Sodium hydride → methyl 6-cyclohexyl-5-phenyl-4-(2-pyrrolidin-1-ylethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 505784Notes

Reaction equation

HRID 505784 reaction equation
[CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH: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[CH2:28][CH2:29][N:30]1[CH2:34][CH2:33][CH2:32][CH2:31]1>CN(C=O)C>[CH:1]1([C:7]2[C:8]3[S:20][C:19]([C:21]([O:23][CH3:24])=[O:22])=[CH:18][C:9]=3[N:10]([CH2:28][CH2:29][N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)[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

5

Reactant 3

HCID 24758Sodium hydrideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 68467632methyl 6-cyclohexyl-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

Product 1

HCID 68470773methyl 6-cyclohexyl-5-phenyl-4-(2-pyrrolidin-1-ylethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution (0.1 M) of methyl 6-cyclohexyl-5-phenyl-4H-thieno[3,2-b]pyrrole-2-carboxylate in DMF at 0° C. was treated with NaH (1.5 eq., 60% dispersion in mineral oil), and the suspension was stirred at RT for 30 min then it was treated with 1-(2-chloroethyl)pyrrolidine (3 eq.). The mixture was heated to 80° C. for 16 h then it was quenched with ammonium chloride (saturated solution), basified with aqueous NaOH (1 N) and extracted with AcOEt. The combined organic phase was washed with brine and dried. Evaporation of the solvent gave a residue that was purified by flash chromatography on silica gel (5:95 MeOH/DCM) to afford methyl 6-cyclohexyl-5-phenyl-4-(2-pyrrolidin-1-ylethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate as a solid that was dissolved in MeOH. The resulting solution (0.06 M) was treated with aqueous NaOH (2 N solution, 16 eq.) then the mixture was heated to reflux for 2 h. After cooling down, the mixture was concentrated and the residue was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 10×100 mm; flow: 5 mL/min; Gradient: A: H2O+0.05% TFA; B: MeCN+0.05% TFA; 60% A isocratic for 2 min, linear to 60% A in 3 min, linear to 50% in 2 min then linear to 40% A in 3 min) to afford the title compound (62%) as a solid.

Workup

  1. temperatureThe mixture was heated to 80° C. for 16 h
  2. customit was quenched with ammonium chloride (saturated solution)
  3. extractionextracted with AcOEt
  4. washThe combined organic phase was washed with brine
  5. customdried
  6. customEvaporation of the solvent
  7. customgave a residue that
  8. customwas purified by flash chromatography on silica gel (5:95 MeOH/DCM)

Sources & evidence

ORD record
ord-e8080da5ab284cad87f7b346f937419d
Source dataset
uspto-grants-2010_08
Patent number
US07781431B2

Reaction notes

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