Tri(N-succinimidyl) nitrilotriacetate → 2,2',2''-nitrilotris(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 45746Notes

Reaction equation

[N:1]([CH2:24][C:25]([O:27]N1C(=O)CCC1=O)=O)([CH2:13][C:14]([O:16]N1C(=O)CCC1=O)=O)[CH2:2][C:3]([O:5]N1C(=O)CCC1=O)=O.[NH2:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH:47][S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([CH:57]2[C:66]3[C:61](=[C:62]([Cl:68])[CH:63]=[C:64]([Cl:67])[CH:65]=3)[CH2:60][N:59]([CH3:69])[CH2:58]2)[CH:52]=1)(=[O:50])=[O:49]>>[N:1]([CH2:2][C:3]([NH:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH:47][S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([CH:57]2[C:66]3[C:61](=[C:62]([Cl:68])[CH:63]=[C:64]([Cl:67])[CH:65]=3)[CH2:60][N:59]([CH3:69])[CH2:58]2)[CH:52]=1)(=[O:50])=[O:49])=[O:5])([CH2:13][C:14]([NH:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH:47][S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([CH:57]2[C:66]3[C:61](=[C:62]([Cl:68])[CH:63]=[C:64]([Cl:67])[CH:65]=3)[CH2:60][N:59]([CH3:69])[CH2:58]2)[CH:52]=1)(=[O:50])=[O:49])=[O:16])[CH2:24][C:25]([NH:35][CH2:36][CH2:37][O:38][CH2:39][CH2:40][O:41][CH2:42][CH2:43][O:44][CH2:45][CH2:46][NH:47][S:48]([C:51]1[CH:56]=[CH:55][CH:54]=[C:53]([CH:57]2[C:66]3[C:61](=[C:62]([Cl:68])[CH:63]=[C:64]([Cl:67])[CH:65]=3)[CH2:60][N:59]([CH3:69])[CH2:58]2)[CH:52]=1)(=[O:50])=[O:49])=[O:27]

Participants

Reactant 2

HCID 4150925Tri(N-succinimidyl) nitrilotriacetate

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 866723612,2',2''-nitrilotris(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 11.6%

Procedure

Compound 213 was prepared following the procedure outlined in Example 168 using tris(2,5-dioxopyrrolidin-1-yl) 2,2′,2″-nitrilotriacetate (75 mg, 0.156 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, 254 mg, 0.467 mmol). Purification by preparative HPLC gave the title compound (32.0 mg) as the TFA salt. 1H-NMR (400 MHz, CD3OD): δ 7.88 (d, 3H), 7.75 (s, 3H), 7.63 (t, 3H), 7.54 (t, 6H), 6.82 (s, 3H), 4.84-4.75 (m, 6H), 4.48 (d, 3H), 3.86 (m, 3H), 3.85-3.37 (m, 54H), 3.14 (s, 9H), 3.02 (t, 6H). MS (m/z): 1777.07 [M+H]+.

Workup

customPurification by preparative HPLC

Sources & evidence

ORD record: ord-66f8c323a19d488aaffd6e8339bd4f7b
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541448B2

Reaction notes

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