N-(2-amino-2-methylpropyl)methanesulfonamide

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:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(2-Amino-2-methyl-propyl)-methanesulfonamide (1.15 g, 6.90 mmol, 1.2 eq.) in THF (20 mL) was cooled to 0° C. and 2,4,5-trichloropyrimidine (1.05 g, 5.75 mmol, 656 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (2.07 mL) was added. After 5 minutes, external cooling was removed and the reaction was heated at 60° C. overnight under a nitrogen atmosphere. The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (75 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto basic alumina. Purification by basic alumina chromatography (dry loaded) using a gradient of 0-60% EtOAc/hex as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide as a white solid (868 mg, 48%). m.p.=156-158° C.; LCMS (m/e) 313 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.57 (bs, 1H), 5.25-5.16 (m, 1H), 3.54 (d, 2H, J=6.8 Hz), 3.00 (s, 3H), 1.53 (s, 6H). After 5 minutes external cooling was removed The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL) The layers were separated the aqueous layer was extracted with CH2Cl2 (75 mL) The combined organic layers were dried (sodium sulfate) filtered concentrated under reduced pressure onto basic alumina Purification by basic alumina chromatography (dry loaded)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(2-Amino-2-methyl-propyl)-methanesulfonamide (1.15 g, 6.90 mmol, 1.2 eq.) in THF (20 mL) was cooled to 0° C. and 2,4,5-trichloropyrimidine (1.05 g, 5.75 mmol, 656 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (2.07 mL) was added. After 5 minutes, external cooling was removed and the reaction was heated at 60° C. overnight under a nitrogen atmosphere. The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (75 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto basic alumina. Purification by basic alumina chromatography (dry loaded) using a gradient of 0-60% EtOAc/hex as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide as a white solid (868 mg, 48%). m.p.=156-158° C.; LCMS (m/e) 313 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.57 (bs, 1H), 5.25-5.16 (m, 1H), 3.54 (d, 2H, J=6.8 Hz), 3.00 (s, 3H), 1.53 (s, 6H). After 5 minutes external cooling was removed The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL) The layers were separated the aqueous layer was extracted with CH2Cl2 (75 mL) The combined organic layers were dried (sodium sulfate) filtered concentrated under reduced pressure onto basic alumina Purification by basic alumina chromatography (dry loaded)

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

実験手順: 2-Methyl-propane-1,2-diamine (2.00 g, 22.7 mmol, 2.38 mL, 1.1 eq.) was placed in CH2Cl2 (100 mL). Mesyl chloride (2.35 g, 20.7 mmol, 1.59 mL, 1.0 eq.) was added over a period of five minutes followed by triethylamine (6.27 g, 62.1 mmol, 8.71 mL, 3.0 eq.). The reaction was stirred for 30 minutes and then concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-15% MeOH/CH2Cl2 as the eluting solvent to obtain N-(2-amino-2-methyl-propyl)-methanesulfonamide as a white solid (1.15 g, 33%). LCMS (m/e) 167 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 2.98 (s, 3H), 2.95 (s, 2H), 1.17 (s, 3H), 1.16 (s, 3H). concentrated under reduced pressure Purification by basic alumina chromatography

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(2-Amino-2-methyl-propyl)-methanesulfonamide (1.15 g, 6.90 mmol, 1.2 eq.) in THF (20 mL) was cooled to 0° C. and 2,4,5-trichloropyrimidine (1.05 g, 5.75 mmol, 656 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (2.07 mL) was added. After 5 minutes, external cooling was removed and the reaction was heated at 60° C. overnight under a nitrogen atmosphere. The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (75 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto basic alumina. Purification by basic alumina chromatography (dry loaded) using a gradient of 0-60% EtOAc/hex as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide as a white solid (868 mg, 48%). m.p.=156-158° C.; LCMS (m/e) 313 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.57 (bs, 1H), 5.25-5.16 (m, 1H), 3.54 (d, 2H, J=6.8 Hz), 3.00 (s, 3H), 1.53 (s, 6H). After 5 minutes external cooling was removed The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL) The layers were separated the aqueous layer was extracted with CH2Cl2 (75 mL) The combined organic layers were dried (sodium sulfate) filtered concentrated under reduced pressure onto basic alumina Purification by basic alumina chromatography (dry loaded)

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

実験手順: 2-Methyl-propane-1,2-diamine (2.00 g, 22.7 mmol, 2.38 mL, 1.1 eq.) was placed in CH2Cl2 (100 mL). Mesyl chloride (2.35 g, 20.7 mmol, 1.59 mL, 1.0 eq.) was added over a period of five minutes followed by triethylamine (6.27 g, 62.1 mmol, 8.71 mL, 3.0 eq.). The reaction was stirred for 30 minutes and then concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-15% MeOH/CH2Cl2 as the eluting solvent to obtain N-(2-amino-2-methyl-propyl)-methanesulfonamide as a white solid (1.15 g, 33%). LCMS (m/e) 167 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 2.98 (s, 3H), 2.95 (s, 2H), 1.17 (s, 3H), 1.16 (s, 3H). concentrated under reduced pressure Purification by basic alumina chromatography

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-(2-Amino-2-methyl-propyl)-methanesulfonamide (1.15 g, 6.90 mmol, 1.2 eq.) in THF (20 mL) was cooled to 0° C. and 2,4,5-trichloropyrimidine (1.05 g, 5.75 mmol, 656 μL, 1.0 eq.) was added. The reaction was stirred for 5 minutes and then NEt3 (2.07 mL) was added. After 5 minutes, external cooling was removed and the reaction was heated at 60° C. overnight under a nitrogen atmosphere. The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (75 mL). The combined organic layers were dried (sodium sulfate), filtered, and concentrated under reduced pressure onto basic alumina. Purification by basic alumina chromatography (dry loaded) using a gradient of 0-60% EtOAc/hex as the eluting solvent to obtain N-[2-(2,5-dichloro-pyrimidin-4-ylamino)-2-methyl-propyl]-methanesulfonamide as a white solid (868 mg, 48%). m.p.=156-158° C.; LCMS (m/e) 313 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 8.04 (s, 1H), 5.57 (bs, 1H), 5.25-5.16 (m, 1H), 3.54 (d, 2H, J=6.8 Hz), 3.00 (s, 3H), 1.53 (s, 6H). After 5 minutes external cooling was removed The reaction was then partitioned between CH2Cl2 (150 mL) and sat. NaHCO3 (150 mL) The layers were separated the aqueous layer was extracted with CH2Cl2 (75 mL) The combined organic layers were dried (sodium sulfate) filtered concentrated under reduced pressure onto basic alumina Purification by basic alumina chromatography (dry loaded)

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

実験手順: 2-Methyl-propane-1,2-diamine (2.00 g, 22.7 mmol, 2.38 mL, 1.1 eq.) was placed in CH2Cl2 (100 mL). Mesyl chloride (2.35 g, 20.7 mmol, 1.59 mL, 1.0 eq.) was added over a period of five minutes followed by triethylamine (6.27 g, 62.1 mmol, 8.71 mL, 3.0 eq.). The reaction was stirred for 30 minutes and then concentrated under reduced pressure. Purification by basic alumina chromatography using a gradient of 0-15% MeOH/CH2Cl2 as the eluting solvent to obtain N-(2-amino-2-methyl-propyl)-methanesulfonamide as a white solid (1.15 g, 33%). LCMS (m/e) 167 (M+1); 1H-NMR (CDCl3, 400 MHz) δ 2.98 (s, 3H), 2.95 (s, 2H), 1.17 (s, 3H), 1.16 (s, 3H). concentrated under reduced pressure Purification by basic alumina chromatography