Triphenylphosphine Oxide → N-{[4-(benzylthio)piperidin-4-yl]methyl}-2-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamide

HRID 453588Notes

Reaction equation

HRID 453588 reaction equation
[CH3:1][C:2]1[S:9][C:8]2[CH:7]=[C:6]([C:10](O)=[O:11])[NH:5][C:4]=2[C:3]=1[N:13]([CH3:22])[S:14]([C:17]1[S:18][CH:19]=[CH:20][CH:21]=1)(=[O:16])=[O:15].[NH2:23][CH2:24][C:25]1([S:38][CH2:39][C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[CH2:30][CH2:29][N:28](C(OC(C)(C)C)=O)[CH2:27][CH2:26]1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(#N)C.O1CCCC1>[CH2:39]([S:38][C:25]1([CH2:24][NH:23][C:10]([C:6]2[NH:5][C:4]3[C:3]([N:13]([CH3:22])[S:14]([C:17]4[S:18][CH:19]=[CH:20][CH:21]=4)(=[O:16])=[O:15])=[C:2]([CH3:1])[S:9][C:8]=3[CH:7]=2)=[O:11])[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)[C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

10

Reactant 7

HCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57475999Tert-butyl 4-(aminomethyl)-4-benzylsulfanylpiperidine-1-carboxylateHCID 594113852-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxylic acid

Product 1

HCID 59411373N-{[4-(benzylthio)piperidin-4-yl]methyl}-2-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamideYield 79%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of 2-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxylic acid (1.0 g), tert-butyl 4-(aminomethyl)-4-(benzylthio)piperidine-1-carboxylate (944 mg), 1H-1,2,3-benzotriazol-1-ol (0.6 g), tetrahydrofuran (20 mL) and acetonitrile (20 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.8 g), and the mixture was stirred at room temperature for 30 min. Saturated aqueous sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated to give a colorless oil. To a solution of triphenylphosphine oxide (2.34 g) in acetonitrile (20 mL) was slowly added trifluoromethanesulfonic anhydride (0.71 mL) at 0° C., the mixture was stirred for 10 min, and the colorless oil was added. The reaction mixture was stirred at room temperature for 3 hr and concentrated. Saturated aqueous sodium hydrogen carbonate was added thereto, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give N-{[4-(benzylthio)piperidin-4-yl]methyl}-2-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxamide (1.03 g, yield 79%) as colorless crystals from a fraction eluted with ethyl acetate-hexane (1:20→1:1, volume ratio). melting point 222° C.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto give a colorless oil
  6. customat 0° C.
  7. stirringthe mixture was stirred for 10 min
  8. additionthe colorless oil was added
  9. stirringThe reaction mixture was stirred at room temperature for 3 hr
  10. concentrationconcentrated
  11. additionSaturated aqueous sodium hydrogen carbonate was added
  12. extractionthe mixture was extracted with ethyl acetate
  13. washThe ethyl acetate layer was washed with saturated brine
  14. dry with materialdried (MgSO4)
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-c2f1be2ef1b346ae952c4ae3cd8422fa
Source dataset
uspto-grants-2013_07
Patent number
US08492405B2

Reaction notes

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