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Diisopropylamine → [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 1592587
Notes
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Reaction equation

HRID 1592587 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>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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 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-methanone
Yield 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 NH2OHHCl (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-1c699eb8aa734af686347c215c2d12bf
Source dataset
uspto-grants-2007_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07291631B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes