6,6-二甲基哌嗪-2-酮

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Following the general procedure of Example 4 and making non-critical variations, but substituting ethyl chloroacetate (VI) for methyl 2-bromo-4-methylpentanoate (V) and 1,2-diamino-2-methylpropane (VI) for ethylenediamine (VII) there are obtained 5,5-dimethylpiperazinone and 6,6-dimethylpiperazinone.

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: N-(4-{4-Amino-7-[(1E)-3-oxoprop-1-enyl]thieno[3,2-c]pyridin-3-yl}-2-methoxyphenyl)-1-methyl-1H-indole-2-carboxamide (60.0 mg, 0.125 mmol) and 6,6-dimethyl-piperazin-2-one (75.7 mg, 0.498 mmol) were reacted according to General Procedure B. The product was purified via flash chromatography to furnish the title compound as a yellow powder. (5.0 mg, 0.0084 mmol): LCMS (Conditions a): MH+=595.0, Rt=3.58 minutes; 1H NMR (DMSO-d6, 400 MHz) δ 9.52 (s, 1H), 7.98 (m, 2H), 7.80 (s, 1H), 7.71 (d, J=7.8 Hz, 1H), 7.62 (s, 1H), 7.58 (d, J=8.2 Hz, 1H), 7.35 (m, 1H), 7.31 (m, 1H), 7.20 (m, 1H), 7.15 (t, J=7.8 Hz, 1H), 7.09 (dd, J=8.2, 1.56 Hz, 1H), 6.74 (d, J=16.0 Hz, 1H), 6.23 (m, 1H), 5.66 (br, 2H), 4.04 (s, 3H), 3.91 (s, 3H), 3.24 (m, 2H), 2.95 (s, 2H), 2.42 (s, 2H), 1.20 (s, 6H). The product was purified via flash chromatography

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

实验步骤: A mixture of (2-tert-butoxycarbonylamino-2-methyl-propylamino)-acetic acid methyl ester (compound N; 26.5 g) in DCM (800 mL) was stirred at ambient temperature, TFA (180 mL) was added drop-wise. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo. The residue was partitioned between dissolved toluene and water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL). K2CO3 (207 g) was added and the mixture was refluxed overnight. The mixture was cooled to room temperature. DCM (2500 mL) was added, and the mixture was stirred for 1 hour at ambient temperature. The solid was filtered off, and the filtrate was concentrated in vacuo to afford 6,6-dimethyl-piperazin-2-one (Compound I; 5.85 g) as a white solid sufficiently pure for the next step. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo The residue was partitioned between dissolved toluene and water The organic layer was dried over Na2SO4 filtered concentrated in vacuo The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL) K2CO3 (207 g) was added the mixture was refluxed overnight The mixture was cooled to room temperature DCM (2500 mL) was added the mixture was stirred for 1 hour at ambient temperature The solid was filtered off the filtrate was concentrated in vacuo

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

实验步骤: Following the general procedure of Example 4 and making non-critical variations, but substituting ethyl chloroacetate (VI) for methyl 2-bromo-4-methylpentanoate (V) and 1,2-diamino-2-methylpropane (VI) for ethylenediamine (VII) there are obtained 5,5-dimethylpiperazinone and 6,6-dimethylpiperazinone.

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

实验步骤: A mixture of (2-tert-butoxycarbonylamino-2-methyl-propylamino)-acetic acid methyl ester (compound N; 26.5 g) in DCM (800 mL) was stirred at ambient temperature, TFA (180 mL) was added drop-wise. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo. The residue was partitioned between dissolved toluene and water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL). K2CO3 (207 g) was added and the mixture was refluxed overnight. The mixture was cooled to room temperature. DCM (2500 mL) was added, and the mixture was stirred for 1 hour at ambient temperature. The solid was filtered off, and the filtrate was concentrated in vacuo to afford 6,6-dimethyl-piperazin-2-one (Compound I; 5.85 g) as a white solid sufficiently pure for the next step. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo The residue was partitioned between dissolved toluene and water The organic layer was dried over Na2SO4 filtered concentrated in vacuo The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL) K2CO3 (207 g) was added the mixture was refluxed overnight The mixture was cooled to room temperature DCM (2500 mL) was added the mixture was stirred for 1 hour at ambient temperature The solid was filtered off the filtrate was concentrated in vacuo

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

实验步骤: A mixture of (2-tert-butoxycarbonylamino-2-methyl-propylamino)-acetic acid methyl ester (compound N, 26.5 g) in DCM (800 mL) was stirred at ambient temperature, TFA (180 mL) was added drop-wise. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo. The residue was partitioned between dissolved toluene and water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo. The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL). K2CO3 (207 g) was added and the mixture was refluxed overnight. The mixture was cooled to room temperature. DCM (2500 mL) was added, and the mixture was stirred for 1 hour at ambient temperature. The solid was filtered off, and the filtrate was concentrated in vacuo to afford 6,6-dimethyl-piperazin-2-one (Compound I; 5.85 g) as a white solid sufficiently pure for the next step. The mixture was stirred at 30-40° C. for 5 h before it was concentrated in vacuo The residue was partitioned between dissolved toluene and water The organic layer was dried over Na2SO4 filtered concentrated in vacuo The residual solid was dissolved in a mixture of ethanol (400 mL) and methanol (90 mL) K2CO3 (207 g) was added the mixture was refluxed overnight The mixture was cooled to room temperature DCM (2500 mL) was added the mixture was stirred for 1 hour at ambient temperature The solid was filtered off the filtrate was concentrated in vacuo

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

实验步骤: Following the general procedure of Example 4 and making non-critical variations, but substituting ethyl chloroacetate (VI) for methyl 2-bromo-4-methylpentanoate (V) and 1,2-diamino-2-methylpropane (VI) for ethylenediamine (VII) there are obtained 5,5-dimethylpiperazinone and 6,6-dimethylpiperazinone.

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

实验步骤: Following the general procedure of Example 4 and making non-critical variations, but substituting ethyl chloroacetate (VI) for methyl 2-bromo-4-methylpentanoate (V) and 1,2-diamino-2-methylpropane (VI) for ethylenediamine (VII) there are obtained 5,5-dimethylpiperazinone and 6,6-dimethylpiperazinone.