Potassium Carbonate → HCID 66890986, compound

HRID 1897942Notes

Reaction equation

HRID 1897942 reaction equation
[CH2:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.C12BC(CCC1)CCC2.Cl[C:25]1[N:30]=[C:29]([NH:31][C:32]2[CH:36]=[CH:35][N:34]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[N:33]=2)[CH:28]=[C:27]([CH3:45])[N:26]=1.C1([As](C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+].C12B(CC3CCN(C(OC(C)(C)C)=O)CC3)C(CCC1)CCC2>O1CCCC1.CN(C)C=O.O>[CH3:45][C:27]1[CH:28]=[C:29]([NH:31][C:32]2[CH:36]=[CH:35][N:34]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:42])([CH3:44])[CH3:43])[N:33]=2)[N:30]=[C:25]([CH2:1][CH:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]2)[N:26]=1

Participants

10

Reactant 6

HCID 11430Potassium Carbonate3×HCID 11773Triphenylarsine3×HCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-MethylenepiperidineHCID 66768828HCID 66768828, compoundHCID 86649624HCID 86649624, compound

Product 1

HCID 66890986HCID 66890986, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To 116.2 mg of tert-butyl 4-methylenepiperidine-1-carboxylate was added a solution of 71.3 mg of 9-borabicyclo[3.3.1] nonane in 2 ml of tetrahydrofuran at room temperature. The reaction mixture was stirred at 90° C. for 1.5 hours, cooled to room temperature, and added to a suspension of 106.8 mg of 2-chloro-6-methyl-N-(1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazol-3-yl)pyrimidin-4-amine, 12.3 mg of (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II)-dichloromethane complex, 4.3 mg of triphenylarsine and 49.8 mg of potassium carbonate in 2 ml of N,N-dimethylformamide and 0.2 ml of water. The reaction mixture was stirred at 60° C. for 8 hours. 12.4 mg of (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II)-dichloromethane complex, 4.8 mg of triphenylarsine and 47.3 mg of potassium carbonate was added to the reaction mixture, followed by stirring the reaction mixture at 60° C. for 13 hours, 90° C. for 1.5 hours and 100° C. for 2.5 hours. 13.7 mg of (1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II)-dichloromethane complex, 5.0 mg of triphenylarsine, 47.1 mg of potassium carbonate and a solution of tert-butyl 4-(9-borabicyclo[3.3.1]non-9-ylmethyl)piperidine-1-carboxylate (prepared from 117.6 mg of tert-butyl 4-methylenepiperidine-1-carboxylate and 145.2 mg of 9-borabicyclo[3.3.1]nonane in 2.5 ml of tetrahydrofuran at 100° C. for 3 hours) were added to the reaction mixture, followed by stirring the reaction mixture at 100° C. for 4.5 hours. The reaction mixture was cooled to room temperature, poured into water, and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=8/1 to ethyl acetate) to give the title compound.

Workup

  1. temperaturecooled to room temperature
  2. stirringThe reaction mixture was stirred at 60° C. for 8 hours
  3. stirringby stirring the reaction mixture at 60° C. for 13 hours
  4. wait90° C. for 1.5 hours
  5. wait100° C. for 2.5 hours
  6. stirringby stirring the reaction mixture at 100° C. for 4.5 hours
  7. temperatureThe reaction mixture was cooled to room temperature
  8. extractionextracted with ethyl acetate
  9. washThe organic layer was washed with brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationThe filtrate was concentrated in vacuo
  13. customThe resulting residue was purified by a silica gel column chromatography (eluent: hexane/ethyl acetate=8/1 to ethyl acetate)

Sources & evidence

ORD record
ord-8436a31cb0094335ae10e4f2fce6d60e
Source dataset
uspto-grants-2013_08
Patent number
US08519136B2

Reaction notes

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