Chloroacetyl chloride → 2-Chloro-N-{(1R,2R)-1-[(chloroacetyl)amino]-2,3-dihydro-1H-inden-2-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamide

HRID 1244735Notes

Reaction equation

HRID 1244735 reaction equation
CCN(CC)CC.[NH2:8][C@@H:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][C@H:10]1[NH:18][C:19]([C:21]1[NH:25][C:24]2[S:26][C:27]([Cl:29])=[CH:28][C:23]=2[CH:22]=1)=[O:20].[Cl:30][CH2:31][C:32](Cl)=[O:33].C([O-])(O)=O.[Na+]>ClCCl>[Cl:29][C:27]1[S:26][C:24]2[NH:25][C:21]([C:19]([NH:18][C@@H:10]3[CH2:11][C:12]4[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=4)[C@H:9]3[NH:8][C:32](=[O:33])[CH2:31][Cl:30])=[O:20])=[CH:22][C:23]=2[CH:28]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 58717470N-[(1R,2R)-1-amino-2,3-dihydro-1H-inden-2-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide

Product 1

HCID 587174892-Chloro-N-{(1R,2R)-1-[(chloroacetyl)amino]-2,3-dihydro-1H-inden-2-yl]-6H-thieno[2,3-b]pyrrole-5-carboxamideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Et3N (3 mL, 21.6 mmol) was added to a suspension of N-[(1R,2R)-1-amino-2,3-dihydro-1H-inden-2-yl]-2-chloro-6H-thieno[2,3-b]pyrrole-5-carboxamide (Method 21, 3.11 g, 6.98 mmol) in anhydrous dichloromethane (55 mL) and stirred at ambient temperature for 5 miuntes. The suspension was cooled to −78° C. and chloroacetylchloride (611 μL, 7.68 mmol) was added and the reaction was warmed to 0° C. and stirred at this temperature for 3 hours. NaHCO3 (50 mL) was added, the phases were separated and the aqueous phase was extracted with THF (2×50 mL). The combined organic fractions were washed with water (100 mL), dried (MgSO4) and the solvent removed under reduced pressure. The residue was triturated (THF:isohexane, 1:5), collected by filtration, washed with hexane (20 mL) and dried to give the title compound (1.92 mg, 68%) as a brown solid.

Workup

  1. temperatureThe suspension was cooled to −78° C.
  2. temperaturethe reaction was warmed to 0° C.
  3. stirringstirred at this temperature for 3 hours
  4. customthe phases were separated
  5. extractionthe aqueous phase was extracted with THF (2×50 mL)
  6. washThe combined organic fractions were washed with water (100 mL)
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed under reduced pressure
  9. customThe residue was triturated (THF:isohexane, 1:5)
  10. filtrationcollected by filtration
  11. washwashed with hexane (20 mL)
  12. customdried

Sources & evidence

ORD record
ord-b8c4002c226c427095a4000038bf57ea
Source dataset
uspto-grants-2006_10
Patent number
US07122567B2

Reaction notes

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