(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochloride → HCID 91801191, compound

HRID 2279930Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[N+:4]([O-:38])[CH:5]=[C:6]([Cl:37])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C:23]1[S:24][C:25]([CH2:28][NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])=[CH:26][CH:27]=1)=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1.Cl.[C:40](Cl)(=[O:50])[O:41][C@@H:42]1[CH:47]2[CH2:48][CH2:49][N:44]([CH2:45][CH2:46]2)[CH2:43]1>C(#N)C>[CH:21]([OH:22])=[O:20].[Cl:1][C:2]1[CH:3]=[N+:4]([O-:38])[CH:5]=[C:6]([Cl:37])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C:23]1[S:24][C:25]([CH2:28][N:29]([C:40]([O:41][C@@H:42]2[CH:47]3[CH2:48][CH2:49][N:44]([CH2:45][CH2:46]3)[CH2:43]2)=[O:50])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])=[CH:26][CH:27]=1)=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A microwave tube was charged with [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-[(2-fluoroanilino)methyl]thiophene-2-carboxylate (50 mg, 0.09 mmol), (R)-quinuclidin-3-yl carbonochloridate hydrochloride (81 mg, 0.36 mmol) and anhydrous acetonitrile (0.8 mL). The mixture was heated at 80° C. for 3 minutes under microwave irradiation. The reaction was evaporated to dryness. The residue was dissolved in DMSO (1.5 mL) and purified by preparative HPLC to afford [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-[(2-fluoro-N-[(3R)-quinuclidin-3-yl]oxycarbonyl-anilino)methyl]-thiophene-2-carboxylate formate salt as a white solid (26 mg, 41%).

Workup

customThe reaction was evaporated to dryness
dissolutionThe residue was dissolved in DMSO (1.5 mL)
custompurified by preparative HPLC

Sources & evidence

ORD record: ord-08fd530b29e7441392e2d92d37fbcf6b
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133185B2

Reaction notes

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