Sodium hydride → HCID 22452066, compound

HRID 2185656Notes

Reaction equation

HRID 2185656 reaction equation
[H-].[Na+].[O:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[O:9][CH2:10][CH2:11][OH:12].[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28](F)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]>O1CCCC1>[Cl:13][C:14]1[CH:15]=[C:16]([NH:21][C:22]2[C:31]3[C:26](=[CH:27][C:28]([O:12][CH2:11][CH2:10][O:9][CH:4]4[CH2:5][CH2:6][CH2:7][CH2:8][O:3]4)=[C:29]([N+:32]([O-:34])=[O:33])[CH:30]=3)[N:25]=[CH:24][N:23]=2)[CH:17]=[CH:18][C:19]=1[F:20]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 41668332-(Oxan-2-yloxy)ethan-1-olHCID 10640649N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

Product 1

HCID 22452066HCID 22452066, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
35 °C

Procedure

3.64 g of sodium hydride (60%) are added batchwise to 13.00 g of 2-(tetrahydropyran-2-yloxy)-ethanol in 250 ml of tetrahydrofuran while cooling with an ice bath. Then the reaction mixture is heated to about 30-40° C. in a water bath and stirred for 15 minutes. It is then cooled again in the ice bath and combined with 15.60 g of 4-[(3-chloro-4-fluoro-phenyl)amino]-7-fluoro-6-nitro-quinazoline in 50 ml of tetrahydrofuran. The reaction mixture immediately turns dark red. After 10 minutes the ice bath is removed and the reaction mixture is stirred for one hour at ambient temperature. Then a total of 1.00 g of sodium hydride is added and stirring is continued for a further 1.5 hours at 50° C. until the reaction is complete. For working up about 200 ml of tetrahydrofuran are distilled off using a rotary evaporator. The residue is added to 1 litre of ice-water and neutralised with citric acid. The aqueous phase is extracted thoroughly with ethyl acetate. The combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution, dried over magnesium sulphate and evaporated down. A yellow precipitate is formed, which is suction filtered and dried in the desiccator. The mother liquor is again evaporated down. The solid yellowish flask residue is triturated with tert.butyl methyl ether, suction filtered and also dried in the desiccator.

Workup

  1. temperaturewhile cooling with an ice bath
  2. customAfter 10 minutes the ice bath is removed
  3. stirringthe reaction mixture is stirred for one hour at ambient temperature
  4. additionThen a total of 1.00 g of sodium hydride is added
  5. stirringstirring
  6. waitis continued for a further 1.5 hours at 50° C. until the reaction
  7. distillationare distilled off
  8. customa rotary evaporator
  9. additionThe residue is added to 1 litre of ice-water and neutralised with citric acid
  10. extractionThe aqueous phase is extracted thoroughly with ethyl acetate
  11. washThe combined organic phases are washed with 250 ml of semi-saturated sodium chloride solution
  12. dry with materialdried over magnesium sulphate
  13. customevaporated down
  14. customA yellow precipitate is formed
  15. filtrationfiltered
  16. customdried in the desiccator
  17. customThe mother liquor is again evaporated down
  18. customThe solid yellowish flask residue is triturated with tert.butyl methyl ether, suction
  19. filtrationfiltered
  20. customalso dried in the desiccator

Sources & evidence

ORD record
ord-ac23722e65f8452d951a479b9240be9c
Source dataset
uspto-grants-2002_06
Patent number
US06403580B1

Reaction notes

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