Propionyl chloride → 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-propanoyl-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Under nitrogen, a mixture of 4-[4-(1-benzofuran-5-yl)phenyl]-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (116 mg, 0.292 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.88 mmol) in dichloromethane (1.3 mL) was stirred at room temperature for 2 min. The mixture was cooled to 0° C. and treated with propionyl chloride (0.026 mL, 0.292 mmol) dropwise by syringe. The mixture became a dark brown solution and the reaction was stirred at 0° C. for 90 min. The reaction was quenched with water (2 mL) and diluted with ethyl acetate (20 mL). The mixture was transferred to a separatory funnel, water (10 mL) was added and the layers were separated. The pH of the aqueous layer was tested by pH paper and found to be pH˜5-6. The aqueous layer was extracted with ethyl acetate (10 mL). The organic layers were combined, dried over magnesium sulfate and concentrated in vacuo to give a tan foamy solid. Purification of the residue by silica gel chromatography (Analogix IF280, SF10-4 g, 0-10% MeOH/EtOAc, 30 min) provided the title product as an ivory solid (74 mg, 61%). MS(ES)+ m/e 417.2 [M+H]+.

1. temperatureThe mixture was cooled to 0° C.
2. stirringthe reaction was stirred at 0° C. for 90 min
3. customThe reaction was quenched with water (2 mL)
4. additiondiluted with ethyl acetate (20 mL)
5. customThe mixture was transferred to a separatory funnel
6. additionwater (10 mL) was added
7. customthe layers were separated
8. extractionThe aqueous layer was extracted with ethyl acetate (10 mL)
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated in vacuo
11. customto give a tan foamy solid
12. customPurification of the residue by silica gel chromatography (Analogix IF280, SF10-4 g, 0-10% MeOH/EtOAc, 30 min)

ORD-Eintrag

ord-6f93a3ef72bd4099a42d75c4d632099b

Quelldatensatz

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08802864B2