Diisopropylethylamine → di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate

HRID 2105020노트

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HRID 2105020 반응식
[Br:1][C:2]1[N:3]=[C:4]([CH:26](Cl)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.CCN(C(C)C)C(C)C.[NH2:48][C:49]1[CH:50]=[C:51]2[C:56](=[CH:57][CH:58]=1)[C:55]([N:59]([C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])=[N:54][CH:53]=[CH:52]2>CC#N.C(Cl)Cl.CCOC(C)=O>[Br:1][C:2]1[N:3]=[C:4]([CH:26]([NH:48][C:49]2[CH:50]=[C:51]3[C:56](=[CH:57][CH:58]=2)[C:55]([N:59]([C:60]([O:62][C:63]([CH3:66])([CH3:65])[CH3:64])=[O:61])[C:67]([O:69][C:70]([CH3:71])([CH3:72])[CH3:73])=[O:68])=[N:54][CH:53]=[CH:52]3)[C:27]2[CH:32]=[C:31]([CH2:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=2[F:37])[N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1

참가 물질

7

반응물 3

HCID 81531DiisopropylethylamineHCID 58717298tert-butyl N-(6-aminoisoquinolin-1-yl)-N-[(tert-butoxy)carbonyl]carbamateHCID 688168844-bromo-2-(chloro(5-ethyl-2-fluoro-3-methoxyphenyl)methyl)-1-trityl-1H-imidazole

생성물 1

HCID 86607941di-tert-butyl (6-{[(4-bromo-1-trityl-1H-imidazol-2-yl)(5-ethyl-2-fluoro-3-methoxyphenyl)methyl]amino}isoquinolin-1-yl)imidodicarbonate수율 78.4%

시약·촉매·용매 3

HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

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온도
40 °C

실험 절차

To a solution of the chloro intermediate (350 mg, 0.594 mmol) in 5 mL CH3CN and 2 mL CH2Cl2 at rt, was added DIEA (0.207 mL, 1.19 mmol), di-tert-butyl (6-aminoisoquinolin-1-yl)imidodicarbonate (235 mg, 0.653 mmol). The mixture was stirred at rt for 18 h and at 40° C. for 3 h, then was diluted with EtOAc. The organic phase was washed with H2O and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient) to afford 425 mg of Intermediate 206.4 as a colorless residue.

후처리

  1. washThe organic phase was washed with H2O and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (0 to 60% EtOAc/hexanes gradient)

출처 및 근거

ORD 기록
ord-ccd74af2b5864045b4ebd8df98b32efb
출처 데이터셋
uspto-grants-2009_08
특허 번호
US07576098B2

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