Triethylamine → N-(4-(4-Ethylaminopyrimidin-6-yl-oxy)-phenyl)-N'[(R)-5-bromo-indan-2-yl]-urea

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Reaction Steps

A solution of triphosgene (117 mg, 0.393 mmol) in CH2Cl2 (12 ml) under N2-atmosphere is cooled by an ice bath. A solution of [(R)-5-bromo-indan-2-yl-amine (250 mg, 1.178 mmol; preparation see Adv. Synth. Catal. 2001, 343, 461) and NEt3 (164 μl; 1.177 mmol) in CH2Cl2 (10 ml) is added dropwise, the dropping funnel rinsed with CH2Cl2 (2 ml) and the resulting suspension stirred for 60 min at rt. Then a solution of 4-(4-ethylaminopyrimidin-6-yl-oxy)-aniline (258 mg, 1.12 mmol) and NEt3 (164 μl; 1.177 mmol) in CH2Cl2 (10 ml) is added dropwise and the dropping funnel rinsed with CH2Cl2 (2 ml). A brown solution is formed, which is stirred for 16 h at rt. SiO2 is then added to the resulting mixture. After concentration in vacuo, the powder is put on top of a MPLC column (SiO2). Eluation with SiO2/AcOEt 4:1→AcOEt, partial concentration and filtration of the crystallized material yields the title compound: m.p.: 247° C.; 1H-NMR (DMSO-d6): 8.33 (s, 1H), 8.06 (s, 1H), 7.43 (s, 1H), 7.36 (d, 2H), 7.30 (m, 1H), 7.26 (t, 1H), 7.19 (d, 1H), 6.96 (d, 2H), 6.43 (d, 1H), 5.63 (s, 1H), 4.40 (m, 1H), 3.2 (m, 4H), 2.75 (AB×d, 2H), 1.07 (t, 3H); Anal.: CHNBr.

Provenance & Evidence