Thionyl Chloride → HCID 57444338, compound

HRID 2373623Notes

Reaction equation

HRID 2373623 reaction equation
C[Al](C)C.[CH3:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][C:12]=2[N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]3[CH:25]=[C:26]([CH:28]=[CH:29][CH:30]=3)[NH2:27])[CH2:18][CH2:17]2)[N:7]=1.[F:31][C:32]1[C:37]2[C:38](=O)[O:39][CH2:40][C:36]=2[CH:35]=[CH:34][CH:33]=1.S(Cl)([Cl:44])=O>ClCCl>[Cl:44][CH2:40][C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([F:31])[C:37]=1[C:38]([NH:27][C:26]1[CH:28]=[CH:29][CH:30]=[C:24]([CH2:23][CH2:22][N:19]2[CH2:18][CH2:17][N:16]([C:12]3[CH:11]=[CH:10][CH:9]=[C:8]4[C:13]=3[CH:14]=[CH:15][C:6]([CH3:5])=[N:7]4)[CH2:21][CH2:20]2)[CH:25]=1)=[O:39]

Participants

6

Reactant 4

HCID 24386Thionyl ChlorideHCID 34023357-Fluoro-1(3H)-isobenzofuranoneHCID 16682925TrimethylaluminumHCID 498521053-(2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline

Product 1

HCID 57444338HCID 57444338, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of trimethylaluminium (2.0 M in hexane, 1 eq) was added slowly to a stirred solution of 3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}aniline (D6) (1 eq) in dichloromethane (0.1 M) at 0° C. The reaction mixture was stirred for 15 min then a solution of 7-fluoro-2-benzofuran-1(3H)-one (1 eq, Chem. Pharm. Bull., 1985, 33(7), 2809-2820) in DCM was added dropwise. The solution was stirred for 2 h at 0° C. then partitioned between saturated aqueous ammonium chloride solution and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated under reduced pressure. The crude 2-fluoro-6-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in DCM and to 0° C. To the stirred solution was added dropwise thionyl chloride (1 eq.). The reaction mixture was warmed to room temperature, stirred for 1 hour then partitioned between saturated aqueous sodium hydrogencarbonate solution and DCM. The organic phase was dried over sodium sulfate, filtered and the solvent removed under reduced pressure. The crude 2-(chloromethyl)-6-fluoro-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide thus obtained was dissolved in methanol and cooled to 0° C. To the stirred solution was added sodium methoxide (1.2 eq.) portionwise. The solution was warmed to room temperature and stirred for 18 hours. The solution was concentrated and partitioned between water and dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on SPE cartridge (Silica) eluting with DCM-methanol (96:4) affording the title compound (yield 24%).

Workup

  1. stirringThe solution was stirred for 2 h at 0° C.
  2. customthen partitioned between saturated aqueous ammonium chloride solution and ethyl acetate
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe crude 2-fluoro-6-(hydroxymethyl)-N-(3-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)benzamide was dissolved in DCM and to 0° C
  6. stirringstirred for 1 hour
  7. customthen partitioned between saturated aqueous sodium hydrogencarbonate solution and DCM
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. filtrationfiltered
  10. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-da80bd1b5e7341b5a81a80e62ce9d878
Source dataset
uspto-grants-2008_12
Patent number
US07459456B2

Reaction notes

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