Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[C:17]([C:18]3[N:26]=[C:25]([CH3:27])[N:24]=[C:23]4[C:19]=3[N:20]=[CH:21][N:22]4C3CCCCO3)=[CH:16][C:13]([CH:14]=O)=[CH:12][N:11]=2)=[CH:5][CH:4]=1.[N:34]1[CH:39]=[CH:38][CH:37]=[C:36]([NH2:40])[N:35]=1.[BH4-].[Na+].Cl>C(O)C.C(Cl)Cl.CO.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][C:10]2[N:11]=[CH:12][C:13]([CH2:14][NH:40][C:36]3[N:35]=[N:34][CH:39]=[CH:38][CH:37]=3)=[CH:16][C:17]=2[C:18]2[N:26]=[C:25]([CH3:27])[N:24]=[C:23]3[C:19]=2[N:20]=[CH:21][NH:22]3)=[CH:5][CH:4]=1
Reactant: COc1ccc(Nc2ncc(C=O)cc2-c2nc(C)nc3c2ncn3C2CCCCO2)cn1
Reactant: Nc1cccnn1
Agent: CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C
Agent: Cl
Agent: [BH4-]
Solvent: CCO
Solvent: CO
Solvent: ClCCl
Product: COc1ccc(Nc2ncc(CNc3cccnn3)cc2-c2nc(C)nc3[nH]cnc23)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 16.6 %

Procedure:
6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)nicotinaldehyde (106.1 mg, 0.2382 mmol) was suspended in ethanol (1.5 mL) and dichloromethane (1.5 mL) and pyridazin-3-amine (39.2 mg, 0.412 mmol) and tetraisopropoxytitanium (0.11 mL, 0.37 mmol) were added. The reaction was stirred overnight at room temperature, and then more DCM (1 mL), 3-aminopyridazine (40.4 mg, 0.425 mmol), and Ti(OiPr)4 (0.12 mL, 0.41 mmol) were added. The flask was fitted with a reflux condenser and placed in a preheated oil bath (50° C.) and stirred for 5 hours. Then, the temperature was raised to 70° C., and stirring was continued overnight. More DCM was added, along with more 3-aminopyridazine (35.2 mg, 0.370 mmol) and Ti(OiPr)4 (0.10 mL, 0.34 mmol) and stirring was continued at 65° C. for 6 hours. Then, the oil bath temperature was raised to 70° C., and stirring was continued. More DCM was added 45 minutes later, and stirring was continued at 70° C. overnight. Then, the reaction was cooled to room temperature, and MeOH (1 mL) was added, followed by sodium borohydride (25.8 mg, 0.682 mmol). The reaction was stirred at room temperature for 75 minutes, and then 5 N HCl (0.50 mL) was added dropwise via syringe and the flask, with a reflux condenser attached, was put in a preheated oil bath (50° C.) and the reaction was stirred for 4.5 hours. The reaction was then cooled to room temperature, diluted with DCM and MeOH, and filtered through a Celite® (diatomaceous earth) pad. The Celite® (diatomaceous earth) pad was washed with DCM, MeOH, and a 1:1 mixture of DCM and MeOH. The filtrate was concentrated and again filtered (no Celite® (diatomaceous earth) pad this time). This filtrate was concentrated and again filtered through Celite® (diatomaceous earth). The filtrate was purified by prep HPLC (10% to 100% MeCN/water with 0.1% TFA over 30 minutes with a total flow rate of 100 mL/min) to give N-((6-(6-methoxypyridin-3-ylamino)-5-(2-methyl-9H-purin-6-yl)pyridin-3-yl)methyl)pyridazin-3-amine (17.4 mg, 17% yield). MS (ESI pos. ion) m/z 441 (M+H)+. 1H NMR (d6-DMSO, 400 MHz) δ 13.65 (br s, 1H), 12.63 (br s, 1H), 9.60 (br s, 1H), 9.16 (br s, 1H), 8.61 (d, J=3.33 Hz, 1H), 8.57 (s, 1H), 8.55 (d, J=2.74 Hz, 1H), 8.38 (d, J=2.35 Hz, 1H), 8.16 (dd, J=8.90 Hz, 2.84 Hz, 1H), 7.78 (dd, J=9.39 Hz, 4.30 Hz, 1H), 7.51 (d, J=9.19 Hz, 1H), 6.86 (d, J=9.0 Hz, 1H), 4.62 (d, J=5.09 Hz, 2H), 3.85 (s, 3H), 2.85 (s, 3H).