Hydrochloric Acid → (2-Fluoromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine

HRID 1876100Notes

Reaction equation

HRID 1876100 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([CH2:12][F:13])[N:3]=1.[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([NH:22][CH3:23])=[CH:18][CH:17]=1.Cl.C([O-])(O)=O.[Na+]>C(O)(C)C>[F:13][CH2:12][C:4]1[N:3]=[C:2]([N:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)[CH3:23])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 22250N-Methyl-4-anisidineHCID 516892Sodium BicarbonateHCID 86598859HCID 86598859, compound

Product 1

HCID 11208709(2-Fluoromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amineYield 9.5%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

(2-Fluoromethyl-quinazolin-4-yl)-(4-methoxy-phenyl)-methyl-amine: A suspension of 2-fluoromethyl-quinazolin-4(3H)-one (70 mg, 0.39 mmol) in phosphoryl chloride (2 ml) and N,N-dimethylaniline (0.035 ml, 0.27 mmol) was heated under reflux for 12 hours. The reaction mixture was poured onto ice and the precipitate was collected by filtration, then washed and dried to give 4-chloro-2-fluoromethyl-quinazoline, which was used directly for the next reaction. To a solution of 4-chloro-2-fluoromethyl-quinazoline with (4-methoxy-phenyl)-methylamine (160 mg, 1.2 mmol) in isopropyl alcohol (5 ml) was added concentrated HCl (0.05 ml) and the solution was stirred at room temperature overnight. The solution was neutralized with saturated aqueous NaHCO3, and was extracted by ethyl acetate. The extracts were evaporated, and the residue was purified by column chromatography on silica gel with ethyl acetate and hexane (1:1) as eluent, yielding 11 mg (9.5%) of the title compound. 1H NMR (CDCl3): 7.87-7.84 (m, 1H), 7.60-7.54 (m, 1H), 7.14-7.10 (m, 2H), 7.04-7.01 (m, 2H), 6.95-6.91 (m, 2H), 5.60 (s, 1H), 5.44 (s, 1H), 3.85 (s, 3H), 3.60 (s, 3H).

Workup

  1. customwas used directly for the next reaction
  2. extractionwas extracted by ethyl acetate
  3. customThe extracts were evaporated
  4. customthe residue was purified by column chromatography on silica gel with ethyl acetate and hexane (1:1) as eluent

Sources & evidence

ORD record
ord-0a7d2e4da5754fa89b28c9f658b0c6e4
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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