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 337033ノート

反応式

HRID 337033 の反応式
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

参加物

10

反応物 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、化合物

生成物 1

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

試薬・触媒・溶媒 4

HCID 23938Palladium触媒HCID 702Ethanol溶媒HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-22b2ed99dde840dda5df07fdeb9b6bfd
出典データセット
uspto-grants-2014_11
特許番号
US08889692B2

反応ノート

読み込み中…