Dimethylformamide → HCID 71115127, compound

HRID 468749Notes

Reaction equation

HRID 468749 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1.[CH3:18][C:19]1[CH:20]=[N:21][N:22]([CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][O:38]2)[C:23]=1[Sn](CCCC)(CCCC)CCCC.CN(C)C=O.[F-].[Cs+]>CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.[Cu]I>[CH3:18][C:19]1[CH:20]=[N:21][N:22]([CH:37]2[CH2:42][CH2:41][CH2:40][CH2:39][O:38]2)[C:23]=1[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([NH:12][C:13]([CH:15]3[CH2:17][CH2:16]3)=[O:14])[N:8]=[CH:9]2)=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 67974626N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamideHCID 67975086HCID 67975086, compound

Product 1

HCID 71115127HCID 71115127, compoundYield 67.6%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418851HCID 178418851, compoundCatalyst

Conditions

Temperature
50 °C

Procedure

To a mixture of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (50.4 mg, 0.173 mmol) and 4-methyl-1-(tetrahydro-2H-pyran-2-yl)-5-(tributylstannyl)-1H-pyrazole (76.9 mg, 0.169 mmol) was added N,N-dimethylformamide (1.5 mL, 19 mmol). Nitrogen gas was bubbled through the reaction mixture for 5 minutes, and then bis(tri-t-butylphosphine)palladium (11.5 mg, 0.0225 mmol), copper(I) iodide (6.1 mg, 0.032 mmol), and cesium fluoride (53.4 mg, 0.352 mmol) was added. The reaction mixture was stirred in a sealed vial at 50° C. for 2 hours, and then at 80° C. for 16 hours. The mixture was then partitioned between ethyl acetate and water, and the organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 20-100% ethyl acetate in heptanes) to yield 43.0 mg (67%) of N-(7-(4-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): M+H=377.2.

Workup

  1. customNitrogen gas was bubbled through the reaction mixture for 5 minutes
  2. waitat 80° C. for 16 hours
  3. customThe mixture was then partitioned between ethyl acetate and water
  4. washthe organic layer was washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customevaporated in vacuo
  8. customThe crude product was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 20-100% ethyl acetate in heptanes)

Sources & evidence

ORD record
ord-cf65bd261fac4250a52d3d9364d03aed
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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