3-(Methoxycarbonyl)benzeneboronic acid → Methyl 3-{2-methyl-3-[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)-carbonyl]indolizin-1-yl}benzoate

HRID 535457노트

반응식

HRID 535457 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7](B(O)O)[CH:8]=[CH:9][CH:10]=1)=[O:4].O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:25]1[C:26]([CH3:48])=[C:27]([C:34]([C:36]2[CH:37]=[C:38]3[C:43](=[CH:44][CH:45]=2)[N:42]=[C:41]([CH3:46])[NH:40][C:39]3=[O:47])=[O:35])[N:28]2[C:33]=1[CH:32]=[CH:31][CH:30]=[CH:29]2>O.CN(C=O)C.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>[CH3:48][C:26]1[C:25]([C:7]2[CH:6]=[C:5]([CH:10]=[CH:9][CH:8]=2)[C:3]([O:2][CH3:1])=[O:4])=[C:33]2[N:28]([C:27]=1[C:34]([C:36]1[CH:37]=[C:38]3[C:43](=[CH:44][CH:45]=1)[N:42]=[C:41]([CH3:46])[NH:40][C:39]3=[O:47])=[O:35])[CH:29]=[CH:30][CH:31]=[CH:32]2

참가 물질

7

반응물 3

HCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 23436936Potassium phosphate dihydrateHCID 1363654746-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2-methylquinazolin-4(3H)-one

생성물 1

HCID 136365475Methyl 3-{2-methyl-3-[(2-methyl-4-oxo-3,4-dihydroquinazolin-6-yl)-carbonyl]indolizin-1-yl}benzoate수율 58.6%

시약·촉매·용매 3

HCID 178418397HCID 178418397, 화합물촉매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
150 °C

실험 절차

0.139 g (0.78 mmol) of [3-(methoxycarbonyl)phenyl]boronic acid, 0.321 g (1.29 mmol) of potassium phosphate dihydrate dissolved in 0.81 ml of water, and 0.0149 g (0.01 mmol) of tetrakis(triphenylphosphine)palladium are added, under an argon atmosphere at ambient temperature, to 0.256 g (0.65 mmol) of 6-[(1-bromo-2-methylindolizin-3-yl)carbonyl]-2-methylquinazolin-4(3H)-one in 9 ml of DMF. The reaction medium is microwave-heated at 150° C. for 15 minutes. After dilution with ethyl acetate, the organic phase is washed with a 1N aqueous solution of hydrochloric acid and then a saturated aqueous solution of sodium chloride, dried over sodium sulphate, filtered, and then concentrated under reduced pressure. The solid obtained is purified by silica gel column chromatography, elution being carried out with a dichloromethane/methanol (95/2) mixture. 172 mg of a yellow solid are obtained.

후처리

  1. washAfter dilution with ethyl acetate, the organic phase is washed with a 1N aqueous solution of hydrochloric acid
  2. dry with materiala saturated aqueous solution of sodium chloride, dried over sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe solid obtained
  6. customis purified by silica gel column chromatography, elution

출처 및 근거

ORD 기록
ord-9fa617bd4b40479ab9e65213502979b4
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859544B2

반응 노트

불러오는 중…