Cumylamine → N-Methoxy-4-methyl-3-[3-[(1-methyl-1-phenylethyl)amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

HRID 337034Notes

Reaction equation

HRID 337034 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.[CH3:21][C:22]([CH3:30])([C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH2:23].Cl.[CH3:32][O:33][NH2:34].C1([Mg]Br)CCCC1.C([O-])=O.[NH4+]>O1CCCC1.[Pd].C(O)C.C(N(CC)CC)C>[CH3:32][O:33][NH:34][C:12](=[O:14])[C:11]1[CH:16]=[CH:17][C:18]([CH3:19])=[C:9]([N:4]2[CH:5]=[CH:6][N:7]=[C:2]([NH:23][C:22]([CH3:30])([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH3:21])[C:3]2=[O:20])[CH:10]=1

Participants

10

Reactant 5

HCID 68509CumylamineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 2723923Ammonium formateHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178419650HCID 178419650, compound

Product 1

HCID 86675663N-Methoxy-4-methyl-3-[3-[(1-methyl-1-phenylethyl)amino]-2-oxo-1(2H)-pyrazinyl]-benzamideYield 41%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 3-(3,5-dibromo-2-oxo-2H-pyrazin-1-yl)-4-methyl-benzoic acid, methyl ester (Example 1b, 0.1 g) in tetrahydrofuran (1 mL) within a microwave vial was added triethylamine (38 μL) and α,α-dimethyl-benzenemethanamine (74 mg). The reaction was heated within a microwave for 120 minutes at 120° C. before being cooled to room temperature and the addition of O-methylhydroxylamine hydrochloride (83 mg) and cyclopentylmagnesium bromide (2M in diethyl ether, 2 mL) added dropwise. After stirring for 30 minutes, ethanol (2 mL) was added followed by the addition of ammonium formate (0.4 g) and 10% palladium on carbon (40 mg). The reaction mixture was heated within a microwave for 120 minutes at 80° C. before being cooled to room temperature, filtered and washed with ethanol. The filtrate was concentrated in vacuo. Purification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent) afforded the title compound as a solid (40 mg).

Workup

  1. temperaturebefore being cooled to room temperature
  2. additionadded dropwise
  3. temperatureThe reaction mixture was heated within a microwave for 120 minutes at 80° C.
  4. temperaturebefore being cooled to room temperature
  5. filtrationfiltered
  6. washwashed with ethanol
  7. concentrationThe filtrate was concentrated in vacuo
  8. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-86e82d59af3c40639e6d0795b6d9e186
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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