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ノート

反応式

HRID 45724 の反応式
[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

参加物

5

反応物 3

HCID 8471TriethylamineHCID 334527Disuccinimidyl tartrate2 回HCID 67460236N-(2-(2-aminoethoxy)ethyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide2 回

生成物 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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-cfcfd86f4ca8452487789d729b129fa2
出典データセット
uspto-grants-2013_09
特許番号
US08541448B2

反応ノート

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