Cesium carbonate → 1-(2-(2-(2-((1H-Pyrazol-4-yl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

HRID 592435노트

반응식

HRID 592435 반응식
Cl[C:2]1[N:7]=[C:6]([CH2:8][CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]2([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]2)[C:5]([CH3:22])=[CH:4][N:3]=1.[NH2:23][C:24]1[CH:25]=[N:26][N:27](C(OC(C)(C)C)=O)[CH:28]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH:26]1[CH:25]=[C:24]([NH:23][C:2]2[N:7]=[C:6]([CH2:8][CH2:9][C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:16]3([C:19]([NH2:21])=[O:20])[CH2:18][CH2:17]3)[C:5]([CH3:22])=[CH:4][N:3]=2)[CH:28]=[N:27]1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 59587648tert-butyl 4-amino-1H-pyrazole-1-carboxylateHCID 867123151-(2-(2-(2-Chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide

생성물 1

HCID 732949421-(2-(2-(2-((1H-Pyrazol-4-yl)amino)-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide수율 12%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
120 °C

실험 절차

A mixture of 1-(2-(2-(2-chloro-5-methylpyrimidin-4-yl)ethyl)phenyl)cyclopropanecarboxamide A40 (0.147 g, 0.465 mmol), tert-butyl 4-amino-1H-pyrazole-1-carboxylate (0.102 g, 0.559 mmol), Cs2CO3 (0.455 g, 1.40 mmol), Xantphos (0.011 g, 0.019 mmol) and Pd(OAc)2 (0.002 g, 0.009 mmol) in 1,4-dioxane (5 mL) was bubbled with N2 for 10 minutes before being heated in the microwave for 20 minutes at 120° C. The reaction mixture was cooled to room temperature, adsorbed onto silica, and purified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 20-100% EtOAc in petroleum benzine 40-60° C., then 0-20% MeOH in EtOAc) to give a white solid. This solid was taken up in DCM and precipitated by the addition of cyclohexane. The suspension was sonicated for 10 minutes and the precipitate was isolated by vacuum filtration and washed with Et2O to give the title compound 46 as a white solid (0.021 g, 12%). LCMS-D: rt 2.98 min; m/z 363 [M+H]+.

후처리

  1. customwas bubbled with N2 for 10 minutes
  2. temperatureThe reaction mixture was cooled to room temperature
  3. custompurified by column chromatography (Biotage Isolera, 24 g SiO2 cartridge, 20-100% EtOAc in petroleum benzine 40-60° C.
  4. custom0-20% MeOH in EtOAc) to give a white solid
  5. customprecipitated by the addition of cyclohexane
  6. customThe suspension was sonicated for 10 minutes
  7. customthe precipitate was isolated by vacuum filtration
  8. washwashed with Et2O

출처 및 근거

ORD 기록
ord-35d76a79639b4e5b8524836945cef21f
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09238644B2

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