Potassium Carbonate → 1-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(4-(piperidin-3-yl)-1H-1,2,3-triazol-1-yl)-1H-benzo[d]imidazole

HRID 706428Notes

Reaction equation

HRID 706428 reaction equation
I[C:2]1[CH:29]=[CH:28][C:5]2[N:6]([CH2:9][C:10]3[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]4[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=4)=[C:12]([O:26][CH3:27])[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.Cl.[C:31]([CH:33]1[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]1)#[CH:32].[N-:39]=[N+:40]=[N-:41].[Na+].[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.O.[OH-].[NH4+].[Cu]I>[CH3:27][O:26][C:12]1[CH:11]=[C:10]([CH:15]=[CH:14][C:13]=1[O:16][CH2:17][C:18]1[CH:19]=[N:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=1)[CH2:9][N:6]1[C:5]2[CH:28]=[CH:29][C:2]([N:39]3[CH:32]=[C:31]([CH:33]4[CH2:38][CH2:37][CH2:36][NH:35][CH2:34]4)[N:41]=[N:40]3)=[CH:3][C:4]=2[N:8]=[CH:7]1

Participants

11

Reactant 6

HCID 11430Potassium CarbonateHCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 534011233-Ethynylpiperidine hydrochlorideHCID 66586226sodium L-ascorbic acidHCID 1181141105-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole

Product 1

HCID 1180097781-(3-Methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-(4-(piperidin-3-yl)-1H-1,2,3-triazol-1-yl)-1H-benzo[d]imidazoleYield 160.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 14923Ammonium HydroxideSolvent

Procedure

To a suspension of 5-iodo-1-(3-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-1H-benzo[d]imidazole (0.32 g, 0.63 mmol) in dimethyl sulfoxide (4 mL) and water (1 mL) was added 3-ethynylpiperidine hydrochloride (0.11 g, 0.75 mmol), sodium azide (0.051 g, 0.79 mmol), L-ascorbic acid sodium salt (0.025 g, 0.13 mmol), trans-N,N′-dimethylcyclohexane-1,2-diamine (0.023 mg, 0.158 mmol), potassium carbonate (0.13 g, 0.95 mmol), and copper(I) iodide (0.024 g, 0.13 mmol). The resulting blue mixture was allowed to stir at room temperature. After 16 h, the yellow mixture was diluted with 5N ammonium hydroxide solution and extracted with chloroform (2×30 mL). The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to provide 0.53 g of a yellow oil. Chromatographic purification (Combi-Flash, 24 g SiO2 gold column, 1-10% 2M ammonia in methanol/dichloromethane elute) afforded 0.15 g (45%) of the product as a white foamy solid: 1H NMR (400 MHz, DMSO-d6) δ 8.61-8.53 (m, 2H), 8.20 (d, J=2.4 Hz, 1H), 8.11 (d, J=1.9 Hz, 1H), 7.79-7.71 (m, 3H), 7.12 (d, J=1.9 Hz, 1H), 7.03 (d, J=8.2 Hz, 1H), 6.89-6.80 (m, 2H), 5.46 (s, 2H), 4.97 (s, 2H), 3.84 (s, 3H), 3.73 (s, 3H), 3.25-3.16 (m, 1H), 3.01-2.91 (m, 1H), 2.90-2.80 (m, 1H), 2.68-2.51 (m, 2H), 2.12-2.03 (m, 1H), 1.72-1.44 (m, 3H) ppm; (M+1)=526.

Workup

  1. extractionextracted with chloroform (2×30 mL)
  2. dry with materialThe combined organic phases were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-52ccc4cad2404620b84f498114a5a00b
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

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