Diethylamine → [2-Amino-6-(2-diethylaminomethyl-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone
Reaction equation
[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=3[CH2:30]Cl)[CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:38]([NH:40][CH2:41][CH3:42])[CH3:39]>C(#N)C>[NH2:1][C:2]1[N:11]=[C:10]([C:12]([N:14]2[CH2:22][C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[CH2:15]2)=[O:13])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[CH:25][C:24]=3[CH2:30][N:40]([CH2:41][CH3:42])[CH2:38][CH3:39])[CH:8]=2)[N:3]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 80 °C
Procedure
200 mg of [2-amino-6-(2-chloromethyl-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone are dissolved in 5 ml of acetonitrile. 301 mg of caesium carbonate and 73 μl of diethylamine are added, and the mixture is stirred at 80° C. for 16 h. After cooling to 25° C., the mixture is filtered, and the filtrate is evaporated to dryness. The residue is taken up in 5 ml of ethyl acetate, the solution is washed with 5 ml of 2N sodium hydroxide solution, and the combined organic phases are dried over sodium sulfate. After filtration, the filtrate is evaporated to dryness and purified by chromatography (reversed phase HPLC).
Workup
- temperatureAfter cooling to 25° C.
- filtrationthe mixture is filtered
- customthe filtrate is evaporated to dryness
- washthe solution is washed with 5 ml of 2N sodium hydroxide solution
- dry with materialthe combined organic phases are dried over sodium sulfate
- filtrationAfter filtration
- customthe filtrate is evaporated to dryness
- custompurified by chromatography (reversed phase HPLC)
Sources & evidence
- ORD record
- ord-863e94a7023244f7b095fe0f66780966
- Source dataset
- uspto-grants-2014_07
- Patent number
- US08791129B2
Reaction notes
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