2,4-Dichlorobenzoic Acid → 7-[(2,4-Dichlorophenyl)carbonyl]-3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine

HATU (274 mg, 0.720 mmol) and DIPEA (0.252 ml, 1.441 mmol) were added to a colourless solution of 2,4-dichlorobenzoic acid (I38 mg, 0.720 mmol, commercially available) in N,N-dimethylformamide (DMF) (4.718 ml). The mixture was stirred at RT for 15 minutes. 3-(1,2,4-thiadiazol-5-yl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyrazine (I115) (100 mg, 0.480 mmol) was added and the reaction mixture was stirred at RT for 18 h. The mixture was diluted in diethyl ether (100 mL) and washed with water (25 mL). The aqueous layer was extracted with diethyl ether (2×50 mL) and DCM (2×50 mL). The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The crude product (brown liquid, 329.0 mg) was purified by flash chromatography (10 g SNAP, 0-100% ethyl acetate in hexane, 12 CV). The obtained oil residue was triturated with hexane. The product was diluted in DCM (100 mL) and washed with brine (3×25 mL). The resulting organic layer was dried over MgSO4 and concentrated under reduced pressure. The obtained product was dried at 50° C. under vacuum 3 days to afford the desired product in 62.05 mg as a white foam.

1. stirringthe reaction mixture was stirred at RT for 18 h
2. washwashed with water (25 mL)
3. extractionThe aqueous layer was extracted with diethyl ether (2×50 mL) and DCM (2×50 mL)
4. dry with materialThe combined organic layers were dried over MgSO4
5. concentrationconcentrated under reduced pressure
6. customThe crude product (brown liquid, 329.0 mg) was purified by flash chromatography (10 g SNAP, 0-100% ethyl acetate in hexane, 12 CV)
7. customThe obtained oil residue was triturated with hexane
8. additionThe product was diluted in DCM (100 mL)
9. washwashed with brine (3×25 mL)
10. dry with materialThe resulting organic layer was dried over MgSO4
11. concentrationconcentrated under reduced pressure
12. customThe obtained product was dried at 50° C. under vacuum 3 days

ORD 기록

ord-c775332af83b4f62af1362e8b1706ea2

출처 데이터셋

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08501946B2