反応 #41432

反応方程式

(S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid

HATU

DIPEA

HCl

(1R,28)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

(1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine

→

title compound

(S)-N-((1R,2S)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-yl)pyrrolidine-2-carboxamide

溶媒

NMP

2-Propanol

water

EtOAc

NMP

反応条件

後処理

1. 1
   抽出extracted with EtOAc (2×10 mL)
2. 2
   洗浄the organic solution was washed with brine
3. 3
   乾燥dried (Na2SO4)
4. 4
   ろ過filtered
5. 5
   その他evaporated
6. 6
   その他to give an oily residue
7. 7
   workup.STIRRINGthe solution was stirred at +40° C. for 1 h
8. 8
   その他Solvents was removed by evaporation
9. 9
   その他The crude material was purified by HPLC, relevant fractions
10. 10
    その他was freezedried

実験手順

(1R,28)-1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1-(1-(4-fluorophenyl)-1H-indazol-5-yloxy)propan-2-amine (19a) (102 mg, 0.24 mmol) dissolved in NMP (1 mL) was added to a solution of (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (77 mg, 0.36 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (170 μl, 0.97 mmol) in NMP (2 mL). The mixture was stirred at r.t. for 1 h. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL), the organic solution was washed with brine, dried (Na2SO4), filtered and evaporated to give an oily residue. The obtained material was dissolved in EtOAc (20 mL) and treated with 5-6N HCl in 2-Propanol (5 mL), the solution was stirred at +40° C. for 1 h. Solvents was removed by evaporation. The crude material was purified by HPLC, relevant fractions was freezedried to give the title compound as a colourless solid. Yield 21 mg (16%)

出典