Hydrochloric Acid → 2-({5-Chloro-2-[2-methoxy-4-(morpholin-4-yl)anilino]pyrimidin-4-yl}amino)-N-methylbenzamide

HRID 2382636Notes

Reaction equation

HRID 2382636 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([Cl:19])=[CH:4][N:3]=1.Cl.Cl.[CH3:22][O:23][C:24]1[CH:30]=[C:29]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)[CH:28]=[CH:27][C:25]=1[NH2:26].Cl.[OH-].[Na+]>COCCO>[Cl:19][C:5]1[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])=[N:7][C:2]([NH:26][C:25]2[CH:27]=[CH:28][C:29]([N:31]3[CH2:32][CH2:33][O:34][CH2:35][CH2:36]3)=[CH:30][C:24]=2[O:23][CH3:22])=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 116233102-Methoxy-4-morpholinoaniline dihydrochlorideHCID 579741322-(2,5-Dichloropyrimidin-4-ylamino)-N-methylbenzamide

Product 1

HCID 99343472-({5-Chloro-2-[2-methoxy-4-(morpholin-4-yl)anilino]pyrimidin-4-yl}amino)-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 80192-MethoxyethanolSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of 2-(2,5-dichloro-pyrimidin-4-yl-amino)-N-methyl-benzamide (5.05 g, 17.0 mmol) in 90 mL of 2-methoxyethanol are added 2-methoxy-4-morpholinoaniline dihydrochloride (4.56 g, 16.2 mmol) and 17.0 mL of 1N ethanolic solution of hydrogen chloride (17.0 mmol). After the reaction mixture is stirred at 110° C. for 4 hours and cooled to room temperature, the mixture is neutralized with 1N aqueous NaOH solution and extracted with EtOAc (100 mL×3). The organic layer is washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The resulting black solid is washed with EtOH (90 mL), then purified with silica gel column chromatography (CH2Cl2 to CH2Cl2:AcOEt=1:2) to give 2-[5-chloro-2-(2-methoxy-4-morpholin-4-yl-phenylamino)-pyrimidin-4-ylamino]-N-methyl-benzamide as a pale yellow solid.

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc (100 mL×3)
  3. washThe organic layer is washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. washThe resulting black solid is washed with EtOH (90 mL)
  7. custompurified with silica gel column chromatography (CH2Cl2 to CH2Cl2:AcOEt=1:2)

Sources & evidence

ORD record
ord-8f32af53e45d4fa7a240ed3787efbe05
Source dataset
uspto-grants-2012_09
Patent number
US08263590B2

Reaction notes

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