Sodium Carbonate → N-{4-[2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]pyridin-2-yl}cyclopropanecarboxamide

HRID 628464Notes

Reaction equation

HRID 628464 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:27]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)=[N:26][N:25]2[CH2:35][CH2:36][CH2:37][C:24]=12.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.C1CCC(P(C2CCCCC2)C2CCCCC2)CC1.[Cl-].[Cl-].[Pd+2]>[F:34][C:31]1[CH:30]=[CH:29][C:28]([C:27]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:24]3[CH2:37][CH2:36][CH2:35][N:25]3[N:26]=2)=[CH:33][CH:32]=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 894883353-bromo-2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole

Product 1

HCID 89488267N-{4-[2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]pyridin-2-yl}cyclopropanecarboxamideYield 46.9%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

140 mg (0.50 mmol) of N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]cyclopropanecarboxamide and 172 mg (1.2 eq 0.60 mmol) of 3-bromo-2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole are dissolved in 3.5 mL 1,4-dioxan. To this are added 36 mg of bis(tricyclohexylphosphine)-palladium(II)dichloride (0.05 mmol, 0.1 eq) and 1.2 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). 85 mg (43%) of N-{4-[2-(4-fluorophenyl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-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-8dbd207cb3fa40d9a44eaff832319063
Source dataset
uspto-grants-2016_04
Patent number
US09314026B2

Reaction notes

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