2-Bromopyridine → N-[(4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methyl]pyridin-2-amine

1-(4-{4-[(1-isopropylazetidin-3-yl)methoxy]phenyl}tetrahydro-2H-pyran-4-yl)methanamine was stirred with 2-bromopyridine (60 μl, 0.63 mmol), tris(dibenzylideneacetone)dipalladium(0) (15 mg, 0.018 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (19 mg, 0.036 mmol) and sodium tert-butoxide (90 mg, 0.94 mmol) and heated at 80° C. in toluene (5 ml) for 3 hours under nitrogen. The reaction mixture was partitioned between aqueous sodium hydroxide (50 ml) and ethyl acetate (80 ml). The organics were dried over Na2SO4, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 90:10:1 by volume) to give the product which required further purification by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 94:6:0.6 by volume) to give a pale yellow oil which crystallized on standing, this was triturated with diethyl ether (2 ml) to give the title compound as a pale yellow powder (65 mg, 26%). 1H NMR (400 MHz, CDCl3) δ 8.02 (d, 1H), 7.31 (t, 1H), 7.25 (d, 2H), 6.91 (d, 2H), 6.50 (t, 1H), 6.20 (d, 1H), 4.09 (d, 2H), 3.99 (t, 1H), 3.82 (m, 2H), 3.59 (m, 2H), 3.48 (d, 2H), 3.45 (m, 2H), 3.03 (m, 2H), 2.88 (m, 1H), 2.33 (m, 1H), 2.13 (m, 2H), 1.92 (m, 2H), 0.93 (d, 6H). LRMS ESI+ m/z 396 [M+H]+. HRMS ESI+ m/z 396.2639 [M+H]+.

1. customThe reaction mixture was partitioned between aqueous sodium hydroxide (50 ml) and ethyl acetate (80 ml)
2. dry with materialThe organics were dried over Na2SO4
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe crude product was purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (97:3:0.3 to 90:10:1 by volume)
6. customto give the product which
7. custompurification by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (96:4:0.4 to 94:6:0.6 by volume)
8. customto give a pale yellow oil which
9. customcrystallized
10. customthis was triturated with diethyl ether (2 ml)

ORD 기록

ord-abf41b8f050c4b768eb906c2e9dfc45f

출처 데이터셋

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07456164B2