[N:1]1([C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([OH:17])=O)[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4])[CH3:2].CCN(C(C)C)[CH:21]([CH3:23])[CH3:22].[NH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH3:2][N:1]1[C:12](=[O:13])[C:11]2[N:10]([CH2:14][C:15]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([CH:21]([CH3:23])[CH3:22])=[CH:30][CH:29]=3)=[O:17])[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4]
To the suspension of theophylline-7-acetic acid (101, 32.5 g, 0.136 mol) in anhydrous DMF (400 mL), was added DIPEA (54 mL, 0.31 mol) at 0° C. The neat aniline (102, 20.4 mL, 0.143 mol) was added followed by addition of DMAP (19.2 g, 0.16 mol) and EDCI (30.1 g, 0.16 mol). The reaction mixture was warmed to room temperature over 18 h, then stirred at 40-43° C. for 1.5 days. The reaction mixture was diluted with CH2Cl2 (1.8 L), washed with H2O (0.7 L), 10% citric acid (0.5 L), NaHCO3 (saturated, 0.6 L), brine, dried over Na2SO4 and concentrated in vacuo and crystallized from ethyl acetate/hexanes to yield compound 200 (41%, 19.8 g): MS (APCI) m/z: 356.2 [M+H]+. Anal. Calcd. for C18H21N5O3: C, 60.83; H, 5.96; N, 19.71. Found: C, 60.53; H, 5.97; N, 19.76.
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