[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:25][CH2:26][C:27](O)=[O:28])[C:10]([NH:12][C:13]2[N:17]([CH3:18])[N:16]=[C:15]([C:19]3[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=3)[CH:14]=2)=[O:11])=[CH:4][CH:3]=1.C(OCC)(=O)C.Cl.[CH2:37]([NH2:39])[CH3:38].[Cl-].[NH4+]>C(N(CC)CC)C.ClCCl>[CH2:37]([NH:39][C:27]([CH2:26][NH:25][C@@H:9]([CH2:8][C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:10]([NH:12][C:13]1[N:17]([CH3:18])[N:16]=[C:15]([C:19]2[CH:24]=[CH:23][N:22]=[CH:21][CH:20]=2)[CH:14]=1)=[O:11])=[O:28])[CH3:38]To a 25 ml flask was added 2-((S)-3-(4-fluorophenyl)-1-(1-methyl-3-(pyridin-4-yl)-1H-pyrazol-5-ylamino)-1-oxopropan-2-ylamino)acetic acid 103.2 (145 mg, 0.36 mmole), 50% propylphosphoric anhydride in ethyl acetate (348 mg, 0.55 mmole), 0.2 ml of triethylamine and 3 ml of dichloromethane. After 20 min, ethylamine hydrochloride (60 mg, 0.73 mmole) was added to the mixture. The reaction was stirred at room temperature for 4 days. The solution was poured into saturated ammonium chloride, and extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous sodium sulfate. After concentration in vacuo, the residue was chromatographed on silica gel to give 103.3 (69 mg, 44% yield) as colorless amorphous. LCMS ESI (pos.) m/e: 425 (M+H); 1H NMR (400 MHz, DMSO-d6) δ ppm 9.91 (s, 1H), 8.58 (dd, J=17.9, 6.2 Hz, 2H), 7.63 (dd, J=19.5, 6.2 Hz, 2H), 7.25 (dd, J=9.2, 6.0 Hz, 2H), 7.05 (t, J=7.7 Hz, 2H), 6.82 (s, 1H), 5.79 (brs, 1H), 3.81 (s, 3H), 3.46 (dd, J=8.6, 4.7 Hz, 1H), 3.31-3.17 (m, 3H), 3.21 (d, J=2.8 Hz, 2H), 2.92 (dd, J=14.1, 8.6 Hz, 1H), 1.09 (t, J=7.2 Hz, 3H).
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