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

HRID 1068505Notes

Reaction equation

HRID 1068505 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>>[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

6

Reactant 5

HCID 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

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.

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-836791aa023346fe8a3c580e4633ac28
Source dataset
uspto-grants-2001_06
Patent number
US06248756B1

Reaction notes

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