Toluene → HCID 10163553, compound

HRID 1062447Notes

Reaction equation

HRID 1062447 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)[CH:10]=[C:11]([C:13]([NH:15][CH:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[O:14])[N:12]=1.Br[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1.CC([O-])(C)C.[Na+].C1(C)C=CC=CC=1>C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:9]([C:22]2[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=2)[CH:10]=[C:11]([C:13]([NH:15][CH:16]2[CH2:17][CH2:18][N:19]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[CH2:20][CH2:21]2)=[O:14])[N:12]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 79732-BromopyridineHCID 22285561HCID 22285561, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 10163553HCID 10163553, compoundYield 50.8%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolvent

Procedure

A flask was charged with 2-(2-chlorophenyl)-1-(4-chlorophenyl)-N-(4-piperidinyl)-1H-imidazole-4-carboxamide (Example 37) (100 mg, 0.24 mmol), 2-bromopyridine (0.55 mg, 0.22 mmol), Pd2(dba)3 (38 mg, 0.24 mmol), BINAP (1.18 mg, 0.0019 mmol), NaOtBu (33.6 mg, 0.35 mmol), and toluene (2 mL). The reaction mixture was heated at reflux overnight, cooled to rt, and diluted with CH2Cl2. The solid was filtered off. The solvent was evaporated. The residue was purified by flash chromatography (33% EtOAc in hexane) to give the product 2-(2-chlorophenyl)-1-(4-chlorophenyl)-N-[1-(2-pyridinyl)-4-piperidinyl]-1H-imidazole-4-carboxamide (55 mg, 47% yield): LC-MS m/z 492.1 (MH+), retention time 2.47 min (method 1); Rf=0.33 (50% EtOAc in hexane).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. filtrationThe solid was filtered off
  4. customThe solvent was evaporated
  5. customThe residue was purified by flash chromatography (33% EtOAc in hexane)

Sources & evidence

ORD record
ord-4f5e988f85d740a0aa724f463b0a5063
Source dataset
uspto-grants-2005_11
Patent number
US06960601B2

Reaction notes

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