Hydrochloric Acid → 3-methyl-2-[2-(4-piperidin-1-ylmethyl-phenyl)ethoxy]-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride

HRID 1468794ノート

反応式

HRID 1468794 の反応式
[Cl:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[N:3]=1.[N:16]1([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([CH2:29][CH2:30][OH:31])=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.N12CCCN=C1CCCCC2.[ClH:43]>CN(C)C=O.C(OCC)(=O)C.O>[ClH:1].[ClH:43].[CH3:8][N:7]1[C:6](=[O:9])[CH:5]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[N:3]=[C:2]1[O:31][CH2:30][CH2:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:24][CH:25]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 112760814(3H)-Pyrimidinone, 2-chloro-3-methyl-6-(4-pyridinyl)-HCID 671652542-(4-Piperidin-1-ylmethylphenyl)ethanol

生成物 1

HCID 679775993-methyl-2-[2-(4-piperidin-1-ylmethyl-phenyl)ethoxy]-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride収率 42%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒2 回

反応条件

温度
100 °C

実験手順

To a mixture of 2-chloro-3-methyl-6-pyridin-4-yl-3H-pyrimidin-4-one (500 mg, 2.26 mmol) and 2-(4-piperidin-1-ylmethyl-phenyl)ethanol (990 mg, 4.51 mmol) in N,N-dimethylformamide (15 ml) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (347 mg, 2.26 mmol) at room temperature. The mixture was stirred at 100° C. for 4 hours. The mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluent; ethyl acetate/methanol=90/10 to 67/33) to afford a pale blue powder. This compound was dissolved into ethyl acetate (1.2 ml), and 4N-hydrogen chloride in ethyl acetate (1.2 ml, 4.8 mmol) was added at room temperature. The mixture was stirred for 30 minutes, then the solvent was removed under reduced pressure to afford 3-methyl-2-[2-(4-piperidin-1-ylmethyl-phenyl)ethoxy]-6-pyridin-4-yl-3H-pyrimidin-4-one dihydrochloride as a pale purple solid (455 mg, 0.952 mmol, 42%).

後処理

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by silica gel column chromatography (eluent; ethyl acetate/methanol=90/10 to 67/33)
  6. customto afford a pale blue powder
  7. additionwas added at room temperature
  8. stirringThe mixture was stirred for 30 minutes
  9. customthe solvent was removed under reduced pressure

出典と根拠

ORDレコード
ord-16ef100bf10a4ee786350d9638076881
出典データセット
uspto-grants-2015_04
特許番号
US09006232B2

反応ノート

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