Potassium Phosphate, Tribasic → (2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrazin-2-yl)methanol

HRID 1029011Notes

Reaction equation

HRID 1029011 reaction equation
Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]([C:11]1[CH:16]=[N:15][CH:14]=[CH:13][N:12]=1)[OH:10].[O:17]1[CH2:22][CH2:21][N:20]([C:23]2[C:24]([NH2:42])=[N:25][C:26]3[C:31]([CH:32]=2)=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=3)[CH2:19][CH2:18]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(CCC)=CC(CCC)=CC=2CCC)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.[Pd].[Pd]>[NH2:42][C:24]1[C:23]([N:20]2[CH2:21][CH2:22][O:17][CH2:18][CH2:19]2)=[CH:32][C:31]2[C:26](=[CH:27][CH:28]=[C:29]([C:2]3[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=3[CH:9]([C:11]3[CH:16]=[N:15][CH:14]=[CH:13][N:12]=3)[OH:10])[CH:30]=2)[N:25]=1

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 21081571Dicyclohexyl(2',4',6'-tripropyl-[1,1'-biphenyl]-2-yl)phosphineHCID 67325817(2-Bromo-3-methylphenyl)(pyrazin-2-yl)methanolHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

Product 1

HCID 53329361(2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrazin-2-yl)methanol

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
140 °C

Procedure

A mixture of (2-bromo-3-methylphenyl)(pyrazin-2-yl)methanol (0.295 g, 1.056 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.25 g, 0.704 mmol, prepared as Example 2, Step 1-2), potassium phosphate tribasic (0.291 mL, 3.52 mmol), Pd2(dba)3 (0.064 g, 0.070 mmol), and 2-(dicyclohexylphosphino)-2′,4′,6′,-tri-1-propyl-1,1′-biphenyl (0.067 g, 0.141 mmol) in dioxane/water (3/1.5 mL) was heated in a microwave for 12 min at 140° C. The mixture was concentrated and chromatographed on silica gel using 0-5% 2M NH3 in MeOH/DCM to afford a brown oil which was re-purified by HPLC to afford (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(pyrazin-2-yl)methanol as a yellow solid. MS (ESI, pos. ion) m/z: 428 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. customchromatographed on silica gel using 0-5% 2M NH3 in MeOH/DCM
  3. customto afford a brown oil which
  4. customwas re-purified by HPLC

Sources & evidence

ORD record
ord-3a7a7471567645eeb92ce8c6b4b67c69
Source dataset
uspto-grants-2014_05
Patent number
US08735384B2

Reaction notes

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