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 1618675Notes

Reaction equation

HRID 1618675 reaction equation
[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

Participants

5

Reactant 3

HCID 24758Sodium hydride2×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

Product 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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-4067688e59dc47559a91441b1fe923bf
Source dataset
uspto-grants-2014_07
Patent number
US08765940B2

Reaction notes

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