Sodium Carbonate → 4-(6-bromopyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl) thiophene-2-carboxamide

HRID 1255863Notes

Reaction equation

HRID 1255863 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[CH:9][C:10]=2I)[CH:7]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[C:22]([C:25]([NH:27][CH:28]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[C:29]([F:32])([F:31])[F:30])=[O:26])[S:23][CH:24]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[Br:1][C:2]1[CH:3]=[N:4][C:5]2[N:6]([N:8]=[CH:9][C:10]=2[C:20]2[CH:21]=[C:22]([C:25]([NH:27][CH:28]([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[C:29]([F:32])([F:31])[F:30])=[O:26])[S:23][CH:24]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 568452436-Bromo-3-iodopyrazolo[1,5-a]pyrimidineHCID 687453684-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide

Product 1

HCID 687765384-(6-bromopyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl) thiophene-2-carboxamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

6-bromo-3-iodopyrazolo[1,5-a]pyrimidine (1 eq) was mixed with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide (1 eq, step B). Dioxane (10 mL) and 1M Na2CO3 (2 eq) were added. The mixture was evacuated and flushed with nitrogen under stirring, then Pd(Ph3P)4 (0.05 eq) was added in a flow of nitrogen. The temperature was brought to 90° C. The reaction mixture was stirred at this temperature overnight and concentrated. The residue was poured into a 5-fold excess of water. The mixture was extracted with chloroform. The organic layer was washed with brine, dried with MgSO4, and concentrated. The residue was purified by column chromatography (dichloromethane-methanol, 100:1) to give 4-(6-bromopyrazolo[1,5-a]pyrimidin-3-yl)-N-(2,2,2-trifluoro-1-pyridin-2-ylethyl)thiophene-2-carboxamide.

Workup

  1. customThe mixture was evacuated
  2. customflushed with nitrogen
  3. customwas brought to 90° C
  4. stirringThe reaction mixture was stirred at this temperature overnight
  5. concentrationconcentrated
  6. additionThe residue was poured into a 5-fold excess of water
  7. extractionThe mixture was extracted with chloroform
  8. washThe organic layer was washed with brine
  9. dry with materialdried with MgSO4
  10. concentrationconcentrated
  11. customThe residue was purified by column chromatography (dichloromethane-methanol, 100:1)

Sources & evidence

ORD record
ord-64c3cdbf9c6743beb1e37c859ce937e9
Source dataset
uspto-grants-2013_06
Patent number
US08461162B2

Reaction notes

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