Water → (R)-tert-butyl 5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

HRID 927274ノート

反応式

HRID 927274 の反応式
[C:1]([O:5][C:6](=[O:32])[CH2:7][CH2:8][CH2:9][CH2:10][C:11]1[N:12]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:13](=[O:24])[C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([C:21](O)=[O:22])=[CH:16][CH:15]=2)([CH3:4])([CH3:3])[CH3:2].[CH:33]1[CH:34]=[CH:35][C:36]2N(O)N=[N:39][C:37]=2[CH:38]=1.O.CCN=C=NCCCN(C)C.[CH3:55][CH2:56][N:57](C(C)C)[CH:58]([CH3:60])[CH3:59].[F:64]C1C=CC(N2CCN[C@H](C)C2)=CC=1.C[C@@H]1CNCCN1C(OC(C)(C)C)=O.FC1C=CC(I)=CC=1.C(O)(C(F)(F)F)=O>ClCCl.[Cu]I>[F:31][C:28]1[CH:29]=[CH:30][C:25]([N:12]2[C:11]([CH2:10][CH2:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:4])[CH3:2])=[O:32])=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:21]([N:57]4[CH2:56][CH2:55][N:39]([C:37]5[CH:38]=[CH:33][C:34]([F:64])=[CH:35][CH:36]=5)[CH2:59][C@H:58]4[CH3:60])=[O:22])[CH:18]=3)[C:13]2=[O:24])=[CH:26][CH:27]=1

参加物

12

反応物 9

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 96054-FluoroiodobenzeneHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 10262201tert-Butyl (2R)-2-methylpiperazine-1-carboxylateHCID 57435413(r)-1-(4-Fluorophenyl)-3-methylpiperazineHCID 900944973-(5-(Tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid

生成物 1

HCID 90094332(R)-tert-butyl 5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6344Dichloromethane溶媒2 回

実験手順

3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid (50 mg, 0.114 mmol)), HOBt.H2O (34.8, 0.228 mmol), EDCI (43.6 mg, 0.228 mmol), Hunig's base (44.1 mg, 0.341 mmol) and (R)-1-(4-fluorophenyl)-3-methylpiperazine (22.1 mg, 0.114 mmol, prepared from the coupling of (R)-tert-butyl 2-methylpiperazine-1-carboxylate and 1-fluoro-4-iodobenzene using CuI followed with deprotection with TFA) were mixed in dichloromethane (1 mL). The mixture was kept stirring at room temperature for 16 hours before it was diluted with dichloromethane (5 mL), washed with aqueous sodium hydrogen carbonate (saturated, 1×3 mL) and hydrochloric acid (0.5 M, 2 mL), dried (MgSO4) and filtered. The solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane=1:1 to give (R)-tert-butyl 5-(2-(4-fluorophenyl)-6-(4-(4-fluorophenyl)-2-methylpiperazine-1-carbonyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (58 mg, 0.094 mmol) as a yellow foam.

後処理

  1. washwashed with aqueous sodium hydrogen carbonate (saturated, 1×3 mL) and hydrochloric acid (0.5 M, 2 mL)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customThe solvent was evaporated under reduced pressure
  5. customThe residue was purified by column chromatography on silica gel
  6. washeluting with EtOAc/isohexane=1:1

出典と根拠

ORDレコード
ord-65c9e10c44ea49368ee1304cc561b6e5
出典データセット
uspto-grants-2016_03
特許番号
US09290454B2

反応ノート

読み込み中…