Reaction SMILES: [CH2:1]([N:3]([CH2:69][CH3:70])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:49])[C:12]2[CH:48]=[CH:47][CH:46]=[C:14]([C:15]([N:17]([CH3:45])[CH2:18][CH2:19][N:20]([CH3:44])[CH2:21][CH2:22][O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][NH:32][C:33](=[O:43])NCCN3CCOCC3)=[O:16])[CH:13]=2)=[C:6]([C:50]2[CH:55]=[C:54]([C:56](=[O:68])[NH:57][C@@H:58]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[CH2:61][CH2:60][CH2:59]3)[CH:53]=[CH:52][N:51]=2)[CH:5]=1)[CH3:2].[NH:71]([CH2:75][CH2:76][OH:77])[CH2:72][CH2:73][OH:74].C(N(CC)C1C=CC(NC(C2C=C(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)OC3C=CC([N+]([O-])=O)=CC=3)C=CC=2)=O)=C(C2C=C(C(=O)N[C@@H]3C4C(=CC=CC=4)CCC3)C=CN=2)C=1)C>C(#N)C.CN(C)C1C=CN=CC=1>[CH2:69]([N:3]([CH2:1][CH3:2])[C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:49])[C:12]2[CH:48]=[CH:47][CH:46]=[C:14]([C:15]([N:17]([CH2:18][CH2:19][N:20]([CH3:44])[CH2:21][CH2:22][O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH2:30][CH2:31][NH:32][C:33](=[O:43])[N:71]([CH2:75][CH2:76][OH:77])[CH2:72][CH2:73][OH:74])[CH3:45])=[O:16])[CH:13]=2)=[C:6]([C:50]2[CH:55]=[C:54]([C:56](=[O:68])[NH:57][C@@H:58]3[C:67]4[C:62](=[CH:63][CH:64]=[CH:65][CH:66]=4)[CH2:61][CH2:60][CH2:59]3)[CH:53]=[CH:52][N:51]=2)[CH:5]=1)[CH3:70]
Reactant: CCN(CC)c1ccc(NC(=O)c2cccc(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)NCCN3CCOCC3)c2)c(-c2cc(C(=O)N[C@H]3CCCc4ccccc43)ccn2)c1
Reactant: OCCNCCO
Agent: CCN(CC)c1ccc(NC(=O)c2cccc(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)Oc3ccc([N+](=O)[O-])cc3)c2)c(-c2cc(C(=O)N[C@H]3CCCc4ccccc43)ccn2)c1
Agent: CN(C)c1ccncc1
Solvent: CC#N
Product: CCN(CC)c1ccc(NC(=O)c2cccc(C(=O)N(C)CCN(C)CCOCCOCCOCCNC(=O)N(CCO)CCO)c2)c(-c2cc(C(=O)N[C@H]3CCCc4ccccc43)ccn2)c1
Temperature: 80 °C
Reaction time: 4 h

Procedure:
This compound was prepared according to the procedure described for the synthesis of (S)—N1-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N3-methyl-N3-(17-methyl-1-morpholino-4-oxo-8,11,14-trioxa-3,5,17-triazanonadecan-19-yl)isophthalamide Example 223 substituting 2,2′-azanediyldiethanol in place of 2-morpholinoethanamine. Into a 100-mL round-bottom flask, was placed a solution of (S)-4-nitrophenyl 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-ylcarbamate (150 mg, 0.15 mmol, 1.00 equiv) in acetonitrile (10 mL), 2,2′-azanediyldiethanol (20 mg, 0.19 mmol, 1.24 equiv), 4-dimethylaminopyridine (28 mg, 0.23 mmol, 1.49 equiv). The resulting solution was stirred for 4 h at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was dissolved in 20 mL of dichloromethane. The resulting mixture was washed with 2×30 mL of NH4Cl (aq). The mixture was dried over sodium sulfate and concentrated under vacuum. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (1#-PreP-HPLC-001 (SHIMADZU)): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, CH3CN and water with 0.05% TFA (22% CH3CN to 38% in 6 min, up to 100% in 1 min, down to 22% in 0.7 min); Detector, Waters2545 UvDector 254&220 nm. This resulted in 11.7 mg (6%) of (S)—N1-(4-(diethylamino)-2-(4-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyridin-2-yl)phenyl)-N3-(1-hydroxy-3-(2-hydroxyethyl)-17-methyl-4-oxo-8,11,14-trioxa-3,5,17-triazanonadecan-19-yl)-N3-methylisophthalamide as yellow oil. LC-MS (ES, m/z): 939 [M+H]+ H-NMR (300 MHz, CD3OD, ppm) 8.96˜8.94 (d, J=5.1 Hz, 1H), 8.74˜8.72 (m, 1H), 8.39 (s, 1H), 8.17˜8.12 (m, 2H), 7.89˜7.87 (m, 2H), 7.78˜7.73 (m, 2H), 7.61˜7.56 (m, 1H), 7.25 (s, 1H), 7.18˜7.16 (m, 3H), 5.41˜5.37 (m, 1H), 4.05˜3.92 (m, 4H), 3.80˜3.39 (m, 26H), 3.13˜3.10 (m, 6H), 2.94˜2.9 (m, 3H), 2.19˜1.86 (m, 4H), 1.26˜1.22 (m, 6H).