Acetic Acid → HCID 71522748, compound

HRID 2178525Notes

Reaction equation

HRID 2178525 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH:11]2[CH2:15][CH2:14][NH:13][CH2:12]2)[N:6]=1)[CH3:3].C(O)(=O)C.C(N(CC)C(C)C)(C)C.C([BH3-])#N.[Na+].[O:33]=[C:34]1[CH2:39][CH2:38][CH2:37][CH2:36][N:35]1[C:40]1[C:45]([CH2:46][CH:47]=O)=[CH:44][CH:43]=[CH:42][N:41]=1.Cl.[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52]>CO.CC(C)=O>[C:50]([OH:55])(=[O:54])[C:51]([OH:53])=[O:52].[CH3:3][CH:2]([O:4][C:5]1[N:6]=[C:7]([CH:11]2[CH2:15][CH2:14][N:13]([CH2:47][CH2:46][C:45]3[C:40]([N:35]4[CH2:36][CH2:37][CH2:38][CH2:39][C:34]4=[O:33])=[N:41][CH:42]=[CH:43][CH:44]=3)[CH2:12]2)[CH:8]=[CH:9][CH:10]=1)[CH3:1]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 971Oxalic AcidHCID 81531DiisopropylethylamineHCID 5003444Sodium cyanoborohydrideHCID 89500355HCID 89500355, compoundHCID 89505938HCID 89505938, compound

Product 1

HCID 71522748HCID 71522748, compoundYield 12.5%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

2-(Propan-2-yloxy)-6-(pyrrolidin-3-yl)pyridine a1-61 (0.302 g, 1.464 mmol, 1 eq) is dissolved in methanol (15 ml) and the solution is cooled at 0° C. Acetic acid (0.527 g, 8.784 mmol, 6 eq), N,N,-diisopropylethylamine (0.378 g, 2.928 mmol, 2 eq) and sodium cyanoborohydride (0.552 g, 8.784 mmol, 6 eq) are added. The reaction mixture is stirred for 5 min, and then poured on crude [2-(2-oxopiperidin-1-yl)pyridin-3-yl]acetaldehyde a4-3 (1.46 mmol, 1 eq) cooled at 0°. After 10 min at 0° C., the reaction mixture is warmed up to room temperature. Hydrochloric acid 1N is added until acidic pH. The solution is catched over an acidic column, washed with methanol and then released with ammonia 1M in methanol. The solvent is evaporated under reduced pressure. The residue is purified by LC-MS basic reverse phase (gradient CH3CN/H2O/NaHCO3 from 5/95/0.5 to 95/5/0.5). The residue of evaporation is dissolved in a minimum of acetone and oxalic acid (1 eq) is added to form the salt. The solvent is removed under reduced pressure. The residue is taken in diethyl ether, the mixture is stirred, sonicated and filtered. The precipitate is washed with diethyl ether (2 times) to afford 75 mg of 1-[3-(2-{3-[6-(propan-2-yloxy)pyridin-2-yl]pyrrolidin-1-yl}ethyl)pyridin-2-yl]piperidin-2-one oxalate 94.

Workup

  1. temperaturecooled at 0°
  2. waitAfter 10 min at 0° C.
  3. temperaturethe reaction mixture is warmed up to room temperature
  4. washwashed with methanol
  5. customThe solvent is evaporated under reduced pressure
  6. customThe residue is purified by LC-MS basic reverse phase (gradient CH3CN/H2O/NaHCO3 from 5/95/0.5 to 95/5/0.5)
  7. customThe residue of evaporation
  8. additionis added
  9. customto form the salt
  10. customThe solvent is removed under reduced pressure
  11. stirringthe mixture is stirred
  12. customsonicated
  13. filtrationfiltered
  14. washThe precipitate is washed with diethyl ether (2 times)

Sources & evidence

ORD record
ord-6dc5dc46754745039959b5ff5c33812c
Source dataset
uspto-grants-2015_06
Patent number
US09067930B2

Reaction notes

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