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1-Methylpiperazine → (+/-)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile

HRID 1247647
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HRID 1247647 반응식
[C:1]([C:3]1[CH:4]=[C:5]([N:9]2[C:14]3[N:15]=[C:16]([NH:19][C:20]4[CH:21]=[C:22]([CH2:26][CH2:27]OS(C)(=O)=O)[CH:23]=[CH:24][CH:25]=4)[N:17]=[CH:18][C:13]=3[CH:12]([CH3:33])[N:11]([C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)[C:10]2=[O:42])[CH:6]=[CH:7][CH:8]=1)#[N:2].[CH3:43][N:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1>C(OCC)(=O)C>[CH3:41][O:40][C:37]1[CH:36]=[CH:35][C:34]([N:11]2[CH:12]([CH3:33])[C:13]3[C:14](=[N:15][C:16]([NH:19][C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][N:47]5[CH2:48][CH2:49][N:44]([CH3:43])[CH2:45][CH2:46]5)[CH:21]=4)=[N:17][CH:18]=3)[N:9]([C:5]3[CH:4]=[C:3]([CH:8]=[CH:7][CH:6]=3)[C:1]#[N:2])[C:10]2=[O:42])=[CH:39][CH:38]=1
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참가 물질

4

반응물 2

HCID 531671-MethylpiperazineHCID 10325979(+/-)-Methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester

생성물 1

HCID 10031292(+/-)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile

시약·촉매·용매 1

HCID 8857Ethyl Acetate
용매

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온도
110 °C

실험 절차

A mixture of (±)-methanesulfonic acid (2-{3-[8-(3-cyano-phenyl)-6-(4-methoxy-phenyl)-5-methyl-7-oxo-5,6,7,8-tetrahydro-pyrimido[4,5-d]pyrimidin-2-ylamino]-phenyl}-ethyl)-ester (0.10 g; 0.16 mmol) (from Example 5a supra) and 1-methylpiperazine (0.25 mL; 2.23 mmol) (Aldrich) and heated at 110° C. for 1 hour. Upon cooling, the mixture was diluted with ethyl acetate and washed with water and brine. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude material was purified by flash chromatography (Biotage 12S; 100:0 to 40:60 ethyl acetate-methanol gradient) and then crystallized from ethyl acetate-hexanes to give (±)-3-(3-(4-methoxy-phenyl)-4-methyl-7-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenylamino}-2-oxo-3,4-dihydro-2H-pyrimido[4,5-d]pyrimidin-1-yl)-benzonitrile. (Yield 60.6 mg; 64.1%).

후처리

  1. temperatureUpon cooling
  2. washwashed with water and brine
  3. dry with materialThe organic phase was dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude material was purified by flash chromatography (Biotage 12S; 100:0 to 40:60 ethyl acetate-methanol gradient)
  7. customcrystallized from ethyl acetate-hexanes

출처 및 근거

ORD 기록
ord-d75fa0c6f2b145bab9dadb185b2ce02b
출처 데이터셋
uspto-grants-2006_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07129351B2

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