Pyridine → 6-chloro-4'-[5-chloro-2-(1-methanesulfonyl-4-piperidinyloxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 504470Notes

Reaction equation

HRID 504470 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:39])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH:24]4[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]4)[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:5]2=[CH:4][CH:3]=1.[CH3:40][S:41](Cl)(=[O:43])=[O:42].N1C=CC=CC=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:39])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][CH:24]4[CH2:29][CH2:28][N:27]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:26][CH2:25]4)[CH2:14][C:13](=[O:30])[NH:12][CH:11]3[C:31]3[CH:36]=[C:35]([F:37])[CH:34]=[CH:33][C:32]=3[CH3:38])[C:5]2=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 749287696-chloro-4'-[5-chloro-2-(4-piperidinyloxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 749287896-chloro-4'-[5-chloro-2-(1-methanesulfonyl-4-piperidinyloxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 6.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of racemic (2′S,3S,4′R)-6-chloro-4′-[5-chloro-2-(4-piperidinyloxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (110 mg, 0.2 mmol), methanesulfonyl chloride (0.0185 mL, 0.24 mmol) in DCM (5 mL) was added pyridine (23 mg, 0.3 mmol) at r.t. The reaction mixture was stirred for 4 h, then concentrated and partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and concentrated. The residue was purified with Prep-HPLC to give the title compound as a white solid (Yield: 8 mg).

Workup

  1. concentrationconcentrated
  2. custompartitioned between ethyl acetate and water
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified with Prep-HPLC

Sources & evidence

ORD record
ord-21b15762b0f64d93ad52515606556ab4
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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