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

HRID 1631161Notes

Reaction equation

HRID 1631161 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+].[NH:38]1[CH2:43][CH2:42][CH:41]([OH:44])[CH2:40][CH2:39]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])[CH:26]=[CH:25][C:24]=3[CH2:30][N:38]3[CH2:43][CH2:42][CH:41]([OH:44])[CH2:40][CH2:39]3)[CH:8]=2)[N:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 79341Piperidin-4-olHCID 66837686[2-Amino-6-(2-chloromethyl-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone

Product 1

HCID 56943680{2-Amino-6-[5-fluoro-2-(4-hydroxypiperidin-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-5-fluorophenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone are dissolved in 5 ml of acetonitrile. 301 mg of caesium carbonate and 57 μl of piperidin-4-ol 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-cd4ca598fe7648918cd64c520092c4c6
Source dataset
uspto-grants-2014_07
Patent number
US08791129B2

Reaction notes

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