1,4-Dioxane hydrochloride → 1-(2-{Methyl[N-(4-{methyl[3-(methylamino)propyl]carbamoyl}phenyl)-beta-alanyl]amino}ethyl)piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446605Notes

Reaction equation

HRID 446605 reaction equation
[C:1]1([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:47])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:20](=[O:46])[CH2:21][CH2:22][NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30](=[O:45])[N:31]([CH2:33][CH2:34][CH2:35][N:36](C(OC(C)(C)C)=O)[CH3:37])[CH3:32])=[CH:26][CH:25]=2)[CH3:19])[CH2:12][CH2:11]1.Cl.O1CCOCC1>C(O)C>[C:1]1([C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:47])[O:9][CH:10]1[CH2:11][CH2:12][N:13]([CH2:16][CH2:17][N:18]([CH3:19])[C:20](=[O:46])[CH2:21][CH2:22][NH:23][C:24]2[CH:25]=[CH:26][C:27]([C:30](=[O:45])[N:31]([CH3:32])[CH2:33][CH2:34][CH2:35][NH:36][CH3:37])=[CH:28][CH:29]=2)[CH2:14][CH2:15]1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 666714911-(2-{[3-({4-[{3-([tert-Butoxycarbonyl)(methyl)amino]propyl}(methyl)carbamoyl]phenyl}amino)propanoyl](methyl)amino}ethyl)piperidin-4-yl biphenyl-2-ylcarbamate

Product 1

HCID 666717151-(2-{Methyl[N-(4-{methyl[3-(methylamino)propyl]carbamoyl}phenyl)-beta-alanyl]amino}ethyl)piperidin-4-yl biphenyl-2-ylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

The compound (150 mg, 0.21 mmol) obtained in Example 94b was dissolved in ethanol (0.5 mL), a 4 N hydrochloric acid-1,4-dioxane solution (5.1 mL, 20.6 mmol) was added, and the mixture was stirred at room temperature under a nitrogen atmosphere for 6 hours. After the reaction was completed, the solvent was evaporated under reduced pressure. Ethyl acetate was added under ice cooling, a saturated aqueous sodium hydrogencarbonate solution was further added to neutralize the mixture and separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v) to give the title compound (98 mg; yield, 76%) as a colorless oily substance.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. additionEthyl acetate was added under ice cooling
  3. additiona saturated aqueous sodium hydrogencarbonate solution was further added
  4. customseparate the layers
  5. customThe resulting organic layer was separated
  6. washwashed with saturated sodium chloride solution
  7. dry with materialdried with anhydrous sodium sulfate
  8. customthe solvent was evaporated under reduced pressure
  9. customThe residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-edb8e6328957437b9e5c278ce0c2f8af
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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