Ethyl 1-cyclopropyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate → Ethyl 1-cyclopropyl-7-[2-[5-(2,4-diamino-pyrimidin-5-yl-methyl)-2,3-dimethoxy-phenyl]ethyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate

HRID 963436Notes

Reaction equation

HRID 963436 reaction equation
[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:36])=[C:11]([C:15]#[C:16][C:17]4[CH:22]=[C:21]([CH2:23][C:24]5[C:25]([NH2:31])=[N:26][C:27]([NH2:30])=[N:28][CH:29]=5)[CH:20]=[C:19]([O:32][CH3:33])[C:18]=4[O:34][CH3:35])[C:12]=3[F:14])[C:7](=[O:37])[C:6]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:5]2)[CH2:3][CH2:2]1.[H][H]>CN(C)C=O.C(O)(=O)C.[Pd]>[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:36])=[C:11]([CH2:15][CH2:16][C:17]4[CH:22]=[C:21]([CH2:23][C:24]5[C:25]([NH2:31])=[N:26][C:27]([NH2:30])=[N:28][CH:29]=5)[CH:20]=[C:19]([O:32][CH3:33])[C:18]=4[O:34][CH3:35])[C:12]=3[F:14])[C:7](=[O:37])[C:6]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[CH:5]2)[CH2:2][CH2:3]1

Participants

6

Reactant 2

HCID 19081771Ethyl 1-cyclopropyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylateHCID 178418361HCID 178418361, compound

Product 1

HCID 19081553Ethyl 1-cyclopropyl-7-[2-[5-(2,4-diamino-pyrimidin-5-yl-methyl)-2,3-dimethoxy-phenyl]ethyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylateYield 80%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

A suspension of 342 mg of ethyl 1-cyclopropyl-7-[5-(2,4-diamino-pyrimidin-5-ylmethyl)-2,3-dimethoxy-phenylethynyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate (Example 12a)) and 70 mg of 10% palladium-on-charcoal in 35 ml of dimethylformamide and 35 ml of acetic acid is hydrogenated at normal hydrogen pressure. After 6 hrs. the reaction mixture is filtered and the filtrate is concentrated in a high vacuum at 50°. The yellow residue is treated with 100 ml of 1N aqueous sodium hydroxide solution and extracted three times with 50 ml of methylene chloride each time. The combined organic phases are washed with 50 ml of water, dried over magnesium sulphate and concentrated. The crude product is triturated with 10 ml of hot ethyl acetate and filtered off under suction. 275 mg (80%) of ethyl 1-cyclopropyl-7-[2-[5-(2,4-diamino-pyrimidin-5-yl-methyl)-2,3-dimethoxy-phenyl]ethyl]-6,8-difluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylate are obtained as a yellowish solid. M.p. 218°-220°.

Workup

  1. filtrationthe reaction mixture is filtered
  2. concentrationthe filtrate is concentrated in a high vacuum at 50°
  3. additionThe yellow residue is treated with 100 ml of 1N aqueous sodium hydroxide solution
  4. extractionextracted three times with 50 ml of methylene chloride each time
  5. washThe combined organic phases are washed with 50 ml of water
  6. dry with materialdried over magnesium sulphate
  7. concentrationconcentrated
  8. customThe crude product is triturated with 10 ml of hot ethyl acetate
  9. filtrationfiltered off under suction

Sources & evidence

ORD record
ord-7f90a8c254094a84a59b1c7c7246d133
Source dataset
uspto-grants-1998_06
Patent number
US05763450

Reaction notes

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