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

HRID 651669

반응식

HRID 651669 반응식
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

참가 물질

4

반응물 3

HCID 996PhenolHCID 517165Ammonium Acetate2회HCID 53899839Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(s)-yl]-amide

생성물 1

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

반응 조건

온도
70 °C

실험 절차

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 AS RP-HPLC.

후처리

  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

출처 및 근거

ORD 기록
ord-7dd4deb7e36f44209a90d0ad3283d3f6
출처 데이터셋
uspto-grants-2001_08
특허 번호
US06281227B1

연결된 노트

불러오는 중…