Reaction SMILES: C([O:5][C:6](=[O:41])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([N:19]2[CH2:40][CH2:39][C:22]3([NH:26]/[C:25](=[N:27]/[C:28]([C:30]4[C:35]([NH2:36])=[N:34][C:33]([NH2:37])=[C:32]([Cl:38])[N:31]=4)=[O:29])/[NH:24][CH2:23]3)[CH2:21][CH2:20]2)=[O:18])=[CH:11][CH:10]=1)(C)(C)C.[OH-].[Na+].C([O-])(O)=O.[Na+].Cl[CH2:50][C:51]([N:53]([CH2:57][CH2:58][CH3:59])[CH2:54][CH2:55][CH3:56])=[O:52]>CC1OCCC1.O.CC(O)C>[CH2:54]([N:53]([CH2:57][CH2:58][CH3:59])[C:51]([CH2:50][O:5][C:6](=[O:41])[CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][C:17]([N:19]2[CH2:40][CH2:39][C:22]3([NH:26]/[C:25](=[N:27]/[C:28]([C:30]4[C:35]([NH2:36])=[N:34][C:33]([NH2:37])=[C:32]([Cl:38])[N:31]=4)=[O:29])/[NH:24][CH2:23]3)[CH2:21][CH2:20]2)=[O:18])=[CH:11][CH:10]=1)=[O:52])[CH2:55][CH3:56]
Reactant: CCCN(CCC)C(=O)CCl
Reactant: CC(C)(C)OC(=O)COc1ccc(CCC(=O)N2CCC3(CC2)CN/C(=N\C(=O)c2nc(Cl)c(N)nc2N)N3)cc1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Solvent: CC1CCCO1
Product: CCCN(CCC)C(=O)COC(=O)COc1ccc(CCC(=O)N2CCC3(CC2)CN/C(=N\C(=O)c2nc(Cl)c(N)nc2N)N3)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a suspension of [4-(3-{2-[(E)-3,5-Diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]dec-8-yl}-3-oxo-propyl)-phenoxy]-acetic acid tert-butyl ester, (WO09074575, Ex. 71, page 134) (6.0 g, 8.2 mmol) in 2-MeTHF/Water (60 ml/10 ml) was added NaOH (1.0 g, 25 mmol) portionwise. The reaction mixture was stirred at RT for 2 h. The organic layer was separated and washed with water (3×10 ml). Water (60 ml) was added and the 2-MeTHF was removed in vacuo THF (30 ml) was added, followed by NaOH (0.68 g, 17 mmol). The reaction mixture was stirred at RT overnight. The organic solvent was removed in vacuo, and the remaining aqueous phase was washed with MTBE (2×30 ml). DMF (30 ml) was added, and the pH adjusted to 7 with 4N HCl (4.25 ml) at RT. PhMe azotropical distillation was performed three times. NaHCO3 (1.0 g, 11.9 mmol) and 2-chloro-N,N-dipropyl-acetamide (2.2 g, 12.4 mmol) were added to the remaining solution, and the resulting reaction mixture was heated at 60° C. overnight. The mixture was partitioned between DCM (60 ml) and water (30 ml). The organic phase was washed with water/sat. aq. NaHCO3 (10:1, 5×30 ml), water (30 ml) and concentrated in vacuo to a volume of ˜20 ml. 5 ml of the DCM solution was added to isopropyl acetate (20 ml) while stirring at RT. The DCM was removed in vacuo. This procedure was repeated until all the DCM solution was added. The resulting suspension was filtered to afford crude [4-(3-{2-[(E)-3,5-diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]dec-8-yl}-3-oxo-propyl)-phenoxy]-acetic acid dipropylcarbamoylmethyl ester as an off-white solid. The solid was suspended in iPrOH (50 ml) and heated to 60° C. for 3 h. A white suspension formed which was cooled to RT and the solid collected by filtration, and dried under vacuum to afford the title compound; 1H NMR (400 MHz, DMSO-d6) δ 8.42 (1, s), 8.36 (1H, s), 7.15 (2H, d), 6.86 (2H, d), 6.72 (2H, br s), 4.88 (2H, s), 4.81 (2H, s), 3.62, 3.40 (2H, m), 3.56, 3.37 (2H, m), 3.38 (2H, s), 3.18-3.12 (4H, m), 2.74 (2H, t), 2.59 (2H, t), 1.67-1.54 (4H, m), 1.54, 1.45 (4H, AB), 0.85 (3H, t), 0.80 (3H, t). LC-MS Rt 5.08 mins; 672.3 [M+H]+, Method (i)