Reaction SMILES: CCN(C(C)C)C(C)C.Cl.Cl.Cl.Cl.[NH2:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][N:26]([CH3:72])[CH2:27][CH2:28][N:29]([CH3:71])[C:30](=[O:70])[C:31]1[CH:69]=[CH:68][CH:67]=[C:33]([C:34]([NH:36][C:37]2[CH:42]=[CH:41][C:40]([N:43]([CH2:46][CH3:47])[CH2:44][CH3:45])=[CH:39][C:38]=2[C:48]2[CH:53]=[C:52]([C:54](=[O:66])[NH:55][C@@H:56]3[C:65]4[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=4)[CH2:59][CH2:58][CH2:57]3)[CH:51]=[CH:50][N:49]=2)=[O:35])[CH:32]=1.[C:73]([O:76][C:77]1[CH:85]=[CH:84][C:80]([C:81](O)=[O:82])=[CH:79][CH:78]=1)(=[O:75])[CH3:74].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(OCC)(=O)C>[C:73]([O:76][C:77]1[CH:85]=[CH:84][C:80]([C:81](=[O:82])[NH:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][O:23][CH2:24][CH2:25][N:26]([CH3:72])[CH2:27][CH2:28][N:29]([CH3:71])[C:30]([C:31]2[CH:69]=[CH:68][CH:67]=[C:33]([C:34](=[O:35])[NH:36][C:37]3[CH:42]=[CH:41][C:40]([N:43]([CH2:44][CH3:45])[CH2:46][CH3:47])=[CH:39][C:38]=3[C:48]3[CH:53]=[C:52]([C:54](=[O:66])[NH:55][C@@H:56]4[C:65]5[C:60](=[CH:61][CH:62]=[CH:63][CH:64]=5)[CH2:59][CH2:58][CH2:57]4)[CH:51]=[CH:50][N:49]=3)[CH:32]=2)=[O:70])=[CH:79][CH:78]=1)(=[O:75])[CH3:74]
Reactant: CCN(CC)c1ccc(NC(=O)c2cccc(C(=O)N(C)CCN(C)CCOCCOCCOCCN)c2)c(-c2cc(C(=O)N[C@H]3CCCc4ccccc43)ccn2)c1
Reactant: CC(=O)Oc1ccc(C(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCOC(C)=O
Product: CCN(CC)c1ccc(NC(=O)c2cccc(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)c3ccc(OC(C)=O)cc3)c2)c(-c2cc(C(=O)N[C@H]3CCCc4ccccc43)ccn2)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.7 %

Procedure:
DIEA (0.11 mL, 0.654 mmol) was added to (S)—N1-(14-amino-3-methyl-6,9,12-trioxa-3-azatetradecyl)-N3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N1-methylisophthalamide tetrahydrochloride 340a (0.101 g, 0.106 mmol), 4-acetoxybenzoic acid (19.1 mg, 0.106 mmol) and HATU (48 mg, 0.127 mmol) in DMF (2 mL) and the mixture stirred for 2 hours at room temperature. The reaction was diluted with ethyl acetate, washed with water and brine, dried (MgSO4) and evaporated. The residue was purified by PTLC (10% methanol/20% ethyl acetate/dichloromethane) to give the intermediate (S)-4-(1-(3-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenylcarbamoyl)phenyl)-2,5-dimethyl-1-oxo-8,11,14-trioxa-2,5-diazahexadecan-16-ylcarbamoyl)phenyl acetate as a yellow foam (0.082 g, 75%); MS (ES, m/z): 972 [M+H]+. Ammonia in methanol (2M, 4 mL) was added and the mixture stirred overnight at room temperature. The reaction was evaporated and the residue purified by PTLC (10% methanol/20% ethyl acetate/dichloromethane) to give product as a yellow foam (0.065 g, 83%); MS (ES, m/z): 928 [M+H]+; NMR (400 MHz, DMSO-d6, ppm): δ 11.7 (m, 1H); 9.93 (s, 1H); 9.13 (d, J=8.4 Hz, 1H); 8.83 (d, J=5.2 Hz, 1H); 8.21 (m, 2H); 7.96-8.06 (m, 1H); 7.84-7.94 (m, 2H); 7.80 (d, J=4.8 Hz, 1H); 7.70 (dd, J=2.0 and 6.8 Hz, 2H); 7.60 (m, 2H); 7.09-7.19 (m, 4H); 7.06 (d, J=3.2 Hz, 1H); 6.85 (dd, J=2.8 and 8.8 Hz, 1H); 6.77 (m, 2H); 5.23 (m, 1H); 3.35-3.60 (m, 25H); 2.99 (m, 3H); 2.92 (m, 2H); 2.33 (m, 1H); 1.90-2.04 (m, 3H); 1.70-1.86 (m, 2H); 1.12 (t, J=6.8 Hz, 6H).