Potassium Carbonate → 7-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione

HRID 2200723ノート

反応式

HRID 2200723 の反応式
[OH:1][CH2:2][CH2:3][CH2:4][N:5]1[C:13](=[O:14])[C:12]2[NH:11][C:10]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:26])([F:25])[F:24])[CH:17]=3)=[N:9][C:8]=2[N:7]([CH3:27])[C:6]1=[O:28].Cl[CH2:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([F:37])[CH:36]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[F:37][C:35]1[CH:36]=[C:31]([CH2:30][N:11]2[C:12]3[C:13](=[O:14])[N:5]([CH2:4][CH2:3][CH2:2][OH:1])[C:6](=[O:28])[N:7]([CH3:27])[C:8]=3[N:9]=[C:10]2[O:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:25])([F:26])[F:24])[CH:17]=2)[CH:32]=[N:33][CH:34]=1

参加物

6

反応物 3

HCID 11430Potassium CarbonateHCID 216984253-(Chloromethyl)-5-fluoropyridineHCID 904027281-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione2 回

生成物 1

HCID 904026457-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione収率 46%

試薬・触媒・溶媒 2

HCID 67553Tetrabutylammonium Iodide触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a solution of 1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (60 mg, 0.15 mmol, intermediate 15) in DMF (5 mL) was added 3-(chloromethyl)-5-fluoropyridine (80 mg, 0.55 mmol), potassium carbonate (0.55 g, 0.6 mmol), and TBAI (2 mg, 0.02 mmol). The reaction was heated at 60° C. for 2 h. The mixture was cooled and partitioned between ethyl acetate and water. The organic phase was dried over sodium sulfate, and concentrated. The residue was purified by preparative HPLC to give 7-((5-fluoropyridin-3-yl)methyl)-1-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione (35 mg, 46% yield) as white solid. LCMS retention time 2.577 min; LCMS MH+ 510.

後処理

  1. temperatureThe mixture was cooled
  2. custompartitioned between ethyl acetate and water
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by preparative HPLC

出典と根拠

ORDレコード
ord-2981850ecac644a6ab06ce36c6fbffc9
出典データセット
uspto-grants-2016_06
特許番号
US09359359B2

反応ノート

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