Ammonium Hydroxide → HCID 68657324, compound

HRID 930777Notes

Reaction equation

HRID 930777 reaction equation
[N:1]1[C:2]([CH2:10][OH:11])=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.[H-].[Na+].Cl[C:15]1[CH:20]=[CH:19][N+:18]([O-:21])=[CH:17][CH:16]=1.[NH4+].[OH-]>O1CCOCC1.CN(C=O)C.O1CCOCC1.C(Cl)Cl.CO>[N:1]1[C:2]([CH2:10][O:11][C:15]2[CH:20]=[CH:19][N+:18]([O-:21])=[CH:17][CH:16]=2)=[CH:3][N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12

Participants

9

Reactant 4

HCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 707244-chloropyridine N-oxideHCID 2795540Imidazo[1,2-a]pyridin-2-ylmethanol

Product 1

HCID 68657324HCID 68657324, compoundYield 54.1%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 217120691,4-dioxane N,N-dimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Imidazo[1,2-a]pyridine-2-ylmethanol (3.01 g, 20.3 mmol) was partially dissolved in 5:1 dioxane/DMF (30 mL) and the resulting slurry was added slowly to a stirring suspension of NaH (60% in mineral oil, 0.812 g, 16.9 mmol) in dioxane (29 mL). The resulting mixture was heated to 60° C. for 15 min. 4-Chloropyridine-N-oxide (1.5 g, 11.5 mmol) was added and the reaction mixture was heated for 1 h at 110° C. Upon cooling, the mixture was diluted with methylene chloride and a 20% NH4OH in MeOH solution. The resulting suspension was filtered through a silica gel plug using CH2Cl2 (200 mL) and 20% 4:1 MeOH/NH4OH in CH2Cl2 (500 mL). The filtrate was collected and concentrated under reduced pressure. Flash chromatography (120 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 to 0:100 over 60 min) provided the title compound (1.5 g, 30%) as an orange-brown solid: 1H NMR (300 MHz, CD3OD) δ 8.42 (m, 1H), 8.24-8.22 (m, 2H), 7.97 (d, J=0.5 Hz, 1H), 7.54 (dd, J=9.1, 0.7 Hz, 1H) 7.37-7.32 (m, 1H), 7.27-7.25 (m, 2H), 6.94 (m, 1H), 5.37 (s, 2H).

Workup

  1. temperaturethe reaction mixture was heated for 1 h at 110° C
  2. temperatureUpon cooling
  3. filtrationThe resulting suspension was filtered through a silica gel plug
  4. customThe filtrate was collected
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-bd86b360138747009d2eb94e1e88c8ef
Source dataset
uspto-grants-2016_03
Patent number
US09296743B2

Reaction notes

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