(2R)-1-phenoxypropan-2-amine

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dissolve (R)-2-(tert-butoxycarbonylamino)-3-phenoxy-propane (340 mg, 1.35 mmol) in DCM (80 mL), add trifluoroacetic acid (35 mL), and stir at 0° C. for 2 h. Evaporate and purify by SCX chromatography to give the title compound as a colorless oil (186 mg, 91%). MS (ES+) m/z: 151 (M+H)+. Evaporate purify by SCX chromatography

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dissolve (R)-2-(tert-butoxycarbonylamino)-3-phenoxy-propane (340 mg, 1.35 mmol) in DCM (80 mL), add trifluoroacetic acid (35 mL), and stir at 0° C. for 2 h. Evaporate and purify by SCX chromatography to give the title compound as a colorless oil (186 mg, 91%). MS (ES+) m/z: 151 (M+H)+. Evaporate purify by SCX chromatography

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-1-phenoxy-2-propylamine (0.56 g, 3 mmol) was reacted with 9-(2,3,5-tri- O-acetyl-β-D-ribofuranosyl)-6-chloro-2-methyl-9H-Purine (0.43 g, 1 mmol) [prepared from 2-methylinosine (Journal of Organic Chemistry, 1967, 32, 3258-3260) by standard acylation and chlorination steps] in dioxan (20 ml) in the presence of triethylamine (0.41 g, 4 mmol). The reaction mixture was heated at 50° C. for 70 h, and at 90° C. for 3 h. before being filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the title 2-methyl- N-[(R)-1-phenoxy-2-propyl]adenosine (after column chromatography) as a foam (0.21 g, 50%), 1H NMR (DMSO-d6)δ 1.30 (3H, d, --CH3), 2.43 (3H, s, --CH3), 3.53-3.60 (1H, m, H-5'a), 3.66-3.73 (1H, m, H-5'b), 3.94 (1H, dd, --C--H), 3.99 (1H, q, H-4'), 4.12-4.22 (2H, m, H-3' and --C--H), 4.54 (1H, dd, H-2'), 4.76 (1H, m, --CH3C H--), 5.20, 5.52 (2H, 2d, 2' and 3'-OH), 5.73 (1H, t, 5'-OH), 5.87 (1H, d, H-1'), 6.90-7.31 (5H, t, m, t, Ar--H), 7.74 (1H, br d, N--H), 8.28 (1H, s, H-8). at 90° C. for 3 h. before being filtered evaporated The product (after purification by flash chromatography)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 9-(2,3,5-Tri- O-acetyl-β-D-ribofuranosyl)-6-chloro-2-fluoro-9H-purine (1.03 g, 2.38 mmol) PCT Publication No. WO 938206, (R)-1-phenoxy-2-propylamine (0.36 g, 2.38 mmol) and triethylamine (0.29 g, 0.28 mmol) in dioxan (20 ml) were stirred at room temperature for 18 h. The reaction mixture was filtered and evaporated to a residue which was purified by flash chromatography. The resultant 2',3',5'-tri- O-acetyl-2-fluoro- N-[(R)-1-phenoxy-2-propyl]adenosine was deprotected using methanolic ammonia to provide the title 2-fluoro- N-[(R)-1-phenoxy-2-propyl]adenosine (0.28 g, 23%)(after column chromatography), mp 148°-150° C.; 1H NMR (DMSO-d6)δ 1.33 (3H, d, -3.59 (1H, m, H-5'a), 3.63-3.71 (1H, m, H-5'b), 3.92-3.99 (2H, m, H-4' and --C--H), 4.10-4.18 (2H, m, H-3' and --C--H), 4.51 (1H, q, H-2'), 4.61 (1H, m, --CH3C H--), 5.06 (1H, t, 5'-OH), 5.22, 5.48 (2H, 2d, 2' and 3'-OH), 5.82 (1H, d, H-1'), 6.89-6.97 (3H, m, Ar--H), 7.25-7.30 (2H, t, Ar--H), 8.39 (1H, s, H-8), 8.49 (1H, d, N--H). The reaction mixture was filtered evaporated to a residue which was purified by flash chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)-1-phenoxy-2-propylamine (4.3 g, 23 mmol) was reacted with 9-(2,3,5-tri- O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (11.2 g, 18 mmol) in dioxan (150 ml) in the presence of diisopropylethylamine (5.3 g, 41 mmol). The reaction mixture was stirred at room temperature for 18 h, heated at 50° C. for 4 h, and stirred at room temperature for 60 h before being filtered and evaporated. The product (after purification by flash chromatography) was debenzoylated with methanolic ammonia to provide the title 2-chloro- N-[(R)-1-phenoxy-2-propyl]adenosine (after column chromatography) as a foam (4.2 g, 64%), 1H NMR (DMSO-d6)δ 1.31 (3H, d, --CH3), 3.52-3.59 (1H, m, H-5'a), 3.63-3.72 (1H, m, H-5'b), 3.92-3.99 and 4.10-4.21 (4H, 2 m, H-3', H-4' and --CH2 --), 4.52 (1H, dd, H-2'), 4.65 (1H, m, --CH3C H--), 5.07 (1H, t, 5'-OH), 5.22, 5.49 (2H, 2d, 2' and 3'-OH), 5.84 (1H, d, H-1 '), 6.88-7.02 (3H, m, Ar--H), 7.24-7.33 (2H, dd, Ar--H), 8.32-8.45 (2H, s & m, H-8 and N--H). heated at 50° C. for 4 h stirred at room temperature for 60 h before being filtered evaporated The product (after purification by flash chromatography)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (R)- N-(tert-Butoxycarbonyl)-1-phenoxy-2-propylamine (8.0 g, 33 mmol) was dissolved in ethyl acetate (100 ml). A solution of hydrochloric acid (g) in ethyl acetate (6N, 100 ml) was added dropwise at room temperature. The reaction mixture was stirred at room temperature for 20 h during which time a heavy precipitate was formed. The reaction mixture was concentrated to half the original volume before the product was collected by filtration and dried in vacuo to provide the title compound as a white solid hydrochloride (4,3 g, 69%) m.p. 186°-189° C. 1H NMR (DMSO-d6)δ 1.31 (3H, d, --CH3), 3.51-3.60 (1H, m, --CH--), 4.05 (1H, dd, --CH2 a-), 4.12 (1H, dd, --CH2 b-), 6.95-7.00 (3H, m. Ar--H), 7.32 (2H, t, Ar--H). was formed The reaction mixture was concentrated to half the original volume before the product was collected by filtration dried in vacuo

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dissolve (R)-2-(tert-butoxycarbonylamino)-3-phenoxy-propane (340 mg, 1.35 mmol) in DCM (80 mL), add trifluoroacetic acid (35 mL), and stir at 0° C. for 2 h. Evaporate and purify by SCX chromatography to give the title compound as a colorless oil (186 mg, 91%). MS (ES+) m/z: 151 (M+H)+. Evaporate purify by SCX chromatography