Water → N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine

HRID 1621448ノート

反応式

HRID 1621448 の反応式
F[C:2]1[C:7]([C:8]2[N:16]=[C:15]([CH3:17])[N:14]=[C:13]3[C:9]=2[N:10]=[CH:11][N:12]3[CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[CH:6][C:5]([CH:24]=[CH2:25])=[CH:4][N:3]=1.[NH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.O>C1COCC1>[CH3:34][O:33][C:30]1[N:31]=[CH:32][C:27]([NH:26][C:2]2[C:7]([C:8]3[N:16]=[C:15]([CH3:17])[N:14]=[C:13]4[C:9]=3[N:10]=[CH:11][N:12]4[CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:6][C:5]([CH:24]=[CH2:25])=[CH:4][N:3]=2)=[CH:28][CH:29]=1

参加物

6

反応物 4

HCID 962WaterHCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 595484346-(2-fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

生成物 1

HCID 59548466N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine収率 31.2%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

6-(2-Fluoro-5-vinylpyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1.007 g, 2.967 mmol) and 5-amino-2-methoxypyridine (0.369 g, 2.97 mmol) were dissolved in THF (25 mL) and the reaction flask was cooled in an ice water bath. Then, LiHMDS (Aldrich, St. Louis, Mo., 1.0 M in THF, 9.0 mL, 9.0 mmol) was added via syringe, and the reaction was stirred under nitrogen for 35 minutes. Then, it was poured into water (50 mL), and the layers were separated. The aqueous phase was extracted with DCM, and the organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel column (40:1 DCM/2N ammonia in MeOH to 30:1 DCM/2N ammonia in MeOH) to give N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (410.3 mg, 85% purity, 20% yield over 2 steps). MS (ESI pos. ion) m/z 444 (M+H)+.

後処理

  1. temperaturethe reaction flask was cooled in an ice water bath
  2. customthe layers were separated
  3. extractionThe aqueous phase was extracted with DCM
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified on a silica gel column (40:1 DCM/2N ammonia in MeOH to 30:1 DCM/2N ammonia in MeOH)

出典と根拠

ORDレコード
ord-f5c063cded7f4ac68e1b401e21c68ba2
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

読み込み中…