Toluene → HCID 24883075, compound

HRID 2421067Notes

Reaction equation

HRID 2421067 reaction equation
Cl.[N:2]1([CH:18]2[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]2)[CH2:7][CH2:6][CH:5]([N:8]2[C@H:12]3[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]3[NH:10][C:9]2=[O:17])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].Cl[C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32].C1(C)C=CC=CC=1>CC(C)=O.ClCCl.O>[O:17]=[C:9]1[N:8]([CH:5]2[CH2:4][CH2:3][N:2]([CH:18]3[CH2:23][CH2:22][N:21]([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[CH2:20][CH2:19]3)[CH2:7][CH2:6]2)[C@H:12]2[CH2:13][CH2:14][CH2:15][CH2:16][C@H:11]2[NH:10]1

Participants

8

Reactant 4

HCID 1140TolueneHCID 7917Isopropyl chloroformateHCID 11430Potassium CarbonateHCID 131728948HCID 131728948, compound

Product 1

HCID 24883075HCID 24883075, compoundYield 56%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of cis-(+/−)-1-(1,4′-bipiperidin-4-yl)octahydro-2H-benzimidazol-2-one hydrochloride salt from step B (70 mg, 0.18 mmol) in 5 ml acetone was added potassium carbonate (49 mg, 0.36 mmol) followed by 1M isopropyl chloroformate in toluene (0.36 mL, 0.36 mmol) and the mixture was stirred at room temperature for 3 h. Removal of solvent gave a residue, which was dissolved in dichloromethane, and then water was added. The mixture was passed through VARIAN CHEM ELUT™ cartridges. The cartridge was rinsed with dichloromethane (2×20 mL). The dichloromethane solution was concentrated in vacuo and the crude product was purified by high pH prep-LCMS H to afford the title compound (40 mg, 56%). 1H NMR (400 MHz, CDCl3): δ ppm 1.14-1.21 (m, 1H), 1.23 (d, J=6.25 Hz, 6H), 1.33-1.48 (m, 3H), 1.48-1.67 (m, 6H), 1.66-1.95 (m, 8H), 2.43 (t, J=10.94 Hz, 1H), 2.71 (t, J=12.21 Hz, 2H), 2.95 (dd, J=21.09, 10.35 Hz, 2H), 3.52-3.63 (m, 2H), 3.68 (t, J=12.01 Hz, 1H), 4.02 (s, 1H), 4.20 (s, 2H), 4.80-4.98 (m, 1H). MS (M+1): 393.3

Workup

  1. customRemoval of solvent
  2. customgave a residue, which
  3. washThe cartridge was rinsed with dichloromethane (2×20 mL)
  4. concentrationThe dichloromethane solution was concentrated in vacuo
  5. customthe crude product was purified by high pH prep-LCMS H

Sources & evidence

ORD record
ord-ec409043a35944e8a28b24005c1350b9
Source dataset
uspto-grants-2011_06
Patent number
US07956069B2

Reaction notes

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