Tris(furan-2-yl)phosphane → Tert-butyl cyclopropyl(2-(3-(trifluoromethoxy)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)carbamate

温度

50 °C

Note: THF was degassed with a stream of N2 for 10 min. in a separate flask. Tert-butyl cyclopropyl(2-(methylthio)pyrazolo[1,5-a][1,3,5]triazin-4-yl)carbamate (100 mg, 0.31 mmol), 3-(trifluoromethoxy)phenyl boronic acid (154 mg, 0.74 mmol), tri(2-furyl)phosphine (86 mg, 0.37 mmol), copper(I) thiophene-2-carboxylate (167 mg, 0.88 mmol), Pd2 dba3 (24 mg, 0.03 mmol) were combined. The flask was evacuated and backfilled with N2. THF (3.7 mL) was added and the reaction was heated to 50° C. for 5 d. The solution was diluted with Et2O (40 mL) and washed with 10% NH4OH (3×30 mL). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The solid residue was triturated with Et2O and filtered. The filtrate was concentrated in vacuo and purified via flash column chromatography (2.5-5% EtOAc/hexanes) to afford tert-butyl cyclopropyl(2-(3-(trifluoromethoxy)phenyl)pyrazolo[1,5-a][1,3,5]triazin-4-yl)carbamate (116 mg, 85%). LCMS (ES): >95% pure, m/z 436 [M+1]+.

1. customTHF was degassed with a stream of N2 for 10 min. in a separate flask
2. customThe flask was evacuated
3. additionTHF (3.7 mL) was added
4. additionThe solution was diluted with Et2O (40 mL)
5. washwashed with 10% NH4OH (3×30 mL)
6. dry with materialThe organic layer was dried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe solid residue was triturated with Et2O
10. filtrationfiltered
11. concentrationThe filtrate was concentrated in vacuo
12. custompurified via flash column chromatography (2.5-5% EtOAc/hexanes)

ORDレコード

ord-4b1004a684d541d989077eab0c1c144c

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08575177B2