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Methyl iodide → (4-Methylthio-phenyl)-(2-methyl-quinazolin-4-yl)-methylamine

HRID 2381012
Notes
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Reaction equation

HRID 2381012 reaction equation
[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]([CH3:20])[N:11]=2)=[CH:5][CH:4]=1.[H-].[Na+].[CH3:23]I>CN(C=O)C.CCOC(C)=O>[CH3:1][S:2][C:3]1[CH:4]=[CH:5][C:6]([N:9]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:13]=[C:12]([CH3:20])[N:11]=2)[CH3:23])=[CH:7][CH:8]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 42625835(4-Methylthio-phenyl)-(2-methyl-quinazolin-4-yl)-amine

Product 1

HCID 11580217(4-Methylthio-phenyl)-(2-methyl-quinazolin-4-yl)-methylamineYield 43.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent
HCID 8857
Ethyl Acetate
Solvent

Conditions

Temperature
0 °C

Procedure

To a solution of (4-methylthio-phenyl)-(2-methyl-quinazolin-4-yl)-amine (263 mg, 0.94 mmol) in DMF (4 ml) at 0° C. was added sodium hydride (56.4 mg, 1.40 mmol, 60% oil dispersion) and followed by methyl iodide (0.09 ml, 1.40 mmol). The mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature and stirred for another 2 h. The reaction mixture was diluted with EtOAc (15 ml), washed with saturated NaHCO3 aq., brine, dried over Na2SO4, filtered and concentrated by vacuum. The residue was purified by chromatography on silica gel with acetate and hexane (1:2 to 1:1) as eluent, yielding 120 mg of title compound (40.7%). 1H NMR (CDCl3): 7.76 (d, J=9.0 Hz, 1H), 7.54 (t, J=7.5 Hz, 1H), 7.24-7.19 (m, 2H), 7.10-6.97 (m, 4H), 3.59 (s, 3H), 2.74 (s, 3H), 2.48 (s, 3H)

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for another 2 h
  3. washwashed with saturated NaHCO3 aq., brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by vacuum
  7. customThe residue was purified by chromatography on silica gel with acetate and hexane (1:2 to 1:1) as eluent

Sources & evidence

ORD record
ord-680a45d5366946a1b0cd9185001409e5
Source dataset
uspto-grants-2012_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08258145B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes