Reaktion #45050

Reaktionsgleichung

NaHMDS

NaHMDS

tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate

methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate

→

title compound

Ausbeute 0.6%

N-[5-[2-(3,5-Dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxamide

Ausbeute 0.6%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturto reflux for 90 min
3. 3
   Temperaturcooled to room temperature
4. 4
   workup.STIRRINGthe mixture stirred for 70 mins
5. 5
   workup.WAITto stand for 96 h
6. 6
   Sonstigepartitioned between ethyl acetate and 2.0M aqueous hydrochloric acid
7. 7
   SonstigeThe aqueous layer was separated
8. 8
   Extraktionextracted with ethyl acetate (75 mL)
9. 9
   WaschenThe organic layer was washed with saturated brine (50 mL)
10. 10
    Trocknendried over MgSO4
11. 11
    Filtrationfiltered
12. 12
    Sonstigeevaporated
13. 13
    Sonstigeto afford crude product
14. 14
    SonstigeThe crude product was purified by preparative LCMS
15. 15
    workup.ADDITIONFractions containing the desired compound
16. 16
    Sonstigewere evaporated to dryness

Vorschrift

A solution of NaHMDS (2.100 ml, 2.10 mmol) in THF (1.0M) was added to a stirred solution of tert-butyl 5-amino-3-[2-(3,5-dimethoxyphenyl)ethyl]-1H-pyrazole-1-carboxylate (0.486 g, 1.4 mmol) and methyl 2-(4-methylpiperazin-1-yl)pyrimidine-5-carboxylate (0.397 g, 1.68 mmol) in THF (7.00 ml, cooled to −20° C.), over a period of 5 mins under nitrogen. The resulting solution was stirred at room temperature for 18 h. The mixture was heated to reflux for 90 min, then cooled to room temperature. More NaHMDS (2.100 ml, 2.10 mmol) was added and the mixture stirred for 70 mins. The mixture was allowed to stand for 96 h and then partitioned between ethyl acetate and 2.0M aqueous hydrochloric acid. The aqueous layer was separated and basified with 50% aqueous sodium hydroxide solution and then extracted with ethyl acetate (75 mL). The organic layer was washed with saturated brine (50 mL) and then dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by preparative LCMS using decreasingly polar mixtures of water (containing 1% ammonia) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford the title compound (4.00 mg, 0.633%) as a white solid; 1H NMR (500.13 MHz, DMSO-d6, CD3CO2D) δ 2.34 (3H, s), 2.53 (4H, t), 2.90 (4H, t), 3.74 (6H, s), 3.89 (4H, t), 6.33 (1H, t), 6.35 (1H, s), 6.42 (2H, d), 8.89 (2H, s)

Quelle