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

HRID 870620ノート

反応式

HRID 870620 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-656eccbfdce44c81b3dc64194046e40e
出典データセット
uspto-grants-2015_03
特許番号
US08969565B2

反応ノート

読み込み中…