Hydrochloric Acid → 6-Ethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride

HRID 2064089Notes

Reaction equation

HRID 2064089 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH3:9])=[CH:4][C:3]=1[NH:10][CH:11]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)[CH2:13][CH2:12]1.[C:23](N1C=CN=C1)(N1C=CN=C1)=[O:24].[ClH:35]>ClCCl.O1CCOCC1>[ClH:35].[CH2:8]([C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:23](=[O:24])[N:10]([CH:11]3[CH2:12][CH2:13][N:14]([CH:17]4[CH2:18][CH2:19][O:20][CH2:21][CH2:22]4)[CH2:15][CH2:16]3)[C:3]=2[CH:4]=1)[CH3:9]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 59863026(2-amino-5-ethylphenyl)[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]amine

Product 1

HCID 691226656-Ethyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one hydrochlorideYield 29%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (2-amino-5-ethylphenyl)[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]amine D26 (251 mg, 0.83 mmol) in dichloromethane (10 mL) was added 1,1′-carbonyldiimidazole (403 mg, 2.49 mmol). The mixture was stirred under room temperature for 1 hour and 2 mL of 4 M HCl in 1,4-dioxane was added. The resulting mixture was stirred for 5 min and concentrated in vacuo. The residue was dissolved in MeOH and purified by using a Gilson preparative HPLC system with a Waters Xterra (C-18) column 100 mm by 50 mm ID, eluting with 10% B to 90% B in 10 min, where A=H2O and B=CH3CN pumped at 150 mL/min to yield 89 mg of the title compound (29% yield). MS (ESI): 330 [M+H]+; 1H NMR (HCl salt) (400 MHz, CDCl3): δ 1.30 (3H, t), 1.99 (5H, m), 2.25 (2H, d), 2.75 (2H, q), 3.03 (2H, m), 3.44 (4H, d), 3.68 (2H, m), 4.14 (2H, d), 4.69 (1H, m), 6.91 (1H, d), 7.00 (1H, d), 7.84 (1H, s), 9.36 (1H, s), 12.91 (1H, br).

Workup

  1. stirringThe resulting mixture was stirred for 5 min
  2. concentrationconcentrated in vacuo
  3. dissolutionThe residue was dissolved in MeOH
  4. custompurified
  5. washeluting with 10% B to 90% B in 10 min

Sources & evidence

ORD record
ord-7df423e5d9314c8ba79d098fdbdb0788
Source dataset
uspto-grants-2012_10
Patent number
US08288413B2

Reaction notes

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