Potassium Acetate → 4,2'-Difluoro-5'-(3-methyl-4-oxo-3,4-dihydroimidazo[2,1-f][1,2,4] triazin-7-yl)biphenyl-2-carbonitrile

HRID 895110ノート

反応式

HRID 895110 の反応式
[CH3:1][N:2]1[C:7](=[O:8])[C:6]2=[N:9][CH:10]=[CH:11][N:5]2[N:4]=[CH:3]1.Br[C:13]1[CH:14]=[CH:15][C:16]([F:28])=[C:17]([C:19]2[C:20]([C:26]#[N:27])=[CH:21][C:22]([F:25])=[CH:23][CH:24]=2)[CH:18]=1.C([O-])(=O)C.[K+]>CN(C)C(=O)C.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:25][C:22]1[CH:21]=[C:20]([C:26]#[N:27])[C:19]([C:17]2[CH:18]=[C:13]([C:11]3[N:5]4[C:6]([C:7](=[O:8])[N:2]([CH3:1])[CH:3]=[N:4]4)=[N:9][CH:10]=3)[CH:14]=[CH:15][C:16]=2[F:28])=[CH:24][CH:23]=1

参加物

8

反応物 3

HCID 517044Potassium AcetateHCID 114151595'-Bromo-2',4-difluoro-[1,1'-biphenyl]-2-carbonitrileHCID 116223593-methyl-3H-imidazo[2,1-f][1,2,4]triazin-4-one

生成物 1

HCID 98419394,2'-Difluoro-5'-(3-methyl-4-oxo-3,4-dihydroimidazo[2,1-f][1,2,4] triazin-7-yl)biphenyl-2-carbonitrile収率 77%

試薬・触媒・溶媒 4

HCID 11776Triphenylphosphine触媒HCID 167845palladium(II) acetate触媒HCID 8857Ethyl Acetate溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
120 °C

実験手順

3-Methyl-3H-imidazo[2,1-f][1,2,4]triazin-4-one (75 mg, 0.5 mmol), 5′-bromo-4,2′-difluorobiphenyl-2-carbonitrile (prepared according to the procedure described in WO 02/38568) (220 mg, 0.75 mmol) and potassium acetate (74 mg, 0.75 mmol) were suspended in N,N-dimethylacetamide (2 ml) and degassed with nitrogen for 10 min. Palladium(II) acetate (5.6 mg, 0.025 mmol) and triphenylphosphine (6.6 mg, 0.025 mmol) were added and the mixture heated at 120° C. for 1 h. The mixture was allowed to cool to ambient temperature, diluted with ethyl acetate (100 ml), washed with water (50 ml) and brine (30 ml), dried over anhydrous sodium sulfate, filtered and evaporated to give a brown solid. The solid was purified by flash column chromatography on silica, eluting with dichloromethane on a gradient of methanol (0-2%). The appropriate fractions were collected and concentrated, and the residue triturated with diethyl ether, which gave 4,2′-difluoro-5′-(3-methyl-4-oxo-3,4-dihydroimidazo[2,1-f][1,2,4] triazin-7-yl)biphenyl-2-carbonitrile (139 mg, 77%) as a white solid: δH (500 MHz, CDCl3) 3.55 (3H, s), 7.27 (1H, dd, J9 and 9), 7.35 (1H, ddd, J8, 8 and 3), 7.45 (1H, dd, J8 and 3), 7.47-7.49 (1H, m), 7.71 (1H, s), 7.73 (1H, s), 7.89-7.92 (2H, m); m/z (ES+) 364 (M++H).

後処理

  1. customdegassed with nitrogen for 10 min
  2. temperatureto cool to ambient temperature
  3. washwashed with water (50 ml) and brine (30 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto give a brown solid
  8. customThe solid was purified by flash column chromatography on silica
  9. washeluting with dichloromethane on a gradient of methanol (0-2%)
  10. customThe appropriate fractions were collected
  11. concentrationconcentrated
  12. customthe residue triturated with diethyl ether, which

出典と根拠

ORDレコード
ord-2af46ae4363048a08d6d883c4fe4c6bd
出典データセット
uspto-grants-2005_07
特許番号
US06914060B2

反応ノート

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