Реакция #1128059

Уравнение реакции

2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide

7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one

DL-10-Camphorsulfonic acid

→

2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide

Выход 56.1%

Растворители

isopropanol

Условия реакции

Обработка

1. 1
   ДругоеMicrowaved
2. 2
   Другоеreaction at 120° C. for 30 minutes
3. 3
   ДругоеEvaporated off solvent
4. 4
   workup.DISSOLUTIONdissolved residue in methylene chloride
5. 5
   Промывкаwashed with saturated sodium bicarbonate solution
6. 6
   СушкаDried with magnesium sulfate
7. 7
   Фильтрацияfiltered
8. 8
   Другоеpurified with normal phase chromatography
9. 9
   Промывкаeluting with hexane/ethyl acetate

Методика

Combined 2-(2,5-Dichloro-pyrimidin-4-ylamino)-3-fluoro-N-methyl-benzamide (77 mg, 0.244 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (60 mg, 0.258 mmol), DL-10-Camphorsulfonic acid (70 mg, 0.301 mmol) and isopropanol (4 mL) in a microwave tube. Microwaved reaction at 120° C. for 30 minutes. Evaporated off solvent, dissolved residue in methylene chloride and washed with saturated sodium bicarbonate solution, then brine. Dried with magnesium sulfate, filtered and purified with normal phase chromatography eluting with hexane/ethyl acetate to yield a yellow solid, 2-[5-Chloro-2-(1-ethyl-5,5-dimethyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-7-ylamino)-pyrimidin-4-ylamino]-3-fluoro-N-methyl-benzamide (70 mg, 56%). LCMS: m/z=511.11 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.98 (s, 1H), 8.07 (s, 1H), 7.59 (d, 1H, J=8.6 Hz), 7.52 (s, 1H), 7.37 (d, 1H, J=6.8 Hz), 7.24 (m, 1H), 7.10 (s, 1H), 6.97 (d, 1H, J=8.8 Hz), 6.80 (d, 1H, J=3.8 Hz), 3.72 (m, 2H), 2.91 (d, 3H, J=4.3 Hz), 2.14 (m, 2H), 1.87 (m, 2H), 1.25 (m, 3H), 1.18 (s, 6H).

Источник