Potassium Carbonate → 6'-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-amine

HRID 873755노트

반응식

HRID 873755 반응식
Br[C:2]1[CH:3]=[C:4]2[C:31](=[CH:32][CH:33]=1)[O:30][CH2:29][C:25]1([CH2:28][O:27][CH2:26]1)[C:5]12[CH2:9][O:8][C:7]([N:10](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:6]1.O1CCOCC1.[NH:40]1[C:48]2[C:43](=[C:44](B(O)O)[CH:45]=[CH:46][CH:47]=2)[CH:42]=[N:41]1.C([O-])([O-])=O.[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH:40]1[C:48]2[C:43](=[C:44]([C:2]3[CH:3]=[C:4]4[C:31](=[CH:32][CH:33]=3)[O:30][CH2:29][C:25]3([CH2:28][O:27][CH2:26]3)[C:5]34[CH2:9][O:8][C:7]([NH2:10])=[N:6]3)[CH:45]=[CH:46][CH:47]=2)[CH:42]=[N:41]1

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 441183101H-Indazole-4-boronic acidHCID 86724239Di-tert-butyl (6'-bromodispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-yl)imidodicarbonate

생성물 1

HCID 867243066'-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4'-chromene-3',3''-oxetan]-2-amine수율 68.6%

시약·촉매·용매 2

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매

반응 조건

온도
100 °C

실험 절차

Under argon atmosphere, to a mixture of di-tert-butyl (6′-bromodispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-yl)imidodicarbonate (300 mg, 0.571 mmol), dioxane (3.0 mL) and water (1.5 mL) were added 1H-indazol-4-ylboronic acid (185 mg, 1.14 mmol), K2CO3 (237 mg, 1.71 mmol) and bis(triphenylphosphine)palladium(II) dichloride (40 mg, 0.057 mmol), and the mixture was stirred for 3 hours at 100° C. The reaction mixture was cooled down to ambient temperature, partitioned between H2O and 10% MeOH in CHCl3. The organic layer was dried over Na2SO4 and filtered, and the filtrate was concentrated at reduced pressure. The residue was dissolved with dioxane (3.0 mL), and silica gel (neutral; 900 mg) was added to the mixture. After stirring for 2.5 hours at 110° C., the reaction mixture was cooled down to ambient temperature, and concentrated at reduced pressure. Purification of the residue with column chromatography on silica gel (CHCl3-EtOH, a linear gradient of EtOH from 0 to 20%) afforded 6′-(1H-indazol-4-yl)dispiro[1,3-oxazole-4,4′-chromene-3′,3″-oxetan]-2-amine (142 mg).

후처리

  1. temperatureThe reaction mixture was cooled down to ambient temperature
  2. custompartitioned between H2O and 10% MeOH in CHCl3
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated at reduced pressure
  6. dissolutionThe residue was dissolved with dioxane (3.0 mL), and silica gel (neutral; 900 mg)
  7. additionwas added to the mixture
  8. stirringAfter stirring for 2.5 hours at 110° C.
  9. temperaturethe reaction mixture was cooled down to ambient temperature
  10. concentrationconcentrated at reduced pressure
  11. customPurification of the residue with column chromatography on silica gel (CHCl3-EtOH

출처 및 근거

ORD 기록
ord-c6773bcc93c6420eb7c36b2b1aba2886
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975415B2

반응 노트

불러오는 중…