2,3,4-Trihydroxybenzaldehyde → Pandacostat

HRID 1020516

반응식

HRID 1020516 반응식
[OH:1][C:2]1[C:9]([OH:10])=[C:8]([OH:11])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH:12]([C:14]([C:16]1[CH:21]=[CH:20][C:19](/[CH:22]=[CH:23]/[C:24]([NH:26][OH:27])=[O:25])=[CH:18][CH:17]=1)=[O:15])[NH2:13]>CS(C)=O>[OH:27][NH:26][C:24](=[O:25])/[CH:23]=[CH:22]/[C:19]1[CH:18]=[CH:17][C:16]([C:14]([NH:12]/[N:13]=[CH:4]/[C:3]2[CH:6]=[CH:7][C:8]([OH:11])=[C:9]([OH:10])[C:2]=2[OH:1])=[O:15])=[CH:21][CH:20]=1

참가 물질

4

반응물 2

HCID 750642,3,4-TrihydroxybenzaldehydeHCID 86669388(E)-3-(4-(hydrazinecarbonyl)phenyl)-N-hydroxyacrylamide

생성물 1

HCID 135928012Pandacostat수율 23.3%

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

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온도
70 °C

실험 절차

Compound 6a was resynthesized and purified to be re-subjected to the biochemical assay to confirm the results from the initial library screen. To a 4 dram vial charged with 2,3,4-trihydroxybenzaldehyde (25.9 mg, 0.168 mmol) was added 420 μL of a 200 mM solution of hydrazine 5a (0.084 mmol) in DMSO. The solution was heated on a rotating heating block at 70° C. for 16 h. Reaction progress was monitored via LCMS. Following purification by reverse phase preparatory LCMS (44 mL/min, CH3CN/H2O with 1% formic acid, 5 min gradient), 6a (7 mg) was isolated as a yellow powder (98% pure, by analytical LCMS). 1H NMR (300 MHz, DMSO) δ 12.01 (s, 1H), 11.51 (s, 1H), 10.84 (s, 1H), 9.49 (s, 1H), 9.13 (s, 1H), 8.54 (s, 1H), 8.48 (s, 1H), 7.96 (d, J=8.3, 2H), 7.73 (d, J=8.2, 2H), 7.53 (d, J=16.2, 1H), 6.80 (d, J=8.6, 1H), 6.59 (d, J=15.9, 1H), 6.40 (d, J=8.4, 1H); m/z (ES−) 356 ([M-H]).

후처리

  1. customCompound 6a was resynthesized
  2. custompurified
  3. customresults from the initial library screen
  4. temperatureThe solution was heated on
  5. customReaction progress
  6. custompurification by reverse phase preparatory LCMS (44 mL/min, CH3CN/H2O with 1% formic acid, 5 min gradient)

출처 및 근거

ORD 기록
ord-36c1ba40bb754b12aef0398483c01933
출처 데이터셋
uspto-grants-2014_05
특허 번호
US08716344B2

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