3,4-dihydro-2H-pyran → 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2079553Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][NH:12][C:4]=2[CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:25]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26]1>C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH:26]3[CH2:27][CH2:28][CH2:29][CH2:30][O:25]3)[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 60 °C

Procedure

6-Chloro-1H-imidazo[4,5-c]pyridine-4-carbonitrile (620 mg) and p-toluenesulfonic acid monohydrate (10 mg) were suspended in ethyl acetate (10 ml) and heated to 60° C. 3,4-Dihydro-2H-pyran (0.48 ml) was added dropwise and the reaction stirred at 60° C. overnight. The reaction was quenched with 5 mL ammonium hydroxide before addition of water (100 mL) and ethyl acetate (200 mL). Organic layer was separated, dried over sodium sulphate and solvent was evaporated under reduced pressure. The crude product was dissolved in a minimum volume of EtOAc and heptane added. The resulting brown solid was collected by filtration to yield 6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (630 mg). 1H NMR (DMSO) δ: 8.92 (s, 1H), 8.30 (s, 1H), 5.80 (d, 1H), 4.05 (m, 1H), 3.75 (m, 1H), 2.19 (m, 1H), 2.11 (m, 1H), 1.62 (m, 4H).

Workup

customThe reaction was quenched with 5 mL ammonium hydroxide before addition of water (100 mL) and ethyl acetate (200 mL)
customOrganic layer was separated
dry with materialdried over sodium sulphate and solvent
customwas evaporated under reduced pressure
dissolutionThe crude product was dissolved in a minimum volume of EtOAc and heptane
additionadded
filtrationThe resulting brown solid was collected by filtration

Sources & evidence

ORD record: ord-660f1a11aecf4e669c2a5ca4526844d2
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932251B2

Reaction notes

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