Hydrochloric Acid → HCID 74928794, compound

HRID 504608Notes

Reaction equation

HRID 504608 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([C:29](O)=[O:30])([CH2:27][CH3:28])[CH2:25][CH3:26])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][C:3]=1[F:42].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH3:55][S:56]([NH2:59])(=[O:58])=[O:57].[H-].[Na+].Cl>CN(C=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:41])[C:10]3([CH:15]([C:16]4[CH:21]=[C:20]([Cl:22])[CH:19]=[CH:18][C:17]=4[O:23][C:24]([CH2:27][CH3:28])([CH2:25][CH3:26])[C:29]([NH:59][S:56]([CH3:55])(=[O:58])=[O:57])=[O:30])[CH2:14][C:13](=[O:32])[NH:12][CH:11]3[C:33]3[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=3[CH3:40])[C:5]2=[CH:4][C:3]=1[F:42]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 72879MethanesulfonamideHCID 72296196HCID 72296196, compound

Product 1

HCID 74928794HCID 74928794, compoundYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of racemic (2′S,3S,4′R)-6-chloro-5-fluoro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-ethyl-propoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (100 mg, 0.16 mmol) and CDI (123 mg, 0.64 mmol) in DMF (3 mL) was heated at 75° C. for 3 h. Then to this solution was added a mixture of methanesulfonamide (144 mg, 1.5 mmol) and NaH (53 mg, 60%,1.3 mmol) in DMF (1.5 mL), which had been previously stirred at room temperature for 2 h. After the resulting mixture was stirred at room temperature for 20 mins, it was poured into water and the aqueous solution was acidified by diluted HCl solution. After the aqueous phase was extracted with EtOAc twice, the combined organic phases were dried over anhydrous Na2SO4, concentrated and the residue was purified by flash column to give the title compound (50 mg).

Workup

  1. additionThen to this solution was added
  2. stirringAfter the resulting mixture was stirred at room temperature for 20 mins
  3. extractionAfter the aqueous phase was extracted with EtOAc twice
  4. dry with materialthe combined organic phases were dried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customthe residue was purified by flash column

Sources & evidence

ORD record
ord-8e279f02180445a68a7fd4b035167a11
Source dataset
uspto-grants-2010_08
Patent number
US07776875B2

Reaction notes

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