Ammonium Chloride → 5-[(2S)-1-methylpyrrolidin-2-yl]pyridin-2-amine

温度

90 °C

In a 75 mL sealed tube, (S)-2-chloro-5-(1-methylpyrrolidin-2-yl)pyridine (622 mg, 3.16 mmol) and 2-(dicyclohexylphosphino)biphenyl (222 mg, 633 μmol) were combined with THF (15 ml) to give a light yellow solution. The solution was degassed with argon. Tris(dibenzylideneacetone)dipalladium (0) (290 mg, 316 μmol) was added. LiHMDS (9.49 ml of 1M solution in THF, 9.49 mmol) was added. The reaction was placed under an argon atmosphere and sealed. The reaction mixture was heated to 90° C. and stirred for 15 h. Reaction was complete by tlc. The reaction mixture was cooled to room temperature and diluted with EtOAc. The reaction mixture was poured into 150 mL sat NH4Cl and extracted with EtOAc (4×75 mL). The organic layers were dried over MgSO4 and concentrated in vacuo. The crude material was purified by flash chromatography with stepwise gradient (silica gel, 40 g, 10% to 50% (60:10:1 CH2Cl2:methanol: NH4OH)/CH2Cl2) gradient to afford the desired product (560 mg, 99%). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.57-2.03 (m, 3H) 2.04-2.39 (m and overlapping s, 5H) 2.92 (t, J=8.12 Hz, 1H) 3.14-3.29 (m, 1H) 4.40 (br. s., 2H) 6.51 (d, J=8.69 Hz, 1H) 7.47 (dd, J=8.31, 2.27 Hz, 1H) 7.95 (d, J=2.27 Hz, 1H)

1. customIn a 75 mL sealed tube
2. customto give a light yellow solution
3. customThe solution was degassed with argon
4. customsealed
5. customReaction
6. temperatureThe reaction mixture was cooled to room temperature
7. additionThe reaction mixture was poured into 150 mL
8. extractionextracted with EtOAc (4×75 mL)
9. dry with materialThe organic layers were dried over MgSO4
10. concentrationconcentrated in vacuo
11. customThe crude material was purified by flash chromatography with stepwise gradient (silica gel, 40 g, 10% to 50% (60:10:1 CH2Cl2:methanol: NH4OH)/CH2Cl2) gradient

ORDレコード

ord-308582f2a7184d62b4773bc5b0496651

出典データセット

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08481540B2