Hydrochloric Acid → HCID 58431198, compound

HRID 1040525Notes

Reaction equation

HRID 1040525 reaction equation
[C:1]([C@H:4]([NH:6][C:7]([C@@H:9]([NH:11][C:12]([C:14]1[N:18]2[C@@:19]([CH2:32][C:33]3[CH:38]=[CH:37][C:36]([C:39]#[N:40])=[CH:35][CH:34]=3)([CH3:31])[C:20](=[O:30])[N:21]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)[C:17]2=[N:16][CH:15]=1)=[O:13])[CH3:10])=[O:8])[CH3:5])(=[S:3])[NH2:2].[CH2:41](OC(OCC)CBr)[CH3:42].Cl>CC(C)=O.O1CCOCC1>[S:3]1[CH:42]=[CH:41][N:2]=[C:1]1[CH:4]([NH:6][C:7]([C@@H:9]([NH:11][C:12]([C:14]1[N:18]2[C@@:19]([CH2:32][C:33]3[CH:34]=[CH:35][C:36]([C:39]#[N:40])=[CH:37][CH:38]=3)([CH3:31])[C:20](=[O:30])[N:21]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)[C:17]2=[N:16][CH:15]=1)=[O:13])[CH3:10])=[O:8])[CH3:5]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 58431092HCID 58431092, compound

Product 1

HCID 58431198HCID 58431198, compoundYield 89.1%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneCatalystHCID 180AcetoneSolvent

Procedure

To a solution of (R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid [(S)-1-((R)-1-thiocarbamoyl-ethylcarbamoyl)-ethyl]-amide (132 mg, 0.22 mmol) in 1 mL of acetone was added bromoacetaldehyde diethyl acetal (0.166 mL, 1.10 mmol) and HCl in dioxane (4 M, 0.003 mL, 0.01 mmol). The reaction mixture was heated at reflux for 5 h, and then cooled to room temperature and concentrated in vacuo. The residue was dissolved in 25 mL of ethyl acetate and washed with 10 mL of saturated NaHCO3 solution. The organic phase was washed with water and brine (10 mL each), dried over Na2SO4, filtered, and concentrated in vacuo to a pale brown oil. The crude product was purified by flash chromatography on silica gel, eluting with 0-5% MeOH in CH2Cl2, to furnish 122 mg (89%) of the title compound as a pale brown foam, obtained as a 1:1 mixture of thiazole α-methyl diastereomers, m/z 622.3 [M+1]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 5 h
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in 25 mL of ethyl acetate
  5. washwashed with 10 mL of saturated NaHCO3 solution
  6. washThe organic phase was washed with water and brine (10 mL each)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo to a pale brown oil
  10. customThe crude product was purified by flash chromatography on silica gel
  11. washeluting with 0-5% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-82744e57e3114bdbbd8d1bfe3fa77071
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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