Pyridine → (R)-N-(2-(benzyl(2-hydroxypropyl)amino)-6-bromopyridin-3-yl)acetamide

HRID 1485683Notes

Reaction equation

[C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C:9]1[C:10]([N:16]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:17][C@H:18]([OH:20])[CH3:19])=[N:11][C:12]([Br:15])=[CH:13][CH:14]=1.N1C=CC=CC=1>ClCCl>[CH2:21]([N:16]([CH2:17][C@H:18]([OH:20])[CH3:19])[C:10]1[C:9]([NH:8][C:1](=[O:3])[CH3:2])=[CH:14][CH:13]=[C:12]([Br:15])[N:11]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 40 °C

Procedure

Acetic anhydride (0.623 mL, 6.60 mmol) was added to a solution of crude (R)-1-((3-amino-6-bromopyridin-2-yl)(benzyl)amino)propan-2-ol (2.22 g, 6.60 mmol) and pyridine (1.60 mL, 19.8 mmol) in dichloromethane (60 mL). The reaction mixture was then heated to 40° C. for 39 h. The reaction mixture was concentrated under reduced pressure. The crude residue was dissolved in toluene (ca. 100 mL), which was then concentrated under reduced pressure in order to remove residual pyridine. The crude product was purified by column chromatography on silica gel (eluting with 2:1 dichloromethane-ethyl acetate followed by 3:2 dichloromethane-ethyl acetate) to afford (R)-N-(2-(benzyl(2-hydroxypropyl)amino)-6-bromopyridin-3-yl)acetamide (1.39 g, 56% yield). MS (ESI, pos. ion) m/z 378, 380 [M+1]+.

Workup

concentrationThe reaction mixture was concentrated under reduced pressure
dissolutionThe crude residue was dissolved in toluene (ca. 100 mL)
concentrationwhich was then concentrated under reduced pressure in order
customto remove residual pyridine
customThe crude product was purified by column chromatography on silica gel (eluting with 2:1 dichloromethane-ethyl acetate followed by 3:2 dichloromethane-ethyl acetate)

Sources & evidence

ORD record: ord-6b68f2f81ee04a288111d4457ad374e6
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09422281B2

Reaction notes

Loading…