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 337033Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 337033
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

Komponenten

10

Edukt 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, Verbindung

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 23938PalladiumKatalysatorHCID 702EthanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-22b2ed99dde840dda5df07fdeb9b6bfd
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889692B2

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