Formaldehyde → 7-(4-Phenyl-1-piperidinyl)-3-[(4-phenyl-1-piperidinyl)methyl]-1,2,4-triazolo[4,3-a]pyridine-8-carbonitrile

HRID 587657Notes

Reaction equation

HRID 587657 reaction equation
[C:1]([C:3]1[C:4]2[N:5]([CH:21]=[N:22][N:23]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][CH:12]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)#[N:2].[C:24]1([CH:30]2[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]2)[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[CH2:36]=O>C(O)(=O)C.C(Cl)Cl>[C:15]1([CH:12]2[CH2:13][CH2:14][N:9]([C:8]3[CH:7]=[CH:6][N:5]4[C:21]([CH2:36][N:33]5[CH2:32][CH2:31][CH:30]([C:24]6[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=6)[CH2:35][CH2:34]5)=[N:22][N:23]=[C:4]4[C:3]=3[C:1]#[N:2])[CH2:10][CH2:11]2)[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 712FormaldehydeHCID 698734-PhenylpiperidineHCID 667888318-Cyano-7-(4-phenylpiperidinyl)[1,2,4]triazolo[4,3-a]pyridine

Product 1

HCID 574594867-(4-Phenyl-1-piperidinyl)-3-[(4-phenyl-1-piperidinyl)methyl]-1,2,4-triazolo[4,3-a]pyridine-8-carbonitrile

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of D8 (0.301 g, 0.992 mmol) in acetic acid (4.5 ml) were added 4-phenylpiperidine (0.160 g, 0.992 mmol) and formaldehyde (0.223 ml, 0.992 mmol; 37%). The resulting mixture was heated in a sealed tube at 80° C. for 16 h. The reaction mixture was diluted with DCM and washed with 2M NaOH. The organic layer was separated, dried (MgSO4) and concentrated in vacuo. The crude product thus obtained was purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent). The desired fractions were collected and concentrated in vacuo to yield a residue that was purified by HPLC (C18Xbridge 19×100; mobile phase AcONH4/CH3CN gradient as eluent). The desired fractions were collected and concentrated in vacuo to yield final compound E12 (0.085 g, 18%).

Workup

  1. washwashed with 2M NaOH
  2. customThe organic layer was separated
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customThe crude product thus obtained
  6. customwas purified by column chromatography (silica gel; DCM/7M solution of NH3 in MeOH up to 2% as eluent)
  7. customThe desired fractions were collected
  8. concentrationconcentrated in vacuo
  9. customto yield a residue that
  10. customwas purified by HPLC (C18Xbridge 19×100; mobile phase AcONH4/CH3CN gradient as eluent)
  11. customThe desired fractions were collected
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-fc8076d4f52d48e9906f2b7e173d06bc
Source dataset
uspto-grants-2016_01
Patent number
US09226930B2

Reaction notes

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