3-(bromomethyl)benzaldehyde

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of K2CO3 (2.09 g, 15.2 mmol, 3.00 equiv) in absolute ethanol (20 mL) was treated with pyrroldine (439 μL, 5.05 mmol, 1.00 equiv). 3-(bromomethyl)-benzaldehyde (1.00 g, 5.05 mmol, 1.00 equiv) was introduced, and the reaction was heated to 65° C. for 1 h. The reaction was cooled and filtered. The cake was washed with more ethanol. The filtrate was concentrated to a cloudy oil and partitioned between DCM (50 mL) and 2% w/v aq NaHCO3 (50 mL). The organic phase was collected, and the aq layer was extracted with DCM (2×50 mL). All organic layers were combined, dried (Na2SO4), filtered, and concentrated, giving 3-(pyrrolidin-1-ylmethyl)-benzaldehyde (846 mg, 88% yield) as a pale yellow oil, which was used without further purification. 1H-NMR: 300 MHz, (CDCl3) d: 10.00 (s, 1H), 7.84 (s, 1H), 7.76 (d, J=7.6 Hz, 1H), 7.62 (d, J=7.6 Hz, 1H), 7.47 (dd, J=7.6 Hz, 7.6 Hz, 1H), 3.69 (s, 2H), 2.52 (m, 4H), 1.79 (m, 4H). LCMS-ESI+: calc'd for C12H16NO: 190.1 (M+H+); Found: 190.1 (M+H+). The reaction was cooled filtered The cake was washed with more ethanol The filtrate was concentrated to a cloudy oil partitioned between DCM (50 mL) and 2% The organic phase was collected the aq layer was extracted with DCM (2×50 mL) dried (Na2SO4) filtered concentrated

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 3-(bromomethyl)benzaldehyde (1.00 g, 5.02 mmol) was dissolved in MeOH (100 mL) and treated with 0.5M solution of MeONa (5 equiv.) in MeOH. The mixture was stirred overnight at RT and MeOH was evaporated under reduced pressure. The residue was acidified to pH ˜6 with 1M aqueous HCl solution. DCM (100 mL) was added and the mixture was vigorously stirred overnight. The organic layer was separated, dried over Na2SO4 and the solvent was removed under reduce pressure to furnish the desired material as yellowish oil (560 mg, 3.75 mmol, 74%). 1H NMR (DMSO, 400 MHz): 3.33 (s, 3H), 4.51 (s, 1H), 7.62 (m, 2H), 7.85 (m, 2H), 10.02 (s, 1H). MS 151 (MH+). MeOH was evaporated under reduced pressure DCM (100 mL) was added the mixture was vigorously stirred overnight The organic layer was separated dried over Na2SO4 the solvent was removed

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

実験手順: Prepared as in example 10-5 from 3-(1-((3,5-dimethylisoxazol-4-yl)methyl)-1H-pyrazol-4-yl)imidazolidine-2,4-dione (example 10-1) and 3-(bromomethyl)benzaldehyde. Yield: 35%. 1H NMR (DMSO, 400 MHz): δ2.123 (s, 3H), 2.388 (s, 3H), 4.035 (s, 2H), 4.631 (s, 2H), 5.186 (s, 2H), 7.581 (m, 1H), 7.643 (m, 1H), 7.787 (m, 3H), 8.178 (s, H), 9.997 (s, H). The title compound was shown to inhibit hT2R08 bitter receptor and had an IC50 of 0.2 uM.

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 0.60 g of 3-(bromomethyl)benzaldehyde and 0.45 ml of trimethyl phosphite was stirred at 100° C. for 3 hours. The reaction mixture was subjected to silica gel column chromatography to obtain 0.62 g of oily dimethyl (3-formylbenzyl)phosphonate [Compound No. (x)].

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

実験手順: To a mixture of 1.00 g of 3-(bromomethyl)benzaldehyde and 20 ml of ethanol were added 0.65 ml of methyl thioglycolate and 0.47 g of potassium carbonate, and the mixture was stirred at room temperature for 2.5 hours. To the reaction mixture was added diethyl ether, this was washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.36 g of oily 3-[(methoxycarbonylmethylthio)methyl]benzaldehyde [Compound No. (u)]. this was washed with an aqueous saturated sodium chloride solution dried over anhydrous sodium sulfate concentrated under reduced pressure

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

実験手順: To a mixture of 1.00 g of 3-(bromomethyl)benzaldehyde and 20 ml of ethanol were added 0.65 ml of methyl thioglycolate and 0.47 g of potassium carbonate, and the mixture was stirred at room temperature for 2.5 hours. To the reaction mixture was added diethyl ether, this was washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 0.36 g of oily 3-[(methoxycarbonylmethylthio)methyl]benzaldehyde [Compound No. (u)]. this was washed with an aqueous saturated sodium chloride solution dried over anhydrous sodium sulfate concentrated under reduced pressure

反応条件: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 1.99 g of 3-(bromomethyl)benzaldehyde, 0.80 g of sodium hydroxide and 8 ml of ethylene glycol was heated at 55° C. for 6 hours. After water was added, the mixture was extracted with chloroform and then washed with an aqueous saturated sodium chloride solution. After dried over anhydrous sodium sulfate and then concentration under reduced pressure, the resulting residue was subjected to silica gel column chromatography to obtain 0.79 g of oily 3-[(2-hydroxyethoxy)methyl]benzaldehyde [Compound No. (g)]. the mixture was extracted with chloroform washed with an aqueous saturated sodium chloride solution After dried over anhydrous sodium sulfate concentration under reduced pressure

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

実験手順: To a solution of 3-(bromomethyl)-benzaldehyde (0.467 g, 2.44 mmol) in dichloroethane (20 mL) was added cycloleucine cyclopentyl ester (0.802 g, 4.06 mmol) and sodium triacetoxyborohydride (1.18 g, 5.56 mmol). The mixture was stirred at room temperature for 3 hours, then poured into ethyl acetate (200 mL) and washed with saturated ammonium chloride solution (3 times 50 mL). The organic fraction was dried (MgSO4), concentrated and purified by flash column chromatography (SiO2, 7:3 heptane:ethyl acetate) to yield the desired product (0.568 g, 61% yield). LC/MS: m/z 380/382 [M+H]+ washed with saturated ammonium chloride solution (3 times 50 mL) The organic fraction was dried (MgSO4) concentrated purified by flash column chromatography (SiO2, 7:3 heptane:ethyl acetate)

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

実験手順: To a solution of 3-(bromomethyl)-benzaldehyde (0.503 g, 2.52 mmol) in dichloroethane (20 mL) was added α,α-dimethylglycine cyclopentyl ester (0.893 g, 5.2 mmol) and sodium triacetoxyborohydride (1.47 g, 6.9 mmol). The mixture was stirred at room temperature for 3 hours, then poured into ethyl acetate (200 mL) and washed with saturated ammonium chloride solution (3 times 50 mL). The organic fraction was dried (MgSO4), concentrated and purified by flash column chromatography (SiO2, 7:3 heptane:ethyl acetate) to yield the desired product (0.350 g, 39% yield). LC/MS: m/z 354/356 [M+H]+ washed with saturated ammonium chloride solution (3 times 50 mL) The organic fraction was dried (MgSO4) concentrated purified by flash column chromatography (SiO2, 7:3 heptane:ethyl acetate)

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

実験手順: To a solution of 3-(bromomethyl)-benzaldehyde (0.513 g, 2.57 mmol) in dichloroethane (10 mL) was added L-leucine cyclopentyl ester tosylate (1.29 g, 3.46 mmol) and sodium triacetoxyborohydride (1.37 g, 6.46 mmol). The mixture was stirred for 30 minutes at room temperature then poured into ethyl acetate (200 mL). The organic extracts were washed with saturated ammonium chloride (2 times 50 mL) and water (50 mL). The organic extracts were then dried (MgSO4) and concentrated. The residue was dissolved in ethanol (30 mL) and methylamine hydrochloride (4.17 g, 61.7 mmol) was added followed by sodium hydrogen carbonate (4.32 g, 51 mmol). The mixture was stirred at room temperature for 18 hours then concentrated under vacuum, loaded directly onto a silica gel column and eluted with 95:5 dichloromethane:methanol to yield the desired product (0.130 g, 15% yield). LC/MS: m/z 333.25 [M+H]+ The organic extracts were washed with saturated ammonium chloride (2 times 50 mL) and water (50 mL) The organic extracts were then dried (MgSO4) concentrated The residue was dissolved in ethanol (30 mL) The mixture was stirred at room temperature for 18 hours then concentrated under vacuum eluted with 95:5 dichloromethane