Reaction SMILES: [NH2:1][C@H:2]([C:12]([NH:14][C@H:15]([C:19]([NH:21][C@H:22]([C:26]([NH:28][C@H:29]([C:39]([NH:41][C@H:42]([C:52]([NH:54][C@H:55]([C:57]([NH:59][C@H:60]([C:70]([NH:72][C@H:73]([C:78]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])=[O:79])[CH2:74][C:75](=[O:77])[NH2:76])=[O:71])[CH2:61][CH2:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:58])[CH3:56])=[O:53])[CH2:43][CH2:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:40])[CH2:30][CH2:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:27])[CH:23]([CH3:25])[CH3:24])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[NH:85]([C:131]([O:133][CH2:134][C:135]1[CH:140]=[CH:139][CH:138]=[CH:137][CH:136]=1)=[O:132])[C@H:86]([C:96]([NH:98][C@H:99]([C:112]([NH:114][C@H:115]([C:128](O)=[O:129])[CH2:116][CH2:117][CH2:118][CH2:119][NH:120][C:121]([O:123][C:124]([CH3:127])([CH3:126])[CH3:125])=[O:122])=[O:113])[CH2:100][CH2:101][CH2:102][CH2:103][NH:104][C:105]([O:107][C:108]([CH3:111])([CH3:110])[CH3:109])=[O:106])=[O:97])[CH2:87][CH2:88][C:89](=[O:95])[O:90][C:91]([CH3:94])([CH3:93])[CH3:92].C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.CN1CCOCC1.N1C(=O)CC[C@H]1C(O)=O.Cl.N[C@H](C(O)=O)C(C)C>CC(O)=O.CO.C(Cl)(Cl)Cl.O.CCCCO.CS(C)=O.CN(C=O)C>[NH:85]([C:131]([O:133][CH2:134][C:135]1[CH:136]=[CH:137][CH:138]=[CH:139][CH:140]=1)=[O:132])[C@H:86]([C:96]([NH:98][C@H:99]([C:112]([NH:114][C@H:115]([C:128]([NH:1][C@H:2]([C:12]([NH:14][C@H:15]([C:19]([NH:21][C@H:22]([C:26]([NH:28][C@H:29]([C:39]([NH:41][C@H:42]([C:52]([NH:54][C@H:55]([C:57]([NH:59][C@H:60]([C:70]([NH:72][C@H:73]([C:78]([O:80][C:81]([CH3:84])([CH3:83])[CH3:82])=[O:79])[CH2:74][C:75](=[O:77])[NH2:76])=[O:71])[CH2:61][CH2:62][C:63](=[O:69])[O:64][C:65]([CH3:68])([CH3:67])[CH3:66])=[O:58])[CH3:56])=[O:53])[CH2:43][CH2:44][C:45](=[O:51])[O:46][C:47]([CH3:48])([CH3:49])[CH3:50])=[O:40])[CH2:30][CH2:31][C:32](=[O:38])[O:33][C:34]([CH3:35])([CH3:36])[CH3:37])=[O:27])[CH:23]([CH3:25])[CH3:24])=[O:20])[CH:16]([CH3:18])[CH3:17])=[O:13])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:129])[CH2:116][CH2:117][CH2:118][CH2:119][NH:120][C:121]([O:123][C:124]([CH3:127])([CH3:126])[CH3:125])=[O:122])=[O:113])[CH2:100][CH2:101][CH2:102][CH2:103][NH:104][C:105]([O:107][C:108]([CH3:111])([CH3:110])[CH3:109])=[O:106])=[O:97])[CH2:87][CH2:88][C:89](=[O:95])[O:90][C:91]([CH3:92])([CH3:93])[CH3:94]
Reactant: CC(C)[C@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(=O)OC(C)(C)C)C(C)C)C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)OC(C)(C)C
Reactant: CC(C)(C)OC(=O)CC[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(=O)N[C@@H](CCCCNC(=O)OC(C)(C)C)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CC(C)[C@H](N)C(=O)O
Agent: Cl
Solvent: CCCCO
Solvent: CN(C)C=O
Solvent: CO
Product: CC(C)[C@H](NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@H](CCCCNC(=O)OC(C)(C)C)NC(=O)[C@H](CCC(=O)OC(C)(C)C)NC(=O)OCc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)OC(C)(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)OC(C)(C)C)C(C)C
Reaction time: 21 h

Procedure:
The DMF:DMSO-containing solution of H-Glu(OtBu)-Val-Val-Glu(OtBu)-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu (~32 mmol) from Example 3 was combined with Z-Glu(OtBu)-Lys(Boc)-Lys(Boc)-OH, III, Ro 22-4541 (36.8 g, 46 mmol, 1.44 eq.) and HOBt (14.7 g, 96 mmol, 3 eq.) added and the solution cooled to 0°. DCC (10.9 g, 52 mmol, 1.65 eq.) was added to the cold stirring (mechanical) reaction mixture and the pH was maintained at 7.5-8.0 by addition of N-methylmorpholine (21 mL). Stirring proceeded for 2 h at 0° and 21 h at 25°. The resultant gelatenous reaction mixture was poured into H2O (9.0 L) and stirred for 4 h. The product was collected by filtration, washed with H2O (8×500 mL), dried and washed with MeOH using the centrifuge to separate the 2 phases. When all the dicyclohexylurea was removed the product was combined and dried in vacuo to give 45.22 g (71.5 %); mp 312° dec; [α]D25 -18.20° (c 1, DMSO); [α]D25 -13.27° (c 1, TFE); Rf 0.81 (n-BuOH:AcOH:Pyr:H2O; 15-3-10-12); Rf 0.52 (CHCl3 :MeOH:AcOH; 85-10-5). Amino Acid Anal. (6M HCl, 110°, 24 h): Asp(1.04); Glu(5.04); Ala(1.02); Lys(1.90); Val (1.67).(a)Anal. calc. for C96H160N14O29 (1974.4): C, 58.40; H, 8.17; N, 9.93. Found: C, 57.84; H, 8.28; N, 9.94.