反応式
[CH3:1][N:2]1[C:7]2[N:8]=[CH:9][C:10]([O:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:22])([F:21])[F:20])[CH:14]=3)=[CH:11][C:6]=2[C:5](=[O:23])[N:4]([CH2:24][CH2:25][CH2:26][O:27][CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][O:29]2)[C:3]1=[O:34].[Li+].CC([N-]C(C)C)C.[CH3:43][CH:44]([CH3:48])[CH2:45][CH:46]=[O:47]>C1COCC1.C(Cl)Cl.O>[OH:47][CH:46]([C:11]1[C:6]2[C:5](=[O:23])[N:4]([CH2:24][CH2:25][CH2:26][O:27][CH:28]3[CH2:33][CH2:32][CH2:31][CH2:30][O:29]3)[C:3](=[O:34])[N:2]([CH3:1])[C:7]=2[N:8]=[CH:9][C:10]=1[O:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:19]([F:20])([F:21])[F:22])[CH:14]=1)[CH2:45][CH:44]([CH3:48])[CH3:43]参加物
反応物 3
生成物 1
試薬・触媒・溶媒 3
反応条件
- 温度
- -78 °C
実験手順
To a solution of 1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (100 mg, 0.21 mmol) in THF (8 mL) at −78° C. was added LDA (2M in THF, 0.4 mL, 0.82 mmol) dropwise. The reaction was stirred at −78° C. for 40 min then 3-methylbutanal (35.9 mg, 0.42 mmol) in THF (2 mL) was added. The reaction was stirred at −78° C. for 30 min then diluted with DCM (10 mL) and water (10 mL). The organic layer was dried over Na2SO4 and concentrated to a residue which was purified by chromatography eluted with PE/EA (10:1 to 5:1) to give 5-(1-hydroxy-3-methylbutyl)-1-methyl-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)propyl)-6-(3-(trifluoromethyl)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (60 mg, 50.8% yield) as a solid. LCMS: [M+-THP-OH] 465 and TR=2.180 min.
後処理
- stirringThe reaction was stirred at −78° C. for 30 min
- dry with materialThe organic layer was dried over Na2SO4
- concentrationconcentrated to a residue which
- customwas purified by chromatography
- washeluted with PE/EA (10:1 to 5:1)
出典と根拠
- ORDレコード
- ord-2f22f3c69fce49869025d4033c89a4d4
- 出典データセット
- uspto-grants-2016_09
- 特許番号
- US09440972B2
関連ノート
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