反応 #2358582

反応方程式

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

(S)-2-aminosuccinamide

DIEA

HBTU

→

2-(4-((S)-1,2-Dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamido)succinamide

収率 59.0%

溶媒

DMF

反応条件

後処理

1. 1
   その他then partitioned between 50 mL EtOAc and 50 mL brine
2. 2
   抽出The aqueous layer was extracted once more with 25 mL EtOAc
3. 3
   乾燥The organics were dried over Na2SO4
4. 4
   ろ過filtered
5. 5
   その他evaporated in vacuo
6. 6
   その他The residue was crystallized from 4 mL
7. 7
   温度warm acetone
8. 8
   ろ過the solid filtered off
9. 9
   洗浄rinsed with additional acetone
10. 10
    その他dried under vacuum at 50° C.

実験手順

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-aminosuccinamide (0.076 g, 0.45 mmol), DIEA (0.20 mL, 1.1 mmol) and HBTU (0.203 g, 0.54 mmol). The reaction was stirred overnight then partitioned between 50 mL EtOAc and 50 mL brine. The aqueous layer was extracted once more with 25 mL EtOAc and combined. The organics were dried over Na2SO4, filtered and evaporated in vacuo. The residue was crystallized from 4 mL warm acetone, the solid filtered off, rinsed with additional acetone and dried under vacuum at 50° C. to yield the product S)-2-(4-((S)-1,2-Dihydroxyethyl)-6-(4-(4-fluorophenoxy)phenyl)picolinamido)succinamide as a light tan powder (0.125 g, 0.26 mmol, 59% yield, LC/MS: m/z=483.1 [M+H]+, 1H NMR (400 MHz, DMSO-d6): δ 9.29 (d, J=8.4 Hz, 1H), 8.25 (d, J=8.8 Hz, 2H), 8.06 (s, 1H), 7.99 (s, 1H), 7.48 (s, 1H), 7.40 (s, 1H), 7.32-7.25 (m, 2H), 7.21-7.15 (m, 2H), 7.14-7.07 (m, 3H), 6.99 (s, 1H), 5.64 (d, J=4.8 Hz, 1H), 4.85 (t, J=6.0 Hz, 1H), 4.75-4.64 (m, 2H), 3.62-3.49 (m, 2H), 2.79-2.70 (m, 1H), 2.61-2.53 (m, 1H).

出典