Cesium carbonate → tert-butyl (1S,2R)-2-(5-(5-bromo-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate

温度

85 °C

Dioxane (25 ml) was added to a nitrogen purged flask containing tert-butyl (1S,2R)-2-(5-bromo-6-cyanopyridin-3-ylamino)cyclohexylcarbamate (PrepEx 1.1) (2500 mg, 6.32 mmol), 5-bromo-6-methylpyridin-2-amine (1540 mg, 8.22 mmol), Xantphos (732 mg, 1.27 mmol), Pd2(dba)3 (579 mg, 0.632 mmol) and cesium carbonate (3090 mg, 9.49 mmol). Nitrogen was bubbled through the reaction mixture for 5 minutes, and the reaction mixture was heated at 85° C. for 4.5 hours. The reaction was then cooled to room temperature and poured into 10% aq. KHSO4 (300 mL). The pH was adjusted to 4 with 10% aq. KHSO4, and the mixture was sonicated. The solids were collected by filtration, dried under nitrogen, and diluted with DCM (50 mL). Sonication of the resulting suspension afforded a thick slurry. The solids were collected by filtration, and washed with DCM (10 mL) and hexanes (20 mL) to afford tert-butyl (1S,2R)-2-(5-(5-bromo-6-methylpyridin-2-ylamino)-6-cyanopyridin-3-ylamino)cyclohexylcarbamate. MS ESI calc'd. for C23H30BrN6O2 [M+H]+ 501 and 503 found 501 and 503. 1H NMR (500 MHz, CD3OD) δ 7.78 (s, 1H), 7.73-7.71 (m, 2H), 7.75 (d, J=8.8 Hz, 1H), 3.85 (br s, 1H), 3.75 (br s, 1H), 2.54 (s, 3H), 1.90-1.10 (m, 8H), 1.34 (s, 9H).

1. customNitrogen was bubbled through the reaction mixture for 5 minutes
2. temperatureThe reaction was then cooled to room temperature
3. additionpoured into 10% aq. KHSO4 (300 mL)
4. customthe mixture was sonicated
5. filtrationThe solids were collected by filtration
6. customdried under nitrogen
7. additiondiluted with DCM (50 mL)
8. customSonication of the resulting suspension
9. customafforded a thick slurry
10. filtrationThe solids were collected by filtration
11. washwashed with DCM (10 mL) and hexanes (20 mL)

ORDレコード

ord-ce4c20558eee47a4b2cc9549b6dce431

出典データセット

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09216173B2