Hydrochloric Acid → HCID 42635657, compound

HRID 1040561Notes

Reaction equation

HRID 1040561 reaction equation
[C:1]([C:4]1([NH:7][C:8]([C:10]2([NH:13][C:14]([C:16]3[N:20]4[C@@:21]([CH2:34][C:35]5[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=5)([CH3:33])[C:22](=[O:32])[N:23]([C:24]5[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=5)[C:19]4=[N:18][CH:17]=3)=[O:15])[CH2:12][CH2:11]2)=[O:9])[CH2:6][CH2:5]1)(=[S:3])[NH2:2].[CH2:43](OC(OCC)CBr)[CH3:44].Cl.O1CCOCC1>CC(C)=O>[S:3]1[CH:44]=[CH:43][N:2]=[C:1]1[C:4]1([NH:7][C:8]([C:10]2([NH:13][C:14]([C:16]3[N:20]4[C@@:21]([CH2:34][C:35]5[CH:40]=[CH:39][C:38]([C:41]#[N:42])=[CH:37][CH:36]=5)([CH3:33])[C:22](=[O:32])[N:23]([C:24]5[CH:25]=[C:26]([Cl:31])[CH:27]=[C:28]([Cl:30])[CH:29]=5)[C:19]4=[N:18][CH:17]=3)=[O:15])[CH2:12][CH2:11]2)=[O:9])[CH2:6][CH2:5]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 74852Ethane, 2-bromo-1,1-diethoxy-HCID 58431059HCID 58431059, compound

Product 1

HCID 42635657HCID 42635657, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 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 [1-(1-thiocarbamoyl-cyclo-propylcarbamoyl)-cyclopropyl]-amide (92 mg, 0.15 mmol) in 1.5 mL of acetone was added bromoacetaldehyde diethyl acetal (0.089 mL, 0.59 mmol) and HCl in dioxane (4 M, 0.002 mL, 0.01 mmol). The reaction mixture was heated at reflux for 15 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 yield a pale brown oil. The crude product was purified by flash chromatography on silica gel (1-5% MeOH in CH2Cl2), to furnish 30 mg (31%) of the title compound as a pale brown foam, m/z 646.7 [M+1]+.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 15 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
  10. customto yield a pale brown oil
  11. customThe crude product was purified by flash chromatography on silica gel (1-5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-77e6ae9d43a74fb199e9be11b7b5c689
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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