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 2200723노트

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HRID 2200723 반응식
[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

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 216984253-(Chloromethyl)-5-fluoropyridineHCID 904027281-(3-hydroxypropyl)-3-methyl-8-(3-(trifluoromethoxy)phenoxy)-1H-purine-2,6(3H,7H)-dione2회

생성물 1

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

시약·촉매·용매 2

HCID 67553Tetrabutylammonium Iodide촉매HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-2981850ecac644a6ab06ce36c6fbffc9
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359359B2

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