Potassium Carbonate → 2-(2-Fluorophenyl)-5-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341063ノート

反応式

HRID 341063 の反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:30](=[O:31])[C:11]2=[CH:12][N:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]2=[N:9]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.I[C:67]1[CH:68]=[N:69][N:70]([CH3:72])[CH:71]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:30](=[O:31])[C:11]2=[CH:12][N:13]([CH2:20][C:21]3[CH:26]=[CH:25][C:24]([C:67]4[CH:68]=[N:69][N:70]([CH3:72])[CH:71]=4)=[CH:23][CH:22]=3)[C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][C:19]=3[C:10]2=[N:9]1

参加物

8

反応物 4

HCID 11430Potassium CarbonateHCID 27347731-Methyl-4-iodo-1H-pyrazoleHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 68154377(4-{[2-(2-Fluorophenyl)-3-oxo-2,3-dihydro-5H-pyrazolo[4,3-c]quinolin-5-yl]methyl}phenyl)boronic acid

生成物 1

HCID 529147282-(2-Fluorophenyl)-5-{[4-(1-methyl-1H-pyrazol-4-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒

実験手順

(4-{[2-(2-Fluorophenyl)-3-oxo-2,3-dihydro-5H-pyrazolo[4,3-c]quinolin-5-yl]methyl}phenyl)boronic acid (Example 370, 60 mg, 0.14 mmol) was dissolved in degassed dimethylsulfoxide (1 mL), treated with 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (10 mg, 0.022 mmol, 0.15 equiv), 4-iodo-1-methyl-1H-pyrazole (33 mg, 0.16 mmol, 1.1 equiv), an aqueous solution (0.2 mL) of potassium carbonate (50 mg, 0.36 mmol, 2.5 equiv) and palladium(II) acetate (1.6 mg, 0.0073 mmol, 0.05 equiv) and placed into a preheated oil bath at 80° C. for 1 hour. The mixture was cooled to ambient temperature, poured into water (25 mL) and extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed once with water (10 mL) and brine (10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 95:5; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.45 (1H, s), 8.42 (1H, br d, 7.1 Hz), 7.74 (1H, s), 7.65 (1H, td, J=7.7, 2.0 Hz), 7.60 (1H, s), 7.54-7.46 (5H, m), 7.38-7.33 (1H, m), 7.29-7.23 (2H, m), 7.20 (2H, d, J=8.2 Hz), 5.46 (2H, s), 3.94 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 450.1739 [(M+H)+; calculated for C27H21FN5O: 450.1725].

後処理

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. washThe combined organic extracts were washed once with water (10 mL) and brine (10 mL)
  3. dry with materialdried with sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (100:0 to 95:5; chloroform:methanol)

出典と根拠

ORDレコード
ord-ab742202dfde40bd886fc273f94e235b
出典データセット
uspto-grants-2014_11
特許番号
US08895580B2

反応ノート

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