Sodium Carbonate → N-{4-[6-(4-fluorophenyl)-2,3-dihydropyrazolo[5,1-b][1,3]oxazol-7-yl]pyridin-2-yl}cyclopropanecarboxamide

HRID 570135Notes

Reaction equation

HRID 570135 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([CH:18]3[CH2:20][CH2:19]3)=[O:17])[CH:10]=2)O1.Br[C:23]1[C:24]([C:31]2[CH:36]=[CH:35][C:34]([F:37])=[CH:33][CH:32]=2)=[N:25][N:26]2[CH2:30][CH2:29][O:28][C:27]=12.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:37][C:34]1[CH:33]=[CH:32][C:31]([C:24]2[C:23]([C:9]3[CH:14]=[CH:13][N:12]=[C:11]([NH:15][C:16]([CH:18]4[CH2:19][CH2:20]4)=[O:17])[CH:10]=3)=[C:27]3[O:28][CH2:29][CH2:30][N:26]3[N:25]=2)=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 67074038N-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-YL)pyridin-2-YL)cyclopropanecarboxamideHCID 894883787-Bromo-6-(4-fluorophenyl)-2,3-dihydropyrazolo[5,1-b]oxazole

Product 1

HCID 89488629N-{4-[6-(4-fluorophenyl)-2,3-dihydropyrazolo[5,1-b][1,3]oxazol-7-yl]pyridin-2-yl}cyclopropanecarboxamideYield 61.7%

Reagents, catalysts & solvents 2

HCID 11556747Bis(tricyclohexylphosphine)palladium(II) DichlorideCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

115 mg (0.40 mmol) of N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]cyclopropanecarboxamide and 124 mg (1.1 eq 0.44 mmol) of 7-bromo-6-(4-fluorophenyl)-2,3-dihydropyrazolo[5,1-b][1,3]oxazole are dissolved in 2 mL 1,4-dioxan. To this are added 30 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.04 mmol, 0.1 eq) and 2 mL sodium carbonate solution (2M in H2O). The reaction mixture is flushed for 5 mins with argon and then sealed. Next the mixture is heated for 12 mins at 120° C. in the microwave (CEM Explorer). After cooling, insoluble components are filtered off and the salt residue washed with 1,4-dioxan. The organic phase is evaporated and the crude product purified by silica gel chromatography (eluent cyclohexane/ethyl acetate). 90 mg (61%) of N-{4-[6-(4-fluorophenyl)-2,3-dihydropyrazolo[5,1-b][1,3]oxazol-7-yl]pyridin-2-yl}cyclopropanecarboxamide are obtained as a colourless solid.

Workup

  1. customThe reaction mixture is flushed for 5 mins with argon
  2. customsealed
  3. temperatureAfter cooling
  4. filtrationinsoluble components are filtered off
  5. washthe salt residue washed with 1,4-dioxan
  6. customThe organic phase is evaporated
  7. customthe crude product purified by silica gel chromatography (eluent cyclohexane/ethyl acetate)

Sources & evidence

ORD record
ord-58bdbd58585e464387387845f9f42ff8
Source dataset
uspto-grants-2015_05
Patent number
US09023844B2

Reaction notes

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