Dichloromethane → 3-Amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbohydrazide

HRID 331508Notes

Reaction equation

HRID 331508 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([CH3:12])([CH3:11])[C:9]#[N:10])[CH:3]=1.CC1(C)C(C)(C)OB(B2OC(C)(C)C(C)(C)O2)O1.C([O-])(=O)C.[K+].[NH2:36][C:37]1[C:38]([C:44]([NH:46][NH2:47])=[O:45])=[N:39][C:40](Br)=[CH:41][N:42]=1.C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH2:36][C:37]1[C:38]([C:44]([NH:46][NH2:47])=[O:45])=[N:39][C:40]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([C:8]([C:9]#[N:10])([CH3:12])[CH3:11])[CH:3]=2)=[CH:41][N:42]=1

Participants

10

Reactant 6

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 580702563-Amino-6-bromopyrazine-2-carbohydrazideHCID 592937172-(4-Iodopyridin-2-yl)-2-methylpropanenitrile

Product 1

HCID 708186113-Amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbohydrazideYield 58.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

2-(4-iodo-2-pyridyl)-2-methyl-propanenitrile (100 mg, 0.3675 mmol), PdCl2(PCy3)2 (20.87 mg, 0.02827 mmol), 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,3,2-dioxaborolane (96.90 mg, 0.3816 mmol), potassium acetate (83.23 mg, 0.8481 mmol) in 1,4-dioxane (1.615 mL). The reaction mixture was degassed with 5× vacuum/nitrogen cycles then heated at 110° C. for 4 hours. 3-amino-6-bromo-pyrazine-2-carbohydrazide (65.60 mg, 0.2827 mmol), potassium carbonate (136.7 mg, 0.9894 mmol), [PdCl2(dppf)].dichloromethane (23.09 mg, 0.02827 mmol) and water (0.89 mL) was added and the mixture was heated at 100° C. for 18 hours. The reaction mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and water. Combined organic extract were dried over MgSO4 and concentrated in vacuo yielding an oil. Purified by silica gel chromatography eluted with 5% methanol/dichloromethane. Product fractions were combined and concentrated in vacuo to yield 3-amino-6-[2-(1-cyano-1-methyl-ethyl)-4-pyridyl]pyrazine-2-carbohydrazide as a beige solid (49.5 mg, 57.1%) LC/MS m/z 298.1 [M+H]+.

Workup

  1. customThe reaction mixture was degassed with 5× vacuum/nitrogen cycles
  2. temperaturethe mixture was heated at 100° C. for 18 hours
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. customThe residue was partitioned between dichloromethane and water
  5. extractionCombined organic extract
  6. dry with materialwere dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customyielding an oil
  9. customPurified by silica gel chromatography
  10. washeluted with 5% methanol/dichloromethane
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-12ffb93157d8413c976c21379243b727
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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