Methanol → 4-Quinazolinamine, N-(4-azidophenyl)-N,2-dimethyl-

HRID 1876125Notes

Reaction equation

HRID 1876125 reaction equation
[CH3:1][C:2]1[N:11]=[C:10]([N:12]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH3:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.CO.N([O-])=O.[Na+].[N-:27]=[N+:28]=[N-].[Na+]>Cl.O.C(OCC)(=O)C>[N:20]([C:17]1[CH:16]=[CH:15][C:14]([N:12]([C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=[C:2]([CH3:1])[N:11]=2)[CH3:13])=[CH:19][CH:18]=1)=[N+:27]=[N-:28]

Participants

9

Reactant 4

HCID 887MethanolHCID 33557Sodium Azide2×HCID 11311597N-methyl-N-(2-methylquinazolin-4-yl)benzene-1,4-diamineHCID 23668193Sodium Nitrite

Product 1

HCID 113123184-Quinazolinamine, N-(4-azidophenyl)-N,2-dimethyl-Yield 90%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (2-methyl-quinazolin-4-yl)-(4-amino-phenyl)-methylamine (20 mg, 0.076 mmol) in 1.2 mL of 1N HCl was added 100 uL of methanol and it was cooled 0° C. One drop of concentrated HCl was added and the solution was stirred at 0° C. for 0.25 h. To the solution was added dropwise a solution of sodium nitrite (25 mg, 0.36 mmol) in 200 uL of water. The reaction mixture was stirred for 0.5 h, then was added a solution of sodium azide (25 mg, 0.38 mmol) in 300 uL of water followed by another batch of sodium azide (25 mg, 0.38 mmol). The reaction mixture was stirred at the 0° C. for 1 h. The reaction mixture was diluted with 50 mL of ethyl acetate, washed with saturated sodium bicarbonate followed by saturated sodium chloride. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (20-25% ethyl acetate/hexanes) on silica gel to give the title compound (19.8 mg, 0.068 mmol, 90%). 1H NMR (CDCl3): 7.76 (m, 1H), 7.56 (ddd, J=8.1, 6.3, 1.8, 1H), 7.13 (m, 2H), 6.98-7.13 (m, 4H), 3.61 (s, 3H), 2.74 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred for 0.5 h
  2. stirringThe reaction mixture was stirred at the 0° C. for 1 h
  3. washwashed with saturated sodium bicarbonate
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (20-25% ethyl acetate/hexanes) on silica gel

Sources & evidence

ORD record
ord-7a9f3a538e124326b9da46b1cf736e6b
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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