Lithium diisopropylamide → 5-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 60478

反応式

HRID 60478 の反応式
[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]([O:19][C:20]([F:23])([F:22])[F:21])[CH:14]=3)=[CH:11][C:6]=2[C:5](=[O:24])[N:4]([CH2:25][CH2:26][CH2:27][O:28][CH:29]2[CH2:34][CH2:33][CH2:32][CH2:31][O:30]2)[C:3]1=[O:35].[Li+].CC([N-]C(C)C)C.[F:44][C:45]([F:55])([F:54])[C:46]1[CH:53]=[CH:52][C:49]([CH:50]=[O:51])=[CH:48][N:47]=1>C1COCC1.C(Cl)Cl.O>[OH:51][CH:50]([C:49]1[CH:48]=[N:47][C:46]([C:45]([F:55])([F:44])[F:54])=[CH:53][CH:52]=1)[C:11]1[C:6]2[C:5](=[O:24])[N:4]([CH2:25][CH2:26][CH2:27][O:28][CH:29]3[CH2:34][CH2:33][CH2:32][CH2:31][O:30]3)[C:3](=[O:35])[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]([O:19][C:20]([F:21])([F:22])[F:23])[CH:14]=1

参加物

7

反応物 3

HCID 2724682Lithium diisopropylamideHCID 27777626-(Trifluoromethyl)pyridine-3-carboxaldehydeHCID 118875520HCID 118875520、化合物

生成物 1

HCID 1188755065-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione収率 18.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a solution of 1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy) phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (156 mg, 0.32 mmol) in THF (6 mL) at −78° C. was added LDA (0.8 mL, 1.6 mmol) dropwise. The reaction was stirred at −78° C. for 1 h then 6-(trifluoromethyl)nicotinaldehyde (112 mg, 0.64 mmol) in THF (3 mL) was added dropwise. The reaction was stirred at −78° C. for 45 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 (4:6) to give 5-(hydroxy(6-(trifluoromethyl)-pyridin-3-yl)methyl)-1-methyl-3-(3-(tetrahydro-2H-pyran-2-yloxy)propyl)-6-(3-(trifluoromethoxy)phenoxy)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (40 mg, 18.6% yield) as a solid. LCMS: [M+-THP-OH—H] 569 and TR=2.162 min.

後処理

  1. stirringThe reaction was stirred at −78° C. for 45 min
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated to a residue which
  4. customwas purified by chromatography
  5. washeluted with PE/EA (4:6)

出典と根拠

ORDレコード
ord-c3b7a993d54142b7bbfed056b6be3737
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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