Potassium Carbonate → 2-(2-Fluorophenyl)-5-[(2'-methyl-3,3'-bipyridin-6-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3one

HRID 341059

反応式

HRID 341059 の反応式
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[F:29])[C:21](=[O:22])[C:11]3=[CH:10]2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[CH3:64][C:65]1[C:70](B(O)O)=[CH:69][CH:68]=[CH:67][N:66]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[CH:10][N:9]([CH2:8][C:5]3[N:6]=[CH:7][C:2]([C:70]4[C:65]([CH3:64])=[N:66][CH:67]=[CH:68][CH:69]=4)=[CH:3][CH:4]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 201116472-Methylpyridine-3-boronic acidHCID 681544925-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

生成物 1

HCID 681535342-(2-Fluorophenyl)-5-[(2'-methyl-3,3'-bipyridin-6-yl)methyl]-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3one

試薬・触媒・溶媒 2

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

実験手順

5-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (51 mg, 0.11 mmol), 2-dicyclohexylphosphino-2′,4′,6′-tri-iso-propyl-1,1′-biphenyl (16 mg, 0.034 mmol, 0.3 equiv), (2-methylpyridin-3-yl)boronic acid (26 mg, 0.19 mmol, 1.7 equiv), palladium(II) acetate (2.6 mg, 0.011 mmol, 0.1 equiv) and an aqueous solution (0.1 mL) of potassium carbonate (39 mg, 0.28 mmol, 2.5 equiv) were combined in dimethylsulfoxide (0.5 mL) and placed into a preheated oil bath at 85° C. for 90 minutes. The mixture was cooled to ambient temperature, stirred with Quadrapure® (50 mg, 1 wt equiv) for 1 hour, filtered and purified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid), providing the titled compound: 1H-NMR (500 MHz, d6-DMSO) δ 9.10 (1H, s), 8.57 (1H, d, J=2.1 Hz), 8.55 (1H, d, J=4.6 Hz), 8.21 (1H, dd, J=7.9, 1.4 Hz), 7.96 (1H, dd, J=8.1, 2.4 Hz), 7.84 (1H, d, J=8.7 Hz), 7.80 (1H, br s), 7.72 (1H, d, J=8.3 Hz), 7.65 (1H, ddd, J=8.6, 7.3, 1.5 Hz), 7.61 (1H, td, J=7.8, 1.6 Hz), 7.54 (1H, br t, J=7.6 Hz), 7.48-7.38 (3H, m), 7.34 (1H, td, J=7.6, 1.5 Hz), 5.92 (2H, s), 2.44 (3H, s) ppm; low resolution mass spectrometry (ES+) m/z 462.1709 [(M+H)+; calculated for C28H21FN5O: 462.1725].

後処理

  1. filtrationfiltered
  2. custompurified by reverse phase HPLC (80:20 to 5:95; water containing 0.1% trifluoroacetic acid:acetonitrile containing 0.1% trifluoroacetic acid)

出典と根拠

ORDレコード
ord-b0464dfc0e8d4ea1a11b9aad8cd03096
出典データセット
uspto-grants-2014_11
特許番号
US08895580B2

関連ノート

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