2-piperidin-2-ylethanol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A! A solution of 1N sodium hydroxide (156 ml, 0.156 mole) was added to a mixture of 2-piperidine-ethanol (20 ml, 0.156 mole) and butyl bromide (21 ml, 0.187 mole) in ethanol (200 ml). The reaction mixture was refluxed for 4 hours, then the solvent was evaporated under vacuum. The aqueous solution was acidified with HCl and washed with ethyl ether, then it was treated with a 32% solution of sodium hydroxide until pH-12 and extracted with ethyl ether. The combined organic phases were anhydrified over sodium sulfate and the solvent was evaporated under vacuum. The resulting crude was purified by distillation yielding 1.7 g of N-butyl-2-piperidine-ethanol (b.p.: 88°-99° C./0mmHg) (yield: 40%). The reaction mixture was refluxed for 4 hours the solvent was evaporated under vacuum washed with ethyl ether it was treated with a 32% solution of sodium hydroxide until pH-12 extracted with ethyl ether the solvent was evaporated under vacuum The resulting crude was purified by distillation

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Piperidine ethanol (39.6 ml, 0.31 mol) was dissolved in 5M aq NaOH (62 ml, 0.31 mol) and dioxan (100 ml). The mixture was cooled to 0° C. and treated with benzyl chloroformate (45.3 ml, 0.32 mol) and 5M NaOH (62 ml, 0.31 mol). Stirring was continued at room temp. for 18 hours. Dioxan was removed in vacuo and the aqueous phase extracted with ether before acidifying with 5N HCl and extracting again with ether. The organic phase was dried and evaporated in vacuo and the residue purified by chromatography on silica gel to give the title compound (77.2 g. 95%). MH+ 264. Dioxan was removed in vacuo the aqueous phase extracted with ether extracting again with ether The organic phase was dried evaporated in vacuo the residue purified by chromatography on silica gel

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The above synthesis may be carried out as follows: To DMF (100 ml) was added 4-chloro-2-imidazol-1-ylpyrimidine (0.50 g, 2.77 mmol), 2-piperidineethanol (0.359 g, 2.77 mmol), and Hünig's base (0.536 g, 4.15 mmol). After heating at 80° C. for 5 hours, the solvent was removed in vacuo and the residue was chromatographed (CH2Cl2/MeOH, 19/1) to give 349 mg (46%) of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (the compound of formula (XVI)), (1H NMR (CDCl3) δ8.54 (s, 2), 8.11 (d, 1), 7.82 (t, 1), 7.11 (d, 1), 6.44 (d, 1), 3.60 (m, 2), 3.03 (m, 1), 1.77 (m); MS: 2.74 (M+H)+). To a solution of 1-[(1H-imidazol-1-yl)pyrimidin-4-yl]piperidine-2-ethanol (25 mg, 0.092 mmol) dissolved in DMF (5 ml) was added NaH (60% dispersion in oil, 5.5 mg, 0.14 mmol) followed by piperonyl chloride (17 mg, 0.10 mmol) and t-butyl ammonium chloride. After stirring for 16 hours at 80° C., the solvent was removed in vacuo and the residue was partitioned with saturated NH4Cl and CH2Cl2. The organic layer was separated, dried (MgSO4), the solvent removed in vacuo, and the residue chromatographed (CH2Cl2/MeOH, 19/1) to give 13 mg (35%) of 4-[2-[[(1,3-benzodioxol-5-yl)methoxy]ethyl]piperidin -1-yl]-2-(1H-imidazol-1-yl)pyrimidine (the compound of formula (Icc)); 1H NMR (CDCl3) δ8.52 (s, 1), 8.05 (d, 1), 7.80 (s, 1), 7.09 (s, 1), 6.73 (m, 3), 6.45 (d, 1), 5.93 (s, 2), 4.30 (s, 2), 3.45 (m, 2),2.95 (m, 1), 1.55 (m); MS: 408.7 (M+H)+. The above synthesis the solvent was removed in vacuo the residue was chromatographed (CH2Cl2/MeOH, 19/1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3 g (14.7 mmol) of 2-chloro-3,5-dinitropyridine, 1.0 ml of THF and 30 mmol of 2-piperidinethanol were placed in a round-bottomed flask. The mixture was maintained at 60° C. for 15 hours with stirring and was then poured into an ice-water mixture with stirring. The precipitate formed was filtered off by suction and dried under vacuum to constant weight. 3.71 g of yellow powder were obtained. with stirring The precipitate formed was filtered off by suction dried under vacuum to constant weight

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(2-Hydroxyethyl)piperidine, HOBt and WSCI are added to N,N-dimethylformamide solution of 4-chlorobutyrate while being cooled with ice and the mixture is reacted at room temperature to obtain 1-(4-(chlorobutanoyl)-2-(2-hydroxyethyl)piperidine. while being cooled with ice the mixture is reacted at room temperature

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(2-Hydroxyethyl)piperidine, HOBt and WSCI are added to N,N-dimethylformamide solution of 4-chlorobutyrate while being cooled with ice and the mixture is reacted at room temperature to obtain 1-(4-(chlorobutanoyl)-2-(2-hydroxyethyl)piperidine. while being cooled with ice the mixture is reacted at room temperature