ethyl 2-formylcyclopropane-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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: This was prepared using the same procedure as for 4-(6-bromo-2-(4-(dimethylamino)phenyl)-3H-imidazo[4,5-b]pyridin-7-yl)-N-phenylpiperazine-1-carboxamide, but here using 2-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide (63 mg, 0.14 mmol), DMF (1.3 mL), ethanol (0.2 mL), 1M Na2S2O4 (3 eq, 0.43 mmol, 0.43 mL) and ethyl 2-formyl-1-cyclopropanecarboxylate (1.1 eq, 0.16 mmol, 0.021 mL). After 16 h, concentration in vacuo and preparation by preparative tlc (EtOAc—CH2Cl2-MeOH, 50:50:2) gave the product (19 mg, 25%) as a colourless solid; 1H-NMR (500 MHz, DMSO-d6) 1.21 (t, J=7.1 Hz, 3H, CH2CH3), 1.56 (app. quintet, J=4.6 Hz, 1H, cyclopropane CHAHB), 1.64-1.67 (m, 1H, cyclopropane CHAHB), 2.26 (app. quintet, J=5.0 Hz, cyclopropane CH), 2.73 (br s, 4H, piperazine N(CH2)2), 3.38 (s, 2H, NCH2CO), 3.57 (br s, 4H, piperazine N(CH2)2), 4.13 (q, J=7.1 Hz, 2H, CH2CH3), 7.23 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 7.48 (d, J=3.5 Hz, 1H, thiazole H-4 or H-5), 8.17 (s, 1H, imidazo[4,5-b]pyridine H-5), 11.86 (br s, 1H, CONH or imidazo[4,5-b]pyridine NH), 12.94 (br s, 1H, CONH or imidazo[4,5-b]pyridine NH); This was prepared concentration in vacuo and preparation by preparative tlc (EtOAc—CH2Cl2-MeOH, 50:50:2)

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

実験手順: Ethyl 2-formyl-1-cyclopropanecarboxylate (2 ml, 15.11 mmol) was dissolved in methanol (35 ml) and cooled to 0° C. under N2. Sodium borohydride (1.2 g, 31.7 mmol) was added in portions and resulting solution stirred at 0° C. for 2 h. The solution was then diluted by the dropwise addition of water, followed by the addition of EtOAc (100 mL). The aqueous layer was separated and extracted with EtOAc (2×50 mL). The combined organic layers were washed with brine, dried over sodium sulphate and concentrated in vacuo to give the title compound. TLC: 20% EtOAc/hexanes, high Rf: 0.35, low Rf: 0.3. resulting solution The aqueous layer was separated extracted with EtOAc (2×50 mL) The combined organic layers were washed with brine dried over sodium sulphate concentrated in vacuo

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

実験手順: A mixture of 12.4g of 1'-hydroxy-2-(methylsulfinyl)-2'-acetonaphthone, 7.1g of ethyl 2-formyl-1-cyclopropane carboxylate, 250ml of toluene and 0.5ml of piperidine was refluxed for 8 hrs. The toluene was then removed under reduced pressure, and the oily residue was recrystallized from Skelly B with the aid of charcoal, mp. 106°-07.5°; yield 6.5g (42%); λ max mμ (ε) 219 (50,000), 259 (36,800), 327 (3,990), 341 (4,100); ν max 760 (m), 825 (ms), 1195 (s), 1640 (s), 1650 (s), 1730 (s) cm-1. was refluxed for 8 hrs The toluene was then removed under reduced pressure the oily residue was recrystallized from Skelly B with the aid of charcoal, mp. 106°-07 5°

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: 1-Amino-5-chloro-3,6-dimethylpyridin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (100 mg, 269 μmol, Eq: 1.00) was added to a solution of ethyl 2-formylcyclopropanecarboxylate (38.2 mg, 269 μmol, Eq: 1.00) in methanol (2 ml). 2 N KOH aq (200 μl, 400 μmol, Eq: 1.49) was added and the yellow mixture was stirred for 1 h at room temperature under air. 1 N LiOH aq (4 mL, 4 mmol, Eq: 14.9) and tetrahydrofuran (8 ml) were added and the mixture was stirred for 30 min at room temperature. Volatile organic solvents were evaporated, water (10 ml) was added and the mixture was washed with diethyl ether (10 ml). The aqueous phase was acidified with 2 N HCl aq and then extracted with ethyl acetate (3×10 ml). The combined organic layers were dried over sodium sulfate and then concentrated to give the desired product (70 mg, 98%) as a white solid. MS: m/z=266.1 (M+H+) the mixture was stirred for 30 min at room temperature Volatile organic solvents were evaporated water (10 ml) was added the mixture was washed with diethyl ether (10 ml) extracted with ethyl acetate (3×10 ml) The combined organic layers were dried over sodium sulfate concentrated

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

実験手順: 1-Amino-5-chloro-3,6-dimethylpyridin-2(1H)-iminium 2,4,6-trimethylbenzenesulfonate (100 mg, 269 μmol, Eq: 1.00) was added to a solution of ethyl 2-formylcyclopropanecarboxylate (38.2 mg, 269 μmol, Eq: 1.00) in methanol (2 ml). 2 N KOH aq (200 μl, 400 μmol, Eq: 1.49) was added and the yellow mixture was stirred for 1 h at room temperature under air. 1 N LiOH aq (4 mL, 4 mmol, Eq: 14.9) and tetrahydrofuran (8 ml) were added and the mixture was stirred for 30 min at room temperature. Volatile organic solvents were evaporated, water (10 ml) was added and the mixture was washed with diethyl ether (10 ml). The aqueous phase was acidified with 2 N HCl aq and then extracted with ethyl acetate (3×10 ml). The combined organic layers were dried over sodium sulfate and then concentrated to give the desired product (70 mg, 98%) as a white solid. MS: m/z=266.1 (M+H+) the mixture was stirred for 30 min at room temperature Volatile organic solvents were evaporated water (10 ml) was added the mixture was washed with diethyl ether (10 ml) extracted with ethyl acetate (3×10 ml) The combined organic layers were dried over sodium sulfate concentrated

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 2-formyl-1-cyclopropanecarboxylate (predominately trans, 331 μL, 2.5 mmol) in tetrahydrofuran (5 mL) was cooled down to −70° C. Ethynylmagnesium bromide (0.5 M in tetrahydrofuran, 5 mL, 2.5 mmol) was added to the above solution under an atmosphere of nitrogen dropwise, and stirred at −70° C. for 1 h. The reaction was quenched with water, and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated to get 419 mg of the title compound (yield 100%, unpurified) as a pale yellow oil. The reaction was quenched with water extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered concentrated

反応条件: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of ethyl 2-formyl-1-cyclopropanecarboxylate (predominately trans, 331 μL, 2.5 mmol) in tetrahydrofuran (5 mL) was cooled down to −70° C. Ethynylmagnesium bromide (0.5 M in tetrahydrofuran, 5 mL, 2.5 mmol) was added to the above solution under an atmosphere of nitrogen dropwise, and stirred at −70° C. for 1 h. The reaction was quenched with water, and extracted with ethyl acetate. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated to get 419 mg of the title compound (yield 100%, unpurified) as a pale yellow oil. The reaction was quenched with water extracted with ethyl acetate The organic phase was washed with brine dried over MgSO4 filtered concentrated

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 0.10 g (0.25 mmol) [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (Example 3) were added 0.036 g (0.25 mmol) ethyl 2-formyl-1-cyclopropane-carboxylate (commercially available, CAS RN 20417-61-2), 0.008 g (0.026 mmol) dibutyltin dichloride and 0.06 mL (0.50 mmol) phenylsilane. The resulting solution was heated for 10 min. in a microwave oven at 150° C. The light yellow solution was evaporated and dissolved in acetonitrile containing a few drops of N,N-dimethylformamide. The suspension was filtered using a syringe micro filter and purified on a preparative HPLC system (Phenomenex Gemini column) using a gradient of acetonitrile:water (containing 0.05% formic acid) (10:90 to 98:2) to give 60 mg (46%) of the desired compound as a light brown foam. MS (ESI): m/z=526.13 [M+H]+. The light yellow solution was evaporated dissolved in acetonitrile containing a few drops of N,N-dimethylformamide The suspension was filtered micro filter purified on a preparative HPLC system (Phenomenex Gemini column)