Reaction #10506

Reaction equation

KO-tBu

4-bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine

→

title compound

Yield 61.2%

5-Bromo-2-[2-(2-(R)-methyl-pyrrolidin-1-yl)-ethyl]-1H-indole

Yield 61.2%

Solvents

NMP

NMP

Conditions

Workup

1. 1
   TemperatureTo a cooled
2. 2
   Otherthe temperature below 5° C
3. 3
   Otherwas consumed
4. 4
   workup.ADDITIONH2O (400 mL) was added slowly to the reaction mixture
5. 5
   workup.ADDITIONfollowed by addition of IPAc (500 mL)
6. 6
   workup.STIRRINGThe resulting mixture was stirred for 5 min.
7. 7
   Otherthe organic layer was separated
8. 8
   WashThe organic layer was then washed with 20% brine (3×200 mL)
9. 9
   Dryingdried over Na2SO4
10. 10
    workup.ADDITIONtreated with activated carbon
11. 11
    FiltrationAfter filtration
12. 12
    Concentrationthe filtrate was concentrated under reduced pressure

Procedure

To a cooled (0° C.) suspension of KO-tBu (95%, 7.8 g, 66 mmol) in NMP (150 mL) was added a solution of 4-bromo-2-[4-(2-methyl-pyrrolidin-1-yl)-but-1-ynyl]-phenylamine (10 g, 33 mmol) in NMP (50 mL) dropwise keeping the temperature below 5° C. The resulting mixture was then stirred at room temperature for 3 hours under nitrogen. HPLC indicated that all the starting material was consumed. H2O (400 mL) was added slowly to the reaction mixture followed by addition of IPAc (500 mL). The resulting mixture was stirred for 5 min. and the organic layer was separated. The organic layer was then washed with 20% brine (3×200 mL), dried over Na2SO4 and treated with activated carbon. After filtration, the filtrate was concentrated under reduced pressure to give the title compound as a thick oil (6.2 g), which was used in the next coupling reaction without further purification. 1H NMR (400 MHz, CDCl3) δ 10.21 (s, 1H), 7.73 (s, 1H), 7.27 (s, 2H), 6.24 (s, 1H), 3.42–3.50 (m, 1H), 3.21–3.28 (m, 1H), 2.97–3.10 (m, 2H), 2.49–2.60 (m, 2H), 2.33 (q, J=8.78 Hz, 1H), 2.10–2.17 (m, 1H), 1.87–2.02 (m, 2H), 1.58–1.67 (m, 1H), 1.24 (d, J=6.2 Hz, 3H). 13C NMR (400 MHz, CDCl3) δ 140.89, 133.92, 129.91, 122.98, 121.77, 112.16, 111.75, 98.32, 60.47, 53.60, 53.34, 33.19, 26.30, 22.14, 19.56. [M+H]+ at m/z 307.

Source