Hydrochloric Acid → 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-N-{4-methyl-3-[4-(4-pyridyl)thiazol-2-ylamino]phenyl}benzamide

HRID 13795

Reaction equation

HRID 13795 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:28]=[CH:27][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([NH:23][C:24]([NH2:26])=[S:25])[CH:17]=3)=[O:14])=[CH:11][C:10]=2[C:29]([F:32])([F:31])[F:30])[CH2:4][CH2:3]1.Cl.Br.Br[CH2:36][C:37]([C:39]1[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=1)=O.C(=O)([O-])O.[Na+]>O.C(O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:9]2[CH:28]=[CH:27][C:12]([C:13]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[C:18]([NH:23][C:24]4[S:25][CH:36]=[C:37]([C:39]5[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=5)[N:26]=4)[CH:17]=3)=[O:14])=[CH:11][C:10]=2[C:29]([F:32])([F:31])[F:30])[CH2:4][CH2:3]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 27762394-(Bromoacetyl)pyridine hydrobromideHCID 231459314-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-N-[4-methyl-3-(thioureido)phenyl]benzamide

Product 1

HCID 117863684-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-N-{4-methyl-3-[4-(4-pyridyl)thiazol-2-ylamino]phenyl}benzamideYield 82.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent2×

Conditions

Temperature
65 °C

Procedure

To 697 mg of 4-(4-methylpiperazin-1-ylmethyl)-3-trifluoromethyl-N-[4-methyl-3-(thioureido)phenyl]benzamide (Reference Example 33) were added in turn 3 ml of ethanol, 1.5 ml of water and 1.5 ml of 1 N hydrochloric acid, and the mixture was heated in an oil bath at 65° C. 6 ml of an aqueous solution of 421 mg of 4-(bromoacetyl)pyridine hydrobromide (J. Heterocycl. Chem., 1970, 7, 1137-1141) was added thereto, and the mixture was stirred for 2 hours. After air-cooling the reaction solution, the reaction solution was diluted with water, alkalified by adding an aqueous saturated sodium hydrogen carbonate solution, followed by extraction with ethyl acetate and dried over anhydrous magnesium sulfate. Then, the solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain 701 mg of the objective compound as colorless crystals.

Workup

  1. temperatureAfter air-cooling the reaction solution
  2. extractionfollowed by extraction with ethyl acetate
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationThen, the solvent was distilled off under reduced pressure
  5. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9954bf6b7f9d434e8cf4c3772dbef2b1
Source dataset
uspto-grants-2010_06
Patent number
US07728131B2

Linked notes

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