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 1811812노트

반응식

HRID 1811812 반응식
[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

참가 물질

8

반응물 4

HCID 8028Tetrahydrofuran2회HCID 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

생성물 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-amine수율 60.9%

시약·촉매·용매 3

HCID 962Water용매HCID 8857Ethyl Acetate용매HCID 25517Ammonium Chloride용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-75ae2794721344f4ad69e8d582274e13
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362241B2

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