Methyl iodide → Methyl 1-(6-(3,5-dimethyl-1H-1,2,4-triazol-1-yl)-2-methylpyrimidin-4-yl)azetidine-3-carboxylate

HRID 2202824Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([N:8]2[C:12]([CH3:13])=[N:11][C:10]([CH3:14])=[N:9]2)[N:5]=[C:4]([CH3:15])[N:3]=1.Cl.[NH:17]1[CH2:20][CH:19]([C:21]([O:23][CH3:24])=[O:22])[CH2:18]1.C(=O)([O-])[O-].[Cs+].[Cs+].IC.C(=O)(O)[O-].[Na+]>CN(C=O)C>[CH3:14][C:10]1[N:11]=[C:12]([CH3:13])[N:8]([C:6]2[N:5]=[C:4]([CH3:15])[N:3]=[C:2]([N:17]3[CH2:20][CH:19]([C:21]([O:23][CH3:24])=[O:22])[CH2:18]3)[CH:7]=2)[N:9]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Intermediate 2 (0.45 g, 2.0 mmol), methyl azetidine-3-carboxylate hydrochloride (0.61 g, 4.0 mmol), and cesium carbonate (2.0 g, 6.0 mmol) were combined in degassed DMF (10 mL) and heated at 100° C. for 14 h. The mixture was cooled to room temperature and treated with iodomethane (0.13 mL, 2.0 mmol). After stirring for 1 h, the mixture was poured into sodium bicarbonate (200 mL, aqueous saturated) and extracted with ethyl acetate (2×100 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (0-100% EtOAc/hexanes), providing 107-1 as an off-white solid. MS: m/z=303.3 (M+H).

Workup

temperatureThe mixture was cooled to room temperature
extractionextracted with ethyl acetate (2×100 mL)
dry with materialThe combined organic extracts were dried with sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record: ord-d8f1673c89c34f78ae07ad06df07f800
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09365562B2

Reaction notes

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