Ammonium Chloride → (4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-5-methylphenyl)-2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-hydroxy-N,N-dimethyl-L-prolinamide

HRID 1662704Notes

Reaction equation

HRID 1662704 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:10](O)([C:11]3[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=3[O:18][CH3:19])[C:9](=[O:21])[N:8]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=3[O:33][CH3:34])(=[O:24])=[O:23])[C:5]2=[N:6][CH:7]=1.CS(OS(C)(=O)=O)(=O)=O.FC(F)(F)C(O)=O.[OH:51][C@H:52]1[CH2:56][NH:55][C@H:54]([C:57]([N:59]([CH3:61])[CH3:60])=[O:58])[CH2:53]1.[NH4+].[Cl-]>C(Cl)(Cl)Cl.CCN(CC)CC>[Cl:1][C:2]1[CH:3]=[C:4]2[C:10]([N:55]3[CH2:56][C@H:52]([OH:51])[CH2:53][C@H:54]3[C:57]([N:59]([CH3:61])[CH3:60])=[O:58])([C:11]3[CH:16]=[C:15]([CH3:17])[CH:14]=[CH:13][C:12]=3[O:18][CH3:19])[C:9](=[O:21])[N:8]([S:22]([C:25]3[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=3[O:33][CH3:34])(=[O:23])=[O:24])[C:5]2=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 81560Methanesulfonic anhydrideHCID 674279735-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-hydroxy-3-(2-methoxy-5-methylphenyl)-1,3-dihy dro-2H-pyrrolo[2,3-b]pyridin-2-oneHCID 67429482HCID 67429482, compound

Product 1

HCID 59867866(4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-5-methylphenyl)-2-oxo-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-3-yl]-4-hydroxy-N,N-dimethyl-L-prolinamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 8471TriethylamineSolvent2×

Procedure

To a solution of 500 mg of the compound obtained in Step 119-1 and 200 mg of Et3N in CHCl3 (5 ml) was added 207 mg of methane sulfonic acid anhydride under ice cooling. The solution was stirred at the same temperature for 20 minutes, then, 1.90 g of Et3N was added. Thereafter, a solution of (4R)-4-hydroxy-N,N-dimethyl-L-prolinamide trifluoroacetate (4.95 mmol) in CHCl3 (5 ml) was added dropwise at the same temperature. The solution was stirred at the same temperature for one hour, then, was gradually warmed and stirred for 30 minutes under room temperature conditions, then, was poured into a saturated aqueous solution of NH4Cl and extracted with CHCl3. The combined organic layer was washed with saturated brine, dried over Na2SO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was separated and purified by column chromatography (first time: silicagel 60N; mobile phase: CHCl3/MeOH=10/0 to 9/1; v/v, first time: silicagel 60N; mobile phase: EtOAc/MeOH=10/0 to 9/1; v/v) to obtain respectively 7.6 mg (Isomer A: brown amorphous) and 18.9 mg (Isomer B: brown amorphous) of two species of diastereoisomers of the title compound.

Workup

  1. stirringThe solution was stirred at the same temperature for one hour
  2. temperaturewas gradually warmed
  3. stirringstirred for 30 minutes under room temperature conditions
  4. extractionextracted with CHCl3
  5. washThe combined organic layer was washed with saturated brine
  6. dry with materialdried over Na2SO4
  7. customthe drying agent was separated by filtration
  8. customthe solvent was evaporated under reduced pressure
  9. customThe obtained residue was separated
  10. custompurified by column chromatography (first time: silicagel 60N; mobile phase: CHCl3/MeOH=10/0 to 9/1; v/v, first time: silicagel 60N; mobile phase: EtOAc/MeOH=10/0 to 9/1; v/v)

Sources & evidence

ORD record
ord-8d688e446c304cb1b0574ff82d6f0c0e
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

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