Pyridine → HCID 76284977, compound

HRID 1754321Notes

Reaction equation

HRID 1754321 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:47])[CH:5]=[C:6]([Cl:46])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C@@H:23]1[CH2:27][CH2:26][CH2:25][N:24]1[S:28]([C:31]1[CH:36]=[CH:35][C:34]([CH2:37][NH:38][C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])=[CH:33][CH:32]=1)(=[O:30])=[O:29])=[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:49](Cl)(=[O:59])[O:50][C@@H:51]1[CH:56]2[CH2:57][CH2:58][N:53]([CH2:54][CH2:55]2)[CH2:52]1.N1C=CC=CC=1>C(#N)C>[Cl:1][C:2]1[CH:3]=[N+:4]([O-:47])[CH:5]=[C:6]([Cl:46])[C:7]=1[CH2:8][C@H:9]([O:20][C:21]([C@@H:23]1[CH2:27][CH2:26][CH2:25][N:24]1[S:28]([C:31]1[CH:36]=[CH:35][C:34]([CH2:37][N:38]([C:49]([O:50][C@@H:51]2[CH:56]3[CH2:57][CH2:58][N:53]([CH2:54][CH2:55]3)[CH2:52]2)=[O:59])[C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[F:45])=[CH:33][CH:32]=1)(=[O:29])=[O:30])=[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

5

Reactant 3

HCID 1049PyridineHCID 86676896(3R)-1-azabicyclo[2.2.2]octan-3-yl carbonochloridate hydrochloride2×HCID 86720281HCID 86720281, compound

Product 1

HCID 76284977HCID 76284977, compoundYield 16.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl](2S)-1-[4-[(2-fluoroanilino)methyl]phenyl]sulfonylpyrrolidine-2-carboxylate (105 mg, 0.15 mmol) in acetonitrile (3.2 mL) was added (R)-quinuclidin-3-yl carbonochloridate hydrochloride (131 mg, 0.6 mmol) and pyridine (0.12 mL), and the mixture was heated to 80° C. in a microwave for 6 minutes. Further (R)-quinuclidin-3-yl carbonochloridate hydrochloride (34 mg, 0.15 mmol) was added, and the mixture was heated to 80° C. in a microwave for 6 minutes. The solvent was removed in vacuo and the mixture was partitioned between ethyl acetate (10 mL) and water (10 mL). The layers were separated and the water was removed in vacuo. Purification of the residue from the aqueous layer was achieved by preparative HPLC to afford the title compound as a white solid (21 mg, 16%).

Workup

  1. temperaturethe mixture was heated to 80° C. in a microwave for 6 minutes
  2. customThe solvent was removed in vacuo
  3. customthe mixture was partitioned between ethyl acetate (10 mL) and water (10 mL)
  4. customThe layers were separated
  5. customthe water was removed in vacuo
  6. customPurification of the residue from the aqueous layer

Sources & evidence

ORD record
ord-97930279429c447192f51297050be16e
Source dataset
uspto-grants-2015_10
Patent number
US09169245B2

Reaction notes

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