Reactions of Amines. V. Synthesis of α-Amino Ketones^1,2

Alkylating reactivity and herbicidal activity of chloroacetamides

“…Compounds 24 – 29 , chloroacetamides of 1‐amino‐2,2‐dialkoxyethane derivatives, were prepared either by amination of haloacetals or N ‐alkylation of aminoacetaldehyde acetals, followed by chloroacetylation, the products being purified by distillation under reduced pressure. Compounds 30 – 36 , chlorocetamides of 6‐amino‐1,4‐dioxaspiro‐[4,5]‐decanes, resulted from ketalisation of 2‐aminocyclohexane hydrochloride,9 followed by N ‐alkylation and chloroacetylation. Solid derivatives were purified by recrystallisation and liquids were purified by column chromatography.…”

Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

“…Although 6-alkoxy and 6-alkyl groups differ with regard to both their electronic and steric character, as well as lipophilicity, the high potency of the 6-triisopropylsilyethynylpurine (40; IC 50 = 17 nM) shows that steric bulk, as well as electronic factors, is an important feature for binding in the ribose pocket of CDK2. The modest improvement in potency observed for the prop-1-ynyl (48) and phenylethynyl (49) derivatives compared with the parent 6-ethynylpurine 41 also suggests that the overall shape of the 6-substituent is an important factor for occupancy of the ribose-binding pocket, supported by the activity of the 6-cyclopropylpurine 55 (IC 50 = 19 nM). These data also suggest that the oxygen atom of the 6-alkoxypurines, which would act as a weak hydrogen bond acceptor, does not make a significant contribution to binding affinity.…”

“…The suspension was heated under reflux for 1 h before filtering through a pad of Celite, eluting with methanol (20 mL). Removal of volatiles under reduced pressure afforded 11 as a white solid (240 mg, 100%); mp 219 °C (dec.) (lit., 48 decomposed at 216 °C). 1 H NMR (300 MHz, DMSO- d 6 ) δ 8.60 (1H, s, H-8), 9.01 (1H, s, H-6), 13.9 (1H, s, N H ).…”

“…The crude material was purified by chromatography (silica; 10% MeOH:DCM) to afford 10 as a white crystalline solid (4.52 g, 75%); mp 171−173 °C (lit., 47 2-Fluoro-9H-purine (11). 48,49 To a stirred suspension of 6-chloro-2-fluoropurine (10) (0.30 g, 1.74 mmol) and palladium hydroxide on carbon (20% w/w, 0.30 g) in methanol (15 mL) was added ammonium formate (0.34 g, 5.35 mmol). The suspension was heated under reflux for 1 h before filtering through a pad of Celite, eluting with methanol (20 mL).…”

“…Purification by chromatography (silica; 0−80% EtOAc:petrol) gave 47 as a colorless glassy compound (94 mg, 78%); R f 0.53 (65% EtOAc:petrol). 1 N-Phenyl-6-(prop-1-yn-1-yl)-9H-purin-2-amine (48). Prepared in accordance with general procedure E from 46 (0.061 g, 0.18 mmol).…”