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Potassium Carbonate → Ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate

HRID 340289
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HRID 340289 반응식
Cl[C:2]1[CH:3]=[C:4]([C:10]#[C:11][C:12]2[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][C:13]=2[CH3:23])[CH:5]=[N:6][C:7]=1[C:8]#[N:9].[CH3:24][C:25]1[CH:26]=[CH:27][C:28](B2OC(C)(C)C(C)(C)O2)=[C:29]([NH:31]C(=O)OC(C)(C)C)[CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.CO.C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:9][C:8]1[C:7]2[N:6]=[CH:5][C:4]([C:10]#[C:11][C:12]3[CH:22]=[CH:21][C:15]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:14][C:13]=3[CH3:23])=[CH:3][C:2]=2[C:28]2[CH:27]=[CH:26][C:25]([CH3:24])=[CH:30][C:29]=2[N:31]=1
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참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 46737997tert-Butyl (5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 66875033Ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate

생성물 1

HCID 66892595Ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate

시약·촉매·용매 4

HCID 178418397
HCID 178418397, 화합물
촉매
HCID 887Methanol용매
HCID 6344Dichloromethane용매
HCID 21863594Toluene ethanol용매

실험 절차

A solution of ethyl 4-((5-chloro-6-cyanopyridin-3-yl)ethynyl)-3-methylbenzoate (from the previous step) (1.0 eq.), tert-butyl 5-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylcarbamate (from Example 5/Step 2) (1.1 eq.), tetrakis(triphenylphosphine)palladium (8 mol %), and potassium carbonate (3.0 eq.) in toluene/ethanol (9:1, 0.2 M) was stirred at 100° C. overnight. After cooling to ambient temperature, the reaction mixture was diluted with 2% MeOH in DCM. The two phases were separated. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in toluene to give ethyl 4-((5-amino-8-methylbenzo[f][1,7]naphthyridin-2-yl)ethynyl)-3-methylbenzoate.

후처리

  1. customwas stirred at 100° C. overnight
  2. customThe two phases were separated
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated en vacuo
  6. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)

출처 및 근거

ORD 기록
ord-1bb0700d4afb4af2abd03f27cc8fab58
출처 데이터셋
uspto-grants-2014_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08895577B2

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