Sodium Hydroxide → 11-Bromo-6-chloro-15-oxa-2,4,8,25-tetraazatetracyclo[17.3.1.1(3,7).1(10,14)]pentacosa-1(23),3(25),4,6,10(24),11,13,19,21-nonaene

温度

35 °C

To a solution of 4-bromo-3-{[(2-{[3-(3-bromopropyl)phenyl]amino}-5-chloropyrimidin-4-yl)amino]methyl}phenol (1.00 g, 1.90 mmol) in tetrahydrofuran (9.0 mL) was added a solution of sodium hydroxide in water (18 mL, 4.0 M). The resultant solution was then treated with benzyltriethylammonium chloride (30.0 mg, 0.13 mmol) and heated at 35° C. for 40 hours. The reaction mixture could not be purified by silica gel column chromatography or prep-HPLC. However, after cooling, THF and alkaline NaOH layers could be separated. THF layer was washed with brine and concentrated to give a light yellow solid residue, which was triturated with MeOH/EtOAc (90:10). After vacuum filtration, the cake was washed with MeOH to provide the desired pure product (300 mg, 35%) as an off-white powder. LCMS for C20H18BrClN4O (M+H)+: m/z=444.9, 446.9. 1H NMR (400 MHz, DMSO-d6): δ 8.76 (s, 1H), 7.86 (s, 1H), 7.50 (s, 1H), 7.31 (d, J=8.8 Hz, 1H), 7.27 (m, 1H), 7.16 (m, 1H), 7.04 (m, 2H), 6.68 (m, 1H), 6.20 (m, 1H), 4.23 (m, 2H), 4.02 (t, 2H), 3.15 (m, 1H), 2.65 (m, 2H), 1.96 (m, 2H).

1. customThe reaction mixture could not be purified by silica gel column chromatography
2. temperatureHowever, after cooling
3. customTHF and alkaline NaOH layers could be separated
4. washTHF layer was washed with brine
5. concentrationconcentrated
6. customto give a light yellow solid residue, which
7. customwas triturated with MeOH/EtOAc (90:10)
8. filtrationAfter vacuum filtration
9. washthe cake was washed with MeOH

ORDレコード

ord-c27a294af5b54e56b22dbc055e0c7d9e

出典データセット

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08765727B2