2-Methylbenzimidazole → HCID 49785640, compound

HRID 1909034Notes

Reaction equation

HRID 1909034 reaction equation
Br[C:2]1[CH:7]=[C:6]([C:8]([C:10]2[NH:14][C:13]3[CH:15]=[C:16]([N:19]4[CH2:24][CH2:23][CH:22]([N:25]([CH3:27])[CH3:26])[CH2:21][CH2:20]4)[CH:17]=[CH:18][C:12]=3[N:11]=2)=[O:9])[CH:5]=[CH:4][N:3]=1.[CH3:28][C:29]1[NH:30][C:31]2[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=2[N:33]=1.CN[C@@H]1CCCC[C@H]1NC>CN(C=O)C.CCOC(C)=O.[Cl-].[Na+].O.[Cu]I>[CH3:26][N:25]([CH3:27])[CH:22]1[CH2:23][CH2:24][N:19]([C:16]2[CH:17]=[CH:18][C:12]3[N:11]=[C:10]([C:8]([C:6]4[CH:5]=[CH:4][N:3]=[C:2]([N:30]5[C:31]6[CH:37]=[CH:36][CH:35]=[CH:34][C:32]=6[N:33]=[C:29]5[CH3:28])[CH:7]=4)=[O:9])[NH:14][C:13]=3[CH:15]=2)[CH2:20][CH2:21]1

Participants

8

Reactant 3

HCID 119842-MethylbenzimidazoleHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 86664349HCID 86664349, compound

Product 1

HCID 49785640HCID 49785640, compoundYield 14.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of (2-bromo-pyridin-4-yl)-[6-(4-dimethylamino-piperidin-1-yl)-1H-benzoimidazol-2-yl]-methanone (0.46 mmol, 1.0 mol eq.) [Example 102 (Method 1, Step 3)], 2-methyl benzimidazole (0.56 mmol, 1.2 mol eq), CuI (0.047 mmol, 0.5 mol eq.), (1R,2R)—N,N′-dimethyl-cyclohexane-1,2-diamine (0.093 mmol, 0.2 mol eq.) in 2 mL of DMF was heated at 130° C. for 48 h under nitrogen. The reaction was diluted with 50 mL EtOAc and 50 mL brine. The organic layer was separated and dried over Na2SO4, filtered and evaporated to dryness. HPLC purification gave the title compound (31 mg, 14%). HRMS m/z 480.2502 (M+H)+. 1H NMR (400 MHz, DMSO-d6): 8.96 (1H, d), 8.65 (1H, s), 8.30 (1H, d), 7.74-7.63 (3H, m), 7.31-7.29 (2H, m), 7.17 (1H, d), 6.93 (1H, s), 4.16 (1H, bs), 3.77-3.74 (2H, m), 2.80-2.71 (2H, m), 2.70 (3H, s), 2.20 (6H, s), 1.89-1.85 (2H, m), 1.57-1.48 (2H, m).

Workup

  1. customThe organic layer was separated
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customHPLC purification

Sources & evidence

ORD record
ord-66d01852ce5541aab92c7c7a6cd323dc
Source dataset
uspto-grants-2013_12
Patent number
US08598217B2

Reaction notes

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