3-Methoxypropylamine → Tert-butyl (3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)(3-methoxypropyl)carbamate

A mixture of 4-(4-((3-bromopropyl)amino)-6-methoxynaphthalen-2-yl)-N-methylpyrimidin-2-amine (189) (0.10 g, 0.25 mmol) and N,N-dimethylacetamide (2 mL) were treated with 3-methoxypropan-1-amine (0.10 mL, 1.0 mmol). The resulting mixture was stirred at room temperature 16 h. The reaction mixture was dried down and treated with di-tert-butyl carbonate solution (1 mL of 0.6 M solution in methanol, 0.6 mmol) and triethylamine (0.5 mL, 3.6 mmol). The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was concentrated (rotary) and dissolved in ethyl acetate (20 mL) and water (10 mL). The aqueous layer was extracted with ethyl acetate (2×10 mL). The combined organics were dried over Na2SO4, filtered and concentrated (rotary). The residue was purified by column chromatography (silica gel) using 85% ethyl acetate/hexanes as the eluent to afford tert-butyl (3-((7-methoxy-3-(2-(methylamino)pyrimidin-4-yl)naphthalen-1-yl)amino)propyl)(3-methoxypropyl)carbamate (190) as an orange oil (0.05 g). The residue was dissolved in dioxane (1 mL) and then treated with HCl (4 M in dioxane, 0.5 mL, 7.2 mmol). The reaction mixture was stirred at room temperature and then filtered to afford N-{7-methoxy-3-[2-(methylamino)pyrimidin-4-yl]-1-naphthyl}-N′-(3-methoxypropyl)propane-1,3-diamine was isolated as a red-orange solid. M.p.=130-132° C. 400 MHz 1H NMR (DMSO-d6) δ: 8.88 (br s, 2H), 8.44 (d, J=6.3 Hz, 1H), 8.11 (br s, 1H), 7.90 (d, J=9.0 Hz, 1H), 7.66-7.56 (m, 2H), 7.28-7.24 (m, 2H), 3.96 (s, 3H), 3.56-3.41 (m, 4H), 3.22 (s, 3H), 3.20-2.95 (m, 7H); Experimental Elemental Analysis (3.2 equivalents of HCl)=52.49% C, 6.19% H, 12.82% N; Calculated Elemental Analysis 52.50% C, 6.55% H, 13.31% N; LCMS (m/z): 410 [M+H].

1. customThe reaction mixture was dried down
2. stirringThe resulting mixture was stirred at room temperature for 16 h
3. concentrationThe reaction mixture was concentrated (rotary)
4. dissolutiondissolved in ethyl acetate (20 mL)
5. extractionThe aqueous layer was extracted with ethyl acetate (2×10 mL)
6. dry with materialThe combined organics were dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated (rotary)
9. customThe residue was purified by column chromatography (silica gel)

ORD record

ord-ac88514fcc75401e8891789eed6b13fb

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08173808B2