Potassium Carbonate → 2-(Trifluoromethyl)benzo[f][1,7]naphthyridin-5-amine

HRID 1479504

반응식

HRID 1479504 반응식
C(OC([NH:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1B(O)O)=O)(C)(C)C.Cl[C:19]1[C:20]([C:29]#[N:30])=[N:21][CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CO.ClCCl.O>[F:26][C:25]([F:28])([F:27])[C:23]1[CH:22]=[N:21][C:20]2[C:19]([CH:24]=1)=[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]1=[N:8][C:29]=2[NH2:30]

참가 물질

8

반응물 3

HCID 11430Potassium CarbonateHCID 14733743-Chloro-5-(trifluoromethyl)pyridine-2-carbonitrileHCID 2773226(2-BOC-aminophenyl)boronic acid

생성물 1

HCID 582136402-(Trifluoromethyl)benzo[f][1,7]naphthyridin-5-amine

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 1140Toluene용매HCID 6344Dichloromethane용매

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온도
100 °C

실험 절차

A solution of 2-(tert-butoxycarbonylamino)phenylboronic acid (1.0 eq.) and 3-chloro-5-(trifluoromethyl)picolinonitrile (from step 2) (1.0 eq.) in toluene (0.44 M) was mixed with tetrakis(triphenyl-phosphine)palladium (5 mol %) and 2N aqueous potassium carbonate solution (2.0 eq.). The reaction was heated to 100° C. and stirred overnight. After cooling to ambient temperature, the reaction content was diluted with 2% methanol in dichloromethane and water. The two phases were separated, and the aqueous layer was extracted twice with 2% methanol in dichloromethane. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated en vacuo. The crude product was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-50% ethyl acetate in hexane to give 2-(trifluoromethyl)benzo[f][1,7]naphthyridin-5-amine. 1H NMR (acetone d-6): δ 9.44 (s, 1H), 9.20 (s, 1H), 8.65-8.63 (d, 1H), 7.70-7.61 (m, 2H), 7.44-7.36 (m, 1H), 6.84 (br, 2H). LRMS [M+H]=264.2

후처리

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

출처 및 근거

ORD 기록
ord-92a6c5878e064c9f89d138e382a3a77e
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09408907B2

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