Dimethylformamide → HCID 12136435, compound

HRID 2374787Notes

Reaction equation

HRID 2374787 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4][CH3:5])C.[Cl:8][C:9]1[CH:10]=[C:11]([N:16]2[C:20]3=[N:21][CH:22]=[C:23]([S:24](Cl)(=[O:26])=[O:25])[N:19]3[C@:18]([CH3:40])([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=3)[C:17]2=[O:41])[CH:12]=[C:13]([Cl:15])[CH:14]=1.CCO[C:45]([CH3:47])=[O:46].C[N:49]([CH:51]=[O:52])C>C(Cl)Cl>[OH:46][CH2:45][CH2:47][NH:49][C:51]([C@@H:6]1[CH2:7][CH2:5][CH2:4][N:3]1[S:24]([C:23]1[N:19]2[C@:18]([CH3:40])([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([O:35][C:36]([F:39])([F:38])[F:37])=[CH:31][CH:30]=3)[C:17](=[O:41])[N:16]([C:11]3[CH:10]=[C:9]([Cl:8])[CH:14]=[C:13]([Cl:15])[CH:12]=3)[C:20]2=[N:21][CH:22]=1)(=[O:26])=[O:25])=[O:52]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 11497703HCID 11497703, compound

Product 1

HCID 12136435HCID 12136435, compoundYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of (S)-2-(2-hydroxy-ethylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.200 g, 0.774 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 4 h. Concentration of the mixture was followed by addition of CH2Cl2. This process was repeated twice and final pumping under high vacuum for 12 h afforded the deprotected amine HCl salt as a white oil. This crude amine HCl salt was dissolved in 3 mL of DMF and treated with triethylamine (0.212 mL, 1.52 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 (Example 2) (0.211 g, 0.380 mmol) in 4 mL of CH2Cl2 was added rapidly dropwise via cannula. The reaction mixture was stirred at room temperature for 2 h. Following the addition of 75 mL of EtOAc, the organic layer was washed with three portions of water, then brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by preparative TLC to afford 0.218 g (85%) of the title compound as a white foam (676.1, M+1).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2 h
  2. washthe organic layer was washed with three portions of water
  3. dry with materialbrine, dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude product was purified by preparative TLC

Sources & evidence

ORD record
ord-dfbc372d4bad4c339cc9e43ab6e69c13
Source dataset
uspto-grants-2008_12
Patent number
US07462637B2

Reaction notes

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