Water → 4-(4-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 729621노트

반응식

HRID 729621 반응식
ClC(Cl)(Cl)CO[C:5](=[O:25])[NH:6][C:7]1[N:8]([C:18]2[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=2)[N:9]=[C:10]([C:12]([CH2:16][F:17])([CH3:15])[CH2:13][F:14])[CH:11]=1.CCN(C(C)C)C(C)C.[C:37]([O:41][C:42]([N:44]1[CH2:49][CH2:48][CH:47]([O:50][C:51]2[C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:54]([NH2:61])=[CH:53][N:52]=2)[CH2:46][CH2:45]1)=[O:43])([CH3:40])([CH3:39])[CH3:38].O>CS(C)=O>[C:37]([O:41][C:42]([N:44]1[CH2:45][CH2:46][CH:47]([O:50][C:51]2[C:60]3[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=3)[C:54]([NH:61][C:5]([NH:6][C:7]3[N:8]([C:18]4[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=4)[N:9]=[C:10]([C:12]([CH2:16][F:17])([CH3:15])[CH2:13][F:14])[CH:11]=3)=[O:25])=[CH:53][N:52]=2)[CH2:48][CH2:49]1)=[O:43])([CH3:40])([CH3:38])[CH3:39]

참가 물질

6

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 578328234-(4-Amino-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl esterHCID 68538054[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester

생성물 1

HCID 690593934-(4-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
85 °C

실험 절차

Add [5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-carbamic acid 2,2,2-trichloro-ethyl ester (Preparation 27, 2.7 mmol, 1.2 g) and DIPEA (2.9 mmol, 0.5 mL) to a solution of 4-(4-amino-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (Preparation 22, 2.9 mmol, 1.0 g) in 4 mL of DMSO and stir at 85° C. overnight. Cool down, add water and extract with dichloromethane. Combine the organic layers and wash with saturated aq. sodium chloride. Dry over sodium sulfate, filter, and concentrate under reduced pressure to give a residue. Subject residue to silica gel chromatography eluting with hexanes/ethyl acetate in gradient (from 15 to 70%) to yield 4-(4-{3-[5-(2-fluoro-1-fluoromethyl-1-methyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-ureido}-isoquinolin-1-yloxy)-piperidine-1-carboxylic acid tert-butyl ester. LCMS ES+ (m/z) 635 [M+H].

후처리

  1. temperatureCool down,
  2. extractionextract with dichloromethane
  3. washwash with saturated aq. sodium chloride
  4. dry with materialDry over sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate under reduced pressure
  7. customto give a residue
  8. washSubject residue to silica gel chromatography eluting with hexanes/ethyl acetate in gradient (from 15 to 70%)

출처 및 근거

ORD 기록
ord-59e9d4eb2ee742469451bf382e9aace8
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582638B2

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