吡啶 → 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 1754314笔记

反应方程式

HRID 1754314 反应方程式
[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]

参与物

5

反应物 3

HCID 1049吡啶HCID 20812191(R)-氯甲酸异丙酯 1-氮杂双环[2,2,2]辛-3-基酯HCID 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

产物 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 salt收率 27.3%

试剂、催化剂与溶剂 1

HCID 313盐酸溶剂

实验过程

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).

后处理

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

来源与证据

ORD记录
ord-e35fcfb8d659454e99076003969802cb
来源数据集
uspto-grants-2015_10
专利号
US09169245B2

反应笔记

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