Potassium Phosphate, Tribasic → 8-((Tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[f][1,7]naphthyridin-5-amine

HRID 2167638노트

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HRID 2167638 반응식
Cl[C:2]1[C:3]([C:19]#[N:20])=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=2[CH3:18])[CH:7]=1.[Si:21]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][C:33](B2OC(C)(C)C(C)(C)O2)=[C:34]([NH:36]C(=O)OC(C)(C)C)[CH:35]=1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C(O)CCC>[Si:21]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][C:33]2=[C:2]3[C:3](=[C:19]([NH2:20])[N:36]=[C:34]2[CH:35]=1)[N:4]=[CH:5][C:6]([C:8]#[C:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][C:11]=1[CH3:18])=[CH:7]3)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22]

참가 물질

8

반응물 4

HCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 581665223-Chloro-5-[2-(4-methoxy-2-methylphenyl)ethynyl]-2-pyridinecarbonitrileHCID 66890509Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate

생성물 1

HCID 670655328-((Tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[f][1,7]naphthyridin-5-amine

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 2631-Butanol용매HCID 962Water용매

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온도
100 °C

실험 절차

To a round bottom flask with refluxing condenser were added 3-chloro-5-((4-methoxy-2-methylphenyl)ethynyl)picolinonitrile (from the step 3) (1 equiv.), tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from step 2) (1.25 equiv.), K3PO4 (2 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.05 equiv.), and 2-Dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (0.1 equiv.). n-Butanol and water (5:2, 0.2 M) were added, and the content were degassed (vacuum followed by nitrogen flush) for three times. The reaction mixture was stirred vigorously under nitrogen at 100° C. overnight in an oil bath. The contents were cooled down and were taken up in water followed by extraction with methylene chloride. Combined organic layers were dried (Na2SO4) and concentrated. Flash chromatography (silica gel, 0-50% EtOAc in CH2Cl2) afforded 8-((tert-butyldimethylsilyloxy)methyl)-2-((4-methoxy-2-methylphenyl)ethynyl)benzo[f][1,7]naphthyridin-5-amine as a solid.

후처리

  1. temperatureTo a round bottom flask with refluxing condenser
  2. customthe content were degassed
  3. custom(vacuum followed by nitrogen flush) for three times
  4. temperatureThe contents were cooled down
  5. extractionfollowed by extraction with methylene chloride
  6. dry with materialCombined organic layers were dried (Na2SO4)
  7. concentrationconcentrated

출처 및 근거

ORD 기록
ord-858c35fa3ada4ddda326d08076cd0e21
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045470B2

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