Reaction SMILES: [NH:1]([C:42]([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43])[C@H:2]([C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][C:19]([NH:21][C@H:22]([C:30]([NH:32][C@H:33]([C:38]([NH:40]N)=[O:39])[CH2:34][CH2:35][S:36][CH3:37])=[O:31])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])=[O:16])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.Cl.CCN(CC)CC.N[C@H:61]([C:72]([NH:74][C@H:75]([C:85]([NH:87][C@H:88]([C:101]([NH:103][C@H:104]([C:120]([OH:122])=[O:121])[CH2:105][CH2:106][CH2:107][CH2:108][NH:109][C:110]([O:112][CH2:113][C:114]1[CH:119]=[CH:118][CH:117]=[CH:116][CH:115]=1)=[O:111])=[O:102])[CH2:89][CH2:90][C:91](=[O:100])[O:92][CH2:93][C:94]1[CH:99]=[CH:98][CH:97]=[CH:96][CH:95]=1)=[O:86])[CH2:76][O:77][CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)=[O:73])[C@@H:62]([CH3:71])[O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CN(C=O)C.C1COCC1.C(O)(=O)C>[NH:1]([C:42]([O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)=[O:43])[C@H:2]([C:11]([NH:13][CH2:14][C:15]([NH:17][CH2:18][C:19]([NH:21][C@H:22]([C:30]([NH:32][C@H:33]([C:38]([NH:40][C@H:61]([C:72]([NH:74][C@H:75]([C:85]([NH:87][C@H:88]([C:101]([NH:103][C@H:104]([C:120]([OH:122])=[O:121])[CH2:105][CH2:106][CH2:107][CH2:108][NH:109][C:110]([O:112][CH2:113][C:114]1[CH:119]=[CH:118][CH:117]=[CH:116][CH:115]=1)=[O:111])=[O:102])[CH2:89][CH2:90][C:91](=[O:100])[O:92][CH2:93][C:94]1[CH:95]=[CH:96][CH:97]=[CH:98][CH:99]=1)=[O:86])[CH2:76][O:77][CH2:78][C:79]1[CH:84]=[CH:83][CH:82]=[CH:81][CH:80]=1)=[O:73])[C@@H:62]([CH3:71])[O:63][CH2:64][C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:39])[CH2:34][CH2:35][S:36][CH3:37])=[O:31])[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:20])=[O:16])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1
Reactant: CSCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OCc1ccccc1)C(=O)NN
Reactant: C[C@@H](OCc1ccccc1)[C@H](N)C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O
Agent: Cl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: CC(=O)O
Product: CSCC[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](COCc1ccccc1)C(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)N[C@@H](CCCCNC(=O)OCc1ccccc1)C(=O)O)[C@@H](C)OCc1ccccc1
Temperature: -20 °C
Reaction time: 0.5 h

Procedure:
Compound II (3.13 g, 4.33 mmol) was dissolved in DMF (50 ml, purged with Argon for 15 min), cooled to -20° C and treated with 5.93 ml of 4 N HCl in THF followed by 0.88 ml of i-amylnitrite. After 30 min, the mixture was cooled down to -30° C and 3.64 ml of Et3N and H-Thr(Bzl)-Ser(Bzl)-Glu(OBzl)-Lys(Z)-OH were added. The mixture was stirred at 4° C for 72 hours during which time some more Et3N was added in order to maintain the pH between 7 and 8. The reaction was acidified to pH 3 with acetic acid. Evaporation of the solvent and trituration of the residue in water gave a white glassy product which was washed with 5% AcOH and water; it was then triturated in EtOH several times and dried, yield 5.5 g (81.5%); mp 227°-231° C dec. [α]D25 - 3.2° (c 1, DMF). Anal. Calcd for C82H96N10O19S (1157.79): C, 63.22; H, 6.21; N, 8.99; S, 2.06. Found: C, 63.03; H, 6.24; N, 9.12; S, 2.12. Amino acid Analysis (6N HCl/phenol, 100° C, 24 hr): Lys, 1.11; Thr, 1.05; Ser, 0.86; Glu, 1.07; Gly, 1.86; Met, 0.95; Tyr, 0.81; Phe, 1.02.