Triethylamine → 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine

HRID 2036773Notes

Reaction equation

HRID 2036773 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1.C(N(CC)CC)C.[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][NH2:33]>C1COCC1>[Cl:1][C:2]1[N:11]=[C:10]([NH:33][CH2:32][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:3]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 195092-PyridinemethanamineHCID 71741791HCID 71741791, compound

Product 1

HCID 866706132-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amineYield 75.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,4-Dichloro-5-phenylquinazoline (1.38 g, 5.03 mmol) was dissolved in THF (80 mL) and triethylamine (1.33 mL, 9.56 mmol) was added dropwise. The mixture was stirred for 5 min at room temperature and then pyridin-2-ylmethanamine (0.57 mL, 5.53 mmol) was added dropwise. The resulting mixture was stirred at ambient temperature for 14 hours. After this time, the mixture was filtered through a medium porosity glass frit, concentrated to dryness under reduced pressure and then purified by ISCO flash column chromatography (80 g silica gel column) eluting with 0-100% ethyl acetate/hexanes over 30 min to provide 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4-amine (1.32 g, 75%). LCMS Method A [M+1] observed 347.1. HPLC Method B: Purity 99.1% retention time 6.66 min. 1H NMR (400 MHz, chloroform-d) δ ppm 8.16 (1H, d, J=4.77 Hz), 7.79 (1H, d, J=7.28 Hz), 7.70 (1H, t, J=7.78 Hz), 7.59 (1H, dt, J=7.53, 1.51 Hz), 7.40-7.55 (5H, m), 7.08-7.25 (4H, m), 4.66 (2H, d, J=4.02 Hz).

Workup

  1. stirringThe resulting mixture was stirred at ambient temperature for 14 hours
  2. filtrationAfter this time, the mixture was filtered through a medium porosity glass frit
  3. concentrationconcentrated to dryness under reduced pressure
  4. custompurified by ISCO flash column chromatography (80 g silica gel column)
  5. washeluting with 0-100% ethyl acetate/hexanes over 30 min

Sources & evidence

ORD record
ord-7716253c92b2408dbd1801fb5e933477
Source dataset
uspto-grants-2013_11
Patent number
US08575184B2

Reaction notes

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