Acetic Acid → 2-[5-(4-Azepan-1-yl-piperidin-1-yl)-2-chloro-phenyl]-1H-benzoimidazole

HRID 2047382Notes

Reaction equation

HRID 2047382 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:11]=[C:12]([N:17]2[CH2:22][CH2:21][C:20](=O)[CH2:19][CH2:18]2)[CH:13]=[CH:14][C:15]=1[Cl:16].[NH:24]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[N:24]1([CH:20]2[CH2:21][CH2:22][N:17]([C:12]3[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([C:2]4[NH:3][C:4]5[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=5[N:1]=4)[CH:11]=3)[CH2:18][CH2:19]2)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8119Azepane2×HCID 5049666Sodium triacetoxyborohydrideHCID 595682431-[3-(1H-benzo[d]imidazol-2-yl)-4-chlorophenyl]piperidin-4-one

Product 1

HCID 441241202-[5-(4-Azepan-1-yl-piperidin-1-yl)-2-chloro-phenyl]-1H-benzoimidazoleYield 58%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 1-[3-(1H-benzoimidazol-2-yl)-4-chloro-phenyl]-piperidin-4-one (0.10 g, 0.31 mmol) in dichloromethane (2 mL) was added azepane (0.05 mL, 0.46 mmol). After 30 min stirring at room temperature a drop of acetic acid was added, and after 1 h a further aliquot of azepane (0.05 mL, 0.46 mmol) was added, followed by sodium triacetoxyborohydride (NaB(OAc)3H) (0.10 g, 0.46 mmol). The reaction mixture was stirred at room temperature overnight, then the solvent was removed under reduced pressure, and the crude product dissolved in dichloromethane (10 mL). To the solution PS-isocyanate resin (PS-NCO) (Argonaut, loading 0.93 mmol/g) was added, then the mixture was shaken at room temperature overnight and filtered. The solvent was removed under reduced pressure to obtain a solid residue that was washed with EtOAc and Et2O then dried to give the desired product (0.07 g, 58%).

Workup

  1. additionwas added
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe crude product dissolved in dichloromethane (10 mL)
  4. additionTo the solution PS-isocyanate resin (PS-NCO) (Argonaut, loading 0.93 mmol/g) was added
  5. stirringthe mixture was shaken at room temperature overnight
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure
  8. customto obtain a solid residue that
  9. washwas washed with EtOAc and Et2O
  10. customthen dried

Sources & evidence

ORD record
ord-c92a700be4a84b15b19ba1d6ccec95b2
Source dataset
uspto-grants-2013_11
Patent number
US08592463B2

Reaction notes

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