Reaction SMILES: [NH:1]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:2]([C:7]([NH:9][C@H:10]([C:15]([OH:17])=O)[CH2:11][CH:12]([CH3:14])[CH3:13])=[O:8])[C@H:3]([CH2:5][CH3:6])[CH3:4].C1C=C2C(N(O)N=NC2=CC=1)=O.[NH2:37][C@H:38]([C:46]([NH:48][C@H:49]([C:60]([N:62]1[CH2:156][CH2:155][CH2:154][C@H:63]1[C:64]([NH:66][C@H:67]([C:78]([NH:80][C@H:81]([C:92]([N:94]1[CH2:153][CH2:152][CH2:151][C@H:95]1[C:96]([NH:98][C@H:99]([C:110]([NH:112][C@H:113]([C:121]([NH:123][C@H:124]([C:132]([NH:134][C@H:135]([C:148]([NH2:150])=[O:149])[CH2:136][CH2:137][CH2:138][CH2:139][NH:140][C:141]([O:143][C:144]([CH3:147])([CH3:146])[CH3:145])=[O:142])=[O:133])[CH2:125][CH2:126][CH2:127][NH:128][C:129](=[NH:131])[NH2:130])=[O:122])[CH2:114][CH2:115][CH2:116][NH:117][C:118](=[NH:120])[NH2:119])=[O:111])[CH2:100][C:101]1[C:109]2[C:104](=[CH:105][CH:106]=[CH:107][CH:108]=2)[NH:103][CH:102]=1)=[O:97])=[O:93])[CH2:82][C:83]1[C:91]2[C:86](=[CH:87][CH:88]=[CH:89][CH:90]=2)[NH:85][CH:84]=1)=[O:79])[CH2:68][C:69]1[C:77]2[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=2)[NH:71][CH:70]=1)=[O:65])=[O:61])[CH2:50][C:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[NH:53][CH:52]=1)=[O:47])[CH2:39][CH2:40][CH2:41][NH:42][C:43](=[NH:45])[NH2:44].C(Cl)CCl.Cl>CC(N(C)C)=O.C(Cl)Cl.C(Cl)Cl.C(O)C(C)C.[Na+].[Cl-]>[NH:1]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[C@H:2]([C:7]([NH:9][C@H:10]([C:15]([NH:37][C@H:38]([C:46]([NH:48][C@H:49]([C:60]([N:62]1[CH2:156][CH2:155][CH2:154][C@H:63]1[C:64]([NH:66][C@H:67]([C:78]([NH:80][C@H:81]([C:92]([N:94]1[CH2:153][CH2:152][CH2:151][C@H:95]1[C:96]([NH:98][C@H:99]([C:110]([NH:112][C@H:113]([C:121]([NH:123][C@H:124]([C:132]([NH:134][C@H:135]([C:148]([NH2:150])=[O:149])[CH2:136][CH2:137][CH2:138][CH2:139][NH:140][C:141]([O:143][C:144]([CH3:147])([CH3:146])[CH3:145])=[O:142])=[O:133])[CH2:125][CH2:126][CH2:127][NH:128][C:129](=[NH:130])[NH2:131])=[O:122])[CH2:114][CH2:115][CH2:116][NH:117][C:118](=[NH:119])[NH2:120])=[O:111])[CH2:100][C:101]1[C:109]2[C:104](=[CH:105][CH:106]=[CH:107][CH:108]=2)[NH:103][CH:102]=1)=[O:97])=[O:93])[CH2:82][C:83]1[C:91]2[C:86](=[CH:87][CH:88]=[CH:89][CH:90]=2)[NH:85][CH:84]=1)=[O:79])[CH2:68][C:69]1[C:77]2[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=2)[NH:71][CH:70]=1)=[O:65])=[O:61])[CH2:50][C:51]1[C:59]2[C:54](=[CH:55][CH:56]=[CH:57][CH:58]=2)[NH:53][CH:52]=1)=[O:47])[CH2:39][CH2:40][CH2:41][NH:42][C:43](=[NH:44])[NH2:45])=[O:17])[CH2:11][CH:12]([CH3:13])[CH3:14])=[O:8])[C@H:3]([CH2:5][CH3:6])[CH3:4]
Reactant: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)O
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)[C@@H](N)CCCNC(=N)N)C(N)=O
Agent: Cl
Agent: O=c1c2ccccc2nnn1O
Agent: [Cl-]
Solvent: CC(=O)N(C)C
Solvent: CC(C)CO
Solvent: ClCCl
Product: CC[C@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(N)=O
Temperature: 0 °C
Reaction time: 4 h

Procedure:
1.05 equivalents of Boc-Ile-Leu-OH (Mw=344.4) and 1.10 equivalents of HOOBt (Mw=163.13) are added to a cold (0±5° C.) solution of 1.00 equivalent of 3HCl.H-Arg-Trp-Pro-Trp-Trp-Pro-Trp-Arg-Arg-Lys(Boc)-NH2 (Mw=1652.9; purity=89.0%) in DMA and CH2Cl2. 1.20 equivalents of EDC(N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; Mw=191.7; purity=100.0%) was then added to the reaction mixture which was further stirred at 0±5° C. for about 4 hours, then at least 8 hours at room temperature. After the completion of the reaction had been checked by HPLC, the reaction mixture was diluted with a CH2Cl2/iso-butanol mixture (8/2), and washed with a 5% (weight) aqueous NaCl solution+HCl (0.3 eq.). After concentration of the organic layer, the residual oil was precipitated by slowly pouring into cold (0±5° C.) acetonitrile. After stirring at least for 30 min at 0±5° C., the suspension was filtered and washed twice with cold MTBE. The precipitate was dried at 40±5° C. An off white solid was finally obtained.