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 927274노트

반응식

HRID 927274 반응식
[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

참가 물질

12

반응물 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

생성물 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

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6344Dichloromethane용매2회

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-65c9e10c44ea49368ee1304cc561b6e5
출처 데이터셋
uspto-grants-2016_03
특허 번호
US09290454B2

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