1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 2-chloro-N-{1-[(methanesulfonylcarbamoyl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide

HRID 1178425Notes

Reaction equation

HRID 1178425 reaction equation
[CH3:1][S:2]([NH2:5])(=[O:4])=[O:3].CCN=C=NCCCN(C)C.[C:17]([CH2:20][N:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH:23]([NH:31][C:32]([C:34]2[NH:38][C:37]3[S:39][C:40]([Cl:42])=[CH:41][C:36]=3[CH:35]=2)=[O:33])[C:22]1=[O:43])(O)=[O:18]>CN(C)C1C=CN=CC=1.C(Cl)Cl.CO.C(Cl)Cl>[Cl:42][C:40]1[S:39][C:37]2[NH:38][C:34]([C:32]([NH:31][CH:23]3[CH2:24][C:25]4[C:30](=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:21]([CH2:20][C:17]([NH:5][S:2]([CH3:1])(=[O:4])=[O:3])=[O:18])[C:22]3=[O:43])=[O:33])=[CH:35][C:36]=2[CH:41]=1

Participants

7

Reactant 3

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 72879MethanesulfonamideHCID 10319016N-[1-(Carboxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide

Product 1

HCID 104129102-chloro-N-{1-[(methanesulfonylcarbamoyl)methyl]-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl}-6H-thieno[2,3-b]pyrrole-5-carboxamide

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

Methanesulphonamide (90 mg, 0.94 mmol), 4-(dimethylamino)pyridine (287 mg, 2.35 mmol) and EDCI (225 mg, 1.17 mmol) were added to a suspension of N-[1-(carboxymethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide (Example 2; 315 mg, 0.78 mmol) in DCM (50 mL) and stirred for 2 days. The reaction was diluted with MeOH:DCM (1:19) (50 mL) and washed with 1M HCl(aq). (50 mL), the organic layer was separated, dried (MgSO4), filtered and evaporated. The residue was purified by applying the material to a 10 g Isolute NH2 column in MeOH:DCM (1:9) (10 mL) and eluted with MeOH:DCM (1:9) (6×10 mL) then MeOH: 2M HCl in Et2O:DCM (5:4:45) (6×10 mL) and the relevant fractions evaporated to give a pink gum which was triturated with refluxing Et2O (25 mL) and after cooling the title product (206 mg, 55%) was collected by filtration as pale pink powder.

Workup

  1. washwashed with 1M HCl(aq)
  2. custom(50 mL), the organic layer was separated
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified
  7. washeluted with MeOH:DCM (1:9) (6×10 mL)
  8. customMeOH: 2M HCl in Et2O:DCM (5:4:45) (6×10 mL) and the relevant fractions evaporated
  9. customto give a pink gum which
  10. customwas triturated with refluxing Et2O (25 mL)
  11. temperatureafter cooling the title product (206 mg, 55%)
  12. filtrationwas collected by filtration as pale pink powder

Sources & evidence

ORD record
ord-301ba58980dd44c18a9f4e1867874244
Source dataset
uspto-grants-2007_10
Patent number
US07276517B2

Reaction notes

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