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

HRID 45724

반응식

HRID 45724 반응식
[NH2:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][S:8]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([CH:17]2[C:26]3[C:21](=[C:22]([Cl:28])[CH:23]=[C:24]([Cl:27])[CH:25]=3)[CH2:20][N:19]([CH3:29])[CH2:18]2)[CH:12]=1)(=[O:10])=[O:9].[OH:30][CH:31]([CH:42]([OH:53])[C:43]([O:45]N1C(=O)CCC1=O)=O)[C:32]([O:34]N1C(=O)CCC1=O)=O.[CH2:54]([N:56]([CH2:59][CH3:60])[CH2:57][CH3:58])C>CN(C=O)C>[Cl:27][C:24]1[CH:25]=[C:26]2[C:21](=[C:22]([Cl:28])[CH:23]=1)[CH2:20][N:19]([CH3:29])[CH2:18][CH:17]2[C:13]1[CH:12]=[C:11]([S:8]([NH:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][NH:1][C:32](=[O:34])[CH:31]([OH:30])[CH:42]([OH:53])[C:43]([NH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][S:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([CH:58]3[C:26]4[C:60](=[C:22]([Cl:28])[CH:23]=[C:24]([Cl:27])[CH:25]=4)[CH2:59][N:56]([CH3:54])[CH2:57]3)[CH:12]=2)(=[O:10])=[O:9])=[O:45])(=[O:10])=[O:9])[CH:16]=[CH:15][CH:14]=1

참가 물질

5

반응물 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2회HCID 67460236N-(2-(2-aminoethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2회

생성물 1

HCID 86672346N1,N4-bis(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethyl)-2,3-dihydroxysuccinamide

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Into a 50-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-(2-aminoethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (intermediate 176.1) (60 mg, 0.13 mmol, 1.00 equiv) in DMF (3 mL), bis(2,5-dioxopyrrolidin-1-yl) 2,3-dihydroxybutanedioate (intermediate 168.1) (21 mg, 0.06 mmol, 0.47 equiv) and triethylamine (50 mg, 0.49 mmol, 3.77 equiv). The resulting solution was stirred overnight at room temperature at which time the mixture was concentrated under vacuum. The crude product was purified by Prep-HPLC with acetonitrile:water (0.05% CF3COOH) (10%-100%). This resulted in 21 mg (13%) of a TFA salt of N1,N4-bis(2-(2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)phenylsulfonamido)ethoxy)ethyl)-2,3-dihydroxysuccinamide as a white 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, 10H), 3.18 (s, 6H), 3.07 (t, J=5.4 Hz, 4H). MS (m/z): 517 [½M+1]+.

후처리

  1. customInto a 50-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationwas concentrated under vacuum
  4. customThe crude product was purified by Prep-HPLC with acetonitrile

출처 및 근거

ORD 기록
ord-cfcfd86f4ca8452487789d729b129fa2
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08541448B2

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