Ethylenediamine → 3-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

HRID 2097387Notes

Reaction equation

HRID 2097387 reaction equation
CN(C)C=O.[CH:6]1([O:10][CH2:11][C:12]2[C:20]3[C:19](=[O:21])[N:18](COCC[Si](C)(C)C)[N:17]=[CH:16][C:15]=3[NH:14][C:13]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[C:32]([O:40][CH:41]3[CH2:43][CH2:42]3)[CH:31]=2)[CH2:9][CH2:8][CH2:7]1.[Br-].[Li+].C(N)CN.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>C(OCC)(=O)C.C(Cl)(Cl)Cl.O1CCCC1>[CH:6]1([O:10][CH2:11][C:12]2[C:20]3[C:19](=[O:21])[NH:18][N:17]=[CH:16][C:15]=3[NH:14][C:13]=2[C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[C:32]([O:40][CH:41]3[CH2:43][CH2:42]3)[CH:31]=2)[CH2:9][CH2:8][CH2:7]1

Participants

9

Reactant 5

HCID 3301EthylenediamineHCID 6228DimethylformamideHCID 82050Lithium BromideHCID 2724141Tetrabutylammonium FluorideHCID 1363466633-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one

Product 1

HCID 1358450213-Cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-oneYield 47%

Reagents, catalysts & solvents 3

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To 1 ml of N,N-dimethylformamide containing 193 mg (0.352 mmol) of 3-cyclobutoxymethyl-2-(3-cyclopropoxy-4-difluoromethoxyphenyl)-5-(2-trimethylsilylethoxymethyl)-1,5-dihydropyrrolo[2,3-d]pyridazin-4-one obtained in Example 13-(b) were added 38.2 mg (0.440 mmol) of lithium bromide, 10 μl of ethylenediamine and 3 ml of tetrahydrofuran solution containing 1M tetrabutylammonium fluoride, and the mixture was stirred at 100° C. for 8 hours while removing tetrahydrofuran. After completion of the reaction, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained crude solid was applied to silica gel column chromatography (Eluent; chloroform:ethyl acetate=1:0→0:1 (V/V)), the fractions containing the desired compound were concentrated under reduced pressure, and recrystallized from a mixed solvent of ethanol and water to obtain 70 mg of the title compound as a white solid. (Yield: 47%)

Workup

  1. customwhile removing tetrahydrofuran
  2. customAfter completion of the reaction, water
  3. additionwas added to the reaction mixture
  4. filtrationthe precipitated solid was collected by filtration
  5. customThe obtained crude solid

Sources & evidence

ORD record
ord-d99da030e52b4abd939d860506e9562b
Source dataset
uspto-grants-2013_05
Patent number
US08450319B2

Reaction notes

Loading…