N-methylpropyn-2-ylamine → 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(2-[N-methyl-N-(2-propynyl)amino]ethoxy)quinazoline
Reaction equation
Br[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([O:15][C:16]3[C:17]([F:26])=[C:18]4[C:22](=[CH:23][CH:24]=3)[NH:21][C:20]([CH3:25])=[CH:19]4)=[N:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:27][CH3:28].[CH3:29][NH:30][CH2:31][C:32]#[CH:33]>CN(C=O)C>[F:26][C:17]1[C:16]([O:15][C:9]2[C:8]3[C:13](=[CH:14][C:5]([O:4][CH2:3][CH2:2][N:30]([CH3:29])[CH2:31][C:32]#[CH:33])=[C:6]([O:27][CH3:28])[CH:7]=3)[N:12]=[CH:11][N:10]=2)=[CH:24][CH:23]=[C:22]2[C:18]=1[CH:19]=[C:20]([CH3:25])[NH:21]2Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A stirred solution of 7-(2-bromoethoxy)-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (250 mg, 0.56 mmol), (prepared as described for the starting material in Example 17), in DMF (2.5 ml) was treated with N-methylpropargylamine (116 mg, 1.68 mmol) and stirred at ambient temperature overnight. The solvent was evaporated under vacuum and the residue purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (92/8). The relevant fractions were combined and evaporated under vacuum to give 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-{2-[N-methyl-N-(2-propynyl)amino]ethoxy}quinazoline as a white solid. (165 mg, 68%).
Workup
- customThe solvent was evaporated under vacuum
- customthe residue purified by column chromatography
- washeluting with methylene chloride/methanol (saturated with ammonia) (92/8)
- customevaporated under vacuum
Sources & evidence
- ORD record
- ord-640e6709bba04ba8a6fcd460c23be473
- Source dataset
- uspto-grants-2007_09
- Patent number
- US07268230B2
Reaction notes
Loading…