Pyridine → 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-((phenyl(((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide formate salt

HRID 1754314노트

반응식

HRID 1754314 반응식
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:50])[CH:5]=[C:6]([Cl:49])[C:7]=1[CH2:8][C@@H:9]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:48][CH2:47]2)[CH:35]=1)[O:10][C:11]([C@H:13]1[N:17]([C:18](=[O:33])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:20]=2)[CH2:16][CH2:15][S:14]1)=[O:12].N1C=CC=CC=1.[C:57](Cl)(=[O:67])[O:58][C@@H:59]1[CH:64]2[CH2:65][CH2:66][N:61]([CH2:62][CH2:63]2)[CH2:60]1>Cl>[CH:11]([OH:12])=[O:10].[Cl:1][C:2]1[CH:3]=[N+:4]([O-:50])[CH:5]=[C:6]([Cl:49])[C:7]=1[CH2:8][C@@H:9]([C:34]1[CH:39]=[CH:38][C:37]([O:40][CH:41]([F:43])[F:42])=[C:36]([O:44][CH2:45][CH:46]2[CH2:47][CH2:48]2)[CH:35]=1)[O:10][C:11]([C@H:13]1[N:17]([C:18](=[O:33])[C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([CH2:25][N:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:57]([O:58][C@@H:59]3[CH:64]4[CH2:65][CH2:66][N:61]([CH2:62][CH2:63]4)[CH2:60]3)=[O:67])[CH:20]=2)[CH2:16][CH2:15][S:14]1)=[O:12]

참가 물질

5

반응물 3

HCID 1049PyridineHCID 20812191(R)-quinuclidin-3-yl carbonochloridateHCID 867202723,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-((phenylamino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide

생성물 1

HCID 867202733,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-((phenyl(((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide formate salt수율 27.3%

시약·촉매·용매 1

HCID 313Hydrochloric Acid용매

실험 절차

3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-((phenylamino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide (120 mg, 0.161 mmol) was dissolved in Pyridine (1 ml, 12.36 mmol). (R)-quinuclidin-3-yl carbonochloridate (76 mg, 0.403 mmol) was added under N2 atmosphere and at 0° C. The reaction was stirred at RT for two days to achieve completion. The reaction mixture was diluted with HCl 1N and the precipitate was filtered, washed with Water and purified by preparative HPLC to give 3,5-dichloro-4-((S)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((S)-3-(3-((phenyl(((R)-quinuclidin-3-yloxy)carbonyl)amino)methyl)benzoyl)thiazolidine-2-carbonyloxy)ethyl)pyridine 1-oxide formate salt (20 mg, 0.022 mmol, 13.82% yield).

후처리

  1. filtrationthe precipitate was filtered
  2. washwashed with Water
  3. custompurified by preparative HPLC

출처 및 근거

ORD 기록
ord-e35fcfb8d659454e99076003969802cb
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09169245B2

반응 노트

불러오는 중…