Potassium Phosphate, Tribasic → HCID 67376680, compound

HRID 1028992Notes

Reaction equation

HRID 1028992 reaction equation
[O:1]1[CH2:6][CH:5]=[C:4]([C:7]2[C:8]([NH2:26])=[N:9][C:10]3[C:15]([CH:16]=2)=[CH:14][C:13](B2OC(C)(C)C(C)(C)O2)=[CH:12][CH:11]=3)[CH2:3][CH2:2]1.C([O-])(=O)C.[K+].I[C:33]1[C:38]([CH3:39])=[CH:37][CH:36]=[CH:35][C:34]=1[C:40]([N:42]1[CH2:46][CH2:45][CH2:44][CH2:43]1)=[O:41].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)CCCCC1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH2:26][C:8]1[C:7]([C:4]2[CH2:3][CH2:2][O:1][CH2:6][CH:5]=2)=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:33]3[C:38]([CH3:39])=[CH:37][CH:36]=[CH:35][C:34]=3[C:40]([N:42]3[CH2:46][CH2:45][CH2:44][CH2:43]3)=[O:41])[CH:14]=2)[N:9]=1

Participants

8

Reactant 5

HCID 62657Potassium Phosphate, TribasicHCID 517044Potassium AcetateHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 67324630HCID 67324630, compoundHCID 71253416HCID 71253416, compound

Product 1

HCID 67376680HCID 67376680, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)Catalyst

Conditions

Temperature
130 °C

Procedure

A glass microwave reaction vessel was charged with 3-(3,6-dihydro-2H-pyran-4-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.058 g, 0.165 mmol), potassium acetate (0.032 g, 0.329 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (5.83 mg, 8.23 μmol), and (2-iodo-3-methylphenyl)(pyrrolidin-1-yl)methanone (0.078 g, 0.247 mmol). The vessel was evacuated and flushed with N2 gas 3× before EtOH1 (1.6 mL) and water (0.23 mL) (each degassed by bubbling N2 gas through the solution for 10 min prior to addition) was added. The reaction mixture was stirred and heated in a microwave reactor at 130° C. for 10 min. 2-(Dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.012 g, 0.026 mmol), potassium phosphate tribasic (0.041 mL, 0.494 mmol), Pd2(dba)3 (7.54 mg, 8.23 μmol) were added and the reaction was degassed and heated in the Initiator microwave reactor again for 20 min at 130° C. The reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide and extracted with EtOAc. The combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, water, saturated sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to give the crude material which was purified by silica gel chromatography by eluting with 1:20 2M NH3 in MeOH/DCM, to provide (2-(2-amino-3-(3,6-dihydro-2H-pyran-4-yl)quinolin-6-yl)-3-methylphenyl)(pyrrolidin-1-yl)methanone.

Workup

  1. customA glass microwave reaction vessel
  2. customThe vessel was evacuated
  3. customflushed with N2 gas 3× before EtOH1 (1.6 mL) and water (0.23 mL) (
  4. customeach degassed
  5. customby bubbling N2 gas through the solution for 10 min
  6. additionto addition)
  7. additionwas added
  8. customthe reaction was degassed
  9. temperatureheated in the Initiator microwave reactor again for 20 min at 130° C
  10. additionThe reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide
  11. extractionextracted with EtOAc
  12. washThe combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, water, saturated sodium chloride
  13. dry with materialdried over sodium sulfate
  14. filtrationThe solution was filtered
  15. concentrationconcentrated in vacuo
  16. customto give the crude material which
  17. customwas purified by silica gel chromatography
  18. washby eluting with 1:20 2M NH3 in MeOH/DCM

Sources & evidence

ORD record
ord-288ae381e22e45ddb943e45a43ec9c2d
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

Loading…