Potassium Carbonate → HCID 117667023, compound

HRID 1526248Notes

Reaction equation

HRID 1526248 reaction equation
[CH2:1]([N:4]1[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1)[CH:2]=[CH2:3].C12BC(CCC1)CCC2.[NH2:19][C:20]1[CH:21]=[C:22]([CH:48]=[CH:49][CH:50]=1)[O:23][C:24]1[N:25]=[C:26]([NH:33][C:34]2[CH:39]=[CH:38][C:37]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]3)=[C:36](Br)[CH:35]=2)[C:27]([C:30]([NH2:32])=[O:31])=[N:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)(Cl)Cl.O.CN(C)C=O.O1CCCC1>[NH2:19][C:20]1[CH:21]=[C:22]([CH:48]=[CH:49][CH:50]=1)[O:23][C:24]1[N:25]=[C:26]([NH:33][C:34]2[CH:35]=[CH:36][C:37]([N:40]3[CH2:45][CH2:44][N:43]([CH3:46])[CH2:42][CH2:41]3)=[C:38]([CH2:3][CH2:2][CH2:1][N:4]3[CH2:9][CH2:8][O:7][CH2:6][CH2:5]3)[CH:39]=2)[C:27]([C:30]([NH2:32])=[O:31])=[N:28][CH:29]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 789669-Borabicyclo(3.3.1)nonaneHCID 136522AllylmorpholineHCID 117667097HCID 117667097, compound

Product 1

HCID 117667023HCID 117667023, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Under an argon atmosphere, to a mixture of N-allylmorpholine (274 μL) and tetrahydrofuran (5 mL) was added 9-borabicyclo[3.3.1]nonane (0.5 M tetrahydrofuran solution 4.01 mL) under ice-cooling, followed by stirring at 60° C. for 1 hour. After leaving to be cooled, to the reactant were added a mixture of 5-(3-aminophenoxy)-3-{[3-bromo-4-(4-methylpiperazin-1-yl)phenyl]amino}pyrazine-2-carboxamide (1 g), N,N-dimethylformamide (10 mL), and potassium carbonate (1.39 g), water (1 mL), and a 1,1′-bis(diphenylphosphino)ferrocene palladium (II) dichloride-dichloromethane complex (164 mg), followed by stirring at 60° C. for 40 hours. The reactant was left to be cooled, and then chloroform was added thereto. Then, the insoluble matter was separated by filtration. The filtrate was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent: chloroform:methanol:28% aqueous ammonia=1000:10:1-150:10:1) to obtain 5-(3-aminophenoxy)-3-({4-(4-methylpiperazin-1-yl)-3-[3-(morpholin-4-yl) propyl]phenyl}amino)pyrazine-2-carboxamide (67 mg) as a pale yellow amorphous substance.

Workup

  1. temperaturecooling
  2. customAfter leaving
  3. temperatureto be cooled, to the reactant
  4. additionwere added
  5. stirringby stirring at 60° C. for 40 hours
  6. waitThe reactant was left
  7. temperatureto be cooled
  8. customThen, the insoluble matter was separated by filtration
  9. washThe filtrate was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated under reduced pressure
  12. customThe obtained residue was purified by silica gel column chromatography (eluent: chloroform:methanol:28% aqueous ammonia=1000:10:1-150:10:1)

Sources & evidence

ORD record
ord-0644686c17184e42b1be5643fb9c5c9a
Source dataset
uspto-grants-2015_07
Patent number
US09085540B2

Reaction notes

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