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

반응식

HRID 626300 반응식
[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

참가 물질

7

반응물 4

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

생성물 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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5efcf14e764745f1b5ef3ec3c4f537ea
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09309216B2

연결된 노트

불러오는 중…