chlorocyclohexane

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: Under an inert gas, 24.3 g magnesium chips (1.0 mol) were combined with about 10 ml methyl-tert-butylether, an iodine crystal and 3.6 g cyclohexylchloride (0.03 mol). To start the reaction, a solution of 152.0 g isobutyltrimethoxysilane (0.85 mol) and 115.0 g cyclohexylchloride (0.97 mol) in 130 ml methyl-tert-butylether was added dropwise, with stirring, to the first mixture at a rate to maintain a moderate reflux. At the end of this addition, the reaction was allowed to reflux for two more hours. After cooling the reaction mixture, 4.8 g methanol (0.15 mol) was added, stirred for a few minutes and then the precipitate was removed by filtration. The filter cake was washed with several portions of methyl-tert-butylether. The solvent was evaporated from the combined filtrates by water vacuum. The remaining residue consisted of 192.5 g (98.4% of the theoretical yield) isobutylcyclohexyldimethoxysilane which had a purity of 98% according to GC. Isobutyldicyclohexylmethoxysilane was not detected by GC. the reaction to maintain a moderate reflux At the end of this addition to reflux for two more hours was added stirred for a few minutes the precipitate was removed by filtration The filter cake was washed with several portions of methyl-tert-butylether The solvent was evaporated from the combined filtrates by water vacuum

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.83 g of aluminum chloride was added to 20.0 g of benzene, and the mixture was stirred under cooling at 3° C. Subsequently, 40.4 g of cyclohexyl chloride was slowly added dropwise and after the dropwise addition, the reaction solution was stirred at room temperature for 5 hours and then poured in ice water. The organic layer was extracted with ethyl acetate, and the obtained organic layer was distilled off under reduced pressure at 40° C., further distilled off under reduced pressure at 170° C., then cooled to room temperature and recrystallized by charging 50 ml of acetone thereinto. The precipitated crystals were collected by filtration to obtain 14 g of tricyclohexylbenzene. after the dropwise addition the reaction solution was stirred at room temperature for 5 hours The organic layer was extracted with ethyl acetate the obtained organic layer was distilled off under reduced pressure at 40° C. further distilled off under reduced pressure at 170° C. cooled to room temperature recrystallized The precipitated crystals were collected by filtration

Conditions: temp:200.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 10 mL microwave tube was charged with 3-bromo-N-propyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine (0.052 g, 0.2 mmol), K2CO3 (0.14 g, 1.0 mmol), DMF (2 mL), and cyclohexyl chloride (0.072 g, 0.6 mmol). The resulting mixture was heated at 200° C. for 30 minutes under microwave irradiation. After the reaction was cooled to room temperature, phenylboronic acid (0.37 g, 0.3 mmol), Pd(PPh3)4 (0.023 g, 0.02 mmol), and H2O (1 mL) were added sequentially. The mixture was stirred at room temperature for 3 min and then heated at 150° C. for 15 min. After cooled to room temperature, the mixture was partitioned in H2O and Et2O. The aqueous phase was extracted with ether (3×). The combined organic phase were dried (Na2SO4) and concentrated. The residue was purified by Isco to provide the 1-cyclohexyl-3-phenyl-N-propyl-1H-pyrazolo[3,4-d]pyrimidin-6-amine (UNC702A) (0.045 g, 67%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.93 (s, 1H), 7.90 (d, J=8.0 Hz, 2H), 7.48 (t, J=6.0 Hz, 2H), 7.38 (t, J=6.0 Hz, 1H), 5.42 (s, 1H), 4.60 (tt, J=11.6, 4.1 Hz, 1H), 3.48 (dt, J=13.1, 6.8 Hz, 2H), 2.18-2.08 (m, 2H), 2.04-2.00 (m, 2H), 1.95-1.92 (m, 2H), 1.77-1.74 (m, 1H), 1.74-1.65 (m, 2H), 1.58-1.42 (m, 2H), 1.40-1.28 (m, 1H), 1.03 (t, J=7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 160.73, 155.38, 153.50, 143.71, 133.27, 129.06, 128.60, 127.09, 106.91, 56.10, 43.68, 32.16, 25.91, 25.61, 22.98, 11.77; MS m/z 336.2 [M+1]. After the reaction was cooled to room temperature heated at 150° C. for 15 min After cooled to room temperature the mixture was partitioned in H2O The aqueous phase was extracted with ether (3×) The combined organic phase were dried (Na2SO4) concentrated The residue was purified by Isco

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6.83 g of aluminum chloride was added to 20.0 g of benzene, followed by cooling/stirring at 3° C., and 40.4 g of cyclohexyl chloride was slowly added dropwise. After the dropwise addition, the mixture was stirred at room temperature for 5 hours and poured into ice water. The organic layer was extracted with ethyl acetate, and the obtained organic layer was distilled off under reduced pressure at 40° C. After further distillation off under reduced pressure at 170° C., the product was cooled to room temperature, charged into 50 ml of acetone and thereby recrystallized. The crystal precipitated was collected by filtration to obtain 14 g of tricyclohexylbenzene. After the dropwise addition the mixture was stirred at room temperature for 5 hours The organic layer was extracted with ethyl acetate the obtained organic layer was distilled off under reduced pressure at 40° C After further distillation off under reduced pressure at 170° C. the product was cooled to room temperature charged into 50 ml of acetone recrystallized The crystal precipitated was collected by filtration

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: First, 6.83 g of aluminum chloride was added to 20.0 g of benzene, and agitated while cooling at 3° C. Then, 40.4 g of cyclohexyl chloride was slowly dropped thereinto. After the completion of the dropping, the mixture was agitated at room temperature for five hours and poured into ice water. The organic phase was extracted with ethyl acetate, and the obtained organic phase was subjected to vacuum distillation at 40° C. Further, vacuum distillation was performed at 170° C., and the product was cooled to room temperature. Thereafter, 50 ml of acetone was placed thereinto, and recrystallization was carried out. The resultant crystal was collected by filtration. Thus, 14 g of tricyclohexylbenzene was obtained. After the completion of the dropping, the mixture was agitated at room temperature for five hours The organic phase was extracted with ethyl acetate the obtained organic phase was subjected to vacuum distillation at 40° C Further, vacuum distillation was performed at 170° C. the product was cooled to room temperature recrystallization The resultant crystal was collected by filtration

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

Procedure: Chlorocyclohexane (59.5 mg, 0.5 mmol) and a THF solution (0.77 mL, 0.97 M, 0.75 mmol) of phenylmagnesium bromide were used as starting materials, and reacted as in Entry 1. Conditions: The THF solution of phenylmagnesium bromide was added dropwise at 40° C. over 2 hours. 1H-NMR analysis was conducted using pyrazine (19.4 mg, 0.24 mmol) as an internal standard (yield 85%). materials, and reacted as in Entry 1

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

Procedure: Chlorocyclohexane (59.5 mg, 0.5 mmol) and a THF solution (0.77 mL, 0.97 M, 0.75 mmol) of phenylmagnesium bromide were used as starting materials, and reacted as in Entry 1. Conditions: The THF solution of phenylmagnesium bromide was added dropwise at 40° C. over 2 hours. 1H-NMR analysis was conducted using pyrazine (19.4 mg, 0.24 mmol) as an internal standard (yield 85%). materials, and reacted as in Entry 1

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

Procedure: A solution of 0.30 g (0.93 mmol) 3-benzyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one, 0.14 g (1.0 mmol) 2-chlorocyclohexane, and 0.2 ml (1.4 mmol) triethylamine in ethanol was refluxed overnight. The reaction mixture was cooled to ambient temperature, concentrated and then quenched with saturated NaHCO3 and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4, filtered and evaporated. Purification of the crude product over a silica gel plug (10:1) with n-heptane/AcOEt as eluent provided 0.14 g rac-3-benzyl-8-(2-oxo-cyclohexyl)-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one as a light yellow oil; MS (ISP): 418.4 MH+. concentrated quenched with saturated NaHCO3 extracted with ethyl acetate The combined organic extracts were washed with brine dried over MgSO4 filtered evaporated Purification of the crude product over a silica gel plug (10:1) with n-heptane/AcOEt as eluent

Conditions: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Aluminum chloride (6.38 g) was added to 20.0 g of benzene, followed by stirring under cooling at 3° C., and 40.4 g of cyclohexyl chloride was slowly added dropwise thereto. After the dropwise addition, the resultant was stirred at room temperature for 5 hours, and the obtained reaction solution was added to ice water. The organic layer was extracted by using ethyl acetate, and the obtained organic layer was removed by distillation at 40° C. under reduced pressure. The resultant was further removed by distillation at 170° C. under reduced pressure and then cooled to room temperature, and 50 ml of acetone was added thereto to cause recrystallization. The precipitated crystals were collected through filtering, thereby obtaining 14 g of tricyclohexylbenzene. After the dropwise addition the resultant was stirred at room temperature for 5 hours the obtained reaction solution The organic layer was extracted the obtained organic layer was removed by distillation at 40° C. under reduced pressure The resultant was further removed by distillation at 170° C. under reduced pressure cooled to room temperature 50 ml of acetone was added recrystallization The precipitated crystals were collected through filtering