Water → 1-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

HRID 870620노트

반응식

HRID 870620 반응식
Br[C:2]1[N:6]2[N:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[C:12]([C:15]1[S:19][C:18](B(O)O)=[CH:17][CH:16]=1)(=[O:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].O>C(#N)C.C(OCC)(=O)C.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>[F:11][C:8]1[CH:9]=[CH:10][C:5]2[N:6]([C:2]([C:18]3[S:19][C:15]([C:12](=[O:14])[CH3:13])=[CH:16][CH:17]=3)=[CH:3][N:4]=2)[N:7]=1

참가 물질

8

반응물 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 4143377(5-Acetylthiophen-2-yl)boronic acidHCID 866963183-Bromo-6-fluoroimidazo[1,2-b]pyridazine

생성물 1

HCID 866963171-[5-(6-Fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 3-bromo-6-fluoro-imidazo[1,2-b]pyridazine (620 mg, 2.9 mmol), 5-acetyl-2-thiopheneboronic acid [206551-43-1] (634 mg, 3.7 mmol), potassium carbonate [584-08-7] (792 mg, 5.7 mmol), and bis(triphenylphosphine)palladium(II) dichloride [13965-03-2] (100 mg, 0.1 mmol) was suspended in a microwave reaction vial with a 25% (v/v) solution of water in acetonitrile (4.5 mL) then stirred and irradiated to an internal temperature of 145° C. for 15 minutes. The cooled reaction mixture was diluted with ethyl acetate, filtered, and partitioned between 1N aqueous sodium hydroxide and additional ethyl acetate. The organic extract was flash chromatographed (silica gel, eluted with 20% (v/v) ethyl acetate/hexanes) to provide 1-[5-(6-fluoro-imidazo[1,2-b]pyridazin-3-yl)-thiophen-2-yl]-ethanone as 300 mg of yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.63 (s, 3H) 7.00 (d, J=9.35 Hz, 1H) 7.75 (d, J=4.04 Hz, 1H) 7.83 (d, J=4.04 Hz, 1H) 8.13 (dd, J=9.60, 7.07 Hz, 1H) 8.21 (s, 1H). LRMS (ESI) m/z 262.1 [(M+H)]+, calc'd for C12H8FN30S: 261.28.

후처리

  1. customirradiated to an internal temperature of 145° C. for 15 minutes
  2. customThe cooled reaction mixture
  3. filtrationfiltered
  4. custompartitioned between 1N aqueous sodium hydroxide and additional ethyl acetate
  5. extractionThe organic extract
  6. customchromatographed
  7. wash(silica gel, eluted with 20% (v/v) ethyl acetate/hexanes)

출처 및 근거

ORD 기록
ord-656eccbfdce44c81b3dc64194046e40e
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969565B2

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