N-(5-bromo-2-methylphenyl)-2,2,2-trifluoroacetamide

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Starting from 5-(3-ethoxy-4-iodo-5-methoxymethoxy-benzyl)-pyrimidine-2,4-diamine (2.11 g; 4,9 mmol) and N-(5-bromo-2-methyl-phenyl)-2,2,2-trifluoro-acetamide (prepared from 5-bromo-2-methyl-aniline analogously to example 41) (2.3 g; 8.17 mmol), 0.963 g (30%) 3′-amino-4-(2,4-diamino-pyrimidin-5-ylmethyl)-6-ethoxy-4′-methyl-biphenyl-2-ol is obtained as a beige powder after Suzuki coupling (in situ generation of R2—B(OH)2) and splitting off of the protective group under acid conditions.

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of N-(5-bromo-2-methylphenyl)-2,2,2-trifluoroacetamide (15 g, 54 mmol) in THF (300 mL) was added Pd(PPh3)2Cl2 (3.79 g, 5.4 mmol), CuI (513 mg, 2.7 mmol) and TEA (23 mL, 162 mmol). The solution was heated to 60° C. A solution of trimethylsilylacetylene (11.5 mL, 81 mmol) in THF (200 mL) was added dropwise through an addition funnel over about 60 min. After 16 h, the reaction was concentrated onto silica gel and purified by column chromatography to give the desired product (10.92 g, 67%). 1H NMR (400 MHz, d6-DMSO) δ 10.97 (s, 1H), 7.35-7.30 (m, 3H), 2.18 (S, 3H), 0.21 (s, 9H) ppm. the reaction was concentrated onto silica gel purified by column chromatography