Hydrochloric Acid → HCID 59979237, compound

HRID 1393528Notes

Reaction equation

HRID 1393528 reaction equation
Cl.[CH2:2]([N:4](CC)CC)[CH3:3].[Cl:9][C:10]1[CH:11]=[C:12]([N:17]2[C:21]3=[N:22][CH:23]=[C:24]([S:25](Cl)(=[O:27])=[O:26])[N:20]3[C@:19]([CH3:41])([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=3)[C:18]2=[O:42])[CH:13]=[C:14]([Cl:16])[CH:15]=1.CCO[C:46]([CH3:48])=[O:47].C[N:50]([CH:52]=[O:53])C>O1CCOCC1.C(Cl)Cl>[Cl:9][C:10]1[CH:11]=[C:12]([N:17]2[C:21]3=[N:22][CH:23]=[C:24]([S:25]([NH:4][C@@H:2]([CH3:3])[C:52]([NH:50][CH2:48][CH2:46][OH:47])=[O:53])(=[O:27])=[O:26])[N:20]3[C@:19]([CH3:41])([CH2:29][C:30]3[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=3)[C:18]2=[O:42])[CH:13]=[C:14]([Cl:16])[CH:15]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 11497703HCID 11497703, compound

Product 1

HCID 59979237HCID 59979237, compoundYield 81%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a suspension of N-Boc-L-(N-hydroxyethyl)alaninamide (0.188 g, 0.809 mmol) in 1 mL of dioxane was added HCl (2.0 mL, 4 M in dioxane), and the resulting cloudy mixture was stirred at room temperature for 2.5 h. Concentration of the mixture was followed by addition of CH2Cl2, and this process was repeated twice. Final pumping under high vacuum for 12 h afforded a colorless oil. The crude amine HCl salt was dissolved in 1.5 mL of DMF and treated with triethylamine (0.157 mL, 1.13 mmol). After stirring at room temperature for 10 min, a solution of (R)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-5-(4-trifluoromethoxy-benzyl)-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-sulfonyl chloride (0.125 g, 0.225 mmol) in 3 mL of CH2Cl2 was added rapidly dropwise via cannula. The reaction mixture was stirred at room temperature for 4 h. Following the addition of EtOAc, the organic layer was washed with three portions of 5% NaCl solution, then brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC to afford 0.118 g (81%) of the title compound as a white foam (649.9, M+1).

Workup

  1. waitFinal pumping under high vacuum for 12 h
  2. customafforded a colorless oil
  3. stirringAfter stirring at room temperature for 10 min
  4. stirringThe reaction mixture was stirred at room temperature for 4 h
  5. washthe organic layer was washed with three portions of 5% NaCl solution
  6. dry with materialbrine, dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-ad87f80f432843c199d8438009f275c9
Source dataset
uspto-grants-2008_03
Patent number
US07345074B2

Reaction notes

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