2,3,4-Trihydroxybenzaldehyde → Pandacostat

HRID 1020516

反応式

HRID 1020516 の反応式
[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

参加物

4

反応物 2

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

生成物 1

HCID 135928012Pandacostat収率 23.3%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
70 °C

実験手順

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]).

後処理

  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)

出典と根拠

ORDレコード
ord-36c1ba40bb754b12aef0398483c01933
出典データセット
uspto-grants-2014_05
特許番号
US08716344B2

関連ノート

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