Cesium carbonate → 2-(3-(3-Chloropyrazin-2-yl)azetidin-1-yl)quinazoline

HRID 1850244

Reaction equation

Cl.[NH:2]1[CH2:5][CH:4]([C:6]2[C:11]([Cl:12])=[N:10][CH:9]=[CH:8][N:7]=2)[CH2:3]1.Cl[C:14]1[N:23]=[CH:22][C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[Cl:12][C:11]1[C:6]([CH:4]2[CH2:5][N:2]([C:14]3[N:23]=[CH:22][C:21]4[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=4)[N:15]=3)[CH2:3]2)=[N:7][CH:8]=[CH:9][N:10]=1

Participants

Conditions

Temperature: 110 °C

Procedure

2-(Azetidin-3-yl)-3-chloropyrazine hydrochloride (8) (1.50 g, 7.28 mmol), 2-chloroquinazoline (1.20 g, 7.28 mmol, Parkway Scientific), and cesium carbonate (5.22 g, 16.0 mmol, Fluka) were mixed in DMF (30 mL) in a round bottom flask under a nitrogen atmosphere. The mixture was stirred at 110° C. for 17 h. The reaction mixture was cooled to RT, diluted with water, and extracted with EtOAc (2×). The combined organic extracts were washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mixture was purified via silica gel flash column chromatography eluting with 0% to 100% EtOAc in hexanes to give 1.02 g (47%) of a yellow amorphous solid.

Workup

temperatureThe reaction mixture was cooled to RT
extractionextracted with EtOAc (2×)
washThe combined organic extracts were washed with saturated sodium chloride
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe resulting crude mixture was purified via silica gel flash column chromatography
washeluting with 0% to 100% EtOAc in hexanes

Sources & evidence

ORD record: ord-6fd04f14529d4780856ef1fe8d9ee5a6
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08957073B2

Linked notes

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