Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[C:14]3[C:20]4([NH:23][C:24](=[O:30])[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])[CH2:21][CH2:22][C:17]([CH2:31][O:32]S(C5C=CC(C)=CC=5)(=O)=O)([CH2:18][CH2:19]4)[CH2:16][N:15]3[C:43](=[O:46])[C:44]=2[OH:45])=[O:11])=[CH:4][C:3]=1[CH3:47].C(C(OC(C)(C)C)=O)CC(C(OCC)=O)(C(OCC)=O)CCC(OC(C)(C)C)=O.C([O-])(=O)C.[K+].C([O-])([O-])=O.[K+].[K+].CCO>CN(C)C(=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[N:13]=[C:14]3[C:20]4([NH:23][C:24](=[O:30])[C:25]([N:27]([CH3:29])[CH3:28])=[O:26])[CH2:21][CH2:22][C:17]([CH2:31][OH:32])([CH2:18][CH2:19]4)[CH2:16][N:15]3[C:43](=[O:46])[C:44]=2[OH:45])=[O:11])=[CH:4][C:3]=1[CH3:47]
Reactant: Cc1ccc(S(=O)(=O)OCC23CCC(NC(=O)C(=O)N(C)C)(CC2)c2nc(C(=O)NCc4ccc(F)c(C)c4)c(O)c(=O)n2C3)cc1
Agent: CC(=O)[O-]
Agent: CCOC(=O)C(CCC(=O)OC(C)(C)C)(CCC(=O)OC(C)(C)C)C(=O)OCC
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: CC(=O)N(C)C
Product: Cc1cc(CNC(=O)c2nc3n(c(=O)c2O)CC2(CO)CCC3(NC(=O)C(=O)N(C)C)CC2)ccc1F
Temperature: 145 °C
Reaction time: 5 h
Yield: 55.2 %

Procedure:
A 25 mL round bottom flask was charged with a mixture of N′-[2-[[[(4-fluoro-3-methylphenyl)methyl]amino]carbonyl]-6,7,8,9-tetrahydro-3-hydroxy-7-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-4-oxo-7,10-ethanopyrimido[1,2-a]azepin-10(4H)-yl]-N,N-dimethyl-ethanediamide, Example 1 (0.91 g, 1.4 mmol), potassium acetate (0.400 g, 4.08 mmol), K2CO3 (0.188 g, 1.4 mmol), EtOH (1 ml, 17.13 mmol), N,N-dimethylacetamide (9 mL) and stirred in a pre-heated oil bath (145° C.) for 5 h. The reaction mixture was cooled and then quenched with 1 N HCl (3 mL). It was then diluted with ethyl acetate (100 mL) and the resulting solution washed with water (3×25 mL). The combined aqueous layers were extracted with ethyl acetate (2×50 mL). The organic fractions were combined then washed with brine (50 mL), dried (Na2SO4), filtered and concentrated to afford a brown solid which was crystallized from MeOH/H2O (30 mL) to give the title compound (0.387 g, 0.75 mmol, 55.2% yield) as white crystals. The filtrate was concentrated and the resulting solid was recrystallized to afford an additional lot of product (0.129 g, 18.36% yield) as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 1.59-1.71 (2H, m, 9a, 13a-CH2), 1.72-1.83 (2H, m, 9b, 13b-CH2), 2.08-2.19 (2H, m, 10a, 12a-CH2), 2.28 (3H, d, J=1.8 Hz, 27-CH3), 2.55 (2H, m, 10b, 12b-CH2), 2.94 (3H, s, 18-NCH3), 3.30 (3H, s, 17-NCH3), 3.51 (2H, s, 14-OCH2), 4.10 (2H, s, 7-NCH2), 4.54 (2H, d, J=6.1 Hz, 20-NCH2), 6.97 (1H, t, J=8.7 Hz, 25-CH), 7.17-7.26 (2H, m, 22,26-CH), 8.05 (1H, s, 15-CONH), 8.64 (1H, t, J=6.3 Hz, 19-CONH), 12.07 (1H, br.s, 5-OH). 13C NMR (126 MHz, CDCl3) δ ppm 14.7 (d, J=3.8 Hz, 27-CH3), 26.1 (9,13-CH2), 29.7 (10,12-CH2), 36.4 (17- or 18-NCH3), 37.0 (8-C), 38.2 (17- or 18-NCH3), 42.5 (20-NCH2), 55.0 (7-NCH2), 58.1 (11-C), 70.4 (14-OCH2), 115.1 (d, J=22.1 Hz, 25-CH), 124.6 (4-C), 125.0 (d, 18.2 Hz, 23-C), 127.1 (d, J=7.7 Hz, 26-CH), 131.4 (d, J=5.8 Hz, 22-CH), 133.3 (d, J=3.8 Hz, 21-C), 146.8 (5-OC═), 151.5 (2-C), 159.8 (6-C═O), 160.8 (d, J=245 Hz, 24-FC), 162.0, 163.4 (2s, 15,16-NC═O), 168.1 (19-NC═O). HPLC: 1.99 min (AP 100% at 254 nm, 5 min-run). HPLC: 6.32 min (AP 100% at 254 nm, 25 min-run). LCMS: m/z 516 (M+H). Anal. Calcd. for C22H30FN5O6: C58.24, H5.87, N13.59. found: C58.13, H5.67, N13.35.