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 1754314Notes

Reaction equation

HRID 1754314 reaction equation
[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]

Participants

5

Reactant 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

Product 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 saltYield 27.3%

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Procedure

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).

Workup

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

Sources & evidence

ORD record
ord-e35fcfb8d659454e99076003969802cb
Source dataset
uspto-grants-2015_10
Patent number
US09169245B2

Reaction notes

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