Reaction SMILES: [NH:1]([C:52]([O:54][CH2:55][C:56]1[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=1)=[O:53])[C@H:2]([C:10]([NH:12][C@H:13]([C:21]([N:23]1[CH2:51][CH2:50][CH2:49][C@H:24]1[C:25]([NH:27][C@H:28]([C:36]([NH:38][C@H:39]([C:46](O)=[O:47])[CH2:40][C:41]1[N:45]=[CH:44][NH:43][CH:42]=1)=[O:37])[CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:26])=[O:22])[CH2:14][CH2:15][CH2:16][NH:17][C:18](=[NH:20])[NH2:19])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:9])[NH2:8].Cl.[NH2:63][C@H:64]([C@H:69]([CH2:71][C:72]([NH:74][CH2:75][CH2:76][C:77]([NH:79][C@H:80]([C:87]([NH2:89])=[O:88])[CH2:81][C:82]1[N:86]=[CH:85][NH:84][CH:83]=1)=[O:78])=[O:73])[OH:70])[CH2:65][CH:66]([CH3:68])[CH3:67].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C=O)C.O>[NH:1]([C:52]([O:54][CH2:55][C:56]1[CH:57]=[CH:58][CH:59]=[CH:60][CH:61]=1)=[O:53])[C@H:2]([C:10]([NH:12][C@H:13]([C:21]([N:23]1[CH2:51][CH2:50][CH2:49][C@H:24]1[C:25]([NH:27][C@H:28]([C:36]([NH:38][C@H:39]([C:46]([NH:63][C@H:64]([C@H:69]([CH2:71][C:72]([NH:74][CH2:75][CH2:76][C:77]([NH:79][C@H:80]([C:87]([NH2:89])=[O:88])[CH2:81][C:82]1[N:86]=[CH:85][NH:84][CH:83]=1)=[O:78])=[O:73])[OH:70])[CH2:65][CH:66]([CH3:68])[CH3:67])=[O:47])[CH2:40][C:41]1[N:45]=[CH:44][NH:43][CH:42]=1)=[O:37])[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:26])=[O:22])[CH2:14][CH2:15][CH2:16][NH:17][C:18](=[NH:19])[NH2:20])=[O:11])[CH2:3][CH2:4][CH2:5][NH:6][C:7](=[NH:8])[NH2:9]
Reactant: CC(C)C[C@H](N)[C@@H](O)CC(=O)NCCC(=O)N[C@@H](Cc1c[nH]cn1)C(N)=O
Reactant: N=C(N)NCCC[C@H](NC(=O)OCc1ccccc1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1c[nH]cn1)C(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)C[C@H](NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)[C@H](Cc1ccccc1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)OCc1ccccc1)[C@@H](O)CC(=O)NCCC(=O)N[C@@H](Cc1c[nH]cn1)C(N)=O
Reaction time: 6 h

Procedure:
721 mg of Z-Arg-Arg-Pro-Phe-His-OH×3 HCl (see stage 4.4) (containing 24% by weight of NaCl), 176 mg of H-Sta-β-Ala-His-NH2, 91 mg of HOBt×H2O and 50 μl of N-methylmorpholine are dissolved in 5 ml of DMF. After cooling to 0°, 132 mg of DCCI are added and then the whole is stirred for 6 hours at 0° and left to stand overnight at room temperature. The DCH which has crystallised out is filtered off, the filtrate is concentrated to dryness and the residue is heated for 1 hour at 60° in 14 ml of methanol/glacial acetic acid/H2O (94:3:3). The solution is concentrated to 3 ml and the crude product is precipitated by the addition of 30 ml of diisopropyl ether. In order to convert it into the acetate, the product is dissolved in 5 ml of 0.05N acetic acid, a small amount of insoluble material is filtered off and the solution is filtered slowly through a column (φ=1.2 cm, length=10 cm) of weakly basic ion exchanger in the acetate form (Merck II) equilibrated in 0.05N acetic acid. The eluate is concentrated to approximately 3 ml and lyophilised. Purification is effected by means of Craig partitioning over 750 stages in the system n-pentanol/glacial acetic acid/H2O (4:1:5); K=0.13. The chromatographically pure fractions are combined, concentrated to dryness and the residue is dissolved in 3 ml of H2O and lyophilised. Z-Arg-Arg-Pro-Phe-His-Sta-β-Ala-His-NH2 (acetate form) is obtained in the form of an amorphous, water-soluble powder; Rf (D)=0.17; Rf (M)=0.30; Rf (O)=0.25.