Dichloromethane → HCID 178516664, compound

HRID 1068020Notes

Reaction equation

HRID 1068020 reaction equation
ClC1C=CC(C[C:7]2[C:16]([C:17](=[S:19])[NH2:18])=[C:15]([OH:20])[C:14]3[C:9](=[CH:10][CH:11]=[C:12]([CH2:21]O)[CH:13]=3)[N:8]=2)=CC=1.CN([C:28]1[CH:33]=C[CH:31]=[CH:30][N:29]=1)C.N1[C:39](C)=[CH:38][C:37]([CH3:41])=[CH:36][C:35]=1C.CS(Cl)(=O)=[O:45].[CH2:48]([Cl:50])Cl>CN(C)C=O>[Cl:50][C:48]1[CH:35]=[CH:36][C:37]([CH2:41][NH:18][C:17]([C:16]2[CH:7]=[N:8][C:9]3[C:14]([C:15]=2[OH:20])=[CH:13][C:12]([CH2:21][N:29]2[CH2:30][CH2:31][O:45][CH2:33][CH2:28]2)=[CH:11][CH:10]=3)=[S:19])=[CH:38][CH:39]=1

Participants

7

Reactant 5

HCID 6344DichloromethaneHCID 79532,4,6-TrimethylpyridineHCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 178514133HCID 178514133, compound

Product 1

HCID 178516664HCID 178516664, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-(4-chlorobenzyl-4-hydroxy-6-(hydroxymethyl)-3-quinolinecarbothioamide (0.082 g) from Preparation No. 46 in anhydrous dimethylformamide (4 mL) in a flame-dried flask is added dimethylaminopyridine (0.011 g), 2,4,6-collidine (0.035 mL), and methanesulfonyl chloride (0.017 mL). The reaction mixture is stirred at room temperature for 1 h after which time thin layer chromatography indicates starting material is nearly consumed. Morpholine (0.20 mL) is added in one portion. The reaction is stirred for 1.5 h and then poured into water. The aqueous solution is extracted 2× with CH2Cl2 and 2× with 3% MeOH:CH2Cl2. The organics are combined, dried over Na2SO4, filtered, and concentrated. Residual DMF is removed on the vacuum pump. The residue is dissolved in CH2Cl2 and hexanes was added to give a solid (starting material) which is filtered and dried. Upon allowing this filtrate to evaporate overnight, a second solid is obtained. This solid is dissolved in CH2Cl2 and adsorbed onto silica. Purification by chromatography (eluent CH2Cl2 (1 L), 1% MeOH:CH2Cl2 (1 L), 2% MeOH:CH2Cl2 (1 L) 2.5% MeOH:CH2Cl2 (1 L), 3% MeOH:CH2Cl2 (2 L)) affords N-(4-chlorobenzyl)-4-hydroxy-6-(4-morpholinylmethyl)-3-quinolinecarbothioamide (0.028 g) as a yellow solid.

Workup

  1. customis nearly consumed
  2. additionMorpholine (0.20 mL) is added in one portion
  3. stirringThe reaction is stirred for 1.5 h
  4. additionpoured into water
  5. extractionThe aqueous solution is extracted 2× with CH2Cl2 and 2× with 3% MeOH
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customResidual DMF is removed on the vacuum pump
  10. dissolutionThe residue is dissolved in CH2Cl2
  11. additionhexanes was added
  12. customto give a solid (starting material) which
  13. filtrationis filtered
  14. customdried
  15. customto evaporate overnight
  16. customa second solid is obtained
  17. customPurification by chromatography (eluent CH2Cl2 (1 L), 1% MeOH:CH2Cl2 (1 L), 2% MeOH:CH2Cl2 (1 L) 2.5% MeOH:CH2Cl2 (1 L), 3% MeOH:CH2Cl2 (2 L))

Sources & evidence

ORD record
ord-eef4375eb8f84c2dbe23a5c0f7333df9
Source dataset
uspto-grants-2001_06
Patent number
US06248739B1

Reaction notes

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