Ethyl Acetate → Ethyl 4-methyl-2-(1-methylpyrazol-4-yl)pyrimidine-5-carboxylate

HRID 575692Notes

Reaction equation

HRID 575692 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=1.[CH3:14][N:15]1[CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:17]=[N:16]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CC(=O)OCC>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:8][C:6]1[C:5]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][N:3]=[C:2]([C:18]2[CH:17]=[N:16][N:15]([CH3:14])[CH:19]=2)[N:7]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 62657Potassium Phosphate, TribasicHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 21220624Ethyl 2-chloro-4-methylpyrimidine-5-carboxylate

Product 1

HCID 102972407Ethyl 4-methyl-2-(1-methylpyrazol-4-yl)pyrimidine-5-carboxylateYield 32%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Ethyl 2-chloro-4-methylpyrimidine-5-carboxylate (1.0 g, 5.0 mmol), 1-methyl-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (1.24 g, 6.0 mmol), K3PO4 (3.18 mg, 15.0 mmol) and Pd(dppf)Cl2 (100 mg) in dioxane (15 mL) and H2O (3 mL) were heated at 120° C. for 18 h under N2. Silica gel chromatography (PE:EA=3:1 to 1:1) gave the title compound (72 mg, yield: 32.0%). 1H NMR (CDCl3, 400 MHz) δ 9.08 (s, 1H), 8.22 (s, 1H), 8.15 (s, 1H), 4.40 (q, J=7.2 Hz, 2H), 3.98 (s, 3H), 2.82 (s, 3H), 1.42 (t, J=7.2 Hz, 3H). LCMS: 247.1 (M+1)+.

Sources & evidence

ORD record
ord-9e17c4cf8b0a436c94b0f7760f4c757b
Source dataset
uspto-grants-2015_05
Patent number
US09034900B2

Reaction notes

Loading…