Iodine → HCID 136346625, compound

HRID 1958257Notes

Reaction equation

HRID 1958257 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([NH2:6])=[O:5].[F:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=O)=[CH:15][CH:14]=1.II.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.O>[F:12][C:13]1[CH:20]=[CH:19][C:16]([C:17]2[NH:6][C:4](=[O:5])[C:3]3[C:2](=[CH:10][CH:9]=[C:8]([CH3:11])[CH:7]=3)[N:1]=2)=[CH:15][CH:14]=1

Participants

7

Reactant 4

HCID 807IodineHCID 11430Potassium CarbonateHCID 680234-FluorobenzaldehydeHCID 103294362-Amino-5-methylbenzamide

Product 1

HCID 136346625HCID 136346625, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-amino-5-methylbenzamide (1.0 g, 6.7 mmol), 4-fluorobenzaldehyde (0.83 g, 6.7 mmol), iodine (2.03 g, 8.0 mmol), and potassium carbonate (1.38 g, 10 mmol) in DMF (50 mL) was stirred at 80° C. for 16 hours. The reaction mixture was cooled to 20° C. and poured into icy water. The solid was collected by filtration, washed with water, and air dried to give 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.41 g, 83%). A solution of 2-(4-fluoro-phenyl)-6-methyl-3H-quinazolin-4-one (1.4 g, 5.5 mmol), NBS (0.98 g, 5.6 mmol), and benzoyl peroxide (67.0 mg, 0.276 mmol) in AcOH (150 mL) and chloroform (150 mL) was stirred at 80° C. for 5 hours with light shedding on. The reaction mixture was cooled to 20° C. and concentrated using a rotary evaporator to yield the crude bromide. A solution of the above crude bromide in DMF (20 mL) and 1,4-dioxane (100 mL) was mixed with morpholine (10 mL) and stirred at 80° C. for 4 hours. The reaction was quenched by adding water (200 mL), extracted with dichloromethane (3×100 mL), and concentrated using a rotary evaporator. The residue was further purified by column (SiO2, Hexanes/EtOAc/MeOH=4:3:1) to yield 2-4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 48% over two steps). A solution of 2-(4-fluoro-phenyl)-6-morpholin-4-ylmethyl-3H-quinazolin-4-one (0.89 g, 2.62 mmol) in dichloromethane (100 mL) and MeOH (50 mL) was mixed with HCl in ether (8 mL, 16 mmol) and stirred for 1 hour. The reaction was concentrated using a rotary evaporator. The solid was rinsed with DCM (50 mL) and MeOH (5 mL), collected by filtration, washed with DCM-MeOH (10:1) to afford 2-(4-fluorophenyl)-6-(morpholinomethyl)quinazolin-4(3H)-one (0.82 g, 76%) as an off-white solid; MS (ES) m/z: 340 (M+1); MP 321.8-323.3° C.

Workup

  1. temperatureThe reaction mixture was cooled to 20° C.
  2. filtrationThe solid was collected by filtration
  3. washwashed with water, and air
  4. customdried

Sources & evidence

ORD record
ord-1ea948029c844196915426e81b1b747f
Source dataset
uspto-grants-2013_04
Patent number
US08410109B2

Reaction notes

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