CN([CH2:4][C:5]1[CH:6]=[C:7]([C:11]2[NH:12][C:13]3[CH:14]=[C:15]([NH:25]C(=O)C4C=CC=C(C(F)(F)F)C=4F)[CH:16]=[C:17]4[C:23](=[O:24])NN=C[C:19]=2[C:18]=34)[CH:8]=[CH:9][CH:10]=1)C.Cl.[O:40]1CCOC[CH2:41]1.C[OH:47]>>[CH3:41][O:40][C:23]([C:17]1[C:18]2[CH:19]=[C:11]([C:7]3[CH:8]=[CH:9][CH:10]=[C:5]([CH2:4][OH:47])[CH:6]=3)[NH:12][C:13]=2[CH:14]=[C:15]([NH2:25])[CH:16]=1)=[O:24]Intermediate 73(c) from Example 73 (1.8 g, 5 mmol) was dissolved in methanol (22 mL). 4M HCl in dioxane (22 mL, 75 mmol) was carefully added, and the solution was heated at 90° C. for 1 hour. After cooling to 22° C., the volatiles were removed in vacuo giving 6-amino-2-(3-hydroxymethyl-phenyl)-1H-indole-4-carboxylic acid methyl ester which was then combined with (1R,2R)-2-phenyl-cyclopropanecarboxylic acid (2 g, 12.5 mmol), triethylamine (3.5 mL, 25 mmol), and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (4.7 g, 12.5 mmol) in N,N-dimethylformamide (0.2 M, 25 mL) and stirred at 22° C. for 12 hours. Volatiles were removed in vacuo and the crude mixture dissolved in methanol (25 mL, 0.2 M) was treated with K2CO3 (1.38 g, 10 mmol) for 1 hour at 22° C. Excess K2CO3 was removed by filtration, and acetic acid (2 drops) was added to the filtrate. Following filtrate evaporation, the residue was subjected to silica gel chromatography (90:10 to 100:0 ethyl acetate/hexane) which provided Intermediate 85(a) (1.1 g, 2.5 mmol) in 50% yield.
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