Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10](=[O:45])[CH2:11][NH:12][C:13](=[O:44])[C@H:14]([CH2:39][O:40][CH2:41][CH:42]=[CH2:43])[NH:15][C:16](=[O:38])[C@H:17]([CH:35]([CH3:37])[CH3:36])[NH:18][C:19](=[O:34])[C@H:20]([CH:31]([CH3:33])[CH3:32])[NH:21][C:22](=[O:30])[C@H:23]([CH2:25][O:26][CH2:27][CH:28]=[CH2:29])[NH2:24].[C:46]([O:50][C:51]([N:53]1[CH2:67][CH2:66][CH2:65][C@H:54]1[C:55]([N:57]1[CH2:64][CH2:63][CH2:62][C@H:58]1[C:59](O)=[O:60])=[O:56])=[O:52])([CH3:49])([CH3:48])[CH3:47].C1C=C2N=NN(O)C2=CC=1.O.C(N(CC)C(C)C)(C)C.CCN=C=NCCCN(C)C.Cl>C(Cl)Cl>[CH3:8][O:9][C:10](=[O:45])[CH2:11][NH:12][C:13](=[O:44])[C@H:14]([CH2:39][O:40][CH2:41][CH:42]=[CH2:43])[NH:15][C:16](=[O:38])[C@H:17]([CH:35]([CH3:36])[CH3:37])[NH:18][C:19](=[O:34])[C@H:20]([CH:31]([CH3:33])[CH3:32])[NH:21][C:22](=[O:30])[C@H:23]([CH2:25][O:26][CH2:27][CH:28]=[CH2:29])[NH:24][C:59](=[O:60])[C@@H:58]1[CH2:62][CH2:63][CH2:64][N:57]1[C:55](=[O:56])[C@@H:54]1[CH2:65][CH2:66][CH2:67][N:53]1[C:51]([O:50][C:46]([CH3:47])([CH3:49])[CH3:48])=[O:52]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)O
Reactant: C=CCOC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)COCC=C)C(C)C)C(C)C)C(=O)NCC(=O)OC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: C=CCOC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](COCC=C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)OC(C)(C)C)C(C)C)C(C)C)C(=O)NCC(=O)OC
Temperature: 25 °C
Reaction time: 21 h
Yield: 73 %

Procedure:
O-allyl L-seryl L-valyl L-valyl O-allyl L-seryl glycine methyl ester trifluoroacetate 32 (SEQ ID NO: 1) (0.524 g, 0.799 mmol), N-tert-butoxycarbonyl L-prolyl L-proline 2 (0.250 g, 0.800 mmol) and HOBt hydrate (0.122 g, 0.797 mmol) were dissolved in CH2Cl2 (5 mL). N,N-diisopropylethyl amine (0.103 g, 0.797 mmol) dissolved in CH2Cl2 (5 mL) was added. At this stage the reaction mixture turned into a gel. EDC hydrochloride (0.169 g, 0.882 mmol) was added in portions together with an additional 5 mL of CH2Cl2 and the reaction mixture vigorously stirred for 21 hours at room temperature. The volume was subsequently increased to 50 mL by addition of CH2Cl2. The solution was washed with 2M aqueous H2SO4 (3×20 mL), 7.5%. (w/w) K2CO3 solution (3×20 mL) and saturated brine (30 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording the title compound as an off-white solid (0.489 g, 73%); δH (300 MHz; CDCl3) 7.50-7.37 (3H, m, NH(Valx)/NH(Gly)/NH(Ser(All)x)), 7.12 and 6.85 (1H, d, J 6, NH(Ser(All)y)), 7.02 (1H, d, J 5, NH(Valy)), 5.89-5.71 (2H, m, CH═CH2), 5.24-5.07 (4H, m, CH═CH2), 4.83-4.76 (1H, m, CαH(Ser(All)x)), 4.48-4.38 (3H, m, CαH(Ser(All)y)/CαH(Prox)/CαH(Proy)), 4.31-4.27 (1H, m, CαH(Valy)), 4.23-4.19 (1H, m, CαH(Valx)), 4.09 (1H, dd, J 6 and 18, CαHH(Gly)), 3.99-3.92 (5H, m, CαHH(Gly)/CH2CH═CH2), 3.87-3.37 (8H, m, H2(Ser(All)x)/CH2(Ser(All)y)/CδH2(Prox)/CδH2(Proy)), 3.68 (3H, s, OCH3), 2.34-1.81 (10H, m, CH2(Prox)/CH2(Proy)/CH(CH3)2), 1.44 and 1.36 (9H, s, (CH3)3), 1.02-0.85 (12H, m, CH3); δC (75 MHz; CDCl3) 172.8, 172.6, 171.9, 171.9, 171.8, 171.8, 171.7, 171.3, 171.1, 170.5, 170.4, 170.1, 170.1, 154.5, 153.3, 134.7, 134.6, 133.8, 133.6, 118.0, 117.6, 116.7, 116.6, 80.2, 79.7, 72.3, 72.0, 71.7, 69.5, 68.4, 62.1, 61.6, 61.0, 60.9, 60.1, 59.2, 57.7, 57.7, 55.1, 54.6, 53.2, 53.0, 52.0, 51.9, 47.3, 46.7, 46.5, 41.3, 30.6, 29.9, 29.8, 29.4, 28.9, 28.9, 28.4, 28.3, 25.5, 25.3, 24.5, 23.8, 19.4, 19.0, 18.9, 18.2, 18.1, 18.0, 17.9; m/z (ESI) 858.4575 ([M+Na]+; C40H65N7O12Na requires 858.4588)