Reaction #41431

Reaction equation

(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

Solvents

NMP

water

NMP

Conditions

Workup

1. 1
   Otherhad formed
2. 2
   Extractionextracted with EtOAc (2×10 mL)
3. 3
   Washthe organic phases was then washed with brine
4. 4
   Dryingdried over Na2SO4
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   OtherThe remaining oily residue was purified by HPLC
8. 8
   workup.ADDITIONFractions containing product
9. 9
   Otherwas freezedried

Procedure

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).

Source