Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:21])[N:7]([CH3:20])[C:8]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([OH:19])[CH2:15][CH2:14]3)=[N:9]2)=[CH:4][C:3]=1[CH2:22][N:23]([C:27]1[CH:39]=[CH:38][C:30]([C:31]([O:33]C(C)(C)C)=O)=[CH:29][CH:28]=1)[CH2:24][C:25]#[CH:26].[NH2:40][CH2:41][C:42]1[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C.Cl.[OH-].[Na+]>ClCCl.FC(F)(F)C(O)=O.CN(C=O)C.O>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:21])[N:7]([CH3:20])[C:8]([CH2:12][N:13]3[CH2:14][CH2:15][CH:16]([OH:19])[CH2:17][CH2:18]3)=[N:9]2)=[CH:4][C:3]=1[CH2:22][N:23]([C:27]1[CH:39]=[CH:38][C:30]([C:31]([NH:40][CH2:41][C:42]2[CH:43]=[N:44][CH:45]=[CH:46][CH:47]=2)=[O:33])=[CH:29][CH:28]=1)[CH2:24][C:25]#[CH:26]
Reactant: C#CCN(Cc1cc2c(=O)n(C)c(CN3CCC(O)CC3)nc2cc1Cl)c1ccc(C(=O)OC(C)(C)C)cc1
Reactant: NCc1cccnc1
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: C#CCN(Cc1cc2c(=O)n(C)c(CN3CCC(O)CC3)nc2cc1Cl)c1ccc(C(=O)NCc2cccnc2)cc1
Reaction time: 0.08 h

Procedure:
A solution of tert-butyl 4-[N-[7-chloro-3-methyl-2-(4-hydroxypiperidin-1-yl)methyl-4-oxo-3,4-dihydroquinazolin-6-ylmethyl]-N-(prop-2-ynyl)amino]benzoate (0.158 g, 0.28 mmol) (Preparation Example 23) in dichloromethane (2 ml) and trifluoroacetic acid (2.5 ml) was stirred at room temperature for 1 hour with protection from the light. The solvents were then removed in vacuo and the residue was treated with toluene/dichloromethane, concentrated in vacuo and the residue was dried in vacuo over P2O5. This material was dissolved in anhydrous DMF (2.5 ml) under argon and the solution was placed in an ice-bath. A solution of 3-(aminomethyl)pyridine (0.045 g, 0.42 mmol) in DMF (0.4 ml) was then added followed by PyBOP® (0.152 g, 0.29 mmol) and diisopropylethylamine (0.210 g, 1.68 mmol). Stirring was continued at 0° C. for 5 min; then the ice-bath was removed and the reaction mixture was stirred for an additional 4 h before being partitioned between ethyl acetate (150 ml) and saturated aqueous sodium bicarbonate (100 ml). The organic layer was washed with more saturated aqueous sodium bicarbonate (100 ml) and brine (100 ml). The aqueous washings were extracted with ethyl acetate (100 ml), dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography using a gradient of methanol in chloroform (5 to 10%) to afford a white solid. This was suspended in water (6 ml) and the pH was first adjusted to ˜1 with 1N HCl, then to ˜10 with 1N NaOH; a white precipitate was obtained. The white solid was collected by filtration, washed with water and dried in vacuo over P2O5 (0.102 g, 63%), mp 134-136° C.; 1H-NMR (DMSO-d6), 1.37 (m, 2H), 1.70 (m, 2H), 2.21 (m, 2H), 2.70 (m, 2H), and 3.46 (m, 1H) (piperidine ring protons), 3.20 (s, 1H, C≡CH), 3.60 (s, 5H, N3-Me, 2-CH2), 4.38 (s, 2H, CH2C≡C), 4.45 (d, J=5.8 Hz, 2H, CONHCH2), 4.77 (s, 2H, 6-CH2), 6.78 (d, J=8.8 Hz, 2H, 3,5′-ArH), 7.33 (dd, J=4.6, 7.6 Hz, 1H, pyr 5-H), 7.68 (d, J=7.8 Hz, 1H, pyr 4-H), 7.76 (d, J=8.8 Hz, 2H, 2′,6′-ArH), 7.81, 7.91 (2×s, 2H, 5-H, 8-H), 8.43 (d, J=4.0 Hz, 1H, pyr 6-H), 8.52 (s, 1H, pyr 2-H), 8.73 (t, J=5.3 Hz, 1H, CONH).; MS (ESI, m/z) 585,587 [(M+H)+, 100%, 37% respectively; Cl isotopic pattern].