2-氨基-5-溴-N,N-二乙基苯甲酰胺

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3C substituting 7-amino-4-bromo-5-fluoro-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 31D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). 1H NMR (CDCl3, 400 MHz): δ 7.75 (d, J=4.5 Hz, 2H), 6.41 (d, J=13.1 Hz, 1H), 4.46 (t, J=6.1 Hz, 2H), 4.39 (s, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.17 (s, 3H), 2.20-2.09 (m, 3H). MS (ESI): m/z=305.14 [M+H]+. UPLC: tR=0.95 min (UPLC-TOF: polar—3 min). tR=0.95 min (UPLC-TOF: polar—3 min)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3C substituting 7-amino-4-bromo-5-fluoro-2-methyl-2,3-dihydro-1H-isoindol-1-one (Compound 31D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). 1H NMR (CDCl3, 400 MHz): δ 7.75 (d, J=4.5 Hz, 2H), 6.41 (d, J=13.1 Hz, 1H), 4.46 (t, J=6.1 Hz, 2H), 4.39 (s, 2H), 3.70 (t, J=5.6 Hz, 2H), 3.17 (s, 3H), 2.20-2.09 (m, 3H). MS (ESI): m/z=305.14 [M+H]+. UPLC: tR=0.95 min (UPLC-TOF: polar—3 min). tR=0.95 min (UPLC-TOF: polar—3 min)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3C substituting 6-amino-3-bromo-2-methoxy-N-methylbenzamide (Compound 30D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). MS (ESI): m/z=305.23 [M+H]+. HPLC: tR=2.48 min (ZQ3: polar—5 min). HPLC: tR=2.48 min (ZQ3: polar—5 min)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3C substituting 6-amino-3-bromo-2-methoxy-N-methylbenzamide (Compound 30D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). MS (ESI): m/z=305.23 [M+H]+. HPLC: tR=2.48 min (ZQ3: polar—5 min). HPLC: tR=2.48 min (ZQ3: polar—5 min)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3C substituting 6-amino-3-bromo-2-methyl-N-methylbenzamide (Compound 29D) for 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D). MS (ESI): m/z=289.29 [M+H]+. UPLC: tR=2.33 min (ZQ3: polar—5 min). tR=2.33 min (ZQ3: polar—5 min)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3D replacing diethylamine with a mixture of methoxylamine hydrochloride (2.07 g, 24.8 mmol) and triethylamine (6.9 mL, 50 mmol) to afford 2.64 g of the title compound (65%). 1H NMR (400 MHz, CD3OD) δ=7.45 (d, J=2.3 Hz, 1H), 7.27 (dd, J=2.3, 8.8 Hz, 1H), 6.69 (d, J=8.8 Hz, 1H), 3.77 (s, 3H).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3D replacing diethylamine with dimethylamine to afford 1.47 g of the title compound (73%). 1H NMR (400 MHz, CD3OD) δ 7.24 (dd, J=2.4, 8.7 Hz, 1H), 7.18 (d, J=2.3 Hz, 1H), 6.70 (d, J=8.8 Hz, 1H), 3.04 (br. s., 6H). MS (ESI): m/z 243.33 [M+H]+. UPLC: tR=0.88 min (UPLC-SQD: analytical—2 min).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared analogously to Compound 3D replacing diethylamine with ethylamine to afford 1.41 g of the title product (70%). 1H NMR (400 MHz, CD3OD) δ 7.55 (d, J=2.3 Hz, 1H), 7.25 (dd, J=2.4, 8.7 Hz, 1H), 6.67 (d, J=8.8 Hz, 1H), 3.32-3.38 (m, 2H), 1.20 (t, J=7.3 Hz, 3H). MS (ESI): m/z 243.33 [M+H]+. UPLC: tR=0.98 min (UPLC-SQD: analytical—2 min).

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 5-Bromoisatoic anhydride (2.00 g, 8.26 mmol) in THF (53.62 mL, 661.1 mmol) was treated with diethylamine (1.28 mL, 12.40 mmol) and allowed to stir overnight at rt. The mixture was concentrated in vacuo and purified using a Teledyne ISCO Combiflash® Rf system [0→4% MeOH in DCM] to afford 326 mg of the title compound (15%). 1H NMR (400 MHz, CD3OD) δ 7.24 (dd, J=2.27, 8.84 Hz, 1H), 7.13 (d, J=2.27 Hz, 1H), 6.71 (d, J=8.59 Hz, 1H), 3.43 (br. s., 4H), 1.18 (br. s., 6H). MS (ESI): m/z 271.41 [M+H]+. UPLC: tR=1.09 min (UPLC-SQD: analytical—2 min). The mixture was concentrated in vacuo purified

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A suspension of 2-amino-5-bromo-N,N-diethylbenzamide (Compound 3D, 326 mg, 1.20 mmol), 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-1-ol (Compound 3E, 0.33 g, 1.32 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (106.8 mg, 0.13 mmol) and potassium carbonate (0.50 g, 3.64 mmol) in 1,4-dioxane (4 mL, 50 mmol) to H2O (1 mL, 60 mmol) was evacuated and charged with argon (3×). The sample was irradiated in a microwave reactor for 30 min at 100° C. The crude product was concentrated in vacuo to a solid and purified using a Teledyne ISCO Combiflash® Rf system [0→5% MeOH in DCM] to yield the desired product (197 mg, 52%). 1H NMR (400 MHz, CD3OD) δ 7.86 (d, J=0.51 Hz, 1H), 7.71 (d, J=0.76 Hz, 1H), 7.36 (dd, J=2.02, 8.34 Hz, 1H), 7.22 (d, J=2.02 Hz, 1H), 6.81 (d, J=8.34 Hz, 1H), 4.24 (t, J=6.82 Hz, 2H), 3.33-3.60 (m, 6H), 2.05 (quin, J=6.57 Hz, 2H), 1.04-1.35 (m, 6H). MS (ESI): m/z 317.59 [M+H]+. UPLC: tR=0.74 min (UPLC-SQD: analytical—2 min). was evacuated charged with argon (3×) The sample was irradiated in a microwave reactor for 30 min at 100° C The crude product was concentrated in vacuo to a solid purified