2-Fluorophenol → 7-(4-fluorobenzyl)-8-(2-fluorophenoxy)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

HRID 2200721노트

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HRID 2200721 반응식
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][OH:23])[C:6](=[O:24])[N:5]([CH3:25])[C:4]=2[N:3]=1.[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[OH:33].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[F:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][N:10]2[C:9]3[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][OH:23])[C:6](=[O:24])[N:5]([CH3:25])[C:4]=3[N:3]=[C:2]2[O:33][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[F:26])=[CH:13][CH:14]=1

참가 물질

5

반응물 3

HCID 97072-FluorophenolHCID 11430Potassium CarbonateHCID 904026238-bromo-7-(4-fluorobenzyl)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione2회

생성물 1

HCID 904024357-(4-fluorobenzyl)-8-(2-fluorophenoxy)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione수율 37%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
80 °C

실험 절차

To a solution of 8-bromo-7-(4-fluorobenzyl)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (50 mg, 0.121 mmol, intermediate 62) in DMF (1 mL) was added 2-fluorophenol (16.4 mg, 0.146 mmol) followed by potassium carbonate (25.2 mg, 0.182 mmol). The reaction was stirred at 80° C. for 4 h. The mixture was partitioned between ethyl acetate and brine. The organic phase was washed with saturated aqueous ammonium chloride, dried and concentrated to give crude product, which was purified by preparative HPLC to give 7-(4-fluorobenzyl)-8-(2-fluorophenoxy)-1-(3-hydroxypropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (19.8 mg, 36.9% yield) as white solid. 1H-NMR (CD3OD) δ 7.52-7.56 (m, 2H), 7.43-7.45 (t, 1H), 7.2-7.38 (m, 3H), 7.08-7.13 (t, 1H), 5.51 (s, 2H), 4.09-4.13 (t, 2H), 3.60-3.63 (t, 2H), 3.37 (s, 3H), 1.86-1.90 (m, 2H). LCMS retention time 2.604; LCMS MH+ 443.

후처리

  1. customThe mixture was partitioned between ethyl acetate and brine
  2. washThe organic phase was washed with saturated aqueous ammonium chloride
  3. customdried
  4. concentrationconcentrated
  5. customto give crude product, which
  6. customwas purified by preparative HPLC

출처 및 근거

ORD 기록
ord-b46512d9268e4b21bed19a67899c1758
출처 데이터셋
uspto-grants-2016_06
특허 번호
US09359359B2

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