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

HRID 244564Notes

Reaction equation

Cl.Cl[CH2:3][C:4]1[N:5]=[C:6]([CH2:9][N:10]2[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]2)[S:7][CH:8]=1.[Cl:17][C:18]1[CH:19]=[C:20]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][C:32]([OH:38])=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)[CH:21]=[CH:22][C:23]=1[Cl:24].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][C:32]([O:38][CH2:3][C:4]4[N:5]=[C:6]([CH2:9][N:10]5[CH2:15][CH2:14][N:13]([CH3:16])[CH2:12][CH2:11]5)[S:7][CH:8]=4)=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)[CH:21]=[CH:22][C:23]=1[Cl:24]

Participants

Conditions

Temperature: 70 °C

Procedure

1-{[4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}-4-methylpiperazine hydrochloride (0.067 g, 0.238 mmol) and 4-[(3,4-dichlorophenyl)amino]-6-(methoxy)quinazolin-7-ol (0.080 g, 0.238 mmol) were suspended in DMF (4 mL) and potassium carbonate (0.164 g, 1.19 mmol) was added. The mixture was stirred at 70° C. for 21 h. The reaction mixture was concentrated in vacuo and the residue was purified by reverse phase HPLC to afford the title compound as a colorless solid (0.025 g, 0.046 mmol, 19% yield). 1H NMR (400 MHz; CDCl3): 2.08 (s, 5H); 2.39 (s, 3H); 2.59-2.74 (m, 6H); 3.44-3.78 (m, 5H); 3.86 (s, 2H); 3.98 (s, 3H); 5.30 (s, 2H); 7.10 (s, 1H); 7.33 (s, 1H); 7.37 (s, 1H); 7.43 (d, 1H); 7.61 (dd, 1H); 7.99 (d, 1H); 8.60 (s, 1H); MS (EI) for C25H26Cl2N6O2S: 545 (MH+).

Workup

concentrationThe reaction mixture was concentrated in vacuo
customthe residue was purified by reverse phase HPLC

Sources & evidence

ORD record: ord-1e6446134f4241b28061fcdc6872737d
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658654B2

Reaction notes

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