Sodium Carbonate → N4-(3,4-Dimethoxy-phenyl)-N2,N4-dimethyl-quinazoline-2,4-diamine

HRID 1876167Notes

Reaction equation

HRID 1876167 reaction equation
Cl.Cl[C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[C:17]([O:23][CH3:24])[CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.Cl.[CH3:26][NH2:27].C(=O)([O-])[O-].[Na+].[Na+]>CC(O)C>[CH3:24][O:23][C:17]1[CH:16]=[C:15]([N:13]([CH3:14])[C:11]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[N:4]=[C:3]([NH:27][CH3:26])[N:12]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH3:22]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 6364545Methylamine hydrochlorideHCID 86639965(2-Chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine hydrochloride

Product 1

HCID 59242114N4-(3,4-Dimethoxy-phenyl)-N2,N4-dimethyl-quinazoline-2,4-diamine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

A suspension of (2-chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine hydrochloride (106 mg; 0.289 mmol), methylamine hydrochloride (198 mg; 2.93 mmol) and sodium carbonate (340 mg; 3.21 mmol) in i-PrOH (4 mL) was heated at 90° C. After 41 h, the suspension was concentrated then water (5 mL) was added. The product was extracted into chloroform (3×2 mL) and the combined extracts washed with water (3×2 mL) and brine (2×3 mL). This solution was dried (MgSO4), filtered through silica and washed with 100:10:1 CHCl3:MeOH:concentrated NH4OH, concentrated then purified by MPLC (12 g SiO2/0-30% (20:1 MeOH:concentrated NH4OH) in CHCl3 gradient). Product was obtained as an oil, which solidified to a pale yellow solid under high vacuum (74 mg; 79%). 1H NMR (CDCl3) δ 7.46 (m, 1H), 7.38 (m, 1H), 6.90 (m, 1H), 6.84 (m, 1H), 6.76-6.65 (m, 3H), 3.91 (s, 3H), 3.78 (s, 3H), 3.53 (s, 3H), 3.12 (d, 3H); LC-MS (ESI−; 325 ([M+H]+)).

Workup

  1. concentrationthe suspension was concentrated
  2. additionwater (5 mL) was added
  3. extractionThe product was extracted into chloroform (3×2 mL)
  4. washthe combined extracts washed with water (3×2 mL) and brine (2×3 mL)
  5. dry with materialThis solution was dried (MgSO4)
  6. filtrationfiltered through silica
  7. washwashed with 100:10:1 CHCl3
  8. concentrationMeOH:concentrated NH4OH, concentrated
  9. customthen purified by MPLC (12 g SiO2/0-30% (20:1 MeOH:concentrated NH4OH) in CHCl3 gradient)
  10. customProduct was obtained as an oil, which

Sources & evidence

ORD record
ord-cb92fde4f9fe48ad900a982fbd31970d
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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