Sodium Bicarbonate → Ethyl 3-(5-amino-2-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)-benzo[f][1,7]naphthyridin-8-yl)propanoate

HRID 2167666노트

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HRID 2167666 반응식
Cl[C:2]1[C:3]([C:21]#[N:22])=[N:4][CH:5]=[C:6]([C:8]#[C:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][O:18][CH3:19])=[CH:12][C:11]=2[CH3:20])[CH:7]=1.C(OC([NH:30]C1C=C(CCC(OCC)=O)C=CC=1B1OC(C)(C)C(C)(C)O1)=O)(C)(C)C.C1(P(C2CCCCC2)C2C=CC=[CH:62][C:61]=2[C:66]2[C:71](OC)=[CH:70][CH:69]=[CH:68][C:67]=2OC)CCCCC1.[C:82](=[O:85])(O)[O-:83].[Na+].C(O)C[CH2:89][CH3:90].O>C(OCC)(=O)C.O.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]>[NH2:30][C:21]1[C:3]2[N:4]=[CH:5][C:6]([C:8]#[C:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][O:18][CH3:19])=[CH:12][C:11]=3[CH3:20])=[CH:7][C:2]=2[C:69]2[CH:70]=[CH:71][C:66]([CH2:61][CH2:62][C:82]([O:83][CH2:89][CH3:90])=[O:85])=[CH:67][C:68]=2[N:22]=1

참가 물질

9

반응물 5

HCID 516892Sodium BicarbonateHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 22253497Water butanolHCID 670655293-Chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrileHCID 67065550Ethyl 3-(3-(tert-butoxycarbonylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate

생성물 1

HCID 67065523Ethyl 3-(5-amino-2-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)-benzo[f][1,7]naphthyridin-8-yl)propanoate

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 8857Ethyl Acetate용매

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온도
100 °C

실험 절차

A solution of 3-chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrile (6-10) (1.0 equiv.), ethyl 3-(3-(tert-butoxycarbonylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate (6-5) (1.25 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.10 equiv.), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.20 equiv.), and sodium bicarbonate (3.0 equiv.) in n-butanol/H2O (5:1, 0.2 M) was degassed and stirred at 100° C. overnight. After cooling to ambient temperature, the reaction content was diluted with ethyl acetate and water. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in DCM first to remove the impurity, then 0-4% MeOH in DCM to give ethyl 3-(5-amino-2-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)-benzo[f][1,7]naphthyridin-8-yl)propanoate (6-11). Further purification was accomplished by precipitating and washing in hot ether.

후처리

  1. temperatureAfter cooling to ambient temperature
  2. customThe two phases were separated
  3. extractionthe aqueous layer was extracted twice with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
  8. customto remove the impurity

출처 및 근거

ORD 기록
ord-9384f68eeb89427ba776ccc0c3910888
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09045470B2

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