Dimethylformamide → tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate

HRID 467510Notes

Reaction equation

HRID 467510 reaction equation
CN(C=O)C.Br[C:7]1[O:11][C:10]([C:12]2[CH:13]=[C:14]([CH:31]=[CH:32][CH:33]=2)[CH2:15][N:16]2[C:21](=[O:22])[CH:20]=[CH:19][C:18]([C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=3)=[N:17]2)=[N:9][CH:8]=1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[N:44][N:45]([CH:47]3[CH2:52][CH2:51][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:49][CH2:48]3)[CH:46]=2)O1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C(N(CC)CC)C.COCCOC.C1COCC1.[Pd](Cl)Cl>[F:30][C:25]1[CH:24]=[C:23]([C:18]2[CH:19]=[CH:20][C:21](=[O:22])[N:16]([CH2:15][C:14]3[CH:13]=[C:12]([C:10]4[O:11][C:7]([C:42]5[CH:43]=[N:44][N:45]([CH:47]6[CH2:48][CH2:49][N:50]([C:53]([O:55][C:56]([CH3:59])([CH3:58])[CH3:57])=[O:54])[CH2:51][CH2:52]6)[CH:46]=5)=[CH:8][N:9]=4)[CH:33]=[CH:32][CH:31]=3)[N:17]=2)[CH:28]=[C:27]([F:29])[CH:26]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 18407952Tripotassium phosphate trihydrateHCID 45480279tert-butyl 4-[4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]piperidine-1-carboxylateHCID 584972522-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one

Product 1

HCID 58497250tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate

Reagents, catalysts & solvents 4

HCID 8471TriethylamineCatalystHCID 24290Palladium ChlorideCatalystHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

21 mg (0.029 mmol) of bistriphenylphosphine)palladium(II) chloride, one drop of triethylamine and 200 μl of DMF are added to a suspension, kept under nitrogen, of 131 mg (0.294 mmol) of 2-[3-(5-bromooxazol-2-yl)benzyl]-6-(3,5-difluorophenyl)-2H-pyridazin-3-one, 144 mg (0.382 mmol) of tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]-piperidine-1-carboxylate and 135 mg (0.382 mmol) of tripotassium phosphate trihydrate in 1.2 ml of 1,2-dimethoxyethane, and the mixture is stirred at 80° C. for 18 hours. The reaction mixture is diluted with THF and filtered off with suction. The filtrate is washed twice with saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is chromatographed on a silica-gel column with dichloromethane/methanol, giving tert-butyl 4-[4-(2-{3-[3-(3,5-difluorophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]phenyl}oxazol-5-yl)pyrazol-1-yl]piperidine-1-carboxylate as yellow-ish crystals; ESI 615.

Workup

  1. filtrationfiltered off with suction
  2. washThe filtrate is washed twice with saturated sodium chloride solution
  3. dry with materialdried over sodium sulfate
  4. customevaporated
  5. customThe residue is chromatographed on a silica-gel column with dichloromethane/methanol

Sources & evidence

ORD record
ord-65be4291df3b4f8386e4451ab30537e7
Source dataset
uspto-grants-2014_01
Patent number
US08623870B2

Reaction notes

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