Triethylamine → N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide

HRID 45719

반응식

HRID 45719 반응식
[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].[OH:36][CH:37]([CH:48]([OH:59])[C:49]([O:51]N1C(=O)CCC1=O)=O)[C:38]([O:40]N1C(=O)CCC1=O)=O.[CH2:60]([N:62]([CH2:65][CH3:66])[CH2:63][CH3:64])C>CN(C=O)C>[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][C:38](=[O:40])[CH:37]([OH:36])[CH:48]([OH:59])[C:49]([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]2[CH:22]=[CH:21][CH:20]=[C:19]([CH:64]3[C:32]4[C:66](=[C:28]([Cl:34])[CH:29]=[C:30]([Cl:33])[CH:31]=4)[CH2:65][N:62]([CH3:60])[CH2:63]3)[CH:18]=2)(=[O:16])=[O:15])=[O:51])(=[O:16])=[O:15])[CH:22]=[CH:21][CH:20]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2회HCID 67458308N-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2회

생성물 1

HCID 46240063N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To 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) (1.2 g, 2.28 mmol, 1.00 equiv) in DMF (8 mL) was added bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxysuccinate (intermediate 168.1) (393 mg, 1.14 mmol, 0.50 equiv) and triethylamine (1.5 g, 14.82 mmol, 6.50 equiv) and the resulting solution was stirred overnight at room temperature. The mixture was concentrated under vacuum and the crude product was purified by Flash-Prep-HPLC with the following conditions: Column, silica gel; mobile phase, methanol:water=1:9 increasing to methanol:water=9:1 within 30 min; Detector, UV 254 nm. This resulted in 591 mg (43%) of N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide as a light yellow 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, 30H), 3.18 (s, 6H), 3.07 (t, J=5.4 Hz, 4H). MS (m/z): 603 [½M+H]+.

후처리

  1. concentrationThe mixture was concentrated under vacuum
  2. customthe crude product was purified by Flash-Prep-HPLC with the following conditions
  3. waitmobile phase, methanol:water=1:9 increasing to methanol:water=9:1 within 30 min
  4. customThis resulted in 591 mg (43%) of N1,N4-bis(2-(2-(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethoxy)ethoxy)ethyl)-2,3-dihydroxysuccinamide as a light yellow solid

출처 및 근거

ORD 기록
ord-6d1b9710a5a94f9d9d7d083e4cbd5ed4
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541448B2

연결된 노트

불러오는 중…