Reaktion #1128058

Reaktionsgleichung

3-Chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide

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

DL-10-Camphorsulfonic acid

→

3-Chloro-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]-N-methyl-benzamide

Ausbeute 10.3%

Lösungsmittel

2-methoxyethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturHeated
2. 2
   Sonstigereaction to 120° C. for 2.5 hours
3. 3
   SonstigeEvaporated off solvent
4. 4
   workup.DISSOLUTIONdissolved residue in methylene chloride
5. 5
   Waschenwashed with saturated sodium bicarbonate solution
6. 6
   TrocknenDried with magnesium sulfate
7. 7
   Filtrationfiltered
8. 8
   Sonstigepurified with normal phase chromatography

Vorschrift

Combined 3-Chloro-2-(2,5-dichloro-pyrimidin-4-ylamino)-N-methyl-benzamide (91 mg, 0.275 mmol), 7-Amino-1-ethyl-5,5-dimethyl-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (64 mg, 0.275 mmol), DL-10-Camphorsulfonic acid (82 mg, 0.353 mmol) and 2-methoxyethanol (3 mL). Heated reaction to 120° C. for 2.5 hours. 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 using basic alumina silica gel to yield a yellow solid, 3-Chloro-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]-N-methyl-benzamide (15 mg, 10%). LCMS: m/z=527.54 (M+H+), 1H NMR (400 MHz, CDCl3) δ 8.12 (d, 1H, J=1.0 Hz), 8.02 (br s, 1H), 7.59 (d, 1H, J=8.1 Hz), 7.51 (m, 2H), 7.28 (m, 1H), 7.21 (m, 2H), 7.02 (d, 1H, J=8.6 Hz), 6.25 (d, 1H, J=4.6 Hz), 4.13 (m, 2H), 3.76 (m, 2H), 2.82 (d, 3H, J=4.3 Hz), 2.22 (m, 2H), 1.27 (m, 9H).

Quelle