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Urea → N-(6-Fluoro-1H-indazol-5-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide

HRID 227718
ノート
印刷プレビュー

反応式

HRID 227718 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[NH2:11].[CH2:12]=[C:13]1[O:17][C:15](=O)[CH2:14]1.[F:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=1.[NH2:27][C:28]([NH2:30])=[O:29].[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>CC#N.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[NH:11][C:15]([C:14]1[CH:23]([C:22]2[CH:25]=[CH:26][C:19]([F:18])=[CH:20][CH:21]=2)[NH:27][C:28](=[O:29])[NH:30][C:13]=1[CH3:12])=[O:17]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 1176UreaHCID 12661DiketeneHCID 680234-FluorobenzaldehydeHCID 2733225Ytterbium triflateHCID 450905046-fluoro-1H-indazol-5-amine

生成物 1

HCID 57755913N-(6-Fluoro-1H-indazol-5-yl)-4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydro-5-pyrimidinecarboxamide収率 3%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
80 °C

実験手順

The product of Step (d) (41.0 mg, 0.276 mmol, 1.0 equiv) was dissolved in CH3CN (1 mL) and diketene (0.021 mL, 0.276 mmol, 1.0 equiv) was added. The reaction was heated to 80° C. for 2 hours, then cooled to room temperature and concentrated. The residue was dissolved in CH3CN (1 mL). 4-Fluorobenzaldehyde (0.030 mL, 0.276 mmol, 1.00 equiv), urea (25 mg, 0.41 mmol, 1.5 equiv), and ytterbium triflate (17 mg, 0.028 mmol, 0.10 equiv) and heated to 80° C. for 3 hours. The reaction was cooled to room temperature and water was added. The precipitate was collected by filtration and washed alternately with CH3CN and Et2O. The residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min) to provide 3 mg (3%) of the title compound. MS (ES+) m/e 384 [M+H].

後処理

  1. temperaturecooled to room temperature
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in CH3CN (1 mL)
  4. temperatureThe reaction was cooled to room temperature
  5. filtrationThe precipitate was collected by filtration
  6. washwashed alternately with CH3CN and Et2O
  7. customThe residue was purified by reverse phase HPLC (740% CH3CN/5 mM NH4HCO3, 19×50 mm Xterra Prep MS over 8 min)

出典と根拠

ORDレコード
ord-5511ecf4142c4108b0f328f25724d995
出典データセット
uspto-grants-2009_07
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07560467B2

反応ノート

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