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

HRID 1811860ノート

反応式

HRID 1811860 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/2 N ammonia in MeOH to 30:1 DCM/2 N 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/2 N ammonia in MeOH to 30:1 DCM/2 N ammonia in MeOH)

出典と根拠

ORDレコード
ord-0a8a655f59254c00b1a67ad211fd15fa
出典データセット
uspto-grants-2013_01
特許番号
US08362241B2

反応ノート

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