Potassium Phosphate, Tribasic → HCID 67326082, compound

HRID 1029002Notes

Reaction equation

HRID 1029002 reaction equation
[O:1]1[CH2:6][CH2:5][N: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.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:70]1[C:75]([CH3:76])=[CH:74][CH:73]=[CH:72][C:71]=1[C:77]1[O:78][C:79]([CH3:82])=[CH:80][N:81]=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:76][C:75]1[CH:74]=[CH:73][CH:72]=[C:71]([C:77]2[O:78][C:79]([CH3:82])=[CH:80][N:81]=2)[C:70]=1[C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[N:9]=[C:8]([NH2:26])[C:7]([N:4]1[CH2:3][CH2:2][O:1][CH2:6][CH2:5]1)=[CH:16]2

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67325513HCID 67325513, compoundHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 67326082HCID 67326082, compound

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
130 °C

Procedure

A glass microwave reaction vessel was charged with 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.055 g, 0.155 mmol, prepared as in Example 2, Step 1-2), potassium phosphate (0.131 g, 0.619 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (0.015 g, 0.031 mmol), Pd2 dba3 (0.142 g, 0.155 mmol), and 2-(2-bromo-3-methylphenyl)-5-methyloxazole (0.078 g, 0.310 mmol). The vessel was evacuated and flushed with N2 3× before dioxane (1.00 mL) and water (0.500 mL) (each degassed by bubbling N2 gas through the solution for 10 min prior to addition) were added. The reaction mixture was stirred and heated in a microwave reactor at 130° C. for 15 min. 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. The crude material was purified by silica gel chromatography by eluting with 1:15:15 2M NH3 in MeOH/dichloromethane/sdiethyl ether, to provide the desired product which after triturating with diethyl ether gave 6-(2-methyl-6-(5-methyloxazol-2-yl)phenyl)-3-morpholinoquinolin-2-amine. MS (ESI, pos. ion) m/z: 401 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. customThe vessel was evacuated
  3. customflushed with N2 3× before dioxane (1.00 mL) and water (0.500 mL) (
  4. customeach degassed
  5. customby bubbling N2 gas through the solution for 10 min
  6. additionto addition)
  7. additionwere added
  8. additionThe reaction mixture was diluted with 10:1 saturated ammonium chloride/ammonium hydroxide
  9. extractionextracted with EtOAc
  10. washThe combined organic extracts were washed with 10:1 saturated ammonium chloride/ammonium hydroxide, water, saturated sodium chloride
  11. dry with materialdried over sodium sulfate
  12. filtrationThe solution was filtered
  13. concentrationconcentrated in vacuo
  14. customto give the crude material
  15. customThe crude material was purified by silica gel chromatography
  16. washby eluting with 1:15:15 2M NH3 in MeOH/dichloromethane/sdiethyl ether

Sources & evidence

ORD record
ord-8bf9a1f3f22145b48585a81823651d4a
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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