Reaction SMILES: [NH:1]([C:69]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)=[O:70])[C@H:2]([C:10]([NH:12][C@H:13]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:46]([NH:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([NH:67]N)=[O:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:55])[CH2:50][C:51](=[O:53])[NH2:52])=[O:47])[CH2:41][CH2:42][C:43](=[O:45])[NH2:44])=[O:38])[C@@H:30]([CH3:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:16]=1)=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl.C(ON=O)(C)(C)C.C(N(CC)C(C)C)(C)C.N[C@H:97]([C:102]([NH:104][C@H:105]([C:118]([NH:120][C@H:121]([C:129]([NH:131][C@H:132]([C:139]([NH:141][C@H:142]([C:150]([NH:152][C@H:153]([C:161]([N:163]1[CH2:207][CH2:206][CH2:205][C@H:164]1[C:165]([NH:167][C@H:168]([C:174]([NH:176][C@H:177]([C:185]([NH:187][C@H:188]([C:190]([NH:192][C@H:193]([C:198]([NH:200][CH2:201][C:202]([OH:204])=[O:203])=[O:199])[C@H:194]([CH2:196][CH3:197])[CH3:195])=[O:191])[CH3:189])=[O:186])[C@@H:178]([CH3:184])[O:179][C:180]([CH3:183])([CH3:182])[CH3:181])=[O:175])[CH2:169][CH2:170][C:171](=[O:173])[NH2:172])=[O:166])=[O:162])[CH2:154][C:155]1[CH:160]=[CH:159][CH:158]=[CH:157][CH:156]=1)=[O:151])[C@@H:143]([CH3:149])[O:144][C:145]([CH3:148])([CH3:147])[CH3:146])=[O:140])[CH2:133][C:134]1[N:138]=[CH:137][NH:136][CH:135]=1)=[O:130])[CH2:122][C:123]1[CH:128]=[CH:127][CH:126]=[CH:125][CH:124]=1)=[O:119])[CH2:106][CH2:107][CH2:108][CH2:109][NH:110][C:111]([O:113][C:114]([CH3:117])([CH3:116])[CH3:115])=[O:112])=[O:103])[CH2:98][C:99](=[O:101])[NH2:100]>CN(C)C=O.O1CCOCC1.CCOCC>[NH:1]([C:69]([O:71][CH2:72][C:73]1[CH:78]=[CH:77][CH:76]=[CH:75][CH:74]=1)=[O:70])[C@H:2]([C:10]([NH:12][C@H:13]([C:26]([NH:28][C@H:29]([C:37]([NH:39][C@H:40]([C:46]([NH:48][C@H:49]([C:54]([NH:56][C@H:57]([C:65]([NH:67][C@H:97]([C:102]([NH:104][C@H:105]([C:118]([NH:120][C@H:121]([C:129]([NH:131][C@H:132]([C:139]([NH:141][C@H:142]([C:150]([NH:152][C@H:153]([C:161]([N:163]1[CH2:207][CH2:206][CH2:205][C@H:164]1[C:165]([NH:167][C@H:168]([C:174]([NH:176][C@H:177]([C:185]([NH:187][C@H:188]([C:190]([NH:192][C@H:193]([C:198]([NH:200][CH2:201][C:202]([OH:204])=[O:203])=[O:199])[C@H:194]([CH2:196][CH3:197])[CH3:195])=[O:191])[CH3:189])=[O:186])[C@@H:178]([CH3:184])[O:179][C:180]([CH3:183])([CH3:182])[CH3:181])=[O:175])[CH2:169][CH2:170][C:171](=[O:173])[NH2:172])=[O:166])=[O:162])[CH2:154][C:155]1[CH:156]=[CH:157][CH:158]=[CH:159][CH:160]=1)=[O:151])[C@@H:143]([CH3:149])[O:144][C:145]([CH3:146])([CH3:147])[CH3:148])=[O:140])[CH2:133][C:134]1[N:138]=[CH:137][NH:136][CH:135]=1)=[O:130])[CH2:122][C:123]1[CH:124]=[CH:125][CH:126]=[CH:127][CH:128]=1)=[O:119])[CH2:106][CH2:107][CH2:108][CH2:109][NH:110][C:111]([O:113][C:114]([CH3:115])([CH3:116])[CH3:117])=[O:112])=[O:103])[CH2:98][C:99](=[O:101])[NH2:100])=[O:66])[CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:55])[CH2:50][C:51](=[O:53])[NH2:52])=[O:47])[CH2:41][CH2:42][C:43](=[O:45])[NH2:44])=[O:38])[C@@H:30]([CH3:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:27])[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:17][CH:16]=1)=[O:11])[C@@H:3]([CH3:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6]
Reactant: C[C@@H](OC(C)(C)C)[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](Cc1ccc(OC(C)(C)C)cc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](Cc1ccccc1)C(=O)NN)[C@@H](C)OC(C)(C)C
Reactant: CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@@H](N)CC(N)=O)[C@@H](C)OC(C)(C)C)[C@@H](C)OC(C)(C)C)C(=O)NCC(=O)O
Agent: CC(C)(C)ON=O
Agent: Cl
Solvent: C1COCCO1
Solvent: CCOCC
Solvent: CCN(C(C)C)C(C)C
Product: CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H](NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](Cc1ccc(OC(C)(C)C)cc1)NC(=O)[C@@H](NC(=O)OCc1ccccc1)[C@@H](C)OC(C)(C)C)[C@@H](C)OC(C)(C)C)[C@@H](C)OC(C)(C)C)[C@@H](C)OC(C)(C)C)C(=O)NCC(=O)O
Temperature: -17.5 °C
Reaction time: 0.25 h

Procedure:
800 mg of Z-Thr(tBu)-Tyr(tBu)-Thr(tBu)-Gln-Asn-Phe-NH-NH2 are dissolved in 18 ml of dimethylformamide, the solution treated at -20° C. with 0.58 ml of 3N-hydrogen chloride in dioxan, and the batch then mixed with 0.16 ml of t-butylnitrite. The batch is then stirred for 15 minutes at -20 to -15° C., 0.30 ml of N,N-diisopropyl-ethylamine and 855 mg of H-Asn-Lys(BOC)-Phe-His-Thr(tBu)-Phe-Pro-Gln-Thr(tBu)-Ala-Ile-Gly-OH (acetate) in 20 ml of dimethylformamide (90% strength) are added, followed by stirring at 0° C. After one hour and after another hour, 0.075 ml of N,N-di-isopropylethylamine (a total of 0.15 ml) is added each time, and the batch is stirred at 0° C. for 15 hours. The whole is then stirred into 600 ml of ether, the precipitate is allowed to settle, and then filtered. For purification, the crude product is recrystallized once from dimethylformamide+ethyl acetate and once from dimethylformamide+aqueous 0.002N-hydrochloric acid.