Chloroform → 1-[4-chloro-7-(methyloxy)quinazolin-2-yl]-N,N-dimethylmethanamine

HRID 241036Notes

Reaction equation

HRID 241036 reaction equation
[CH3:1][N:2]([CH2:4][C:5]1[N:14]=[C:13](O)[C:12]2[C:7](=[CH:8][C:9]([O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=1)[CH3:3].C(Cl)(Cl)[Cl:19]>P(Cl)(Cl)(Cl)=O>[Cl:19][C:13]1[C:12]2[C:7](=[CH:8][C:9]([O:16][CH3:17])=[CH:10][CH:11]=2)[N:6]=[C:5]([CH2:4][N:2]([CH3:3])[CH3:1])[N:14]=1

Participants

4

Reactant 2

HCID 6212ChloroformHCID 178487757HCID 178487757, compound

Product 1

HCID 866478201-[4-chloro-7-(methyloxy)quinazolin-2-yl]-N,N-dimethylmethanamine

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

A solution of 2-[(dimethylamino)methyl]-7-(methyloxy)quinazolin-4-ol (6.6 g, 28.0 mmol) in a mixture of chloroform (15.0 mL) and phosphorous oxychloride (15.0 mL) was heated to reflux for 90 minutes. After cooling it to room temperature the reaction mixture was concentrated and the residue was partitioned between saturated sodium bicarbonate (100 mL) and ethyl acetate (400 mL) and the mixture was stirred for 30 minutes. The organic layer was separated and washed with saturated sodium bicarbonate (2×100 mL) and brine (200 mL), dried over sodium sulfate, filtered and concentrated. Purification by silica gel column chromatography using 15% methanol containing 0.5% triethylamine in ethyl acetate provided 1-[4-chloro-7-(methyloxy)quinazolin-2-yl]-N,N-dimethylmethanamine (7.0 g, quantitative). MS (EI) for C12H14ClN3O: 252 (MH+).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 90 minutes
  3. concentrationwas concentrated
  4. customthe residue was partitioned between saturated sodium bicarbonate (100 mL) and ethyl acetate (400 mL)
  5. customThe organic layer was separated
  6. washwashed with saturated sodium bicarbonate (2×100 mL) and brine (200 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customPurification by silica gel column chromatography

Sources & evidence

ORD record
ord-89d0eb6f45ad4949b002a9ac6e5410c2
Source dataset
uspto-grants-2014_02
Patent number
US08648066B2

Reaction notes

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