Dichloromethane → 2-(1-(4-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-phenyl-4H-chromen-4-one

HRID 1476212노트

반응식

HRID 1476212 반응식
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:30])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10](I)[C:3]=12.[CH3:31][C:32]([OH:36])([C:34]#[CH:35])[CH3:33].ClCCl>C1COCC1.[Cu]I>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:12]([C:14]3[O:15][C:16]4[C:21]([C:22](=[O:30])[C:23]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH3:13])[N:9]=[C:10]([C:35]#[C:34][C:32]([OH:36])([CH3:33])[CH3:31])[C:3]=12

참가 물질

6

반응물 3

HCID 6344DichloromethaneHCID 82582-Methyl-3-butyn-2-olHCID 582691102-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-phenyl-4H-chromen-4-one

생성물 1

HCID 582693022-(1-(4-amino-3-(3-hydroxy-3-methylbut-1-ynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-3-phenyl-4H-chromen-4-one수율 68.1%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of Example 57b (0.500 g, 0.981 mmoles) in THF (14 ml), 2-Methyl-3-butyn-2-ol (0.1 ml, 1.178 mmoles) diisopropylamine (0.70 ml, 4.90 mmoles), copper(I) iodide (18.6 mg, 0.098 mmoles) and) Tetrakistriphenylphosphine Palladium (0.113 g, 0.098 mmoles) were added and the system is degassed for 30 min. and heated to reflux for 4 h. The reaction mixture filtered through celite pad and washed with ethyl acetate. The filtrate was dried over sodium sulphate and concentrated under reduced pressure. The crude product was purified by column chromatography with methanol:dichloromethane to afford the title compound as brown solid (0.311 g, 68% yield). MP: 109-113° C. 1H-NMR (δ ppm, DMSO-d6, 400 MHz): δ 8.05(m,3H), 7.83(dt, J=8.6, 1.5Hz, 1H), 7.61(d, J=8.4Hz, 1H), 7.52(t, J=7.2Hz, 1H), 7.30-7.11(m, 4H), 5.84(q, J=7.1z, 1H)5.74(s,1H), 1.82(d, J=7.0Hz, 3H),1.46(s,6H). Mass: 466.09(M++1).

후처리

  1. customthe system is degassed for 30 min.
  2. temperatureheated
  3. temperatureto reflux for 4 h
  4. filtrationThe reaction mixture filtered through celite pad
  5. washwashed with ethyl acetate
  6. dry with materialThe filtrate was dried over sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by column chromatography with methanol

출처 및 근거

ORD 기록
ord-4216ec10efa942b2a460a1f150ca45af
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09018375B2

반응 노트

불러오는 중…