Diisobutylaluminum hydride → N-(3-{2-[8-(aminomethyl)-1,4-dioxaspiro[4.5]dec-8-yl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Diisobutylaluminum hydride (1M in Hexanes, 0.239 ml, 0.239 mmol, 1.2 equiv) was added to a solution of 8-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1,3-thiazol-2-yl]-1,4-dioxaspiro[4.5]decane-8-carbonitrile (100 mg, 0.20 mmol) at −10° C. and the resulting cloudy mixture was stirred at −10° C. for 1 h. A second addition of DIBAL (1M in Hexanes, 0.239 ml, 0.239 mmol, 1.2 equiv) was made at −10° C. and the reaction was allowed to slowly warm to 23° C. and then stir for 4 days. The reaction was quenched with 1:1:3 mixture of water:aqueous 6N NaOH and the particulate matter was removed via filtration. The remaining filtrate was partitioned between EtOAc (2×55 ml) and water (65 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford N-(3-{2-[8-(aminomethyl)-1,4-dioxaspiro[4.5]dec-8-yl]-1,3-thiazol-5-yl}-5-methylphenyl)-4-(trifluoromethyl)pyrimidin-2-amine (39 mg, 39%), as an off-white solid. MS ESI: [M+H]+ m/z 506.1. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=4.6 Hz, 1H), 7.93 (s, 1H), 7.45 (bs, 1H), 7.28 (s, 1H), 7.08-7.04 (m, 2H), 4.06-3.95 (m, 6H), 2.51-2.35 (m, 7H), 1.95-1.71 (m, 4H).

1. customwas made at −10° C.
2. temperatureto slowly warm to 23° C.
3. stirringstir for 4 days
4. customThe reaction was quenched with 1:1:3 mixture of water
5. customaqueous 6N NaOH and the particulate matter was removed via filtration
6. customThe remaining filtrate was partitioned between EtOAc (2×55 ml) and water (65 ml)
7. dry with materialThe combined organic layers were dried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated

ORD 기록

ord-95c07d92ce4c48b4b2aaf8d36ed99816

출처 데이터셋

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08551984B2