Benzylamine → 3-[5-Cyano-2-oxo-3-[(phenylmethyl)amino]-1(2H)-pyrazinyl]-N-cyclopropyl-4-methylbenzamide

HRID 2070705Notes

Reaction equation

HRID 2070705 reaction equation
Br[C:2]1[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([O:14]C)=O)[CH:5]=[C:6](Br)[N:7]=1.C([N:24](CC)[CH:25]([CH3:27])[CH3:26])(C)C.[C:30]1([CH2:36][NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[CH:38]1([NH2:41])CC1.C1([Mg]Br)CCCC1.[Cl-].[NH4+]>O1CCCC1.C(O)C>[C:38]([C:6]1[N:7]=[C:2]([NH:37][CH2:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[C:3](=[O:20])[N:4]([C:9]2[CH:10]=[C:11]([CH:16]=[CH:17][C:18]=2[CH3:19])[C:12]([NH:24][CH:25]2[CH2:26][CH2:27]2)=[O:14])[CH:5]=1)#[N:41]

Participants

9

Reactant 6

HCID 7504BenzylamineHCID 25517Ammonium ChlorideHCID 69828CyclopropylamineHCID 81531DiisopropylethylamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178419650HCID 178419650, compound

Product 1

HCID 666864873-[5-Cyano-2-oxo-3-[(phenylmethyl)amino]-1(2H)-pyrazinyl]-N-cyclopropyl-4-methylbenzamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.4 g) in tetrahydrofuran (2 mL) within a microwave vial was added N,N-diisopropylethylamine (330 μL) and benzenemethanamine (150 μL). The reaction was stirred overnight before the addition of cyclopropylamine (0.5 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 3 mL) dropwise. The reaction was stirred for 30 minutes before ethanol (2 mL) was added followed by ammonium chloride. The solution was extracted with ethyl acetate and the organics were washed with brine, dried (Na2SO4), filtered and the solvent removed to afford the amide as a solid (543 mg). N,N-dimethylformamide (8 mL), tetrakis(triphenylphosphine)palladium(0) (50 mg) and zinc cyanide (421 mg) were added and the reaction was heated within a microwave at 170° C. for 10 minutes. The reaction was cooled to room temperature. Water was added and the mixture extracted with ethyl acetate. The pooled organics were washed with brine, dried (Na2SO4), filtered and the solvent removed to afford the title compound (570 mg).

Workup

  1. additionwas added
  2. extractionThe solution was extracted with ethyl acetate
  3. washthe organics were washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent removed

Sources & evidence

ORD record
ord-b6412ad62eca46638d4891990ba907fd
Source dataset
uspto-grants-2012_10
Patent number
US08299246B2

Reaction notes

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