Water → HCID 89442647, 화합물

HRID 632725노트

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HRID 632725 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:20]=[C:19]([Cl:21])[C:18]([Cl:22])=[CH:17][C:16]=3[OH:23])[CH2:10][CH2:9]2)[C:3]=1[C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1.C(OC([N:38]1[CH2:41][CH:40](I)[CH2:39]1)=O)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C=O)C>[NH:38]1[CH2:41][CH:40]([O:23][C:16]2[CH:17]=[C:18]([Cl:22])[C:19]([Cl:21])=[CH:20][C:15]=2[CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:4]3[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=3[C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH2:9][CH2:10]2)[CH2:39]1

참가 물질

6

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 11000522Tert-butyl 3-iodoazetidine-1-carboxylateHCID 89442445HCID 89442445, 화합물

생성물 1

HCID 89442647HCID 89442647, 화합물수율 40.8%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
90 °C

실험 절차

A reaction mixture of 2-{4-[6-amino-5-(4-fluoro-phenyl)-pyrimidin-4-yl]-piperazin-1-ylmethyl}-4,5-dichloro-phenol (80.0 mg; 0.18 mmol; 1.00 eq.), 3-iodo-azetidine-1-carboxylic acid tert-butyl ester (60.6 mg; 0.21 mmol; 1.20 eq.) and cesium carbonate (116.2 mg; 0.36 mmol; 2.00 eq.) in DMF (1 ml) was stirred at 90° C. overnight. The reaction solution was poured to water and extracted with ethyl acetate, The separated organic layer was washed with brine, dried and concentrated, which was then dissolved in methanol (1 ml) followed by adding 4.0 M HCl in dioxane (2 ml) and stirred at RT overnight. The reaction mixture was concentrated and purified by Waters prep-HPLC (acidic condition) to yield the title compounds (37 mg, yield 33.6%). LC-MS: (M+1=504, obsd.=504/506).

후처리

  1. extractionextracted with ethyl acetate
  2. washThe separated organic layer was washed with brine
  3. customdried
  4. concentrationconcentrated
  5. dissolutionwhich was then dissolved in methanol (1 ml)
  6. additionby adding 4.0 M HCl in dioxane (2 ml)
  7. stirringstirred at RT overnight
  8. concentrationThe reaction mixture was concentrated
  9. custompurified by Waters prep-HPLC (acidic condition)

출처 및 근거

ORD 기록
ord-291fb5e366ba4ebab0cba7a5a334f975
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321760B2

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