Potassium Carbonate → 3-{[1-(5-fluoro-2-methylphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-yl]amino}isonicotinic acid

HRID 2109935

反応式

HRID 2109935 の反応式
I[C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(=O)([O-])[O-].[K+].[K+].[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:37])=[C:22]([N:24]2[C:28]([NH2:29])=[C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:26]([CH3:36])=[N:25]2)[CH:23]=1.C1(C(C(C)=O)C#N)C=CC=CC=1>CN(C=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[F:17][C:18]1[CH:19]=[CH:20][C:21]([CH3:37])=[C:22]([N:24]2[C:28]([NH:29][C:2]3[CH:10]=[N:9][CH:8]=[CH:7][C:3]=3[C:4]([OH:6])=[O:5])=[C:27]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:26]([CH3:36])=[N:25]2)[CH:23]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 20547Alpha-phenylacetoacetonitrileHCID 6192753-Iodopyridine-4-carboxylic acidHCID 688197371-(5-fluoro-2-methylphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-amine

生成物 1

HCID 441934293-{[1-(5-fluoro-2-methylphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-yl]amino}isonicotinic acid収率 10%

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

A mixture of 3-iodoisonicotinic acid (180 mg, 0.72 mmol), potassium carbonate (199 mg, 1.44 mmol), 1-(5-fluoro-2-methylphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-amine (202 mg, 0.72 mmol, synthesized in the same manner as Intermediate F, using commercially available 2-phenylacetoacetonitrile as the nitrile source), and copper (II) acetate (6.5 mg, 0.04 mmol) in DMF (1 mL) was heated (150° C.) in a sealed tube for 16 h. The mixture was cooled to rt, filtered through a silica gel plug using ethyl acetate as eluent, concentrated to dryness, and subjected to HPLC purification using a gradient elution from 30% to 90% acetonitrile in water to afford 29.1 mg (10%) of the desired product. 1H NMR (300 MHz, CD3CN) δ 9.39 (br s, 1H), 7.93 (s, 1H), 7.86-7.90 (m, 2H), 7.05-7.45 (m, 8H), 2.38 (s, 3H), 2.15 (s, 3H); ES-MS m/z 403.1 (MH+), HPLC RT (min) 2.40.

後処理

  1. customsynthesized in the same manner as Intermediate F
  2. temperatureThe mixture was cooled to rt
  3. filtrationfiltered through a silica gel plug
  4. concentrationconcentrated to dryness
  5. customsubjected to HPLC purification
  6. washa gradient elution from 30% to 90% acetonitrile in water

出典と根拠

ORDレコード
ord-f310d383af404a42a984fc774f7260d8
出典データセット
uspto-grants-2009_04
特許番号
US07517878B2

関連ノート

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