Potassium Phosphate, Tribasic → HCID 53329357, compound

HRID 1029000Notes

Reaction equation

HRID 1029000 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][CH:79]=[C:80]([CH3:82])[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][CH:79]=[C:80]([CH3:82])[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 67325699HCID 67325699, compoundHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 53329357HCID 53329357, 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(dba)3 (7.09 mg, 7.74 μmol), and 2-(2-bromo-3-methylphenyl)-4-methyloxazole (0.078 g, 0.310 mmol). The vessel was evacuated and flushed with nitrogen three times before dioxane (1.0 mL) and water (0.50 mL) (each degassed by bubbling nitrogen gas through the solution for 10 min prior to addition) were added. The reaction mixture was stirred and heated in a microwave 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 which was purified by silica gel chromatography by eluting with 1:15:15 2M NH3 in MeOH/DCM/diethyl ether to provide the desired product which after triturating with diethyl ether gave 6-(2-methyl-6-(4-methyloxazol-2-yl)phenyl)-3-morpholinoquinolin-2-amine as white solid. MS (ESI, pos. ion) m/z: 401 (M+1).

Workup

  1. customA glass microwave reaction vessel
  2. customThe vessel was evacuated
  3. customflushed with nitrogen three times before dioxane (1.0 mL) and water (0.50 mL) (
  4. customeach degassed
  5. customby bubbling nitrogen 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 which
  15. customwas purified by silica gel chromatography
  16. washby eluting with 1:15:15 2M NH3 in MeOH/DCM/diethyl ether

Sources & evidence

ORD record
ord-4135699ad4664174823cb930288e4abd
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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