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 45751

반응식

HRID 45751 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].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

참가 물질

5

반응물 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)benzenesulfonamide2회

생성물 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-disulfonamide수율 28%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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]+.

후처리

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

출처 및 근거

ORD 기록
ord-7235bef144b94468bb9b6372aeefaaf5
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541448B2

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