4-Methyl-2-(methylsulfanyl)pyrimidine → 1-Cyclopropyl-3-[2-(methylsulfanyl)pyrimidin-4-yl]propan-2-one

HRID 1397133

反応式

HRID 1397133 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=1.[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH:20]1([CH2:23][C:24](N(OC)C)=[O:25])[CH2:22][CH2:21]1>C1COCC1>[CH:20]1([CH2:23][C:24](=[O:25])[CH2:1][C:2]2[CH:7]=[CH:6][N:5]=[C:4]([S:8][CH3:9])[N:3]=2)[CH2:22][CH2:21]1

参加物

5

反応物 3

HCID 8212614-Methyl-2-(methylsulfanyl)pyrimidineHCID 2733832Lithium HexamethyldisilazideHCID 224737662-cyclopropyl-N-methoxy-N-methylacetamide

生成物 1

HCID 679835361-Cyclopropyl-3-[2-(methylsulfanyl)pyrimidin-4-yl]propan-2-one

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 4-methyl-2-(methylthio)pyrimidine (5.63 mL, 40.4 mmol) in THF (20 mL) at −10° C., LiHMDS (60.6 mL, 60.6 mmol) (1N in MBTE) was added dropwise under nitrogen. The reaction mixture coagulated, and stopped stifling. For this, additional THF (40 mL) was added to dissolve the highly viscous mixture. The reaction was warmed up to rt and was stirred for 30 minutes. The reaction mixture was re-cooled to −10° C., then 2-cyclopropyl-N-methoxy-N-methylacetamide (7.47 g, 40.4 mmol) was added dropwise. The reaction mixture was warmed up to rt, then stirred for an additional 2 hours. The reaction was partitioned between ammonium chloride solution and EtOAc. The organic layer was separated, and the aqueous layer was back-extracted. The organic extracts were combined, washed with brine, dried over sodium sulfate, then concentrated in vacuo. The crude product was purified by Biotage™ silica gel chromatography [100 g SNAP column, 10% EtOAc/heptane to 100% EtOAc] to obtain the desired product, which was still contaminated significantly with the starting material, 4-methyl-2-(methylthio)pyrimidine (5.63 g, 48% yield). The product was carried on to the next step without further purification. MS (ES+): m/z=223.2/224.3 (100/50) [MH+]. HPLC: tR=0.84 minute over 3 minutes. Purity: 77% [HPLC (LC/MS) at 220 nm].

後処理

  1. dissolutionto dissolve the highly viscous mixture
  2. temperatureThe reaction mixture was re-cooled to −10° C.
  3. temperatureThe reaction mixture was warmed up to rt
  4. stirringstirred for an additional 2 hours
  5. customThe reaction was partitioned between ammonium chloride solution and EtOAc
  6. customThe organic layer was separated
  7. extractionthe aqueous layer was back-extracted
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by Biotage™ silica gel chromatography [100 g SNAP column, 10% EtOAc/heptane to 100% EtOAc]

出典と根拠

ORDレコード
ord-d188960803b04d2f94bc2bfb69f83b26
出典データセット
uspto-grants-2014_12
特許番号
US08901147B2

関連ノート

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