Hydrochloric Acid → 2-[3-(4-cyanobenzyl)-3H-imidazol-1-yl]-N-(4-cyanobenzyl)-N-(1-phenylpiperidin-4-yl)acetamide hydrochloride

HRID 443313Notes

Reaction equation

HRID 443313 reaction equation
[C:1]([C:3]1[CH:22]=[CH:21][C:6]([CH2:7][NH:8][CH:9]2[CH2:14][CH2:13][N:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)#[N:2].[C:23]([C:25]1[CH:40]=[CH:39][C:28]([CH2:29][N:30]2[C:34](CC([O-])=O)=[CH:33][N:32]=[CH:31]2)=[CH:27][CH:26]=1)#[N:24].[Li+].[OH2:42].ON1C2C=CC=[CH:52][C:47]=2N=N1.[ClH:53].CN(C)CCCN=C=NCC.C(N(CC)C(C)C)(C)C.Cl>C(#N)C>[ClH:53].[C:23]([C:25]1[CH:26]=[CH:27][C:28]([CH2:29][N:30]2[CH:34]=[CH:33][N:32]([CH2:47][C:52]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:22][CH:21]=3)[CH:9]3[CH2:10][CH2:11][N:12]([C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=4)[CH2:13][CH2:14]3)=[O:42])[CH2:31]2)=[CH:39][CH:40]=1)#[N:24]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 21193414HCID 21193414, compoundHCID 67586058HCID 67586058, compound

Product 1

HCID 211932232-[3-(4-cyanobenzyl)-3H-imidazol-1-yl]-N-(4-cyanobenzyl)-N-(1-phenylpiperidin-4-yl)acetamide hydrochloride

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Cyanobenzyl(1-phenylpiperidin-4-yl)amine (75 mg, 0.26 mmol), lithium [3-(4-cyanobenzyl)-3H-imidazol-4-yl]acetate (70 mg, 0.28 mmol), 1-hydroxybenzotriazole hydrate (52 mg, 0.38 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (99 mg, 0.52 mmol), and N,N-diisopropylethylamine (67 μL, 0.38 mmol) were added to degassed DMF (3 mL) and the mixture was stirred for 18 hrs at room temperature then concentrated in vacuo. The residue was added to sat. NaHCO3 (aq) (5 mL) and extracted with dichloromethane (3×3 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was chromatographed on silica gel, eluting with dichloromethane--2% methanol to give the product as a free base. This was lyophilized from HCl (aq)--acetonitrile to give the title compound as a white solid. Elemental analysis calculated for C32H30N6O.2.5 HCl.1.85 H2O: C: 60.04; H: 5.86; N: 13.13; Found: C: 60.08; H: 5.66; N: 13.09; 1H NMR (CD3OD) δ 8.99-8.92 (1H, m); 7.81-7.40 (14H, m); 5.59-5.53 (2H, m); 4.86-4.66 (3H, m); 4.40-3.69 (6H, m); 2.55-2.42 (2H, m); 2.15-2.02 (2H, m). FAB MS: 515 (MH+).

Workup

  1. customto degassed DMF (3 mL)
  2. concentrationthen concentrated in vacuo
  3. additionThe residue was added to sat. NaHCO3 (aq) (5 mL)
  4. extractionextracted with dichloromethane (3×3 mL)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was chromatographed on silica gel
  9. washeluting with dichloromethane--2% methanol
  10. customto give the product as a free base

Sources & evidence

ORD record
ord-c2adb63ddcbb49d499646cd54e8ff981
Source dataset
uspto-grants-1999_04
Patent number
US05891889

Reaction notes

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