Ethyl Bromide → HCID 46869253, compound

HRID 578665Notes

Reaction equation

HRID 578665 reaction equation
[CH3:1][N:2]([CH3:27])[CH2:3][CH:4]([NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:24]([NH2:26])=[O:25])[CH:19]=[C:20]([OH:23])[CH:21]=2)[N:16]=[CH:15][N:14]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[CH:6]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:34](Br)[CH3:35]>CN(C=O)C>[CH3:1][N:2]([CH3:27])[CH2:3][CH:4]([NH:12][C:13]1[C:22]2[C:17](=[C:18]([C:24]([NH2:26])=[O:25])[CH:19]=[C:20]([O:23][CH2:34][CH3:35])[CH:21]=2)[N:16]=[CH:15][N:14]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[CH:6]=1

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 10796Cesium carbonateHCID 66763069HCID 66763069, compound

Product 1

HCID 46869253HCID 46869253, compoundYield 15%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

A Wheaton vial equipped with a stir bar was charged with 4-[2-dimethylamino-1-(3-fluoro-phenyl)-ethylamino]-6-hydroxy-quinazoline-8-carboxylic acid amide, (37 mg, 0.1 mmol) Cs2CO3, (100 mg, 0.3 mmol) and dry DMF, (1 mL). The mixture was heated at 60° C. for 1 h. It was then cooled to RT and ethylbromide (11 mg, 0.1 mmol) was added a solution in DMF (0.5 mL). The mixture was left to stir overnight. After 18 h, LCMS indicated consumption of SM. The mixture was diluted with EtOAc, (30 mL) and added to water, (30 mL). The phases were separated and the aqueous was extracted with EtOAc, (30 mL) (×2). The EtOAc phase was washed with sat. LiCl, (30 mL) dried (Na2SO4) and the solvent was evaporated under reduced pressure. The material was purified by chromatography using a 4 g silica cartridge eluting with DCM-[DCM-MeOH—NH4OH (9:1:0.1)], gradient 0 to 100% cocktail. Amount obtained: 6 mg, 0.015 mmol, 15% yield. LCMS (ESI) 398 (M+H).

Workup

  1. customA Wheaton vial equipped with a stir bar
  2. temperatureIt was then cooled to RT
  3. waitThe mixture was left
  4. waitAfter 18 h
  5. customconsumption of SM
  6. additionThe mixture was diluted with EtOAc, (30 mL)
  7. additionadded to water, (30 mL)
  8. customThe phases were separated
  9. extractionthe aqueous was extracted with EtOAc, (30 mL) (×2)
  10. washThe EtOAc phase was washed with sat. LiCl, (30 mL)
  11. dry with materialdried (Na2SO4)
  12. customthe solvent was evaporated under reduced pressure
  13. customThe material was purified by chromatography
  14. washeluting with DCM-[DCM-MeOH—NH4OH (9:1:0.1)], gradient 0 to 100% cocktail
  15. customAmount obtained

Sources & evidence

ORD record
ord-c66c250c792f4b068fa8a9f626b7fa93
Source dataset
uspto-grants-2015_05
Patent number
US09040560B2

Reaction notes

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