Potassium Fluoride → (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyridin-2-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

HRID 506363ノート

反応式

HRID 506363 の反応式
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22](I)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2].C([Sn](CCCC)(CCCC)[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=1)CCC.[F-].[K+]>C1(C)C=CC=CC=1.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>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12]([O:16][CH3:17])=[CH:13][CH:14]=2)[C@@H:9]([NH:18][C:19]2[N:24]=[C:23]([CH2:25][C:26]3[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=3)[C:22]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=3)=[CH:21][N:20]=2)[CH2:8][C@H:7]1[CH2:41][CH3:42])=[O:5])[CH3:2]

参加物

6

反応物 3

HCID 522689Potassium FluorideHCID 6077842-(Tributylstannyl)pyridineHCID 86610559(2R*,4S*)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

生成物 1

HCID 86610595(2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyridin-2-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester

試薬・触媒・溶媒 2

HCID 178418397HCID 178418397、化合物触媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

(2R,4S)-4-{[3,5-Bis(trifluoromethyl)benzyl]-(5-iodopyrimidin-2-yl)}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (200 mg) is dissolved in toluene (2 ml), then thereto are added 2-tributylstannylpyridine (105 μl) and tetrakis(triphenylphosphine)palladium (16 mg), and the mixture is stirred at 100° C. under nitrogen flow overnight. After allowing to cool to room temperature, 10% aqueous potassium fluoride solution is added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer is washed with a 10% aqueous potassium fluoride solution and a saturated brine successively, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1) to give (2R,4S)-4-{[3,5-bis(trifluoromethyl)benzyl]-[5-(pyridin-2-yl)pyrimidin-2-yl]}amino-2-ethyl-6-methoxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (138 mg). MS (m/z): 661 [M+H]+

後処理

  1. temperatureto cool to room temperature
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer is washed with a 10% aqueous potassium fluoride solution
  4. dry with materiala saturated brine successively, dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by column chromatography (silica gel; hexane: ethyl acetate=4:1)

出典と根拠

ORDレコード
ord-736d1b785c9e4b9cb5d3bd20eb388f8e
出典データセット
uspto-grants-2010_08
特許番号
US07781443B2

反応ノート

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