Reaction SMILES: [F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[C:4](=[O:49])[N:5]1[C:15]([NH:16][C:17]3[CH:25]=[C:24]4[C:20]([CH2:21][CH2:22][N:23]4[C:26](=[O:33])[C@H:27]4[CH2:31][CH2:30][CH2:29][N:28]4[CH3:32])=[CH:19][C:18]=3[O:34][CH3:35])=[N:14][C:13]3[N:36](S(C4C=CC(C)=CC=4)(=O)=O)[CH:37]=[CH:38][C:12]=3[C:6]1=[N:7]2.[CH3:50][NH2:51]>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:7][C:6]2[N:5]=[C:15]([NH:16][C:17]3[CH:25]=[C:24]4[C:20]([CH2:21][CH2:22][N:23]4[C:26](=[O:33])[C@H:27]4[CH2:31][CH2:30][CH2:29][N:28]4[CH3:32])=[CH:19][C:18]=3[O:34][CH3:35])[NH:14][C:13]3=[N:36][CH:37]=[CH:38][C:12]=23)[C:3]=1[C:4]([NH:51][CH3:50])=[O:49]
Reactant: CN
Reactant: COc1cc2c(cc1Nc1nc3c(ccn3S(=O)(=O)c3ccc(C)cc3)c3nc4cccc(F)c4c(=O)n13)N(C(=O)[C@H]1CCCN1C)CC2
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CNC(=O)c1c(F)cccc1Nc1nc(Nc2cc3c(cc2OC)CCN3C(=O)[C@H]2CCCN2C)[nH]c2nccc1-2
Temperature: 25 °C
Reaction time: 6 h
Yield: 58.9 %

Procedure:
A suspension of 5-chloro-8-fluoro-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one hydrogen chloride (550 mg, 1.147 mmol) and 5-(methyloxy)-1-(1-methyl-D-prolyl)-2,3-dihydro-1H-indol-6-amine (363 mg, 1.320 mmol) in 2,2,2-trifluoroethanol (50 ml) was maintained at 80° C. for 2 hours. The solution was cooled, poured into saturated sodium bicarbonate/dichloromethane, and the organic layer was taken to a residue under reduced pressure. The residue was triturated with diethyl ether to afford 8-fluoro-5-{[5-(methyloxy)-1-(1-methyl-D-prolyl)-2,3-dihydro-1H-indol-6-yl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (425 mg, 0.623 mmol, 54.3%) as a pale yellow solid. To a solution of 8-fluoro-5-{[5-(methyloxy)-1-(1-methyl-D-prolyl)-2,3-dihydro-1H-indol-6-yl]amino}-3-[(4-methylphenyl)sulfonyl]pyrrolo[2′,3′:4,5]pyrimido[6,1-b]quinazolin-7(3H)-one (425 mg, 0.623 mmol) in tetrahydrofuran (50 ml) was added 2.0M MeNH2 in THF (3.12 ml, 6.23 mmol) and the resulting solution was stirred at room temperature for 6 hours. The reaction was diluted with ethyl acetate, washed with saturated sodium bicarbonate (aq) and the organic layer was dried over sodium sulfate, filtered, and taken to a residue under reduced pressure. The residue was dissolved in 1,4-dioxane (8 ml)/2.0 N NaOH (aq) (8 ml) and maintained at 120° C. under microwave heating for 12 minutes. The vial was cooled and its contents were dilulted with THF/EtOAc/saturated sodium chloride (aq). The organic layer was dried over sodium sulfate, filtered, stripped onto celite, and purified by column chromatography to afford 2-fluoro-N-methyl-6-[(2-{[5-(methyloxy)-1-(1-methyl-D-prolyl)-2,3-dihydro-1H-indol-6-yl]amino}-1H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]benzamide (0.205 g, 0.367 mmol, 58.9%)as a grey solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.27 (s, 1H), 10.15 (s, 1H), 8.69 (s, 1H), 8.55 (s, 1H), 8.35 (d, J=8.43 Hz, 1H), 7.55 (s, 1H), 7.22-7.38 (m, 1H), 6.92-6.97 (m, 2H), 6.88 (t, J=9.30 Hz, 1H), 6.28 (dd, J=3.51, 1.91 Hz, 1H), 4.08-4.26 (m, 2H), 3.78 (s, 3H), 3.17-3.23 (m, 1H), 3.12 (t, J=7.62 Hz, 2H), 2.93-3.04 (m, 1H), 2.80 (d, J=4.21 Hz, 3H), 2.26 (s, 3H), 2.11-2.22 (m, 1H), 1.70-1.85 (m, 4H). ESIMS (M+H)+=559.