Sodium Carbonate → Ethyl 5-(2-chloro-5-(6-(difluoromethoxy)pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate

HRID 522113Notes

Reaction equation

[Cl:1][C:2]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1)=[O:5].C([O-])([O-])=O.[Na+].[Na+].Br[C:43]1[CH:48]=[CH:47][CH:46]=[C:45]([O:49][CH:50]([F:52])[F:51])[N:44]=1>O1CCOCC1.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([C:43]2[CH:48]=[CH:47][CH:46]=[C:45]([O:49][CH:50]([F:52])[F:51])[N:44]=2)=[CH:23][C:3]=1[C:4]([NH:6][C:7]1[N:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1)=[O:5]

Participants

Conditions

Temperature: 80 °C

Procedure

To a degassed solution of ethyl 5-(2-chloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxylate (Preparation 5, 229 mg, 0.44 mmol) in dioxane (4 mL) and water (0.5 mL) heated to 50° C. was added Na2CO3 (228 mg, 1.32 mmol), Cataxium A (16 mg, 0.044 mmol), a solution of 2-bromo-6-(difluoromethoxy)pyridine (Preparation 58, 100 mg, 0.44 mmol) in dioxane (1 mL) and Pd(OAc)2 (5 mg, 0.022 mmol). The reaction was heated at 80° C. for 3 hours. Further Cataxium A (16 mg, 0.044 mmol) and Pd(OAc)2 (5 mg, 0.022 mmol) were added and the reaction continued at 90° C. for 3 hours. The reaction was cooled and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 10-40% EtOAc in heptanes to afford the title compound (146 mg, 60%).

Workup

temperatureThe reaction was cooled
concentrationconcentrated in vacuo
customThe residue was purified
washeluting with 10-40% EtOAc in heptanes

Sources & evidence

ORD record: ord-0a25d84e8ff0452b9cdeb6e39f72e587
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328096B2

Reaction notes

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