2-Fluorobenzylamine → N-Cyclopropyl-3-[3-(2-fluoro-benzylamino)-2-oxo-2H-pyrazin-1-yl]-4-methylbenzamide

HRID 1697280Notes

Reaction equation

HRID 1697280 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.[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH2:28][NH2:29].[CH:30]1([NH2:33])[CH2:32][CH2:31]1.C1([Mg]Br)CCCC1.C([O-])=O.[NH4+]>O1CCCC1.[Pd].C(O)C.C(N(CC)CC)C>[CH:30]1([NH:33][C:12](=[O:14])[C:11]2[CH:16]=[CH:17][C:18]([CH3:19])=[C:9]([N:4]3[CH:5]=[CH:6][N:7]=[C:2]([NH:29][CH2:28][C:23]4[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=4[F:21])[C:3]3=[O:20])[CH:10]=2)[CH2:32][CH2:31]1

Participants

10

Reactant 5

HCID 666492-FluorobenzylamineHCID 69828CyclopropylamineHCID 2723923Ammonium formateHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178419650HCID 178419650, compound

Product 1

HCID 66686260N-Cyclopropyl-3-[3-(2-fluoro-benzylamino)-2-oxo-2H-pyrazin-1-yl]-4-methylbenzamide

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °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 2-fluoro-benzenemethanamine (31 μL). The reaction was stirred overnight before the addition of cyclopropylamine (0.13 mL) and cyclopentylmagnesium bromide (2M in diethyl ether, 750 μL) dropwise. After stirring for 30 minutes, ethanol (2 mL) was added followed by the addition of ammonium formate (0.3 g) and 10% palladium on carbon (30 mg). The reaction mixture was heated within a microwave for 60 minutes at 100° 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 (58 mg).

Workup

  1. temperaturebefore being cooled to room temperature
  2. filtrationfiltered
  3. washwashed with ethanol
  4. concentrationThe filtrate was concentrated in vacuo
  5. customPurification by preparative HPLC (Gemini column, 0.1% ammonia:acetonitrile eluent)

Sources & evidence

ORD record
ord-d20182a5bcc54a6a84789b81c9da2c64
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

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