Reacción #163081

Ecuación de reacción

ether

(S)-3-(aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine

(S)-3-(Aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine

(S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid

HBTU

→

title compound

Rendimiento 26.2%

(S)-2-Amino-N-((6-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoro-2-((S)-1-(4-fluorophenyl)ethylamino)pyridin-3-yl)methyl)-3-methylbutanamide

Rendimiento 26.2%

Disolventes

MeOH

DCM

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe reaction was then quenched with a saturated aqueous solution of NaHCO3
2. 2
   Extracciónextracted with DCM (2×50 ml)
3. 3
   SecadoThe combined organic fractions were dried over Na2SO4
4. 4
   Filtraciónfiltered
5. 5
   Concentraciónconcentrated
6. 6
   workup.ADDITION4 M HCl in dioxane (1 ml) was then added
7. 7
   ConcentraciónThe reaction was then concentrated
8. 8
   Otroto give a solid which
9. 9
   workup.STIRRINGwith stirring
10. 10
    FiltraciónThe resulting solid was filtered
11. 11
    Lavadowashed with ether
12. 12
    Otrodried

Procedimiento

A solution of (S)-3-(aminomethyl)-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-5-fluoro-N2-(1-(4-fluorophenyl)ethyl)pyridine-2,6-diamine (Example 3; 0.10 g, 0.26 mmol), (S)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (0.06 g, 0.26 mmol), and HBTU (0.10 g, 0.26 mmol) in DCM (3 ml) was stirred at room temperature for 1 hour. The reaction was then quenched with a saturated aqueous solution of NaHCO3, and extracted with DCM (2×50 ml). The combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was then passed through a silica plug. The resulting foam was placed in dioxane (4 ml) and 4 M HCl in dioxane (1 ml) was then added, and the reaction was stirred for 3 hours. The reaction was then concentrated to give a solid which was dissolved in a minimal amount of MeOH (0.5 ml) with stirring, followed by fast addition of ether (50 ml). The resulting solid was filtered, washed with ether, and dried to give the title compound (0.033 g, 26%). 1H NMR (400 MHz, CD3OD) δ 7.58 (d, J=10.7 Hz, 1H), 7.49-7.46 (m, 2H), 7.07-7.02 (m, 2H), 5.80 (s, 1H), 5.09-5.04 (m, 1H), 4.58 (dd, J=15.4, 6.8 Hz, 1H), 4.26 (dd, J=15.4, 5.2 Hz, 1H), 3.71 (d, J=6.0 Hz, 1H), 2.23-2.18 (m, 1H), 2.01-1.97 (m, 1H), 1.63 (d, J=6.8 Hz, 3H), 1.19-1.13 (m, 2H), 1.05-1.03 (m, 6H), 0.85-0.81 (m, 2H). MS: Calcd.: 483. Found: [M+H]+ 484.

Fuente