Sodium Carbonate → 2-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydro-imidazol-4-one

HRID 1455138ノート

反応式

HRID 1455138 の反応式
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[NH2:20][C:21]1[N:25]([CH3:26])[C:24](=[O:27])[C:23]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[C:42](Br)[CH:41]=2)([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[C:30]([F:39])[CH:29]=2)[N:22]=1.[N:48]1[CH:53]=[C:52](B(O)O)[CH:51]=[N:50][CH:49]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.COCCOC>[NH2:20][C:21]1[N:25]([CH3:26])[C:24](=[O:27])[C:23]([C:40]2[CH:45]=[CH:44][C:43]([F:46])=[C:42]([C:52]3[CH:53]=[N:48][CH:49]=[N:50][CH:51]=3)[CH:41]=2)([C:28]2[CH:33]=[CH:32][C:31]([O:34][C:35]([F:38])([F:37])[F:36])=[C:30]([F:39])[CH:29]=2)[N:22]=1

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2795193(Pyrimidin-5-yl)boronic acidHCID 575312642-Amino-5-(3-bromo-4-fluorophenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydroimidazol-4-one

生成物 1

HCID 575313272-Amino-5-(4-fluoro-3-pyrimidin-5-ylphenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydro-imidazol-4-one収率 29%

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 80711,2-Dimethoxyethane溶媒

実験手順

A mixture of ethylene glycol dimethyl ether, tris(dibenzylideneacetone)-dipalladium(0) (0.015 g, 16.5 μmol) and triphenylphosphine (0.008 g, 32.0 μmol) under nitrogen is stirred for 5 min, treated with 2-amino-5-(3-bromo-4-fluorophenyl)-5-[3-fluoro-4-(trifluoromethoxy)phenyl]-3-methyl-3,5-dihydroimidazol-4-one (0.154 g, 0.33 mmol), 5-pyrimidine boronic acid (0.046 g, 0.37 mmol), sodium carbonate (0.105 g, 0.99 mmol) and water, heated at reflux temperature for 1.25 h, cooled to room temperature and concentrated in vacuo. The resultant residue is purified by flash chromatography (silica, 95:5:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent) to afford a viscous oil. This oil is suspended in a mixture of methylene chloride/hexanes and concentrated to afford the title compound as an off-white solid, 0.045 g (29% yield), mp 102-110° C., identified by HNMR and mass spectral analyses. 1H NMR (500 MHz, CD3OD) δ 9.15 (s, 1H), 8.95 (s, 2H), 7.62-7.56 (m, 2H), 7.39-7.27 (m, 4H), 3.12 (s, 3H); IR 3353, 3061, 2956, 1732, 1668, 1498, 1470, 1416, 1251, 1216, 1170 cm−1; ESI MS m/z 464 [C21H14F5N5O2+H]+; HPLC (Method 2) 95.0% (AUC) tR=13.78 min.

後処理

  1. temperatureheated
  2. temperatureat reflux temperature for 1.25 h
  3. concentrationconcentrated in vacuo
  4. customThe resultant residue is purified by flash chromatography (silica, 95:5:0.5 methylene chloride/methanol/concentrated ammonium hydroxide as eluent)
  5. customto afford a viscous oil
  6. concentrationconcentrated

出典と根拠

ORDレコード
ord-70821538e3734d818ddde0a5cf28cfee
出典データセット
uspto-grants-2009_01
特許番号
US07482349B2

反応ノート

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