Sodium Hydroxide → HCID 11177350, compound

HRID 505830Notes

Reaction equation

HRID 505830 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:20]=[C:19]([C:21]([O:23]CC)=[O:22])[S:18][C:9]=3[NH:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Cl[CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31].[OH-].[Na+]>CN(C=O)C.CCOC(C)=O.Cl>[CH:1]1([C:7]2[C:8]3[CH:20]=[C:19]([C:21]([OH:23])=[O:22])[S:18][C:9]=3[N:10]([CH2:29][C:30]([N:32]([CH3:34])[CH3:33])=[O:31])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 758862-chloro-N,N-dimethylacetamideHCID 68470346HCID 68470346, compound

Product 1

HCID 11177350HCID 11177350, compoundYield 27%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution (0.5 M) of ethyl 4-cyclohexyl-5-phenyl-6H-thieno[2,3-b]pyrrole-2-carboxylate in DMF was treated with NaH (2 eq., 60% dispersion in mineral oil), and the suspension was stirred at RT for 30 min, then 2-chloro-N,N-dimethylacetamide (3 eq.) was added. The reaction mixture was heated at 50° C. for 1 h and 25 min. After cooling down, it was diluted with AcOEt and aqueous HCl (1 M) was added. The aqueous phase was separated and extracted with AcOEt. The combined organic phase was washed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution) and brine then dried and evaporated. The residue was dissolved in THF/MeOH (1:1). The resulting solution (0.07 M) was treated with NaOH (2 N, 6 eq.). The reaction mixture was heated to reflux overnight. After cooling down, the reaction was concentrated and acidified to pH 1 with aqueous HCl (3 N). The resulting mixture was diluted with DMSO and purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19×150 mm; flow: 20 mL/min; Gradient: A: H2O+0.1% TFA; B: MeCN+0.1% TFA; linear from 95% A to 5% A in 10 min) to afford the title compound (27%) as a solid.

Workup

  1. temperatureThe reaction mixture was heated at 50° C. for 1 h and 25 min
  2. temperatureAfter cooling down
  3. additionwas added
  4. customThe aqueous phase was separated
  5. extractionextracted with AcOEt
  6. washThe combined organic phase was washed sequentially with aqueous HCl (1 N), aqueous NaHCO3 (saturated solution) and brine
  7. customthen dried
  8. customevaporated
  9. dissolutionThe residue was dissolved in THF/MeOH (1:1)
  10. temperatureThe reaction mixture was heated
  11. temperatureto reflux overnight
  12. temperatureAfter cooling down
  13. concentrationthe reaction was concentrated
  14. additionThe resulting mixture was diluted with DMSO
  15. custompurified by RP-HPLC (Conditions

Sources & evidence

ORD record
ord-5ad79a952b1942aaaad3fa7c900e7fb8
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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