Diphenylmethane → (6S,9aS)-N-Benzyl-6-((2-fluoro-4-hydroxyphenyl)methyl)-8-((6-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide

HRID 707508노트

반응식

HRID 707508 반응식
[CH2:1]([NH:8][C:9]([N:11]1[C@H:16]2[CH2:17][N:18]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34](F)[N:33]=3)[C:19](=[O:30])[C@H:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][C:23]=3[F:29])[N:15]2[C:14](=[O:39])[CH2:13][N:12]1[CH2:40][CH:41]=[CH2:42])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1C(=O)CCC1.[NH:50]1[CH2:53][CH:52]([N:54]2[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]2)[CH2:51]1.C(C1C=CC=CC=1)C1C=CC=CC=1>O>[CH2:1]([NH:8][C:9]([N:11]1[C@H:16]2[CH2:17][N:18]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([N:50]4[CH2:53][CH:52]([N:54]5[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]5)[CH2:51]4)[N:33]=3)[C:19](=[O:30])[C@H:20]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][C:23]=3[F:29])[N:15]2[C:14](=[O:39])[CH2:13][N:12]1[CH2:40][CH:41]=[CH2:42])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

참가 물질

6

반응물 4

HCID 7580DiphenylmethaneHCID 13387N-methyl-2-pyrrolidoneHCID 206598001-(Azetidin-3-yl)-4-methylpiperazineHCID 118162423(6S,9aS)-N-benzyl-6-((2-fluoro-4-hydroxyphenyl)methyl)-8-((6-fluoropyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide

생성물 1

HCID 118162567(6S,9aS)-N-Benzyl-6-((2-fluoro-4-hydroxyphenyl)methyl)-8-((6-(3-(4-methylpiperazin-1-yl)azetidin-1-yl)pyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide수율 53%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

To a mixed solution of (6S,9aS)-N-benzyl-6-((2-fluoro-4-hydroxyphenyl)methyl)-8-((6-fluoropyridin-2-yl)methyl)-4,7-dioxo-2-(prop-2-en-1-yl)-octahydro-1H-pyrazino[2,1-c][1,2,4]triazine-1-carboxamide (40.0 mg, 0.0694 mmol) described in Production Example 1-1-6 and NMP (2.0 mL) was added a mixture (112 mg) of 1-(azetidin-3-yl)-4-methylpiperazine and benzylbenzene described in Production Example 3-2 at room temperature, and the resultant mixture was irradiated with a microwave at 140° C. for 12 hours. After the mixture was cooled to room temperature, water was added to the reaction mixture, the resultant solution was extracted with ethyl acetate, and an organic layer was washed with water and then with saturated brine. An organic layer was dried over anhydrous magnesium sulfate and then filtrated. The solvent was evaporated under a reduced pressure, and the resultant residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1) and then further purified by NH silica gel thin-layer chromatography (ethyl acetate) to give the title compound (26.0 mg, yield: 53%).

후처리

  1. customdescribed in Production Example 3-2 at room temperature
  2. extractionthe resultant solution was extracted with ethyl acetate
  3. washan organic layer was washed with water
  4. dry with materialAn organic layer was dried over anhydrous magnesium sulfate
  5. filtrationfiltrated
  6. customThe solvent was evaporated under a reduced pressure
  7. customthe resultant residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=20:1)
  8. customfurther purified by NH silica gel thin-layer chromatography (ethyl acetate)

출처 및 근거

ORD 기록
ord-f4e5b77e18454e5ab67deda63a386e18
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09174998B2

반응 노트

불러오는 중…