Hydrochloric Acid → HCID 74928539, compound

HRID 658932Notes

Reaction equation

HRID 658932 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][C:24]([C:27]([OH:29])=O)([CH3:26])[CH3:25])[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.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH:52]1([S:55]([NH2:58])(=[O:57])=[O:56])[CH2:54][CH2:53]1.[H-].[Na+].Cl>CN(C=O)C.O>[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][C:24]([CH3:26])([CH3:25])[C:27]([NH:58][S:55]([CH:52]4[CH2:54][CH2:53]4)(=[O:57])=[O:56])=[O:29])[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

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 682631,1'-CarbonyldiimidazoleHCID 15765418CyclopropanesulfonamideHCID 765680156-chloro-4'-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2'-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

Product 1

HCID 74928539HCID 74928539, compoundYield 71.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of chiral (2′S, 3S, 4′R)-6-chloro-4′-[5-chloro-2-(1-hydroxycarbonyl-1-methyl-ethoxy)-phenyl]-2′-(5-fluoro-2-methyl-phenyl) spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (45 mg, 0.079 mmol) prepared in Example 7 and CDI (26 mg, 0.16 mmol) in DMF (0.5 mL) was heated at 60° C. for 2 h. Then to this solution was added a mixture of cyclopropanesulfonamide (48 mg, 0.4 mmol) and NaH (13 mg, 60%, 0.3 mmol) in DMF (1 mL), which had been stirred at room temperature for 1 h. After the resulting mixture was stirred at room temperature for 1 h, it was poured into water (5 mL) and the aqueous solution was acidified to “pH” 2-3 by addition of concentrated aqueous hydrochloride acid. 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 as a white solid (38 mg).

Workup

  1. additionThen to this solution was added
  2. stirringAfter the resulting mixture was stirred at room temperature for 1 h
  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-0c0cd0ea544b4380a0ec7df64db7411e
Source dataset
uspto-grants-2011_12
Patent number
US08076482B2

Reaction notes

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