Reaction SMILES: C[O:2][C:3](=O)[C:4]([CH3:29])([CH3:28])/[CH:5]=[CH:6]/[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][C:13]([C@H:17]([N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH3:20])[CH3:18])=[N:14]2)=[CH:9][CH:8]=1.O.[OH-].[Li+].CC1C=CC=C([N+]([O-])=O)C=1C(OC(=O)C1C([N+]([O-])=O)=CC=CC=1C)=O.C(N(CC)CC)C.[Cl:66][C:67]([Cl:91])([Cl:90])[CH2:68][O:69][C:70]([C@@H:72]1[CH2:77][CH2:76][CH2:75][N:74]([C:78](=[O:89])[C@@H:79]([NH:81][C:82](=[O:88])[C@@H:83]([OH:87])[CH:84]([CH3:86])[CH3:85])[CH3:80])[NH:73]1)=[O:71]>O1CCOCC1.O.CN(C)C1C=CN=CC=1>[Cl:91][C:67]([Cl:90])([Cl:66])[CH2:68][O:69][C:70]([C@@H:72]1[CH2:77][CH2:76][CH2:75][N:74]([C:78](=[O:89])[C@@H:79]([NH:81][C:82](=[O:88])[C@@H:83]([O:87][C:3](=[O:2])[C:4]([CH3:29])([CH3:28])/[CH:5]=[CH:6]/[C:7]2[CH:16]=[C:15]3[C:10]([CH:11]=[CH:12][C:13]([C@H:17]([N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH3:20])[CH3:18])=[N:14]3)=[CH:9][CH:8]=2)[CH:84]([CH3:86])[CH3:85])[CH3:80])[NH:73]1)=[O:71]
Reactant: COC(=O)C(C)(C)/C=C/c1ccc2ccc([C@@H](C)N(C)C(=O)OC(C)(C)C)nc2c1
Reactant: CC(C)[C@H](O)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1
Agent: CN(C)c1ccncc1
Agent: Cc1cccc([N+](=O)[O-])c1C(=O)OC(=O)c1c(C)cccc1[N+](=O)[O-]
Agent: [Li+]
Solvent: O
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Product: CC(C)[C@H](OC(=O)C(C)(C)/C=C/c1ccc2ccc([C@@H](C)N(C)C(=O)OC(C)(C)C)nc2c1)C(=O)N[C@@H](C)C(=O)N1CCC[C@@H](C(=O)OCC(Cl)(Cl)Cl)N1
Temperature: 50 °C
Reaction time: 1 h
Yield: 68 %

Procedure:
A solution of (E)-4-{2-[(R)-1-(tert-butoxycarbonyl-methyl-amino)-ethyl]-quinolin-7-yl}-2,2-dimethyl-but-3-enoic acid methyl ester (193 mg, 0.47 mmol) in 1,4-dioxane (10 mL) was treated with a solution of lithium hydroxide monohydrate (112 mg, 4.7 mmol) in water (5 mL). After stirring at 50° C. for 1 h, the volatiles were removed in vacuo. The residue was partitioned between water and diethyl ether. The aqueous layer was acidified to pH 2 by addition of hydrochloric acid then extracted with ethyl acetate (3×). The organics were combined and the volatiles were removed in vacuo. The residue was dissolved in dichloromethane (10 mL) and was treated with 4-dimethylaminopyridine (57 mg, 0.47 mmol), 2-methyl-6-nitrobenzoic anhydride (275 mg, 0.80 mmol), and triethylamine (0.197 mL, 1.41 mmol). After stirring for 30 min (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (203 mg, 0.47 mmol) was added. After stirring for 16 h, the reaction was quenched by addition of a sodium bicarbonate solution (10 mL), the aqueous layer was extracted with dichloromethane (2×), the organics were combined and the volatiles were removed in vacuo. The residue was purified by silica gel chromatography using a 25 g Biotage cartridge eluted with a continuous gradient of iso-hexanes/acetone 1:0 to 3:1 to afford the title compound (260 mg, 68%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 0.97-1.05 (m, 6H), 1.29 (d, J=6.9 Hz, 3H), 1.44 (br s, 9H), 1.55 (s, 3H), 1.57 (s, 3H), 1.68 (d, J=6.9 Hz, 3H), 1.71-2.00 (m, 4H), 2.02-2.30 (m, 3H), 2.80 (br s, 3H), 3.56 (br s, 1H), 3.78-3.83 (m, 1H), 4.75-4.82 (m, 1H), 4.93-5.01 (m, 2H), 5.35-5.45 (m, 1H), 6.65-6.82 (m, 2H), 7.36 (d, J=8.5 Hz, 1H), 7.72-7.83 (m, 2H), 7.98 (s, 1H), 8.21 (d, J=8.5 Hz, 1H). LCMS (m/z) 814.1 [M+H], Tr=3.97 min.