Tetrahydrofuran → N-(6-methoxypyridin-3-yl)-3-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine

HRID 1621400ノート

反応式

HRID 1621400 の反応式
[Li+].C[Si]([N-][Si](C)(C)C)(C)C.C1COCC1.F[C:17]1[C:22]([C:23]2[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([S:30][CH3:31])[N:24]=2)=[CH:21][C:20]([CH2:32][N:33]2[CH2:38][CH2:37][N:36]([S:39]([CH3:42])(=[O:41])=[O:40])[CH2:35][CH2:34]2)=[CH:19][N:18]=1.[NH2:43][C:44]1[CH:45]=[N:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=1>[NH4+].[Cl-].O.C(OCC)(=O)C>[CH3:51][O:50][C:47]1[N:46]=[CH:45][C:44]([NH:43][C:17]2[C:22]([C:23]3[N:28]=[C:27]([CH3:29])[N:26]=[C:25]([S:30][CH3:31])[N:24]=3)=[CH:21][C:20]([CH2:32][N:33]3[CH2:38][CH2:37][N:36]([S:39]([CH3:42])(=[O:40])=[O:41])[CH2:35][CH2:34]3)=[CH:19][N:18]=2)=[CH:49][CH:48]=1

参加物

8

反応物 4

HCID 8028Tetrahydrofuran2 回HCID 811216-Methoxy-3-pyridinylamineHCID 2733832Lithium HexamethyldisilazideHCID 595481882-(2-Fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine

生成物 1

HCID 66599816N-(6-methoxypyridin-3-yl)-3-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine収率 60.9%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒

実験手順

LiHMDS, 1.0 M in THF (0.754 mL, 0.754 mmol) was added dropwise to a stirred solution of 2-(2-fluoro-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-3-yl)-4-methyl-6-(methylthio)-1,3,5-triazine (0.311 g, 0.754 mmol) (Example 34, Step 5) and 3-amino-6-methoxypyridine (0.094 g, 0.754 mmol) in tetrahydrofuran (10 mL, 0.754 mmol) at −10° C. and the mixture was stirred at the same temperature for 1 h. The reaction mixture was diluted with NH4Cl(aq) and water (10 mL each) and diluted with ethyl acetate (20 mL). The separated aqueous layer was extracted with ethyl acetate (2×20 mL) and the combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by flash column chromatography (ISCO Combiflash system, Teledyne ISCO, Lincoln, Nebr., DCM to 5% MeOH in DCM) to give N-(6-methoxypyridin-3-yl)-3-(4-methyl-6-(methylthio)-1,3,5-triazin-2-yl)-5-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyridin-2-amine (237 mg, 0.459 mmol, 60.8% yield) as a yellow solid.

後処理

  1. extractionThe separated aqueous layer was extracted with ethyl acetate (2×20 mL)
  2. washthe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (ISCO Combiflash system, Teledyne ISCO, Lincoln, Nebr., DCM to 5% MeOH in DCM)

出典と根拠

ORDレコード
ord-39c36db1cfd848eeb2696b1ef047b969
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

反応ノート

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