반응 #2148362

반응 방정식

(S)-2-methoxypropanoic acid

DIPEA

HATU

17

(E)-1-(3-(1,7-dimethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-methylphenyl)-2-hydroxyguanidine

17

(E)-1-(3-(1,7-dimethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-4-methylphenyl)-2-hydroxyguanidine

→

(S)-3-(5-(5-(1-methoxyethyl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one

용매

DMF

DMF

반응 조건

후처리

1. 1
   온도was heated at 100° C. for 3 h
2. 2
   온도Subsequently, the reaction was cooled to rt
3. 3
   기타partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL)
4. 4
   추출The aqueous layer was extracted with fresh EtOAc (2×20 mL)
5. 5
   건조The combined organic layers were dried over magnesium sulfate
6. 6
   여과filtered
7. 7
   기타The crude material was purified by flash column chromatography on silica with DCM/2% MeOH as eluant

실험 절차

To a solution of (S)-2-methoxypropanoic acid (40 mg, 0.4 mmol) in DMF (4 mL) were added DIPEA (65 μL, 0.4 mmol) and HATU (0.14 g, 0.4 mmol). After stirring at rt for 15 min, 17 (0.13 g, 0.4 mmol) was added as a solution in DMF (1 mL). The reaction was stirred at rt until complete consumption of 17 was determined by LC/MS and then was heated at 100° C. for 3 h. Subsequently, the reaction was cooled to rt, partitioned with EtOAc (30 mL) and 5% aq NaHCO3 (20 mL). The aqueous layer was extracted with fresh EtOAc (2×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and reduced to dryness. The crude material was purified by flash column chromatography on silica with DCM/2% MeOH as eluant to give (S)-3-(5-(5-(1-methoxyethyl)-1,2,4-oxadiazol-3-ylamino)-2-methylphenyl)-1,7-dimethyl-1,6-naphthyridin-2(1H)-one (A76) as a clear white glassy solid. 1H NMR (400 MHz, d6-DMSO) δ 9.94 (s, 1H), 8.81 (s, 1H), 7.94 (s, 1H), 7.43 (s, 1H), 7.40 (dd, J=8, 2 Hz, 1H), 7.30 (d, J=2 Hz, 1H), 7.22 (d, J=8 Hz, 1H), 4.68 (d, J=6 Hz, 1H), 3.65 (s, 3H), 3.45 (s, 3H), 2.61 (s, 3H), 2.07 (s, 3H), 1.49 (d, J=6 Hz, 3H). MS m/z 406.4 (M+1).

출처