Glycine ethyl ester, hydrochloride → {5-[2-(4-Acetylamino-phenylsulfanyl)-5-methyl-phenylamino]-[1,8]naphthyridin-2-ylamino}-acetic acid ethyl ester
Reaction equation
Cl[C:2]1[N:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=3[S:20][C:21]3[CH:26]=[CH:25][C:24]([NH:27][C:28](=[O:30])[CH3:29])=[CH:23][CH:22]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.Cl.[CH2:32]([O:34][C:35](=[O:38])[CH2:36][NH2:37])[CH3:33]>CCO>[CH2:32]([O:34][C:35](=[O:38])[CH2:36][NH:37][C:2]1[CH:3]=[CH:4][C:5]2[C:10](=[N:9][CH:8]=[CH:7][C:6]=2[NH:12][C:13]2[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=2[S:20][C:21]2[CH:22]=[CH:23][C:24]([NH:27][C:28](=[O:30])[CH3:29])=[CH:25][CH:26]=2)[N:11]=1)[CH3:33]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
The product from Example 24a (47 mg, 0.10 mmol) was reacted with the glycine ethyl ester hydrochloride (84 mg, 0.10 mmol) in 2 mL of EtOH in a sealed tube at 150° C. for 1 h. Cooled to room temperature and concentrated. Adjusted to pH 7 with 1M HCl and extracted with EtOAc, dried over Na2SO4, filtered and concentrated under vacuum giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid solid (12 mg, 19%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.22 (t, J=6.99 Hz, 3H) 2.04 (s, 3H) 2.33 (s, 3H) 4.15 (q, J=7.23 Hz, 2H) 4.27 (d, J=6.25 Hz, 2H) 6.08 (d, J=6.99 Hz, 1H) 7.04 (d, J=5.52 Hz, 1H) 7.07 (d, J=6.62 Hz, 1H) 7.19-7.30 (m, 4H) 7.57 (d, J=8.46 Hz, 2H) 8.04 (t, J=6.62 Hz, 1H) 8.53 (d, J=9.19 Hz, 1H) 8.72 (t, J=5.88 Hz, 1H) 10.08 (s, 1H) 10.43 (s, 1H) 13.43 (d, J=5.88 Hz, 1H); MS (ESI+) m/z 502(M+H−TFA)+.