Triphenylphosphine Oxide → N-[5-(4,5-dihydro-1,3-thiazol-2-yl)-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl]-N-methylthiophene-2-sulfonamide

HRID 453587Notes

Reaction equation

HRID 453587 reaction equation
[CH3:1][C:2]1[S:9][C:8]2[CH:7]=[C:6]([C:10](O)=O)[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].Cl.C([S:43][CH2:44][CH2:45][NH2:46])(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.N1(O)C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.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>ClCCl.O.CN(C)C=O.C(N(CC)CC)C>[S:43]1[CH2:44][CH2:45][N:46]=[C:10]1[C:6]1[NH:5][C:4]2[C:3]([N:13]([CH3:22])[S:14]([C:17]3[S:18][CH:19]=[CH:20][CH:21]=3)(=[O:16])=[O:15])=[C:2]([CH3:1])[S:9][C:8]=2[CH:7]=1

Participants

11

Reactant 6

HCID 13097Triphenylphosphine OxideHCID 67749Trifluoromethanesulfonic anhydrideHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 184272672-(Tritylthio)ethylamine hydrochlorideHCID 594113852-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxylic acid

Product 1

HCID 24772047N-[5-(4,5-dihydro-1,3-thiazol-2-yl)-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl]-N-methylthiophene-2-sulfonamideYield 29%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To a mixture of 2-methyl-3-[methyl(2-thienylsulfonyl)amino]-4H-thieno[3,2-b]pyrrole-5-carboxylic acid (0.35 g), 2-(tritylthio)ethaneamine hydrochloride (0.43 g), 1H-1,2,3-benzotriazol-1-ol (0.19 g), triethylamine (0.2 mL) and N,N-dimethylformamide (10 mL) was added N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride (0.23 g), and the mixture was stirred at room temperature overnight. Water 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 (0.83 g) in dichloromethane (20 mL) was slowly added trifluoromethanesulfonic anhydride (0.25 mL) at 0° C., the mixture was stirred for 10 min. The colorless oil was added to the mixture and the mixture was stirred at room temperature for 3 hr and concentrated. Saturated aqueous sodium hydrogen carbonate was added, 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-[5-(4,5-dihydro-1,3-thiazol-2-yl)-2-methyl-4H-thieno[3,2-b]pyrrol-3-yl]-N-methylthiophene-2-sulfonamide (111 mg, yield 29%) as colorless crystals from a fraction eluted with ethyl acetate-hexane (1:20→1:1, volume ratio). melting point 140° 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 to the mixture
  9. stirringthe 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-04a4b39448a64750954896354564a815
Source dataset
uspto-grants-2013_07
Patent number
US08492405B2

Reaction notes

Loading…