Potassium Carbonate → N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine

HRID 2199670Notes

Reaction equation

HRID 2199670 reaction equation
[ClH:1].[ClH:2].Cl[CH2:4][C:5]1[N:6]=[C:7]([CH2:10][N:11]([CH3:13])[CH3:12])[S:8][CH:9]=1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][C:25]=1[OH:26])[N:22]=[CH:21][N:20]=[CH:19]2.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:1][C:17]1[CH:18]=[C:23]([NH:22][C:19]2[C:18]3[C:23](=[CH:24][C:25]([O:26][CH2:4][C:5]4[N:6]=[C:7]([CH2:10][N:11]([CH3:13])[CH3:12])[S:8][CH:9]=4)=[C:16]([O:15][CH3:14])[CH:17]=3)[N:22]=[CH:21][N:20]=2)[CH:24]=[CH:25][C:16]=1[Cl:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 187843234-Chloromethyl-2-dimethylaminomethylthiazole dihydrochloride2×HCID 1360078727-Hydroxy-6-methoxyquinazoline

Product 1

HCID 53630973N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amineYield 30%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N-{[4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}-N,N-dimethylamine hydrochloride hydrochloride (0.050 g, 0.220 mmol) and 4-[3,4-dichlorophenyl)amino]-6-(methoxy)quinazolin-7-ol (0.074 g, 0.220 mmol) were suspended in DMF (4 mL) and potassium carbonate (0.152 g, 1.10 mmol) was added. The mixture was stirred at room temperature for 50 h and then at 70° C. for 3.5 h. An additional portion of N-{[4-(chloromethyl)-1,3-thiazol-2-yl]methyl}-N,N-dimethylamine hydrochloride hydrochloride (0.019 g, 0.084 mmol) was added and the mixture was stirred at 70° C. for a further 25 h. The reaction mixture was concentrated in vacuo. and the residue was partitioned between ethyl acetate and brine. The organic portion was washed with 1 N aqueous sodium hydroxide, brine, dried over sodium sulfate, filtered and concentrated in vacuo. to afford a brown solid. Recrystallization from ethyl acetate/diethyl ether afforded the title compound as a pale brown solid (0.016 g, 0.033 mmol, 15% yield). 1H NMR (400 MHz; CDCl3): 2.37 (s, 6H); 3.79 (s, 2H); 4.00 (s, 3H); 5.34 (s, 2H); 7.00 (s, 1H); 7.15 (br s, 1H); 7.34-7.37 (m, 2H); 7.55 (d, 1H); 7.57 (d, 1H); 7.96 (d, 1H); 8.66 (s, 1H); MS (EI) for C22H21Cl2N5O2S: 490 (MH+).

Workup

  1. waitat 70° C. for 3.5 h
  2. stirringthe mixture was stirred at 70° C. for a further 25 h
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customand the residue was partitioned between ethyl acetate and brine
  5. washThe organic portion was washed with 1 N aqueous sodium hydroxide, brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a brown solid
  10. customRecrystallization from ethyl acetate/diethyl ether

Sources & evidence

ORD record
ord-6e64fc8c6be7498a89ac756e7a32900a
Source dataset
uspto-grants-2016_06
Patent number
US09359332B2

Reaction notes

Loading…