O1CCCCC1[O:7][CH2:8][CH2:9][O:10][C:11]1[C:12]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[N:13][CH:14]=[CH:15][CH:16]=1.N.CC(C)([O-])C.[K+].Cl[C:39]1[C:40]([N:45]2[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]2[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=1>CC(O)=O.[Cl-].[Na+].O.O.[Cl-].[Na+].O.C(#N)C>[C:26]([O:25][C:24]([NH:23][CH2:22][CH2:21][O:20][CH2:19][CH2:18][O:17][C:12]1[C:11]([O:10][CH2:9][CH2:8][O:7][C:39]2[C:40]([N:45]3[CH2:50][CH2:49][N:48]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:47][C@H:46]3[CH3:58])=[N:41][CH:42]=[CH:43][N:44]=2)=[CH:16][CH:15]=[CH:14][N:13]=1)=[O:30])([CH3:29])([CH3:28])[CH3:27]tert-Butyl {2-[2-({3-[2-(tetrahydro-2H-pyran-2-yloxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}carbamate (from Step 1; 0.74 g, 1.7 mmol) was suspended in 2 M HOAc (5 mL) and acetonitrile (1 mL) and heated at 50° C. for two days. The solution was neutralized with concentrated aqueous ammonia. Brine was added (3 mL) and the mixture was extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The remaining oil was dissolved in dry DMSO (10 mL), potassium tert-butoxide (0.36 g, 3.2 mmol) was added followed by tert-butyl (3R)-4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate (from Example 5; 0.59 g, 1.9 mmol) and the mixture was heated at 50° C. for 20 minutes. The reaction mixture was diluted with water/brine (90:10) and extracted with CHCl3 (×3). The combined organic phases were dried (MgSO4), the solvent was removed under reduced pressure and the remaining oil was chromatographed on a column of silica with hexane/EtOAc (70:30) as eluent to give 0.43 g (40%) of the title compound as a colorless oil. LC-UV purity: system (A) 100%. HRMS m/z calcd for C30H46N6O8 (M)+ 618.3377. found 618.3381. Step 3: {2-[2-({3-[2-({3-[(2R)-2-Methylpiperazin-1-yl]pyrazin-2-yl}oxy)ethoxy]pyridin-2-yl}oxy)ethoxy]ethyl}amine, bis(trifluoroacetate).
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