Potassium Phosphate, Tribasic → (2-(2-amino-3-morpholinoquinolin-6-yl)phenyl)(tetrahydro-2H-pyran-4-yl)methanone

HRID 1028955Notes

Reaction equation

HRID 1028955 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]([CH:10]1[CH2:15][CH2:14][O:13][CH2:12][CH2:11]1)=[O:9].[O:16]1[CH2:21][CH2:20][N:19]([C:22]2[C:23]([NH2:41])=[N:24][C:25]3[C:30]([CH:31]=2)=[CH:29][C:28](B2OC(C)(C)C(C)(C)O2)=[CH:27][CH:26]=3)[CH2:18][CH2:17]1.[O-]P([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>O1CCOCC1.O.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.C(Cl)(Cl)Cl.[Pd].[Pd]>[NH2:41][C:23]1[C:22]([N:19]2[CH2:20][CH2:21][O:16][CH2:17][CH2:18]2)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[C:8]([CH:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:9])[CH:29]=2)[N:24]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 63936269(2-Bromophenyl)(tetrahydro-2H-pyran-4-yl)methanoneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 53328643(2-(2-amino-3-morpholinoquinolin-6-yl)phenyl)(tetrahydro-2H-pyran-4-yl)methanone

Reagents, catalysts & solvents 3

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

(2-Bromophenyl)(tetrahydro-2H-pyran-4-yl)methanone (0.46 g, 1.69 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.50 g, 1.13 mmol, prepared as in Example 2, Step 1-2), potassium phosphate tribasic (0.37 mL, 4.50 mmol), 2-dicyclohexylphosphino-2′,4′,6′,-triisopropylbiphenyl (0.054 g, 0.113 mmol), and tris(dibenzylideneacetone)dipalladium (0) chloroform adduct (0.029 g, 0.028 mmol) were suspended in a mixture of dioxane (3 mL) and water (0.5 mL) and heated in the microwave to 120° C. for 30 min. The crude material was partitioned between water (100 mL) and ethyl acetate (200 mL). The organic layer was separated, dried with magnesium sulfate and evaporated to dryness under reduced pressure before purification using silica column chromatography (0-5% MeOH in DCM). The isolated material was further purified using silica column chromatography (60-100% ethyl acetate in hexane) to give (2-(2-amino-3-morpholinoquinolin-6-yl)phenyl)(tetrahydro-2H-pyran-4-yl)methanone. MS (ESI, pos. ion) m/z: 418 (M+1).

Workup

  1. customThe crude material was partitioned between water (100 mL) and ethyl acetate (200 mL)
  2. customThe organic layer was separated
  3. dry with materialdried with magnesium sulfate
  4. customevaporated to dryness under reduced pressure before purification
  5. customThe isolated material was further purified

Sources & evidence

ORD record
ord-1f21f75672b84a459e7fa0f278e92218
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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