Phosphine, tris(4-methoxyphenyl)- → (R)-2-(1-(4-amino-3-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one

HRID 626300

反応式

HRID 626300 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:14]2[C:22]3[C:17](=[N:18][CH:19]=[N:20][C:21]=3[NH2:23])[NH:16][N:15]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1.COC1C=CC(P(C2C=CC(OC)=CC=2)C2C=CC(OC)=CC=2)=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[F:63][C:64]1[CH:73]=[CH:72][CH:71]=[C:70]2[C:65]=1[C:66](=[O:84])[C:67]([C:77]1[CH:82]=[CH:81][CH:80]=[C:79]([F:83])[CH:78]=1)=[C:68]([CH:74](O)[CH3:75])[O:69]2>C1COCC1.O>[NH2:23][C:21]1[N:20]=[CH:19][N:18]=[C:17]2[N:16]([C@@H:74]([C:68]3[O:69][C:70]4[C:65]([C:66](=[O:84])[C:67]=3[C:77]3[CH:82]=[CH:81][CH:80]=[C:79]([F:83])[CH:78]=3)=[C:64]([F:63])[CH:73]=[CH:72][CH:71]=4)[CH3:75])[N:15]=[C:14]([C:4]3[CH:5]=[CH:6][C:7]([N:8]4[CH2:9][CH2:10][O:11][CH2:12][CH2:13]4)=[C:2]([F:1])[CH:3]=3)[C:22]=12

参加物

7

反応物 4

HCID 70071Phosphine, tris(4-methoxyphenyl)-HCID 5363146Diisopropyl azodicarboxylateHCID 89154250(+)-5-fluoro-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-oneHCID 178508715HCID 178508715、化合物

生成物 1

HCID 89156419(R)-2-(1-(4-amino-3-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-5-fluoro-3-(3-fluorophenyl)-4H-chromen-4-one

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

This example is also described in Example 59 of WO 2012/151525. To a solution of 3-(3-fluoro-4-morpholinophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.080 g, 0.254 mmol) in THF (2 ml), tris(4-methoxyphenyl)phosphine (0.134 g, 0.381 mmol) and diisopropylazodicarboxylate (0.07 ml, 0.381 mmol) is added and stirred at room temperature (RT) for 10 minutes. To this mixture (−)-5-fluoro-3-(3-fluorophenyl)-2-(1-hydroxyethyl)-4H-chromen-4-one (0.077 g, 0.254 mmol) is added and stirred for 12 h. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic layer is dried over sodium sulphate and concentrated under reduced pressure. The crude product is purified by column chromatography with methanol:dichloromethane to afford the title compound as an off-white solid. MP: 242-245° C. Enantiomeric excess: 96.21% Mass: 599.1 (M++1).

後処理

  1. stirringstirred for 12 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer is dried over sodium sulphate
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product is purified by column chromatography with methanol

出典と根拠

ORDレコード
ord-5efcf14e764745f1b5ef3ec3c4f537ea
出典データセット
uspto-grants-2016_04
特許番号
US09309216B2

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