反応 #964988

反応方程式

(3S,4S)-tert-butyl 3-((3-carbamoyl-6-ethynylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

azidobenzene

→

title compound

収率 44.3%

(3S,4S)-tert-butyl 3-((3-carbamoyl-6-(1-phenyl-1H-1,2,3-triazol-4-yl)pyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate

収率 44.3%

溶媒

toluene

DMF

反応条件

後処理

1. 1
   その他The flask was purged with nitrogen
2. 2
   温度warmed to 95° C
3. 3
   workup.STIRRINGAfter stirring over two nights
4. 4
   温度the reaction was cooled to room temperature
5. 5
   その他The volatiles were removed in vacuo
6. 6
   workup.ADDITIONthe residue was diluted with 3 mL DMF
7. 7
   その他purified by via preparative HPLC with the following conditions
8. 8
   workup.WAITGradient: 30-100% B over 14 minutes
9. 9
   その他a 2-minute hold
10. 10
    workup.ADDITIONFractions containing the desired product
11. 11
    濃縮concentrated via centrifugal evaporation
12. 12
    その他to remove the methanol
13. 13
    その他was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
14. 14
    乾燥The organic layer was dried over sodium sulfate
15. 15
    ろ過Filtration and evaporation

実験手順

To a solution of (3S,4S)-tert-butyl 3-((3-carbamoyl-6-ethynylpyrrolo[1,2-b]pyridazin-4-yl)amino)-4-ethylpyrrolidine-1-carboxylate from Step 2 of Example 292 (71 mg, 0.179 mmol) in toluene (2 mL) and DMF (0.2 mL) was added azidobenzene (149 mg, 1.250 mmol). The flask was purged with nitrogen, and the reaction solution was stirred at room temperature for 1 hour, then warmed to 95° C. After stirring over two nights, the reaction was cooled to room temperature. The volatiles were removed in vacuo and the residue was diluted with 3 mL DMF and purified by via preparative HPLC with the following conditions: Column: Phenomenex Luna C18, 21.5×250 mm, 5-μm particles; Mobile Phase A: 10:90 methanol:water with 0.1% trifluoroacetic acid; Mobile Phase B: 90:10 methanol:water with 0.1% trifluoroacetic acid; Gradient: 30-100% B over 14 minutes, then a 2-minute hold at 100% B; Flow: 25 mL/min. Fractions containing the desired product were combined and concentrated via centrifugal evaporation to remove the methanol. The solution was neutralized with 1N NaOH, and was then partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was dried over sodium sulfate. Filtration and evaporation afforded the title compound (41 mg, 42% yield). MS (ES+) m/z: 517.1 (M+H); LC retention time: 3.385 min (analytical LCMS Method J).

出典