Hydrochloric Acid → [6-(2-Hydroxy-ethylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 1517094Notes

Reaction equation

HRID 1517094 reaction equation
C([O:8][CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([C:18]([N:20]2[CH2:25][CH2:24][CH:23]([N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)[CH2:22][CH2:21]2)=[O:19])[C:15]([CH3:31])=[CH:14][C:13]=1[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1)C1C=CC=CC=1.Cl.[H][H]>CO.[Pd]>[OH:8][CH2:9][CH2:10][NH:11][C:12]1[N:17]=[C:16]([C:18]([N:20]2[CH2:21][CH2:22][CH:23]([N:26]3[CH2:27][CH2:28][CH2:29][CH2:30]3)[CH2:24][CH2:25]2)=[O:19])[C:15]([CH3:31])=[CH:14][C:13]=1[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:41])[F:40])[CH:33]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 67025369[6-(2-Benzyloxy-ethylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone2×HCID 178418361HCID 178418361, compound

Product 1

HCID 44547500[6-(2-Hydroxy-ethylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 77%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 0.14 g (0.25 mmol) of [6-(2-benzyloxy-ethylamino)-3-methyl-5-(3-trifluoromethyl-phenyl)-pyridin-2-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (intermediate 14) in 6.0 ml of MeOH was treated at RT with 0.49 ml (0.49 mmol) of hydrochloric acid (1.0 molar in MeOH), followed by 0.026 g (0.025 mmol) of Pd—C (10%). The reaction mixture was vigorously stirred in an atmosphere of hydrogen for 3 hours. After filtration through dicalite, the solvent was removed by evaporation, then the residue was dissolved in H2O/Na2CO3 and extracted twice with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5) to give 0.091 g (77%) of the title compound as yellow amorphous solid. MS: 477.3 (MH+).

Workup

  1. filtrationAfter filtration through dicalite
  2. customthe solvent was removed by evaporation
  3. dissolutionthe residue was dissolved in H2O/Na2CO3
  4. extractionextracted twice with CH2Cl2
  5. washthe organic phases were washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 95:5)

Sources & evidence

ORD record
ord-e0665309aedb4265bdd48acc88c4d937
Source dataset
uspto-grants-2012_07
Patent number
US08227613B2

Reaction notes

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