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 643478노트

반응식

HRID 643478 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 80711,2-Dimethoxyethane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-d1ff1d8d088e480eb1f191129379c76a
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07700602B2

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