Sodium Bicarbonate → HCID 15998641, compound

HRID 408886Notes

Reaction equation

HRID 408886 reaction equation
Cl[C:2]1[N:11]=[C:10]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([CH3:19])=[CH:15][CH:14]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(O)CO.COC.O.[CH3:28][O:29][C:30]1[CH:31]=[C:32](B(O)O)[CH:33]=[C:34]([O:38][CH3:39])[C:35]=1[O:36][CH3:37].C(=O)(O)[O-].[Na+]>>[C:16]1([CH3:19])[CH:17]=[CH:18][C:13]([NH:12][C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[N:3]=[C:2]([C:32]3[CH:33]=[C:34]([O:38][CH3:39])[C:35]([O:36][CH3:37])=[C:30]([O:29][CH3:28])[CH:31]=3)[N:11]=2)=[CH:14][CH:15]=1

Participants

5

Reactant 4

HCID 516892Sodium BicarbonateHCID 27343903,4,5-Trimethoxybenzeneboronic acidHCID 226926752-Chloro-N-(4-methylphenyl)quinazolin-4-amineHCID 86682550HCID 86682550, compound

Product 1

HCID 15998641HCID 15998641, compound

Procedure

A mixture of (2-chloro-quinazolin-4-yl)-p-tolyl-amine, 3.76 g, 0.014 mol), ethylene-glycol-dimethyl-ether/water (1 l/120 ml), 3,4,5-trimethoxyphenylboronic acid (2.714 g, 0.014 mol) and sodium bicarbonate (3.6 g) was degassed with argon for 15 minutes. Pd(dppf)Cl2 (0.84 g) was added, and the mixture was heated to reflux overnight. After cooling to room temperature CH2Cl2 (1 l) and H2O (500 ml) were added. The organic and aqueous layers were separated, the aqueous layer was extracted with CH2Cl2 (2×500 ml), and the combined organic layers were dried over anhydrous sodium sulfate. The organic solvent was removed under reduced pressure. The crude product was purified by methanol. Filtration in a Büchner apparatus afforded p-tolyl-[2-(3,4,5-trimethoxy-phenyl)-quinazolin-4-yl]-amine, 2 (3.15 g, 0.0078 mol 56%). m.p.: >250° C.; 1H NMR (300 MHz, DMSO-d6) δ 2.33 (s, 3H), 3.74 (s, 3H), 3.91 (s, 6H), 6.81 (s, 2H), 7.24 (d, J=8.4 Hz, 2H), 7.33 (d, J=7.3 Hz, 2H), 7.58 (t, J=8.2 Hz, 1H), 7.83 (t, J=7.2 Hz, 2H), 8.54 (d, J=7.5 Hz, 1H). Anal. (C24H23N3O3) C, H, N.

Workup

  1. customwas degassed with argon for 15 minutes
  2. additionPd(dppf)Cl2 (0.84 g) was added
  3. temperaturethe mixture was heated
  4. temperatureto reflux overnight
  5. additionwere added
  6. customThe organic and aqueous layers were separated
  7. extractionthe aqueous layer was extracted with CH2Cl2 (2×500 ml)
  8. dry with materialthe combined organic layers were dried over anhydrous sodium sulfate
  9. customThe organic solvent was removed under reduced pressure
  10. customThe crude product was purified by methanol
  11. filtrationFiltration in a Büchner apparatus

Sources & evidence

ORD record
ord-43902820818e467398d226aad9d46f81
Source dataset
uspto-grants-2014_06
Patent number
US08759363B2

Reaction notes

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