Hydrochloric Acid → [4-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidin-1-yl]-imidazol-1-yl-methanone

HRID 251171Notes

Reaction equation

HRID 251171 reaction equation
[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.[C:34](N1C=CN=C1)([N:36]1[CH:40]=[CH:39][N:38]=[CH:37]1)=[O:35].C(NC(C)C)(C)C.NO.Cl>C1COCC1.CN(C=O)C>[NH4+:4].[OH-:35].[CH3:1][C:2]1[C:3]([CH2:9][N:10]([CH2:17][C:18]2[C:23]([C:24]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)([CH3:26])[CH3:25])=[CH:22][CH:21]=[CH:20][N:19]=2)[CH:11]2[CH2:12][CH2:13][N:14]([C:34]([N:36]3[CH:40]=[CH:39][N:38]=[CH:37]3)=[O:35])[CH2:15][CH2:16]2)=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 787HydroxylamineHCID 7912DiisopropylamineHCID 682631,1'-CarbonyldiimidazoleHCID 58997004(3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine

Product 2

HCID 14923Ammonium HydroxideHCID 58997016[4-((3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-amino)-piperidin-1-yl]-imidazol-1-yl-methanoneYield 53.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

(3,5-Dimethyl-pyridin-2-ylmethyl)-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-piperidin-4-yl-amine (0.270 g, 0.60 mmol) and 1,1′-carbonyldiimidazole (0.098 g, 0.60 mmol) were combined in THF (6 mL) and the mixture was stirred at room temperature for one hour. The solvent was removed under reduced pressure to give a colorless oil that was resuspended in DMF (5 mL), followed by addition of N,N-diisopropylamine (527 μL, 3.02 mmol) and NH2OH. HCl (0.168 g, 2.40 mmol). The mixture was stirred at room temperature for 16 hours and then the solvent was removed under reduced pressure. The yellow oil was resuspended in CH2Cl2 (30 mL), washed with brine (3×20 mL) and the organic layer was dried (Na2SO4), filtered and concentrated in vacuo to give a yellow oil. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 85:10:5, v/v/v) afforded COMPOUND 318 as a white foamy solid (0.087 g, 27%). 1H NMR (CDCl3) δ 1.29-1.42 (m, 2H), 1.62 (s, 6H), 1.76 (d, 2H, J=12.0 Hz), 2.22 (s, 3H), 2.29 (s+m, 4H), 2.75-2.84 (m, 3H), 3.42 (m, 1H), 3.71 (br s, 2H), 4.02 (d, 2H, J=12.0 Hz), 6.87 (t, 2H, J=9.0 Hz), 7.07 (s, 2H), 7.15 (s, 1H), 7.23 (s, 1H), 7.23 (s, 1H), 7.81 (s, 1H), 7.88 (m, 1H), 8.15 (s, 1H), 8.54 (s, 1H). 13C NMR (CDCl3) δ 17.9, 18.2, 28.2, 31.0, 42.1, 46.3, 54.2, 115.0, 115.3, 118.0, 127.3, 129.6, 132.6, 136.9, 146.5, 150.7, 159.3. HPLC: 91%. ES-MS m/z 541 [M+H]+. Anal. Calcd. for C32H37N6OF.0.15 CH2Cl2: C, 69.78; H, 6.79; N, 15.19. Found: C, 69.74; H, 6.83; N, 15.03.

Workup

  1. customThe solvent was removed under reduced pressure
  2. customto give a colorless oil that
  3. stirringThe mixture was stirred at room temperature for 16 hours
  4. customthe solvent was removed under reduced pressure
  5. washwashed with brine (3×20 mL)
  6. dry with materialthe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a yellow oil
  10. customPurification by column chromatography on silica gel (CH2Cl2

Sources & evidence

ORD record
ord-480dd394aa5e45d4b34363dc63b4b0bf
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

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