3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine → HCID 59371473、化合物

To a solution of 3-bromo-5-[[1-(tert-butoxycarbonyl)-2(R)-pyrrolidinyl]methoxy]pyridine (147 mg, 0.41 mmol) and 4-[2-(3-pyridylmethoxy)ethyl]piperidine (99.8 mg, 0.45 mmol, 1.1 equiv.) in anhydrous toluene (2 mL) were added successively potassium tert-butoxide (75 mg, 0.61 mmol, 1.5 equiv.), tris(dibenzylideneacetone)dipalladium(0) (7.5 mg, 8.0 μmol, 0.02 equiv.), and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos; 14.3 mg, 24 μmol, 0.06 equiv.). The mixture was degassed and purged with Ar (3 cycles), then warmed by microwave irradiation under Ar. After reaction for 30-40 minutes at 130° C., the mixture was cooled to room temperature, diluted with EtOAc, and washed with brine. The solution was dried over Na2SO4 and evaporated, and the residue was purified by CC (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1). The product (182 mg, 89%) was obtained as a pale yellow oil. 1H NMR (CDCl3, 400 MHz) δ 8.56 (br, 2H), 7.80 (m, 3H), 7.46 (m, 1H), 6.94 (m, 1H), 4.51 (s, 2H), 4.12 (m, 2H), 3.83 (m, 1H), 3.66 (m, 2H), 3.54 (m, 2H), 3.39 (m, 2H), 2.76 (t, 2H, J=11.2 Hz), 2.01-1.80 (m, 5H), 1.63 (m, 4H), 1.46 (s, 9H), 1.33 (m, 2H).

1. customThe mixture was degassed
2. custompurged with Ar (3 cycles)
3. temperaturewarmed by microwave irradiation under Ar
4. customAfter reaction for 30-40 minutes at 130° C.
5. washwashed with brine
6. dry with materialThe solution was dried over Na2SO4
7. customevaporated
8. customthe residue was purified by CC (SiO2, CH2Cl2/EtOAc 4:1 followed by CH2Cl2/MeOH 10:1)

ORDレコード

ord-9d94b420c43f45bd9b201bd49d954072

出典データセット

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08445684B2