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1,1-dimethylethyl (2S)-4-{[3'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-5'-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate → N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(5-(methyloxy)-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamide

HRID 564605
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인쇄 미리보기

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HRID 564605 반응식
[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:24]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:53][CH2:52][N:51](C(OC(C)(C)C)=O)[C@@H:50]([CH3:61])[CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:26]=[CH:27][CH:28]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[CH2:1]([N:3]1[C:7]2=[N:8][C:9]([CH2:62][CH3:63])=[C:10]([CH2:19][NH:20][C:21]([C:23]3[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([NH:31][CH2:32][C:33]4[CH:34]=[C:35]([C:41]5[CH:46]=[CH:45][CH:44]=[C:43]([CH2:47][N:48]6[CH2:53][CH2:52][NH:51][C@@H:50]([CH3:61])[CH2:49]6)[CH:42]=5)[CH:36]=[C:37]([O:39][CH3:40])[CH:38]=4)=[O:30])[CH:24]=3)=[O:22])[C:11]([NH:12][CH:13]3[CH2:14][CH2:15][O:16][CH2:17][CH2:18]3)=[C:6]2[CH:5]=[N:4]1)[CH3:2]
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참가 물질

4

반응물 1

HCID 670057901,1-dimethylethyl (2S)-4-{[3'-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}carbonyl)amino]methyl}-5'-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate

생성물 1

HCID 57813294N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N'-[(5-(methyloxy)-3'-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamide수율 50%

시약·촉매·용매 2

HCID 6344
Dichloromethane
용매
HCID 6422Trifluoroacetic acid용매

실험 절차

237(b) A mixture of 1,1-dimethylethyl (2S)-4-{[3′-{[({3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]phenyl}-carbonyl)amino]-methyl}-5′-(methyloxy)-3-biphenylyl]methyl}-2-methyl-1-piperazinecarboxylate (130 mg, 0.19 mmol) in 25% TFA in DCM (3 mL) was stirred at RT for 2 h. It was purified by preparative hplc (NH2OH condition), eluting with 10 to 90% CH3CN in water. The fractions were dried under GeneVac to give a solid. It was purified further using a Gilson HPLC (with 0.1% TFA condition) and eluting with 10 to 90% CH3CN in water. Fractions containing compound were combined and then converted to its free base with saturated NaHCO3. The organic layer was dried over sodium sulfate, filtered and then concentrated to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-[(5-(methyloxy)-3′-{[(3S)-3-methyl-1-piperazinyl]methyl}-3-biphenylyl)methyl]-1,3-benzenedicarboxamide as a white solid (58 mg, 50%). LC-MS m/z 759 (M+H)+.

후처리

  1. customIt was purified by preparative hplc (NH2OH condition)
  2. washeluting with 10 to 90% CH3CN in water
  3. customThe fractions were dried under GeneVac
  4. customto give a solid
  5. customIt was purified further
  6. washeluting with 10 to 90% CH3CN in water
  7. additionFractions containing compound
  8. dry with materialThe organic layer was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

출처 및 근거

ORD 기록
ord-092d34c53e28435995ac288a4071d143
출처 데이터셋
uspto-grants-2011_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08067408B2

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