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 337033노트

반응식

HRID 337033 반응식
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

참가 물질

10

반응물 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, 화합물

생성물 1

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

시약·촉매·용매 4

HCID 23938Palladium촉매HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매HCID 8471Triethylamine용매

반응 조건

온도
100 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-22b2ed99dde840dda5df07fdeb9b6bfd
출처 데이터셋
uspto-grants-2014_11
특허 번호
US08889692B2

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