Hydrogen chloride-ethyl acetate → HCID 67320819, compound

HRID 1509515Notes

Reaction equation

HRID 1509515 reaction equation
[CH3:1][CH:2]([CH3:44])[CH2:3][N:4]([C:26]([C:28]1[N:32]([CH2:33][CH2:34][C:35]2[N:39]=[CH:38][O:37][N:36]=2)[C:31]2[CH:40]=[CH:41][CH:42]=[CH:43][C:30]=2[N:29]=1)=[O:27])[C@H:5]1[CH2:10][C@@H:9]([C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[O:12])[CH2:8][N:7](C(OC(C)(C)C)=O)[CH2:6]1.C(OCC)(=O)C.[ClH:51]>>[ClH:51].[ClH:51].[CH3:1][CH:2]([CH3:44])[CH2:3][N:4]([C@H:5]1[CH2:10][C@@H:9]([C:11]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[O:12])[CH2:8][NH:7][CH2:6]1)[C:26]([C:28]1[N:32]([CH2:33][CH2:34][C:35]2[N:39]=[CH:38][O:37][N:36]=2)[C:31]2[CH:40]=[CH:41][CH:42]=[CH:43][C:30]=2[N:29]=1)=[O:27]

Participants

3

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 67321575HCID 67321575, compound

Product 1

HCID 67320819HCID 67320819, compound

Procedure

Hydroxylamine hydrochloride (125 mg) was dissolved in dimethyl sulfoxide (5 ml), sodium hydrogen carbonate (463 mg) was added and the mixture was stirred at 50° C. for 1 hr. A solution of tert-butyl (3S,5R)-3-[{[1-(2-cyanoethyl)-1H-benzimidazol-2-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (100 mg) in dimethyl sulfoxide (5 ml) was added to the reaction mixture, and the mixture was stirred at 90° C. for 3 hr. The reaction mixture was allowed to cool to room temperature, diluted with water, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was dissolved in trimethyl orthoformate (5 ml) and the mixture was stirred at 100° C. for 5 hr. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to basic silica gel chromatography, and a fraction eluted with ethyl acetate was concentrated under reduced pressure to give tert-butyl (3S,5R)-3-[(2-methylpropyl)({1-[2-(1,2,4-oxadiazol-3-yl)ethyl]-1H-benzimidazol-2-yl}carbonyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate. The obtained tert-butyl (3S,5R)-3-[(2-methylpropyl)({1-[2-(1,2,4-oxadiazol-3-yl)ethyl]-1H-benzimidazol-2-yl}carbonyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate was dissolved in 4M hydrogen chloride-ethyl acetate (3 ml), and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, and the residue was subjected to reversed-phase preparative HPLC and the eluted fraction was concentrated under reduced pressure. The residue was diluted with aqueous sodium bicarbonate, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. 4M Hydrogen chloride-ethyl acetate (1 ml) was added and the mixture was stirred for 5 min. The solvent was evaporated under reduced pressure to give the object product (35 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. concentrationthe eluted fraction was concentrated under reduced pressure
  3. additionThe residue was diluted with aqueous sodium bicarbonate
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. addition4M Hydrogen chloride-ethyl acetate (1 ml) was added
  8. stirringthe mixture was stirred for 5 min
  9. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-c4f0e2e16db2412fbb55479d61488447
Source dataset
uspto-grants-2015_12
Patent number
US09221836B2

Reaction notes

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