O-Methylhydroxylamine hydrochloride → N-Methoxy-4-methyl-3-[3-[[[2-[(4-methyl-1-piperazinyl)methyl]phenyl]methyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide

HRID 1697293Notes

Reaction equation

HRID 1697293 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][N:22]1[CH2:27][CH2:26][N:25]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:35][NH2:36])[CH2:24][CH2:23]1.Cl.[CH3:38][O:39][NH2:40].C1([Mg]Br)CCCC1.C([O-])=O.[NH4+]>O1CCCC1.[Pd].C(O)C.C(N(CC)CC)C>[CH3:38][O:39][NH:40][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:36][CH2:35][C:30]3[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=3[CH2:28][N:25]3[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]3)[C:3]2=[O:20])[CH:10]=1

Participants

10

Reactant 5

HCID 521874O-Methylhydroxylamine hydrochlorideHCID 2723923Ammonium formateHCID 16228064(2-((4-Methylpiperazin-1-yl)methyl)phenyl)methanamineHCID 66688740methyl 3-(3,5-dibromo-2-oxopyrazin-1(2H)-yl)-4-methylbenzoateHCID 178419650HCID 178419650, compound

Product 1

HCID 86669857N-Methoxy-4-methyl-3-[3-[[[2-[(4-methyl-1-piperazinyl)methyl]phenyl]methyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamideYield 11%

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 (2 mL) in a microwave vial was added triethylamine (250 μL) and 2-[(4-methyl-1-piperazinyl)methyl]-benzenemethanamine (90 mg). The reaction was stirred overnight before the addition of O-methylhydroxylamine hydrochloride (83 mg) and cyclopentylmagnesium bromide (2M in diethyl ether, 2 mL) dropwise. After stirring for 60 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 30 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% trifluoroacetic acid:acetonitrile eluent) afforded the title compound (13 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% trifluoroacetic acid:acetonitrile eluent)

Sources & evidence

ORD record
ord-9414269066d24721b04ffa80fd562876
Source dataset
uspto-grants-2012_04
Patent number
US08163905B2

Reaction notes

Loading…