Cesium carbonate → {2-Amino-6-[4,5-difluoro-2-(4-methylpiperazin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

HRID 1631157Notes

Reaction equation

HRID 1631157 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])[C:26]([F:30])=[CH:25][C:24]=3[CH2:31]Cl)[CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:39][N:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>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])[C:26]([F:30])=[CH:25][C:24]=3[CH2:31][N:43]3[CH2:44][CH2:45][N:40]([CH3:39])[CH2:41][CH2:42]3)[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 66837605[2-Amino-6-(2-chloromethyl-4,5-difluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

Product 1

HCID 56943581{2-Amino-6-[4,5-difluoro-2-(4-methylpiperazin-1-ylmethyl)phenyl]quinazolin-4-yl}-(1,3-dihydroisoindol-2-yl)methanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

200 mg of [2-amino-6-(2-chloromethyl-4,5-difluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone are dissolved in 5 ml of acetonitrile. 289 mg of caesium carbonate and 84 μl of methylpiperazine 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

  1. temperatureAfter cooling to 25° C.
  2. filtrationthe mixture is filtered
  3. customthe filtrate is evaporated to dryness
  4. washthe solution is washed with 5 ml of 2N sodium hydroxide solution
  5. dry with materialthe combined organic phases are dried over sodium sulfate
  6. filtrationAfter filtration
  7. customthe filtrate is evaporated to dryness
  8. custompurified by chromatography (reversed phase HPLC)

Sources & evidence

ORD record
ord-26cb5d895de94b67b97b2263f38f2f7c
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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