Reacción #2358581

Ecuación de reacción

(S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid

(S)-2-amino-4-methylpentanamide

DIEA

HBTU

→

N—((S)-1-amino-4-methyl-1-oxopentan-2-yl)-4-((S)-1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothen partitioned between 50 mL EtOAc and 50 mL brine
2. 2
   SecadoThe organics were dried over Na2SO4
3. 3
   Filtraciónfiltered
4. 4
   Concentraciónconcentrated in vacuo
5. 5
   OtroThe residue was chromatographed over silica gel eluting with 25-75% acetone in hexanes
6. 6
   OtroThe product fractions were isolated
7. 7
   Otroevaporated in vacuo
8. 8
   OtroThe residue was triturated with 5 mL 50% EtOAc/hexanes
9. 9
   Filtraciónfiltered
10. 10
    Lavadorinsed with additional 50% EtOAc/hexanes
11. 11
    OtroThe solid was dried under vacuum at 50° C.

Procedimiento

To a solution of (S)-4-(1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinic acid (assume 0.44 mmol) in DMF (5 mL) was added (S)-2-amino-4-methylpentanamide (0.074 g, 0.44 mmol), DIEA (0.20 mL, 1.1 mmol) and HBTU (0.201 g, 0.53 mmol). The reaction was stirred overnight then partitioned between 50 mL EtOAc and 50 mL brine. The organics were dried over Na2SO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel eluting with 25-75% acetone in hexanes. The product fractions were isolated and evaporated in vacuo. The residue was triturated with 5 mL 50% EtOAc/hexanes, filtered and rinsed with additional 50% EtOAc/hexanes. The solid was dried under vacuum at 50° C. to yield N—((S)-1-amino-4-methyl-1-oxopentan-2-yl)-4-((S)-1,2-dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamide (compound 63) as an off-white powder (0.105 g, 0.22 mmol, 50% yield, LC/MS: m/z=482.2 [M+H]+, 1H NMR (400 MHz, DMSO-d6): δ 8.64 (d, J=9.2 Hz, 1H), 8.20 (d, J=8.4 Hz, 2H), 8.05 (s, 1H), 8.00 (s, 1H), 7.62 (s, 1H), 7.32-7.24 (m, 2H), 7.21-7.11 (m, 5H), 5.63 (d, J=4.8 Hz, 1H), 4.88-4.82 (m, 1H), 4.76-4.69 (m, 1H), 4.62-4.53 (m, 1H), 3.63-3.49 (m, 2H), 1.76-1.56 (m, 3H), 0.96-0.89 (m, 6H).

Fuente