Reaction SMILES: [CH2:1]([N:4]([CH2:26][CH2:27][CH3:28])[C:5]([CH2:7][O:8][C:9]([CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20](O)=[O:21])(=[O:16])=[O:15])=[O:10])=[O:6])[CH2:2][CH3:3].CN1CCOCC1.C1C=C2N=NN(O)C2=CC=1.O.Cl.[NH:48]1[C:52]2([CH2:57][CH2:56][NH:55][CH2:54][CH2:53]2)[CH2:51][NH:50]/[C:49]/1=[N:58]\[C:59]([C:61]1[C:66]([NH2:67])=[N:65][C:64]([NH2:68])=[C:63]([Cl:69])[N:62]=1)=[O:60].CCN=C=NCCCN(C)C.Cl.CC1OCCC1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.O>[CH2:1]([N:4]([CH2:26][CH2:27][CH3:28])[C:5]([CH2:7][O:8][C:9](=[O:10])[CH2:11][CH2:12][NH:13][S:14]([C:17]1[CH:25]=[CH:24][CH:23]=[C:19]([C:20]([N:55]2[CH2:56][CH2:57][C:52]3([NH:48]/[C:49](=[N:58]/[C:59]([C:61]4[C:66]([NH2:67])=[N:65][C:64]([NH2:68])=[C:63]([Cl:69])[N:62]=4)=[O:60])/[NH:50][CH2:51]3)[CH2:53][CH2:54]2)=[O:21])[CH:18]=1)(=[O:16])=[O:15])=[O:6])[CH2:2][CH3:3]
Reactant: CCCN(CCC)C(=O)COC(=O)CCNS(=O)(=O)c1cccc(C(=O)O)c1
Reactant: Nc1nc(N)c(C(=O)/N=C2\NCC3(CCNCC3)N2)nc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC1CCCO1
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: CCCN(CCC)C(=O)COC(=O)CCNS(=O)(=O)c1cccc(C(=O)N2CCC3(CC2)CN/C(=N\C(=O)c2nc(Cl)c(N)nc2N)N3)c1
Temperature: 50 °C

Procedure:
To a stirred solution of 3-(2-dipropylcarbamoylmethoxycarbonyl-ethylsulfamoyl)-benzoic acid (Int. AA) (6.1 g, 12.60 mmol) in THF (50 ml) was added sequentially water (25 ml), N-methylmorpholine (7 ml, 63 mmol) and HOBt hydrate (2.9 g, 18.9 mmol). The internal temperature was maintained at ≦20° C. 3,5-Diamino-6-chloro-pyrazine-2-carboxylic acid [1,3,8-triaza-spiro[4.5]dec-(2E)-ylidene]-amide hydrochloride (WO09074575, Ex. 38, page 123) (65% purity, 6.3 g, 12.6 mmol) was added and stirred until a clear solution had formed. EDCI.HCl (3.6 g, 18.9 mmol) was added, and the reaction was stirred at RT for 24 h. 2-MeTHF (200 ml) and 2% aq. Na2CO3 (150 ml) were added to the reaction mixture. The layers were separated, and the aqueous phase washed with additional 2-MeTHF (100 ml). The combined organic layers were washed with 2% aq. Na2CO3 (200 ml) and water (2×200 ml). Acetonitrile (100 ml) was added, and the solution concentrated at 30° C. to a volume of 70 ml. Acetonitrile (300 ml) was added, and the solution concentrated again at 30° C. to a volume of 150 ml. The solution was heated to 50° C. and maleic acid (1.62 g) was added to the resulting solution. An off-white precipitate formed immediately, the temperature was allowed to cool to RT over 1 h. The solid was collected by filtration to afford 3-(3-{2-[(E)-3,5-Diamino-6-chloro-pyrazine-2-carbonylimino]-1,3,8-triaza-spiro[4.5]decane-8-carbonyl}-benzenesulfonylamino)-propionic acid dipropylcarbamoylmethyl ester as a maleate salt; DCM (200 ml) and 2% aq. Na2CO3 (200 ml) were added and stirred until the solid had fully dissolved. The organic layer was separated, washed with water (2×100 ml) and concentrated in vacuo to afford the title compound. LC-MS 722.1 [M+H]+, Method (i).; 1H NMR (400 MHz, DMSO-d6) δ 9.12-7.57 (4H, br), 7.88 (1H, m), 7.77 (1H, m), 7.70 (1H, m), 7.68 (1H, m), 7.05-6.50 (2H, br s), 6.95-6.20 (1H, br s), 4.73 (2H, s), 3.81-3.39 (2H, m), 3.61-3.31 (2H, m), 3.43 (2H, br s), 3.15-3.11 (4H, m), 3.04 (2H, t), 2.51 (2H, t), 1.79-1.69 (m, 4H), 1.51-1.43 (4H, m), 0.84 (3H, t), 0.78 (3H, t)