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

HRID 1479504

反応式

HRID 1479504 の反応式
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]

参加物

8

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 962Water溶媒HCID 1140Toluene溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

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

後処理

  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)

出典と根拠

ORDレコード
ord-92a6c5878e064c9f89d138e382a3a77e
出典データセット
uspto-grants-2016_08
特許番号
US09408907B2

関連ノート

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