2-chloro-1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazole → (+/-)-cis-1-[3,5-bis(trifluoromethyl)-benzoyl]-4-[4-[1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazol-2-yl]-1-piperazinyl]-2-(phenylmethyl)piperidine

HRID 991366Notes

Reaction equation

HRID 991366 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)[CH2:10][CH:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7].Cl[C:37]1[N:41]([CH2:42][C:43]2[O:47][C:46]([CH3:48])=[N:45][CH:44]=2)[C:40]2[CH:49]=[CH:50][CH:51]=[CH:52][C:39]=2[N:38]=1>C(Cl)Cl>[F:35][C:2]([F:34])([F:1])[C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([C:30]([F:33])([F:31])[F:32])[CH:29]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:14]2[CH2:15][CH2:16][N:17]([C:37]3[N:41]([CH2:42][C:43]4[O:47][C:46]([CH3:48])=[N:45][CH:44]=4)[C:40]4[CH:49]=[CH:50][CH:51]=[CH:52][C:39]=4[N:38]=3)[CH2:18][CH2:19]2)[CH2:10][C@@H:9]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:7]

Participants

4

Reactant 2

HCID 186308472-chloro-1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazoleHCID 18630855(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-(1-piperazinyl)piperidine

Product 1

HCID 15513285(+/-)-cis-1-[3,5-bis(trifluoromethyl)-benzoyl]-4-[4-[1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazol-2-yl]-1-piperazinyl]-2-(phenylmethyl)piperidineYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compound 15 (0.005 mol), 2-chloro-1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazole (0.005 mol) and Cupper (0.005 mol) were stirred at 140° C. for 2 hours. The mixture was cooled, dissolved in CH2Cl2, filtered and washed with CH2Cl2 and a diluted NH4OH solution. The organic layer was separated, washed with a diluted NH4OH solution, dried, filtered and the solvent was evaporated. The residue was purified over silica gel on a glass filter (eluent: CH2Cl2/CH3OH 100/0, 99.5/0.5, 99/1, 98.5/1.5 and 98/2). The pure fractions were collected and the solvent was evaporated. The residue was dried, yielding 1.42 g (40%) (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-4-[4-[1-[(2-methyl-5-oxazolyl)methyl]-1H-benzimidazol-2-yl]-1-piperazinyl]-2-(phenylmethyl)piperidine (compound 70).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationfiltered
  3. washwashed with CH2Cl2
  4. customThe organic layer was separated
  5. washwashed with a diluted NH4OH solution
  6. customdried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified over silica gel on a glass
  10. filtrationfilter (eluent: CH2Cl2/CH3OH 100/0, 99.5/0.5, 99/1, 98.5/1.5 and 98/2)
  11. customThe pure fractions were collected
  12. customthe solvent was evaporated
  13. customThe residue was dried

Sources & evidence

ORD record
ord-92245eb716284c00900082251b88ebf4
Source dataset
uspto-grants-2002_10
Patent number
USRE037886E1

Reaction notes

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