[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH2:10])=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.Cl[CH2:12][CH2:13][O:14][CH2:15][CH2:16]Cl.C([O-])([O-])=O.[Na+].[Na+]>CC(O)(C)C.CCOC(C)=O>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([N:10]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[CH:2]1A heterogeneous, tan solution of 1H-indol-5-amine (4.5547 g, 34.5 mmol), 1-chloro-2-(2-chloroethoxy)ethane (6.06 mL, 51.7 mmol) and Na2CO3 (14.61 g, 138 mmol) in t-BuOH (90 mL) in a sealed pressure tube was heated to 100° C. for 2 days. The reaction was cooled to room temperature, diluted with EtOAc and filtered through a pad of CELITE®, and the filtrate was concentrated in vacuo. Water (50 mL) was added to the residue and basified to pH ˜11 with saturated aqueous NaHCO3; this was extracted with CH2Cl2 (4×75 mL). The organic layers were combined and washed with brine, dried over MgSO4, filtered and concentrated in vacuo to give crude product. This was triturated with Et2O to give the first crop of desired product (3.7495 g) as a tan solid. The filtrate was concentrated in vacuo, and the residue was purified by flash chromatography using an ISCO 120 g column eluting with 20-50% EtOAc/hexanes to give the second crop of the desired product (1.9458 g).
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