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Trifluoroacetic acid → N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-(4-((2,5-dioxopyrrolidin-1-yl)methyl)benzyl)-1H-pyrazole-4-carboxamide

HRID 928397
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HRID 928397 반응식
C(OC(=O)[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[C:11]([CH2:15][NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][N:32]4[C:36](=[O:37])[CH2:35][CH2:34][C:33]4=[O:38])=[CH:27][CH:26]=3)[CH:23]=2)=[O:18])=[C:10]([CH3:39])[N:9]=1)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[N:9]=[C:10]([CH3:39])[C:11]([CH2:15][NH:16][C:17]([C:19]2[CH:20]=[N:21][N:22]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([CH2:31][N:32]4[C:33](=[O:38])[CH2:34][CH2:35][C:36]4=[O:37])=[CH:27][CH:26]=3)[CH:23]=2)=[O:18])=[C:12]([CH3:14])[CH:13]=1
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참가 물질

4

반응물 2

HCID 6422Trifluoroacetic acidHCID 58081290{5-[({1-[4-(2,5-Dioxo-pyrrolidin-1-ylmethyl)-benzyl]-1H-pyrazole-4-carbonyl}-amino)-methyl]-4,6-dimethyl-pyridin-2-yl]-carbamic acid tert-butyl ester

생성물 1

HCID 58081267N-((6-amino-2,4-dimethylpyridin-3-yl)methyl)-1-(4-((2,5-dioxopyrrolidin-1-yl)methyl)benzyl)-1H-pyrazole-4-carboxamide

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

A mixture of {5-[({1-[4-(2,5-Dioxo-pyrrolidin-1-ylmethyl)-benzyl]-1H-pyrazole-4-carbonyl}-amino)-methyl]-4,6-dimethyl-pyridin-2-yl]-carbamic acid tert-butyl ester (48 mg, 0.08 mmol), 1 mL TFA and 2 mL DCM was stirred of room temperature for 2 h. The mixture was evaporated in vacuo and the residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 250×40 mm, 5 to 100% ACN and 0.1% TFA, flow 40ml/min). The product containing fractions were lyophilised, then dissolved in 1 mL MeOH and the resulting mixture was filtered over a MeOH flushed PL-HCO3 MP-resin column. The column was washed with MeOH, the solvent was removed and the product was dissolved in water/ACN and lyophilised to yield the title compound. 1H-NMR (DMSO-d6, 400 MHz) 88.25 (s, 1H), 7.91 (t, 1H), 7.87 (s, 1H), 7.24 (d, 2H), 7.20 (d, 2H), 6.13 (s, 1H), 5.70 (bs, 2H), 5.28 (s, 2H), 4.52 (d, 2H), 2.67 (s, 4H), 2.29 (s, 3H), 2.15 (s, 3H); LCMS (method A) RtA=0.439 min; [M+H]+=447.1.

후처리

  1. customThe mixture was evaporated in vacuo
  2. customthe residue was purified by preparative HPLC (Macherey-Nagel Nucleosil 250×40 mm, 5 to 100% ACN and 0.1% TFA, flow 40ml/min)
  3. additionThe product containing fractions
  4. dissolutiondissolved in 1 mL MeOH
  5. filtrationthe resulting mixture was filtered over a MeOH flushed PL-HCO3 MP-resin column
  6. washThe column was washed with MeOH
  7. customthe solvent was removed
  8. dissolutionthe product was dissolved in water/ACN

출처 및 근거

ORD 기록
ord-f30ff74d3d05462893dda87355a9ae29
출처 데이터셋
uspto-grants-2016_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09290485B2

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