Yield:5305-40-8 95%

Reaction Conditions:

Stage #1:N,N-dimethyl-formamide with trichlorophosphate at 0; for 1 h;
Stage #2:4,6-pyrimidinediol at 20; for 0.5 h;

Steps:

1.a
EXAMPLE 1; 4-[6-Amino-5-(methoxyimino-methyl)-pyrimidin-4-yl]-piperazine-l-carboxylic acid (4-isopropoxy-phenyl)-amidea. 4,6-Dichloro-pyrimidine-5-carbaldehyde; A mixture of DMF (3.2 mL) and POCl₃ (10 mL) at 0 ⁰C was stirred for 1 h, treated with 4,6-dihydroxypyrimidine (2.5 g, 22.3 mmol), and stirred for 0.5 h at ambient EPO temperature. The heterogeneous mixture was heated at reflux for 3 h and the volatiles were removed at reduced pressure. The residue was poured into ice water and extracted six times with ethyl ether. The organic phase was washed with aqueous NaHCO₃, dried over Na₂SO₄ and concentrated to afford a yellow solid (3.7 g, 95%). ¹H NMR (CDCl₃) δ 10.46 (s, IH), 8.90 (s, IH).

References:

JANSSEN PHARMACEUTICA N.V. WO2006/135719, 2006, A1 Location in patent:Page/Page column 46-47

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