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

HRID 1752367Notes

Reaction equation

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

Participants

Conditions

Temperature: 70 °C

Procedure

4-{[4-(Chloromethyl)-1,3-thiazol-2-yl]methyl}morpholine hydrochloride (0.024 g, 0.089 mmol) and 4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-ol (0.030 g, 0.089 mmol) were suspended in DMF (2 mL) and potassium carbonate (0.062 g, 0.449 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 (0.026 g, 0.049 mmol, 54% yield). 1H NMR (400 MHz; CDCl3): 2.50 (br s, 1H); 2.57-2.64 (m, 4H); 3.75 (t, 4H); 3.84 (s, 2H); 3.96 (s, 3H); 5.28 (s, 2H); 7.09 (s, 1H); 7.31 (s, 1H); 7.37 (s, 1H); 7.43 (d, 1H); 7.60 (dd, 1H); 7.97 (d, 1H); 8.61 (s, 1H); MS (EI) for C24H23Cl2N5O3S: 532 (MH+).

Workup

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

Sources & evidence

ORD record: ord-405b69b06fa44d2694e27b3a9ece92c1
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09163006B2

Reaction notes

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