Hydrogen chloride-ethyl acetate → 4-[(3-methoxypropyl)amino]-6-(1-methylethyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyridine-3-carboxamide dihydrochloride

HRID 2192882Notes

Reaction equation

HRID 2192882 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[N:10]=[CH:9][C:8]=1[C:16]([N:18]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:19]1[CH2:24][C@@H:23]([C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20]1)=[O:17].C(OCC)(=O)C.[ClH:50]>>[ClH:50].[ClH:50].[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7]1[CH:12]=[C:11]([CH:13]([CH3:15])[CH3:14])[N:10]=[CH:9][C:8]=1[C:16]([N:18]([CH2:40][CH:41]([CH3:43])[CH3:42])[C@H:19]1[CH2:24][C@@H:23]([C:25]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)=[O:26])[CH2:22][NH:21][CH2:20]1)=[O:17]

Participants

3

Reactant 2

HCID 21866389Hydrogen chloride-ethyl acetateHCID 59625537tert-butyl (3S,5R)-3-[({4-[(3-methoxypropyl)amino]-6-(1-methylethyl)pyridin-3-yl}carbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Product 1

HCID 684336914-[(3-methoxypropyl)amino]-6-(1-methylethyl)-N-(2-methylpropyl)-N-[(3S,5R)-5-(morpholin-4-ylcarbonyl)piperidin-3-yl]pyridine-3-carboxamide dihydrochloride

Procedure

tert-Butyl (3S,5R)-3-[({4-[(3-methoxypropyl)amino]-6-(1-methylethyl)pyridin-3-yl}carbonyl)(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (268 mg) was dissolved in 4 M hydrogen chloride-ethyl acetate (5 ml), and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated, the residue was purified by reversed-phase preparative HPLC, and the object fraction was concentrated under reduced pressure. Aqueous sodium hydrogen carbonate was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. 4 M Hydrogen chloride-ethyl acetate (1 ml) was added to the residue, and the mixture was stirred for 5 min and concentrated under reduced pressure to give the object compound (163 mg).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe residue was purified by reversed-phase preparative HPLC
  3. concentrationthe object fraction was concentrated under reduced pressure
  4. additionAqueous sodium hydrogen carbonate was added to the residue
  5. extractionthe mixture was extracted with ethyl acetate
  6. washThe extract was washed with saturated brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. addition4 M Hydrogen chloride-ethyl acetate (1 ml) was added to the residue
  10. stirringthe mixture was stirred for 5 min
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c97e70c76f6f497387daaa09fd5f604a
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

Loading…