Cesium carbonate → Methyl 2-(6-{[(ethylamino)carbonyl]amino}pyridin-3-yl)-1,3-thiazole-5-carboxylate

반응식

[CH2:1]([NH:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10](B2OC(C)(C)C(C)(C)O2)=[CH:9][N:8]=1)=[O:5])[CH3:2].Br[C:23]1[S:24][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][N:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[N:8]=[CH:9][C:10]([C:23]2[S:24][C:25]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][N:27]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:2]

참가 물질

반응물 3

HCID 10796Cesium carbonate

HCID 2773502Methyl 2-bromothiazole-5-carboxylate

HCID 592084346-(3-Ethylureido)pyridine-3-boronic acid pinacol ester2회

생성물 1

HCID 59208451Methyl 2-(6-{[(ethylamino)carbonyl]amino}pyridin-3-yl)-1,3-thiazole-5-carboxylate

실험 절차

N-Ethyl-N′-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]urea (Intermediate 1, 0.20 g, 0.69 mmol), methyl 2-bromo-1,3-thiazole-5-carboxylate (0.152 g, 0.69 mmol), tetrakis triphenyl phosphine palladium (0.08 g, 0.069 mmol), and cesium carbonate (0.245 mg, 0.754 mmol) were taken in a microwave vial and degassed with argon. Then dioxane:water (4:1, 3 mL) was added to it and microwaved at 110° C. for half an hour. The reaction mixture was partitioned between water and EtOAc and layers separated. The organic layer was washed with sat. sodium bicarbonate solution, water, brine and dried over magnesium sulfate. The solvent was removed and the residue was purified by flash chromatography eluting with 2% MeOH in DCM to 3% MeOH in DCM. MS (ESP): 307 (M+H+) for C13H14N4O3S; NMR: 1.09 (t, 3H), 3.16-3.22 (m, 2H), 3.86 (s, 3H), 7.60 (d, 1H), 7.79 (t, 1H), 8.27 (dd, 1H), 8.49 (s, 1H), 8.83 (s, 1H), 9.56 (s, 1H).