Reaction SMILES: [CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:30])[C@@H:19]([NH2:29])[CH2:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[CH2:6]1)[CH:2]=[CH2:3].[O:31]=[C:32]1[CH2:36][CH2:35][CH2:34][N:33]1[CH:37]([CH2:41][CH:42]=[CH2:43])[C:38](O)=[O:39].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>CN(C=O)C>[CH2:1]([O:4][C@H:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH3:15])=[CH:11][CH:12]=2)[C@@H:7]([NH:16][CH2:17][C@@H:18]([OH:30])[C@@H:19]([NH:29][C:38](=[O:39])[C@@H:37]([N:33]2[CH2:34][CH2:35][CH2:36][C:32]2=[O:31])[CH2:41][CH:42]=[CH2:43])[CH2:20][C:21]2[CH:22]=[C:23]([F:28])[CH:24]=[C:25]([F:27])[CH:26]=2)[CH2:6]1)[CH:2]=[CH2:3]
Reactant: C=CCO[C@@H]1C[C@H](NC[C@@H](O)[C@@H](N)Cc2cc(F)cc(F)c2)c2cc(OC)ccc21
Reactant: C=CCC(C(=O)O)N1CCCC1=O
Agent: O=C([O-])O
Agent: On1nnc2ccccc21
Agent: [Na+]
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: C=CCO[C@@H]1C[C@H](NC[C@@H](O)[C@H](Cc2cc(F)cc(F)c2)NC(=O)[C@H](CC=C)N2CCCC2=O)c2cc(OC)ccc21
Temperature: 25 °C
Reaction time: 18 h
Yield: 26.6 %

Procedure:
Step I (1): A mixture of (2R,3S)-1-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-3-amino-4-(3,5-difluorophenyl)butan-2-ol (73 mg, 0.183 mmol) from stepE(2), 2-(2-oxopyrrolidin-1-yl)pent-4-enoic acid (35 mg, 0.192 mmol) from stepA(2), EDC (35 mg, 0.183 mmol), HOBt (25 mg, 0.192 mmol), DIEA (0.155 mL, 0.870 mmol) in 3 mL of DMF were stirred at room temperature for 18 h. The crude product was purified using reverse phase preparatory HPLC to provide two diastereomers. The fractions containing products were neutralized with solid NaHCO3 prior to concentration in vacuo. Water was added to the solid residues, the aqueous mixtures were extracted with EtOAc, the organic layers were dried over Na2SO4, filtered and concentrated in vacuo to provide 28.4 mg (28% yield) of (S)—N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)-2-(2-oxopyrrolidin-1-yl)pent-4-enamide (diastereomer A, first to elute) and 38.6 mg (38% yield) of (R)—N-((2S,3R)-4-((1S,3R)-3-(allyloxy)-6-methoxy-2,3-dihydro-1H-inden-1-ylamino)-1-(3,5-difluorophenyl)-3-hydroxybutan-2-yl)-2-(2-oxopyrrolidin-1-yl)pent-4-enamide (diastereomer B, second to elute). Data for diastereomer A: LC-MS (M+H)+=584.37, HRMS (M+H)+=584.2927; 1H NMR (500 MHz, CDCl3) δ 7.30 (d, J=8.24 Hz, 1H), 6.91 (d, J=2.14 Hz, 1H), 6.83 (dd, J=8.24, 2.44 Hz, 1H), 6.65-6.80 (m, J=6.10, 6.10 Hz, 2H), 6.54-6.68 (m, 2H), 5.85-6.06 (m, 1H), 5.51-5.72 (m, 1H), 5.31 (dd, J=17.24, 1.68 Hz, 1H), 5.18 (dd, J=10.38, 1.53 Hz, 1H), 4.94-5.12 (m, 2H), 4.77 (dd, J=6.26, 4.43 Hz, 1H), 4.52 (dd, J=9.00, 6.56 Hz, 1H), 3.96-4.24 (m, 4H), 3.79 (s, 3H), 3.39-3.59 (m, 1H), 3.03-3.35 (m, 2H), 2.75-2.93 (m, 2H), 2.46-2.76 (m, 4H), 2.20-2.40 (m, 2H), 2.07-2.22 (m, 1H), 1.79-1.96 (m, 2H), 1.66-1.81 (m, 1H). Data for diasteomer B: LC-MS (M+H)+=584.97; HRMS (M+H)+=584.2955; 1H NMR (500 MHz, CDCl3) δ 7.29 (d, J=8.54 Hz, 1H), 6.97-7.13 (m, 1H), 6.89-6.97 (m, 1H), 6.83 (dd, J=8.39, 2.29 Hz, 1H), 6.73 (m, 2H), 6.57-6.67 (m, 1H), 5.80-6.05 (m, 1H), 5.41-5.59 (m, 1H), 5.24-5.39 (m, 1H), 5.17 (d, J=10.38 Hz, 1H), 4.88-5.10 (m, 2H), 4.67-4.84 (m, 1H), 4.35 (dd, J=8.55, 7.02 Hz, 1H), 3.96-4.23 (m, 4H), 3.70-3.87 (m, 3H), 3.50-3.64 (m, 1H), 3.24-3.45 (m, 2H), 3.00 (dd, J=14.19, 4.12 Hz, 1H), 2.80 (dd, J=12.21, 3.36 Hz, 1H), 2.54-2.76 (m, 3H), 2.39-2.55 (m, 1H), 2.19-2.43 (m, 3H), 1.75-1.99 (m, 3H).