Hydrochloric Acid → HCID 67298513, compound

HRID 1520382Notes

Reaction equation

HRID 1520382 reaction equation
Br[C:2]1[C:3]([CH3:20])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[N:6]=[C:5]2[NH:18][CH3:19].[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[ClH:40]>O1CCOCC1.O.C(O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[ClH:40].[ClH:40].[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[C:2]1[C:3]([CH3:20])=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[N:6]=[C:5]2[NH:18][CH3:19]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 62657Potassium Phosphate, TribasicHCID 27343342,4-Difluorophenylboronic acidHCID 71274524HCID 71274524, compound

Product 1

HCID 67298513HCID 67298513, compoundYield 30%

Reagents, catalysts & solvents 4

HCID 178418807HCID 178418807, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-Bromo-N,5-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine (350 mg, 1.06 mmol), 2,4-difluorophenylboronic acid (252 mg, 1.595 mmol), K3PO4 (677 mg, 3.19 mmol) and Pd(dppf)Cl2—CH2Cl2 (87 mg, 0.106 mmol) were dissolved in the mixed solvent of 1,4-dioxane (10 mL) and water (1 mL). The resulting mixture was stirred at 90° C. for 2.5 hours under N2. After the reaction was completed, water was added to the mixture and extracted with ethyl acetate. The combined organic layers were washed with water and brine, dried over Na2SO4. After filtration and evaporation, the crude product was purified by column chromatography on NH-silica gel (eluted with isocratic 33% ethyl acetate/67% hexane) to give a white powder. The solid was suspended in ethanol and 5N HCl (1.0 mL) was added to the mixture. The mixture was sonicated for 10 min and the resultant precipitate was collected by filtration and dried to give 139 mg of 6-(2,4-difluorophenyl)-N,5-dimethyl-2-(pyridin-3-yl)quinazolin-4-amine dihydrochloride as a pale yellow powder in a 30% yield.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe combined organic layers were washed with water and brine
  3. dry with materialdried over Na2SO4
  4. filtrationAfter filtration and evaporation
  5. customthe crude product was purified by column chromatography on NH-silica gel (eluted with isocratic 33% ethyl acetate/67% hexane)
  6. customto give a white powder
  7. customThe mixture was sonicated for 10 min
  8. filtrationthe resultant precipitate was collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-4ca9318612764db9b4521fc9cf991324
Source dataset
uspto-grants-2015_07
Patent number
US09073890B2

Reaction notes

Loading…