(1,1'-Biphenyl)-4,4'-disulfonyl dichloride → N4,N4'-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)-ethyl)biphenyl-4,4'-disulfonamide

HRID 870243Notes

Reaction equation

[C:1]1([C:11]2[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=2)[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[NH2:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][NH:33][S:34]([C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH:43]2[C:52]3[C:47](=[C:48]([Cl:54])[CH:49]=[C:50]([Cl:53])[CH:51]=3)[CH2:46][N:45]([CH3:55])[CH2:44]2)[CH:38]=1)(=[O:36])=[O:35]>>[Cl:53][C:50]1[CH:51]=[C:52]2[C:47](=[C:48]([Cl:54])[CH:49]=1)[CH2:46][N:45]([CH3:55])[CH2:44][CH:43]2[C:39]1[CH:38]=[C:37]([S:34]([NH:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:27][CH2:26][CH2:25][O:24][CH2:23][CH2:22][NH:21][S:7]([C:4]2[CH:5]=[CH:6][C:1]([C:11]3[CH:16]=[CH:15][C:14]([S:17]([NH:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][O:27][CH2:28][CH2:29][O:30][CH2:31][CH2:32][NH:33][S:34]([C:37]4[CH:42]=[CH:41][CH:40]=[C:39]([CH:43]5[C:52]6[C:47](=[C:48]([Cl:54])[CH:49]=[C:50]([Cl:53])[CH:51]=6)[CH2:46][N:45]([CH3:55])[CH2:44]5)[CH:38]=4)(=[O:36])=[O:35])(=[O:19])=[O:18])=[CH:13][CH:12]=3)=[CH:2][CH:3]=2)(=[O:9])=[O:8])(=[O:36])=[O:35])[CH:42]=[CH:41][CH:40]=1

Participants

Reactant 2

HCID 76950(1,1'-Biphenyl)-4,4'-disulfonyl dichloride

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 86672365N4,N4'-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)-ethyl)biphenyl-4,4'-disulfonamideYield 26.6%

Procedure

Compound 220 was prepared following the procedure outlined in Example 219 using biphenyl-4,4′-disulfonyl dichloride (16.1 mg, 0.0459 mmol) and 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). Purification by preparative HPLC gave the title compound (16.7 mg) as a TFA salt. 1H-NMR (400 MHz, CD3OD): δ 7.96 (d, 4H), 7.88-7.85 (m, 5H), 7.78 (s, 2H), 7.61 (t, 2H), 7.47 (d, 2H), 6.78 (s, 2H), 4.74-4.69 (m, 3H), 4.45 (d, 2H), 3.88-3.83 (m, 2H), 3.62-3.59 (m, 2H), 3.55-3.53 (m, 9H), 3.52-3.43 (m, 17H), 3.13 (s, 6H), 3.11-3.03 (m, 8H). MS (m/z): 1371.02 [M+H]+.

Workup

customCompound 220 was prepared
customPurification by preparative HPLC

Sources & evidence

ORD record: ord-43bb7c5d753648b286b36e337cbd9b90
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08969377B2

Reaction notes

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