Phenol → Thieno(3,2-B)pyridine-2-sulfonic acid (1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrroldin-3-YL)-amide

HRID 394612

反応式

HRID 394612 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]3[CH2:17][CH2:16][C@H:15]([NH:18][S:19]([C:22]4[S:30][C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[CH:23]=4)(=[O:21])=[O:20])[C:14]3=[O:31])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C1(O)C=CC=CC=1.C([O-])(=O)C.[NH4+:43]>>[NH2:43][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]3[CH2:17][CH2:16][C@H:15]([NH:18][S:19]([C:22]4[S:30][C:29]5[C:24](=[N:25][CH:26]=[CH:27][CH:28]=5)[CH:23]=4)(=[O:21])=[O:20])[C:14]3=[O:31])[CH:10]=2)[CH:5]=[CH:4][N:3]=1

参加物

4

反応物 3

HCID 996PhenolHCID 517165Ammonium Acetate2 回HCID 53899839Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(s)-yl]-amide

生成物 1

HCID 445480Thieno(3,2-B)pyridine-2-sulfonic acid (1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrroldin-3-YL)-amide

反応条件

温度
70 °C

実験手順

Thieno[3,2-b]pyridine-2-sulfonic acid [1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-amide (1.36 g, 2.88 mmol) and phenol (2.22 g, 23.6 mmol) are melted together with stirring at 70° C. for 5 minutes. Ammonium acetate (2.71 g, 28.8 mmol) is added and the reaction mixture is heated to 90° C. and stirred overnight. Additional ammonium acetate (0.50 g, 5.31 mmol) is added and the reaction is heated for 20 more hours. The reaction is cooled and the residue is purified by RP-HPLC eluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate product fractions are lyophilized to provide the title compound as a white solid. The enantiomeric purity is 90.5% ee as determined by analytical Chiralpak AS RP-HPLC.

後処理

  1. temperaturethe reaction mixture is heated to 90° C.
  2. stirringstirred overnight
  3. temperaturethe reaction is heated for 20 more hours
  4. temperatureThe reaction is cooled
  5. customthe residue is purified by RP-HPLC
  6. washeluting in a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN

出典と根拠

ORDレコード
ord-4b08a39c19514e579dc74e97f14960ea
出典データセット
uspto-grants-2003_08
特許番号
US06602864B1

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