Dimethylformamide → N4-(3,4-Dimethoxy-phenyl)-N2,N2,N4-trimethyl-quinazoline-2,4-diamine

HRID 1876168Notes

Reaction equation

HRID 1876168 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.[F-].[NH4+].[CH3:27][N:28](C=O)[CH3:29]>>[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]([N:28]([CH3:29])[CH3:27])[N:12]=2)[CH:20]=[CH:19][C:18]=1[O:21][CH3:22]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 25516Ammonium fluorideHCID 86639965(2-Chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine hydrochloride

Product 1

HCID 59242081N4-(3,4-Dimethoxy-phenyl)-N2,N2,N4-trimethyl-quinazoline-2,4-diamine

Procedure

A solution of (2-chloro-quinazolin-4-yl)-(3,4-dimethoxy-phenyl)-methyl-amine hydrochloride (105 mg; 0.287 mmol) and ammonium fluoride (73 mg; 1.97 mmol) in DMF (2 mL) was heated at 90° C. After 4 days the reaction was concentrated on a rotary evaporator then saturated NaHCO3 (5 mL) and water (3 mL) were added. Product was extracted into chloroform (4×2 mL) and the combined extracts washed with water (4×2 mL) and brine (3×3 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 SiO2/0-10% (20:1 MeOH:concentrated NH4OH) in CHCl3 gradient). Product was obtained as an oil, which solidified to a tan solid under high vacuum (68 mg; 70%). 1H NMR (CDCl3) δ 7.45 (m, 1H), 7.35 (m, 1H), 6.89 (m, 1H), 6.83 (m, 1H), 6.75-6.68 (m, 2H), 6.64 (m, 1H), 3.90 (s, 3H), 3.77 (s, 3H), 3.54 (s, 3H), 3.31 (s, 6H); LC-MS (ESI+; 339 ([M+H]+).

Workup

  1. concentrationAfter 4 days the reaction was concentrated on a rotary evaporator
  2. additionsaturated NaHCO3 (5 mL) and water (3 mL) were added
  3. extractionProduct was extracted into chloroform (4×2 mL)
  4. washthe combined extracts washed with water (4×2 mL) and brine (3×3 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 SiO2/0-10% (20:1 MeOH:concentrated NH4OH) in CHCl3 gradient)
  10. customProduct was obtained as an oil, which

Sources & evidence

ORD record
ord-f956fb08dc8048b8b40b5baeb12ba5bb
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

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