Methane → 6'-(2-Fluoro-5-methylpyridin-3-yl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amine

HRID 873761

반응식

HRID 873761 반응식
Br[C:2]1[C:3]([F:9])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].Br[C:34]1[CH:35]=[C:36]2[C:49]3([CH2:53][O:52][C:51]([N:54](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)=[N:50]3)[C:45]3([CH2:48][O:47][CH2:46]3)[C:41]3([CH2:44][CH2:43][CH2:42]3)[O:40][C:37]2=[CH:38][CH:39]=1.C(=O)([O-])[O-].[Na+].[Na+].C>O1CCOCC1.C1(C)C=CC=CC=1.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>[F:9][C:3]1[C:2]([C:34]2[CH:35]=[C:36]3[C:49]4([CH2:53][O:52][C:51]([NH2:54])=[N:50]4)[C:45]4([CH2:46][O:47][CH2:48]4)[C:41]4([CH2:44][CH2:43][CH2:42]4)[O:40][C:37]3=[CH:38][CH:39]=2)=[CH:7][C:6]([CH3:8])=[CH:5][N:4]=1

참가 물질

11

반응물 6

HCID 297MethaneHCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 218165633-Bromo-2-fluoro-5-methylpyridineHCID 86724300Di-tert-butyl (6'-bromotrispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-yl)imidodicarbonate

생성물 1

HCID 900267786'-(2-Fluoro-5-methylpyridin-3-yl)trispiro[cyclobutane-1,2'-chromene-4',4''-[1,3]oxazole-3',3'''-oxetan]-2''-amine수율 61.9%

시약·촉매·용매 4

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 1140Toluene용매HCID 312751,4-Dioxane용매

반응 조건

온도
100 °C

실험 절차

A mixture of 3-bromo-2-fluoro-5-methylpyridine (202 mg, 1.06 mmol), 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi-1,3,2-dioxaborolane (300 mg, 1.17 mmol), potassium acetate (208 mg, 2.12 mmol) and PdCl2(PPh3)2 (37 mg, 0.053 mmol) in dioxane (4 mL) was stirred for 3 hours at 100° C. To the mixture was added di-tert-butyl (6′-bromotrispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-yl)imidodicarbonate (300 mg, 0.531 mmol), sodium carbonate (225 mg, 2.12 mmol) and H2O (1 mL), and the mixture was stirred for 1.5 hours at 100° C. The mixture was treated with charcoal, and filtered off. The filtrate was partitioned between EtOAc and water. The organic layer was washed with brine, dried over MgSO4, filtered, and the filtrate was evaporated to give a pale brown oil. The oil was dissolved in toluene (5 mL) and to the mixture was added silicagel (neutral; 600 mg). The mixture was refluxed for 1 hour. The solvent was evaporated off. Silicagel column chromatography (CHCl3-EtOH, linear gradient of EtOH from 0 to 20%) afforded a solid. The solid was triturated in Et2O and collected by filtration, washed with Et2O and dried in vacuo at 70° C. to give 6′-(2-fluoro-5-methylpyridin-3-yl)trispiro[cyclobutane-1,2′-chromene-4′,4″-[1,3]oxazole-3′,3′″-oxetan]-2″-amine (130 mg).

후처리

  1. stirringthe mixture was stirred for 1.5 hours at 100° C
  2. filtrationfiltered off
  3. customThe filtrate was partitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe filtrate was evaporated
  8. customto give a pale brown oil
  9. additionwas added silicagel (neutral; 600 mg)
  10. temperatureThe mixture was refluxed for 1 hour
  11. customThe solvent was evaporated off
  12. customSilicagel column chromatography (CHCl3-EtOH, linear gradient of EtOH from 0 to 20%) afforded a solid
  13. customThe solid was triturated in Et2O
  14. filtrationcollected by filtration
  15. washwashed with Et2O
  16. customdried in vacuo at 70° C.

출처 및 근거

ORD 기록
ord-6f5290830a3244b1b036cf0baf615bd9
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08975415B2

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