benzene-1,3-disulfonamideYield 28%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To 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, 50 mg, 0.0917 mmol) and DIEA (35.5 mg, 0.275 mmol) in dry DCM (0.183 mL) under N2 was added benzene-1,3-disulfonyl dichloride (12.7 mg, 0.0459 mmol) in DCM (0.183 mL). The reaction mixture was stirred at room temperature for 60 minutes at which point LCMS indicated complete conversion. The solvent was removed and the resulting residue brought up in 4 mL ACN/H2O solution (1:1). Filtration and purification by preparative HPLC gave the title compound (16.6 mg) as a TFA salt. 1H-NMR (400 MHz, CD3OD): δ 8.28 (s, 1H), 8.06 (d, 1H), 7.85 (d, 2H), 7.75 (d, 2H), 7.70 (s, 1H), 7.63 (t, 2H), 7.53 (m, 3H), 6.82 (s, 1H), 4.52 (d, 1H), 3.85 (d, 1H), 3.61-3.46 (m, 28H), 3.13 (s, 6H), 3.09-3.03 (m, 7H). MS (m/z): 1294.99 [M+H]+.

Workup

  1. customThe solvent was removed
  2. filtrationFiltration and purification by preparative HPLC

Sources & evidence

ORD record
ord-5682983d697c4b1381867e81e99e7bb0
Source dataset
uspto-grants-2015_04
Patent number
US09006281B2

Reaction notes

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