反応 #41431

反応方程式

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

1-methylcyclopropanecarboxylic acid

HATU

DIPEA

→

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

溶媒

NMP

water

NMP

反応条件

後処理

1. 1
   その他had formed
2. 2
   抽出extracted with EtOAc (2×10 mL)
3. 3
   洗浄the organic phases was then washed with brine
4. 4
   乾燥dried over Na2SO4
5. 5
   ろ過filtered
6. 6
   その他evaporated
7. 7
   その他The remaining oily residue was purified by HPLC
8. 8
   workup.ADDITIONFractions containing product
9. 9
   その他was freezedried

実験手順

1-methylcyclopropanecarboxylic acid (39 mg, 0.39 mmol), HATU (150 mg, 0.39 mmol) and DIPEA (170 μl, 0.97 mmol) in NMP (2 mL) was stirred at r.t. for 5 min until a solution had formed. To this solution was added (1R,2S)-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). The reaction mixture was stirred for 2 h at r.t. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (2×10 mL), the organic phases was then washed with brine, dried over Na2SO4, filtered and evaporated. The remaining oily residue was purified by HPLC. Fractions containing product was freezedried. Yield 68 mg (55%10).

出典