Step 1

tert-Butyl (3-(6-amino-9H-purin-9-yl)propyl)carbamate (4) To a suspension of

adenine (2) (1.8 g, 13.3 mmol), potassium carbonate (3.7 g, 26.7 mmol), and 18-crown-6

(0.35 g, 1.3 mmol) in anhydrous DMF (70 mL) was added tert-butyl (3-

bromopropyl)carbamate (4.77 g, 20 mmol). The suspension was stirred at 60°C overnight.

The reaction mixture was cooled to room temperature and inorganics removed by filtration.

The filtrate was concentrated under vacuum, then the residue was dissolved in ethyl acetate

(100 mL) and washed with water (3×50 mL). The organic layer was dried over anhydrous

MgSO and concentrated under vacuum. Purification by column chromatography. Product at

4

5% methanol in dichloromethane as white crystals. Yield: 2.63 g (68%). Melting Point

(.MALE.C): 106-110 TLC: 10% methanol in dichloromethane, R = 0.55 H NMR (DMSO-d )

f
1
6

δ: 8.14 (s, 1H, CH-adenine), 8.13 (s, 1H, CH-adenine), 7.17 (bs, 2H, NH ), 6.91 (app.bs, 1H,
2

NH), 4.14 (t, J = 6.9, 2H, CH ), 2.93 (q, J = 6.3, 2H, CH ), 1.91 (quin, J = 6.7, 2H, CH ), 1.38
2 2 2

(s, 9H, 3×CH -tert-butyl). C NMR (DMSO-d6) δ: 155.93 (C), 155.58 (C), 152.31 (CH), 149.46
3
13

(C), 140.85 (CH), 118.75 (C), 77.62 (C), 40.67 (CH ), 37.11 (CH ), 29.81 (CH ), 28.21 (3×CH -
2 2 2 3

tert-butyl). HRMS (EI): Calculated 292.1648 [M+H] , Found 292.1646 [M+H] .

+ +

Step 2

9-(3-Aminopropyl)-9H-purin-6-amine trifluoroacetic acid salt (6) A solution of tert-butyl (3-(6-

amino-9H-purin-9-yl)propyl)carbamate (4)(2.6 g, 8.9 mmol) in trifluoroacetic

acid/dichloromethane (50 mL ,75:25 v/v) was stirred overnight at room temperature. The

solvent was then co-evaporated with ethanol several times. The residue was saturated with

diethyl ether (75 mL) and stirred for 2 h. 9-(3-aminopropyl)-9H-purin-6-amine trifluoroacetic

acid salt (6) a as white solid collected by filtration. Yield = 3.45 g (93%). Melting Point

(.MALE.C): 194-198 TLC: 10% methanol in dichloromethane, R = 0.00 H NMR (CD OD)
f
1
3

δ: 8.40 (s, 1H, CH-Ar), 8.35 (s, 1H, CH-Ar), 4.61 (t, J = 7.0, 2H, CH ), 3.03 (t, J = 7.6, 2H,
2

CH ), 2.31 (quin, J = 7.5, 2H, CH ). C NMR (CD OD) δ: 152.92 (C), 150.53 (C), 146.77 (CH),
2 2
13
3

144.93 (CH), 119.96 (C), 42.41 (CH ), 38.00 (CH ), 29.10 (CH ).
2 2 2