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

HRID 1366270Notes

Reaction equation

HRID 1366270 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-85958b74235a4b0e97f0067cc5893a5f
Source dataset
uspto-grants-2011_02
Patent number
US07893074B2

Reaction notes

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