Hydrochloric Acid → methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate

HRID 1187382ノート

反応式

HRID 1187382 の反応式
Cl[C:2]1[CH:17]=[CH:16][C:5]([C:6]([N:8]([CH3:15])[CH:9]2[CH2:14][CH2:13][O:12][CH2:11][CH2:10]2)=[O:7])=[C:4]([S:18][CH2:19][CH2:20][CH3:21])[N:3]=1.[NH:22]1[CH2:27][CH2:26][CH2:25][C@@H:24]([CH2:28][C:29]([O:31][CH3:32])=[O:30])[CH2:23]1.Cl.C(=O)([O-])[O-].[K+].[K+]>C(#N)CCC.C(Cl)Cl>[CH3:15][N:8]([CH:9]1[CH2:14][CH2:13][O:12][CH2:11][CH2:10]1)[C:6]([C:5]1[CH:16]=[CH:17][C:2]([N:22]2[CH2:27][CH2:26][CH2:25][C@@H:24]([CH2:28][C:29]([O:31][CH3:32])=[O:30])[CH2:23]2)=[N:3][C:4]=1[S:18][CH2:19][CH2:20][CH3:21])=[O:7]

参加物

7

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 40153895methyl 2-[(3S)-piperidin-3-yl]acetateHCID 580008806-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide

生成物 1

HCID 59830659methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate収率 57%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8008Butyronitrile溶媒

実験手順

6-chloro-N-methyl-2-(propylthio)-N-(tetrahydro-2H-pyran-4-yl)nicotinamide (0.398 g, 1.21 mmol) was added to (S)-methyl 2-(piperidin-3-yl)acetate.HCl (0.353 g, 1.82 mmol) and potassium carbonate (0.753 g, 5.45 mmol) in butyronitrile (3 mL) was heated at 150° C. for 4 hours. The reaction mixture was diluted with DCM (60 mL), and washed sequentially with water (20 mL) and brine (20 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM. Pure fractions were evaporated to dryness to afford methyl [(3S)-1-{5-[methyl(tetrahydro-2H-pyran-4-yl)carbamoyl]-6-(propylthio)pyridin-2-yl}piperidin-3-yl]acetate (0.310 g, 57%) as a white solid.

後処理

  1. washwashed sequentially with water (20 mL) and brine (20 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 100% EtOAc in DCM
  7. customPure fractions were evaporated to dryness

出典と根拠

ORDレコード
ord-c3b3b8f63116400d84c7e41afda9c313
出典データセット
uspto-grants-2014_03
特許番号
US08673938B2

反応ノート

読み込み中…