tert-butyl nitrate

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: To a solution of ethyl 2-amino-5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate in THF was slowly added dropwise tert-butyl nitrate under heating under reflux. After completion of dropwise addition, it was further stirred at the same temperature for 4 hours. The reaction mixture was cooled to room temperature, followed by addition of water and extraction with EtOAc. The organic layer was washed with brine, dried, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3) to obtain ethyl 5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate as a yellow oily substance. under heating under reflux After completion of dropwise addition, it The organic layer was washed with brine dried concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3)

反応条件: temp:-5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Concentrated HCl (1.93 mL, 23.16 mmol) was added to a solution of 3-bromo-4-fluoro-phenylamine ((Example 265: part a) 2.2 g, 11.58 mmol) in 18 mL of 2:1 DCM/MeOH. A precipitate appeared and another 9 mL of 2:1 DCM/MeOH was added. The solution was cooled to −5° C. and tert-butylnitrate (2.71 mL, 23.16 mmol) was added dropwise over 8 min. After stirring for 15 min, sulfur dioxide (˜5 mL) was condensed into the reaction, followed by addition of copper(II) chloride (592 mg, 3.47 mmol) (gas evolution). The solvent was removed in vacuo and the residue was purified by SiO2 flash column chromatography to yield the title compound (1.9 g, 59%). 1H-NMR (CDCl3): δ 8.31 (dd, 1H, J=2.3, 5.8 Hz), 8.04 (ddd, 1H, J=2.6, 4.1, 8.8 Hz), 7.39 (dd, 1H, J=7.7, 8.8 Hz). condensed into the reaction The solvent was removed in vacuo the residue was purified by SiO2 flash column chromatography

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

実験手順: To a solution of ethyl 2-amino-5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate in THF was slowly added dropwise tert-butyl nitrate under heating under reflux. After completion of dropwise addition, it was further stirred at the same temperature for 4 hours. The reaction mixture was cooled to room temperature, followed by addition of water and extraction with EtOAc. The organic layer was washed with brine, dried, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3) to obtain ethyl 5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate as a yellow oily substance. under heating under reflux After completion of dropwise addition, it The organic layer was washed with brine dried concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3)

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

実験手順: To a solution of ethyl 2-amino-5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate in THF was slowly added dropwise tert-butyl nitrate under heating under reflux. After completion of dropwise addition, it was further stirred at the same temperature for 4 hours. The reaction mixture was cooled to room temperature, followed by addition of water and extraction with EtOAc. The organic layer was washed with brine, dried, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3) to obtain ethyl 5-(2,6-difluorophenyl)-1,3-thiazole-4-carboxylate as a yellow oily substance. under heating under reflux After completion of dropwise addition, it The organic layer was washed with brine dried concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane:EtOAc=9:1-7:3)

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

実験手順: In a similar manner to Step 4 of Example 140, 7-amino-4-(3-tert-butyldimethylsilyloxyphenyl)isoindolinone (115 mg, 0.324 mmol) was dissolved in acetonitrile (8.0 mL), and the solution was treated with potassium iodide (73.8 mg, 0.441 mmol), copper iodide (84.8 mg, 0.441 mmol), iodine (113 mg, 0.441 mmol) and tert-butyl nitrate (0.071 mL, 0.551 mmol), followed by purification by flash column chromatography (chloroform) to obtain 7-iodo-4-(3-tert-butyldimethylsilyloxyphenyl)isoindolinone (78.6 mg, yield 52%). followed by purification by flash column chromatography (chloroform)

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

実験手順: In a similar manner to Step 4 of Example 140, 7-amino-4-(4-tert-butyldimethylsilyloxyphenyl)isoindolinone (179 mg, 0.505 mmol) was dissolved in acetonitrile (12.5 mL), and the solution was treated with potassium iodide (133 mg, 0.808 mmol), copper iodide (152 mg, 0.808 mmol), iodine (203 mg, 0.808 mmol) and tert-butyl nitrate (0.127 mL, 1.06 mmol), followed by purification by flash column chromatography (chloroform) to obtain 7-iodo-4-(4-tert-butyldimethylsilyloxyphenyl)isoindolinone (109 mg, yield 47%). followed by purification by flash column chromatography (chloroform)

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

実験手順: In a similar manner to Step 4 of Example 140, 7-amino-4-(4-tert-butyldimethylsilyloxy-3-methoxyphenyl)isoindolinone (43.0 mg, 0.110 mmol) was dissolved in acetonitrile (6 mL), and the solution was treated with potassium iodide (29.2 mg, 0.176 mmol), copper iodide (33.5 mg, 0.896 mmol), iodine (44.7 mg, 0.896 mmol) and tert-butyl nitrate (0.059 mL, 0.50 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1) to obtain 7-iodo-4-(4-tert-butyldimethylsilyloxy-3-methoxyphenyl)isoindolinone (33.8 mg, yield 62%). followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1)

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

実験手順: In a similar manner to Step 4 of Example 140, a mixture of 7-amino-4-methylisoindolinone and 7-aminoisoindolinone (10/1, 57.4 mg, 0.357 mmol) was dissolved in acetonitrile (4.6 mL), and the solution was treated with potassium iodide (78 mg, 0.47 mmol), copper iodide (90 mg, 0.47 mmol), iodine (120 mg, 0.471 mmol) and tert-butyl nitrate (0.128 mL, 1.07 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1) to obtain a mixture of 7-iodo-4-methylisoindolinone and 7-iodoisoindolinone (44.8 mg, ratio 10/1, yield 50%). followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1) to obtain

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

実験手順: In a similar manner to Step 4 of Example 140, 7-amino-4-ethylisoindolinone (46.0 mg, 0.260 mmol) was dissolved in acetonitrile (6.2 mL), and the solution was treated with potassium iodide (69.1 mg, 0.416 mmol), copper iodide (79.2 mg, 0.416 mmol), iodine (106 mg, 0.416 mmol) and tert-butyl nitrate (0.139 mL, 1.17 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1) to obtain 7-iodo-4-ethylisoindolinone (37.1 mg, yield 50%). followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile=5/1)

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: In a similar manner to Step 4 of Example 140, 7-amino-4-(3-tert-butyldimethylsilyloxyphenyl)isoindolinone (115 mg, 0.324 mmol) was dissolved in acetonitrile (8.0 mL), and the solution was treated with potassium iodide (73.8 mg, 0.441 mmol), copper iodide (84.8 mg, 0.441 mmol), iodine (113 mg, 0.441 mmol) and tert-butyl nitrate (0.071 mL, 0.551 mmol), followed by purification by flash column chromatography (chloroform) to obtain 7-iodo-4-(3-tert-butyldimethylsilyloxyphenyl)isoindolinone (78.6 mg, yield 52%). followed by purification by flash column chromatography (chloroform)