Benzamidine → 6-(2-methyl-1H-imidazol-1-yl)-2-phenyl-quinazoline

HRID 472152Notes

Reaction equation

HRID 472152 reaction equation
[CH3:1][C:2]1[N:3]([C:7]2[CH:13]=[CH:12][C:10]([NH2:11])=[C:9]([CH2:14][NH2:15])[CH:8]=2)[CH:4]=[CH:5][N:6]=1.Cl.[C:17](=N)(OC)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(N)(=N)C1C=CC=CC=1>CO.O=[Mn]=O>[CH3:1][C:2]1[N:3]([C:7]2[CH:8]=[C:9]3[C:10](=[CH:12][CH:13]=2)[N:11]=[C:17]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:15]=[CH:14]3)[CH:4]=[CH:5][N:6]=1

Participants

6

Reactant 3

HCID 2332BenzamidineHCID 5743287Methyl benzimidate hydrochlorideHCID 582704664-(2-methyl-1H-imidazol-1-yl)-2-aminomethylaniline

Product 1

HCID 446032786-(2-methyl-1H-imidazol-1-yl)-2-phenyl-quinazolineYield 74%

Reagents, catalysts & solvents 2

HCID 14801Manganese dioxideCatalystHCID 887MethanolSolvent

Procedure

4-(2-methyl-1H-imidazol-1-yl)-2-aminomethylaniline (2.0 g, 10 mmol) and methyl benzimidate hydrochloride (3.5 g, 20 mmol; RN: 5873-90-5, Aldrich) were dissolved in methanol (50 mL), the resulting mixture was heated at reflux for 2 hours, during this time the aminomethyl-derivative was converted into the corresponding benzamidine. After that, the methanol was evaporated and the residue taken up with glacial acetic acid (50 mL), the reaction mixture was heated at reflux for 1.5 hours. After cooling at r.t. the reaction mixture was diluted with toluene (50 mL) and evaporated. The residue was taken up with AcOEt (400 mL), washed with aq. ammonia, with water, then dried and concentrated. The obtained oily residue was dissolved in DCM (400 mL) and MnO2 (6.0 g, 70 mmol) was added at r.t., in three portions, over 2 hours. The resulting suspension was stirred at r.t. for 24 hrs, then filtered over celite and the cake was rinsed with DCM. The combined filtrate and washings were concentrated and the residue chromatographed over silica gel (DCM/MeOH/NH3, 85:25.2) the appropriate combined fractions were evaporated and the residue taken up with ethyl ether, heated at reflux for 5 minutes then cooled at 25° C. to crystallize the titled product as slightly brown powder (2.0 g; yield: 74%). C18H14N4, MW: 286.34; MS: m/z 287 (M+H); 1H-NMR (200 MHz, d6-DMSO) ppm: 2.40 (s, 1H), 7.0 (s, 1H), 7.40 (s, 1H), 7.60 (m, 3H), 8.10-8.30 (m, 3H), 8.60 (m, 2H), 9.80 (s, 1H).

Workup

  1. temperaturethe resulting mixture was heated
  2. customAfter that, the methanol was evaporated
  3. temperaturethe reaction mixture was heated
  4. temperatureat reflux for 1.5 hours
  5. additionwas diluted with toluene (50 mL)
  6. customevaporated
  7. washwashed with aq. ammonia, with water
  8. customdried
  9. concentrationconcentrated
  10. dissolutionThe obtained oily residue was dissolved in DCM (400 mL)
  11. filtrationfiltered over celite
  12. washthe cake was rinsed with DCM
  13. concentrationThe combined filtrate and washings were concentrated
  14. customthe residue chromatographed over silica gel (DCM/MeOH/NH3, 85:25.2) the
  15. customwere evaporated
  16. temperatureheated
  17. temperatureat reflux for 5 minutes
  18. temperaturethen cooled at 25° C.
  19. customto crystallize the titled product as slightly brown powder (2.0 g; yield: 74%)

Sources & evidence

ORD record
ord-3bb257ddc0434488a2399c2b40002585
Source dataset
uspto-grants-2014_01
Patent number
US08633208B2

Reaction notes

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