N-(2-Fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester → 7-(2-Fluoro-4-iodo-phenylamino)-pyrrolo[1,2-c]pyrimidine-6-carboxylic acid ethyl ester
Reaction equation
[CH2:1]([O:3][C:4](=[O:24])[CH:5]([CH2:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][N:19]=1)[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=O)[CH3:2].O(Cl)Cl.[P+5]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:5]1[CH:17]=[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][N:19]2[C:6]=1[NH:8][C:9]1[CH:14]=[CH:13][C:12]([I:15])=[CH:11][C:10]=1[F:16])=[O:24])[CH3:2]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of N-(2-fluoro-4-iodo-phenyl)-2-pyrimidin-4-ylmethyl-malonamic acid ethyl ester (4 g, 9.02 mmol) in toluene (120 mL) was added phosphorous (V) oxychloride (4.2 mL, 45.1 mmol). The reaction was heated at reflux for 16 hours then concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (30 mL), washed with saturated aqueous sodium bicarbonate solution (20 mL) and the aqueous fraction extracted twice with ethyl acetate (2×10 mL). The combined organic fractions were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-40% ethyl acetate in cyclohexane) to yield a dark brown solid. The solid was triturated with ether (10 mL) to yield the title compound as a light brown solid (0.63 g, 16%). LCMS (Method B): RT=3.95 min, M+H+=426.