Triethylamine → 6-(3-Chloro-5-methyl-benzoyl)-1-(2,6-difluoro-pyridin-4-ylmethyl)-5-isopropyl-1H-pyrimidine-2,4-dione

HRID 426158ノート

反応式

HRID 426158 の反応式
[F:1][C:2]1[CH:7]=[C:6]([CH2:8]O)[CH:5]=[C:4]([F:10])[N:3]=1.C(N(CC)CC)C.CS(Cl)(=O)=O.[Cl:23][C:24]1[CH:25]=[C:26]([CH:40]=[C:41]([CH3:43])[CH:42]=1)[C:27]([C:29]1[NH:34][C:33](=[O:35])[NH:32][C:31](=[O:36])[C:30]=1[CH:37]([CH3:39])[CH3:38])=[O:28].C(=O)([O-])[O-].[K+].[K+].[I-].[Li+]>C(Cl)(Cl)Cl.CN(C=O)C>[Cl:23][C:24]1[CH:25]=[C:26]([CH:40]=[C:41]([CH3:43])[CH:42]=1)[C:27]([C:29]1[N:34]([CH2:8][C:6]2[CH:7]=[C:2]([F:1])[N:3]=[C:4]([F:10])[CH:5]=2)[C:33](=[O:35])[NH:32][C:31](=[O:36])[C:30]=1[CH:37]([CH3:38])[CH3:39])=[O:28]

参加物

9

反応物 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 66321Lithium iodideHCID 213032376-(3-Chloro-5-methyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dioneHCID 59184676(2,6-Difluoropyridin-4-yl)methanol

生成物 1

HCID 591848676-(3-Chloro-5-methyl-benzoyl)-1-(2,6-difluoro-pyridin-4-ylmethyl)-5-isopropyl-1H-pyrimidine-2,4-dione収率 40.3%

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒

実験手順

(2,6-Difluoro-pyridin-4-yl)-methanol (145 mg, 1 mmol) was dissolved in chloroform (10 ml) and cooled in an ice bath under nitrogen atmosphere. With stirring, triethylamine (210 μl, 1.5 mmol) was added and methanesulfonyl chloride (90 μl, 1.2 mmol) was added dropwise. After stirring for 1.1 hr., the reaction mixture was washed with saturated aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was further dried in high vacuo for ca. 20 min. and mixed with 6-(3-Chloro-5-methyl-benzoyl)-5-isopropyl-1H-pyrimidine-2,4-dione (306 mg, 1 mmol), powdered anhydrous potassium carbonate (138 mg, 1 mmol), and lithium iodide (134 mg, 1 mmol). DMF (5 ml) was then added to the mixture at room temperature and stirred for ca. 4 hr. After evaporation of DMF, the residue was dissolved in methanol-chloroform (1:9) and filtered through celite pad. The filtrate was then evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2)) to afford 175 mg (40%) of a white solid. 1H-NMR (300 MHz, CDCl3) δ 1.18 (3H, d, J=6.7 Hz), 1.25 (3H, d, J=6.8 Hz), 2.26 (1H, m), 4.76 (3H, s), 6.57 (2H, s), 7.67 (3H, s), 9.21 (1H, s); m/z (EI) 433 (M+).

後処理

  1. temperaturecooled in an ice bath under nitrogen atmosphere
  2. stirringAfter stirring for 1.1 hr
  3. wash, the reaction mixture was washed with saturated aqueous sodium bicarbonate
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe residue was further dried in high vacuo for ca. 20 min.
  8. stirringstirred for ca. 4 hr
  9. customAfter evaporation of DMF
  10. dissolutionthe residue was dissolved in methanol-chloroform (1:9)
  11. filtrationfiltered through celite pad
  12. customThe filtrate was then evaporated in vacuo
  13. customthe residue was purified by silica gel column chromatography (eluent, EA:hexanes (1:2))

出典と根拠

ORDレコード
ord-8ad80032a46149b8b4c39327449a98f8
出典データセット
uspto-grants-2012_01
特許番号
US08106064B2

反応ノート

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