Water → 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

HRID 963392Notes

Reaction equation

HRID 963392 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([O:20][CH3:21])[C:17]=1[O:18][CH3:19])[CH2:6][C:7]1[C:8]([NH2:14])=[N:9][C:10]([NH2:13])=[N:11][CH:12]=1)#[CH:2].[CH:22]1([N:25]2[C:34]3[C:29](=[CH:30][C:31]([F:44])=[C:32](OS(C(F)(F)F)(=O)=O)[C:33]=3[F:35])[C:28](=[O:45])[C:27]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:26]2)[CH2:24][CH2:23]1.O>C(N(CC)CC)C.CN(C)C=O>[CH:22]1([N:25]2[C:34]3[C:29](=[CH:30][C:31]([F:44])=[C:32]([C:2]#[C:1][C:3]4[CH:4]=[C:5]([CH2:6][C:7]5[C:8]([NH2:14])=[N:9][C:10]([NH2:13])=[N:11][CH:12]=5)[CH:15]=[C:16]([O:20][CH3:21])[C:17]=4[O:18][CH3:19])[C:33]=3[F:35])[C:28](=[O:45])[C:27]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:26]2)[CH2:23][CH2:24]1

Participants

6

Reactant 3

HCID 962WaterHCID 156368801-Cyclopropyl-7-trifluoromethylsulfonyloxy-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid ethyl esterHCID 178909505-[3-Ethynyl-4,5-dimethoxy-benzyl]-pyrimidine-2,4-diamine

Product 1

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-carboxylateYield 40%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A solution of 200 mg of 5-[3-ethynyl-4,5-dimethoxy-benzyl]-pyrimidine-2,4-diamine (Example 11b)), 207 mg of ethyl 1-cyclopropyl-6,8-difluoro-4-oxo-1,4-dihydro-7-[[(trifluoromethyl)sulphonyl]oxy]-quinoline-3-carboxylate (J. Heterocyclic Chem., 28, 1581 (1991)) and 10 mg of bis-triphenylphosphinepalladium dichloride in 1.5 ml of triethylamine and 7.5 ml of dimethylformamide is stirred at 900 for one hr. The reaction mixture is cooled to room temperature, poured into 50 ml of water and extracted four times with 50 ml of methylene chloride each time. The combined organic phases are washed with 100 ml of saturated, aqueous sodium chloride solution, dried over magnesium sulphate and concentrated. The residue is chromatographed on silica gel with methylene chloride/methanol 9:1. 108 mg (39%) 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 are isolated as a colourless solid. M.p.>230°. Mass spectrum: peaks: inter alia at 575 (M+, 36%), 503 (18%), 481 (20%), 123 (42%), 32(100%).

Workup

  1. extractionextracted four times with 50 ml of methylene chloride each time
  2. washThe combined organic phases are washed with 100 ml of saturated, aqueous sodium chloride solution
  3. dry with materialdried over magnesium sulphate
  4. concentrationconcentrated
  5. customThe residue is chromatographed on silica gel with methylene chloride/methanol 9:1

Sources & evidence

ORD record
ord-05985058678e4fa98fe620b19a978bc6
Source dataset
uspto-grants-1998_06
Patent number
US05763450

Reaction notes

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