3-Methoxypropylamine → HCID 59625564, compound

HRID 2192878Notes

Reaction equation

HRID 2192878 reaction equation
Cl[C:2]1[C:7]([C:8]([N:10]([CH2:32][CH:33]([CH3:35])[CH3:34])[C@H:11]2[CH2:16][C@@H:15]([C:17]([N:19]3[CH2:24][CH2:23][O:22][CH2:21][CH2:20]3)=[O:18])[CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12]2)=[O:9])=[CH:6][CH:5]=[C:4]([C:36]([F:39])([F:38])[F:37])[N:3]=1.C(N(C(C)C)CC)(C)C.[CH3:49][O:50][CH2:51][CH2:52][CH2:53][NH2:54]>CC(O)C>[CH3:49][O:50][CH2:51][CH2:52][CH2:53][NH:54][C:2]1[C:7]([C:8]([N:10]([CH2:32][CH:33]([CH3:34])[CH3:35])[C@H:11]2[CH2:16][C@@H:15]([C:17]([N:19]3[CH2:20][CH2:21][O:22][CH2:23][CH2:24]3)=[O:18])[CH2:14][NH:13][CH2:12]2)=[O:9])=[CH:6][CH:5]=[C:4]([C:36]([F:38])([F:37])[F:39])[N:3]=1

Participants

5

Reactant 3

HCID 16723-MethoxypropylamineHCID 81531DiisopropylethylamineHCID 59625377HCID 59625377, compound

Product 1

HCID 59625564HCID 59625564, compound

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl (3S,5R)-3-[{[2-chloro-6-(trifluoromethyl)pyridin-3-yl]carbonyl}(2-methylpropyl)amino]-5-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate (40 mg) and diisopropylethylamine (37 μl) in 2-propanol (3 ml) was added 3-methoxypropylamine (23 μl) and the mixture was stirred at 80° C. for 15 hr. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was dissolved in methanol (2 ml), 4 M hydrogen chloride-ethyl acetate (2 ml) was added, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was concentrated under reduced pressure, and the residue was subjected to reversed-phase preparative HPLC. Aqueous sodium hydrogen carbonate was added to the object fraction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give the object compound (8.8 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogen carbonate
  2. additionwas added
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe obtained residue was dissolved in methanol (2 ml)
  7. addition4 M hydrogen chloride-ethyl acetate (2 ml) was added
  8. stirringthe mixture was stirred at room temperature for 15 hr
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. additionAqueous sodium hydrogen carbonate was added to the object fraction
  11. extractionthe mixture was extracted with ethyl acetate
  12. washThe extract was washed with saturated brine
  13. dry with materialdried over anhydrous sodium sulfate
  14. customThe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-bc6c8fe5dd6e48a5b773c09d1597e3f0
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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