Reaction #41432

Reaction equation

(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

Solvents

NMP

2-Propanol

water

EtOAc

NMP

Conditions

Workup

1. 1
   Extractionextracted with EtOAc (2×10 mL)
2. 2
   Washthe organic solution was washed with brine
3. 3
   Dryingdried (Na2SO4)
4. 4
   Filtrationfiltered
5. 5
   Otherevaporated
6. 6
   Otherto give an oily residue
7. 7
   workup.STIRRINGthe solution was stirred at +40° C. for 1 h
8. 8
   OtherSolvents was removed by evaporation
9. 9
   OtherThe crude material was purified by HPLC, relevant fractions
10. 10
    Otherwas freezedried

Procedure

(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%)

Source