Sodium hydride → 7-chloro-1-(5-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine

HRID 1618675ノート

反応式

HRID 1618675 の反応式
[Cl:1][C:2]1[CH:11]=[N:10][C:5]2[S:6][CH2:7][CH2:8][NH:9][C:4]=2[CH:3]=1.[H-].[Na+].Cl[C:15]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][C:23]=2[F:25])[N:18]=[C:17]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=2)[C:16]=1[CH3:32]>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[N:10][C:5]2[S:6][CH2:7][CH2:8][N:9]([C:15]3[C:24]4[C:19](=[CH:20][CH:21]=[CH:22][C:23]=4[F:25])[N:18]=[C:17]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][N:27]=4)[C:16]=3[CH3:32])[C:4]=2[CH:3]=1

参加物

5

反応物 3

HCID 24758Sodium hydride2 回HCID 596312094-Chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinolineHCID 672853597-chloro-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine

生成物 1

HCID 672850997-chloro-1-(5-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirred solution of 7-chloro-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine (100 mg, 0.536 mmol) in DMF (2.0 mL) was added sodium hydride (28.0 mg, 0.643 mmol, 55% dispersion in oil) under a N2 atmosphere. The reaction was stirred at rt for 15 min. After this time 4-chloro-5-fluoro-3-methyl-2-(pyridin-2-yl)quinoline (146 mg, 0.536 mmol) in DMF (3.0 mL) was added and the reaction was heated at 60° C. for 1 h and at 100° C. overnight. After this time more NaH (28.0 mg, 0.643 mmol, 55% dispersion in oil) was added and the reaction was heated at 120° C. for 3 h. The reaction was then cooled to rt and partitioned between EtOAc and water. The separated organic layer was washed with LiCl (1.0M aqueous solution) and then it was dried over MgSO4, filtered and evaporated in vacuo. Column chromatography (Hexanes:EtOAc, 1:0 to 1:1) gave 7-chloro-1-(5-fluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-yl)-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazine as a yellow film. Mass Spectrum (ESI) m/e=423.0 (M+1).

後処理

  1. temperaturethe reaction was heated at 60° C. for 1 h and at 100° C. overnight
  2. temperaturethe reaction was heated at 120° C. for 3 h
  3. temperatureThe reaction was then cooled to rt
  4. custompartitioned between EtOAc and water
  5. washThe separated organic layer was washed with LiCl (1.0M aqueous solution)
  6. dry with materialit was dried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo

出典と根拠

ORDレコード
ord-4067688e59dc47559a91441b1fe923bf
出典データセット
uspto-grants-2014_07
特許番号
US08765940B2

反応ノート

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