1-Amino-4-methylpiperazine → 4-(9'-cyclopentyl-5'-methyl-6'-oxo-5',6',8',9'-tetrahydrospiro[cyclobutane-1,7'-pyrimido[4,5-b][1,4]diazepine]-2'-ylamino)-3-fluoro-N-(4-methylpiperazin-1-yl)benzamide

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4-(9′-Cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-fluorobenzoic acid (Intermediate 10) (100 mg, 0.23 mmol, 1 eq), DIPEA (80 μl, 0.46 mmol, 2 eq) and TBTU (80 mg, 0.25 mmol, 1.1 eq) were added to 1 mL DMF and the resulting solution stirred at rt for 10 min before the addition of 1-amino-4-methylpiperazine (33 μL, 0.27 mmol, 1.2 eq). The RM was then stirred at rt for 1 hour before splitting into two equal batches and purifying by preparative RP-HPLC-MS (Preparative 3) to provide 4-(9′-cyclopentyl-5′-methyl-6′-oxo-5′,6′,8′,9′-tetrahydrospiro[cyclobutane-1,7′-pyrimido[4,5-b][1,4]diazepine]-2′-ylamino)-3-fluoro-N-(4-methylpiperazin-1-yl)benzamide (0.05 g, 41%).

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