Piperidine → HCID 178501181, compound

HRID 518603Notes

Reaction equation

HRID 518603 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6]([NH:8][C:9]2[N:13]([C@@H:14]3[CH2:19][CH2:18][C@H:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:16][CH2:15]3)[C:12]3[CH:24]=[C:25]([CH2:28]O)[CH:26]=[CH:27][C:11]=3[N:10]=2)=[O:7])=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:36]1[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]1>C(Cl)Cl.CS(C)=O>[F:1][C:2]1[CH:31]=[CH:30][C:5]([C:6](/[N:8]=[C:9]2\[NH:10][C:11]3[CH:27]=[CH:26][C:25]([CH2:28][N:36]4[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37]4)=[CH:24][C:12]=3[N:13]\2[C@@H:14]2[CH2:15][CH2:16][C@H:17]([C:20]([O:22][CH3:23])=[O:21])[CH2:18][CH2:19]2)=[O:7])=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 8082PiperidineHCID 24386Thionyl ChlorideHCID 178501179HCID 178501179, compound

Product 1

HCID 178501181HCID 178501181, compoundYield 68.2%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

cis-Methyl 4-(2-(4-fluorobenzamido)-6-(hydroxymethyl)-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate (0.19 g, 0.447 mmol) was suspended in DCM (4.47 mL) and cooled to 0° C. under a nitrogen atmosphere. To this mixture was added thionyl chloride (0.652 mL, 8.93 mmol) dropwise, and the reaction mixture was stirred at 0° C. for 1 hour. The ice bath was removed, and the mixture was stirred at RT for 2 hours. The reaction mixture was concentrated under reduced pressure and dried under high vacuum to afford a yellow foam. The foam was suspended in 2 mL of DMSO and treated with piperidine (0.441 mL, 4.47 mmol) followed by TEA (0.248 mL, 1.786 mmol). The resulting mixture was stirred at RT for 2 hours. The reaction mixture was diluted with DCM (2-20 mL) and washed with water (2-20 mL). The organic layer was collected, dried over sodium sulfate, and concentrated. The residue was purified by HPLC (10-70% ACN/H2O; 0.1% TFA) to afford cis-methyl 4-((E)-2-(4-fluorobenzoylimino)-6-(piperidin-1-ylmethyl)-2,3-dihydro-1H-benzo[d]imidazol-1-yl)cyclohexanecarboxylate as a white solid (150 mg, 68.2% yield). MS m/z=493.2 [M+H]. Calc'd for C28H33FN4O3: 492.3. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.33-1.45 (m, 2H) 1.44-1.61 (m, 4H) 1.66-1.93 (m, 4H) 2.19-2.32 (m, 2H) 2.29-2.43 (m, 4H) 2.53-2.65 (m, 2H) 2.81-2.94 (m, 1H) 3.51 (s, 2H) 3.78 (s, 3H) 4.57-4.89 (m, 1H) 7.10-7.18 (m, 1H) 7.21-7.32 (m, 2H) 7.42-7.52 (m, 2H) 8.02-8.48 (m, 2H) 12.78 (s, 1H).

Workup

  1. customThe ice bath was removed
  2. stirringthe mixture was stirred at RT for 2 hours
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customdried under high vacuum
  5. customto afford a yellow foam
  6. stirringThe resulting mixture was stirred at RT for 2 hours
  7. washwashed with water (2-20 mL)
  8. customThe organic layer was collected
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe residue was purified by HPLC (10-70% ACN/H2O; 0.1% TFA)

Sources & evidence

ORD record
ord-cdcd21674173493282720f8337a10991
Source dataset
uspto-grants-2015_08
Patent number
US09115127B2

Reaction notes

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