Hydrochloric Acid → (4R)-1-(5-chloro-3-[2-methoxy-5-(2-piperazin-1-ylethyl)phenyl]-1-{[4-methoxy-2-(trifluoromethoxy)phenyl]sulfonyl}-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-L-prolinamide

HRID 1662765Notes

Reaction equation

HRID 1662765 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][C:24]([F:27])([F:26])[F:25])(=[O:14])=[O:13])[C:7](=[O:28])[C:6]2([C:40]1[CH:41]=[C:42]([CH2:48][CH2:49][N:50]2[CH2:55][CH2:54][N:53](C(OC(C)(C)C)=O)[CH2:52][CH2:51]2)[CH:43]=[CH:44][C:45]=1[O:46][CH3:47])[N:29]1[CH2:33][C@H:32]([OH:34])[CH2:31][C@H:30]1[C:35]([N:37]([CH3:39])[CH3:38])=[O:36].C([O-])(O)=O.[Na+]>CCOC(C)=O>[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([S:12]([C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][C:16]=1[O:23][C:24]([F:25])([F:27])[F:26])(=[O:13])=[O:14])[C:7](=[O:28])[C:6]2([N:29]1[CH2:33][C@H:32]([OH:34])[CH2:31][C@H:30]1[C:35]([N:37]([CH3:38])[CH3:39])=[O:36])[C:40]1[CH:41]=[C:42]([CH2:48][CH2:49][N:50]2[CH2:51][CH2:52][NH:53][CH2:54][CH2:55]2)[CH:43]=[CH:44][C:45]=1[O:46][CH3:47]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 59867855tert-butyl 4-{2-[3-(5-chloro-3-{(2S,4R)-2-[(dimethylamino)carbonyl]-4-hydroxypyrrolidin-1-yl}-1-{[4-methoxy-2-(trifluoromethoxy)phenyl]sulfonyl}-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-methoxyphenyl]ethyl}piperazine-1-carboxylate

Product 1

HCID 59867843(4R)-1-(5-chloro-3-[2-methoxy-5-(2-piperazin-1-ylethyl)phenyl]-1-{[4-methoxy-2-(trifluoromethoxy)phenyl]sulfonyl}-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-L-prolinamideYield 56.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Concentrated hydrochloric acid (3.0 ml) was added to 120 mg of the compound obtained in Example 228, and the solution was stirred at room temperature for 30 minutes. The stirred solution was poured into a saturated aqueous solution of NaHCO3, and extraction was carried out with EtOAc. The extract was dried over Na2SO4, then, the drying agent was separated by filtration and the solvent was evaporated under reduced pressure. The obtained residue was purified by a preparative TLC plate (2 mm; mobile phase: CHCl3/8M ammonia MeOH solution=8/1; v/v) to obtain 60 mg of the title compound (colorless amorphous).

Workup

  1. dry with materialThe extract was dried over Na2SO4
  2. customthe drying agent was separated by filtration
  3. customthe solvent was evaporated under reduced pressure
  4. customThe obtained residue was purified by a preparative TLC plate (2 mm; mobile phase: CHCl3/8M ammonia MeOH solution=8/1; v/v)

Sources & evidence

ORD record
ord-640f983aed2849969315d45b81ad7513
Source dataset
uspto-grants-2011_10
Patent number
US08030499B2

Reaction notes

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