prop-2-enylhydrazine

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

実験手順: To the solution of 70%-allylhydrazine 7.73 g (75 mmol) and triethylamine 8.38 ml (60 mmol), ethyl 2-bromoacetate in dichloromethane 25 ml was added and stirred at room temperature for 24 hours and reflux for additional 1 hour. The reaction mixture was diluted with ethyl acetate 150 ml and washed with brine 100 ml. The organic phase was dried with magnesium sulfate and filtered and the mother solution was concentrated in vacuo to obtain the title compound 6.90 g (87%). reflux for additional 1 hour washed with brine 100 ml The organic phase was dried with magnesium sulfate filtered the mother solution was concentrated in vacuo

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

実験手順: Allylhydrazine (70% in water, Wako) and 4,4-dimethyl-3-oxopentanenitrile (Aldrich) were processed as described for Example 30A to obtain the title compound. MS (ESI+) m/z 180 (M+H)+.

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

実験手順: Allylhydrazine (70% in water, Wako) and 4,4-dimethyl-3-oxopentanenitrile (Aldrich) were processed as described for Example 30A to obtain the title compound. MS (ESI+) m/z 180 (M+H)+.

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

実験手順: The title compound was prepared as described in Example 6, substituting benzoyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 451 (M+H)+; 1H NMR (400 MHz, DMSO-d6): δ ppm 0.91-1.26 (m, 4H), 2.89 (s, 3H), 3.21-3.30 (m, 1H), 3.41-3.51 (m, 1H), 4.22 (s, 2H), 4.78 (d, J=5.2 Hz, 2H), 5.21 (s, 1H), 5.24 (d, J=2.8 Hz, 1H), 6.01-6.08 (m, 1H), 6.79 (d, J=8.4 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.54-7.62 (m, 3H), 7.65 (s, 1H), 7.86 (d, J=6.4 Hz, 2H), 9.37 (s, 1H), 10.63 (s, 1H), 11.07 (s, 1H).

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

実験手順: The title compound was prepared as described in Example 6, substituting furan-2-carbonyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 441 (M+H)+; 1H NMR (400 MHz, CDCl3): δ ppm 1.04-1.09 (m, 4H), 2.97 (s, 3H), 3.24-3.31 (m, 2H), 4.44 (s, 2H), 4.77 (d, J=5.6 Hz, 2H), 5.16-5.24 (m, 2H), 5.97-6.06 (m, 1H), 6.78 (s, 1H), 6.93 (d, J=8.8 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 9.34 (s, 1H).

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

実験手順: The title compound was prepared as described in Example 6, substituting furan-2-carbonyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 441 (M+H)+; 1H NMR (400 MHz, CDCl3): δ ppm 1.04-1.09 (m, 4H), 2.97 (s, 3H), 3.24-3.31 (m, 2H), 4.44 (s, 2H), 4.77 (d, J=5.6 Hz, 2H), 5.16-5.24 (m, 2H), 5.97-6.06 (m, 1H), 6.78 (s, 1H), 6.93 (d, J=8.8 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 9.34 (s, 1H).

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

実験手順: The title compound was prepared as described in Example 6, substituting furan-2-carbonyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 441 (M+H)+; 1H NMR (400 MHz, CDCl3): δ ppm 1.04-1.09 (m, 4H), 2.97 (s, 3H), 3.24-3.31 (m, 2H), 4.44 (s, 2H), 4.77 (d, J=5.6 Hz, 2H), 5.16-5.24 (m, 2H), 5.97-6.06 (m, 1H), 6.78 (s, 1H), 6.93 (d, J=8.8 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 9.34 (s, 1H).

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

実験手順: To a solution of 70%-allylhydrazine (7.73 ml, 75 mmol) and triethylamine (1048 ml, 75 mmol) in chloroform (25 ml) was added ethyl 2-bromo-2-methylpropanoate (9.75 g, 50 mmol) and the mixture was sittred for 1 hr and then refluxed overnight. The reaction mixture was diluted with ethylacetate (150 ml) and washed with water (100 ml) and brine (100 ml). Then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The crude residue was subjected to silica gel column chromatography (eluent: chloroform:methanol=95:5) to obtain the title compound (5.0 g, 54%). refluxed overnight washed with water (100 ml) and brine (100 ml) Then the organic layer was dried over magnesium sulfate filtered The filtrate was concentrated in vacuo

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

実験手順: To a solution of 70%-allylhydrazine (7.73 ml, 75 mmol) and triethylamine (1048 ml, 75 mmol) in chloroform (25 ml) was added ethyl 2-bromo-2-methylpropanoate (9.75 g, 50 mmol) and the mixture was sittred for 1 hr and then refluxed overnight. The reaction mixture was diluted with ethylacetate (150 ml) and washed with water (100 ml) and brine (100 ml). Then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The crude residue was subjected to silica gel column chromatography (eluent: chloroform:methanol=95:5) to obtain the title compound (5.0 g, 54%). refluxed overnight washed with water (100 ml) and brine (100 ml) Then the organic layer was dried over magnesium sulfate filtered The filtrate was concentrated in vacuo

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

実験手順: To a solution of 70%-allylhydrazine (7.73 ml, 75 mmol) and triethylamine (1048 ml, 75 mmol) in chloroform (25 ml) was added ethyl 2-bromo-2-methylpropanoate (9.75 g, 50 mmol) and the mixture was sittred for 1 hr and then refluxed overnight. The reaction mixture was diluted with ethylacetate (150 ml) and washed with water (100 ml) and brine (100 ml). Then the organic layer was dried over magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The crude residue was subjected to silica gel column chromatography (eluent: chloroform:methanol=95:5) to obtain the title compound (5.0 g, 54%). refluxed overnight washed with water (100 ml) and brine (100 ml) Then the organic layer was dried over magnesium sulfate filtered The filtrate was concentrated in vacuo

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

実験手順: The title compound was prepared as described in Example 6, substituting benzoyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 451 (M+H)+; 1H NMR (400 MHz, DMSO-d6): δ ppm 0.91-1.26 (m, 4H), 2.89 (s, 3H), 3.21-3.30 (m, 1H), 3.41-3.51 (m, 1H), 4.22 (s, 2H), 4.78 (d, J=5.2 Hz, 2H), 5.21 (s, 1H), 5.24 (d, J=2.8 Hz, 1H), 6.01-6.08 (m, 1H), 6.79 (d, J=8.4 Hz, 1H), 7.53 (d, J=8.4 Hz, 1H), 7.54-7.62 (m, 3H), 7.65 (s, 1H), 7.86 (d, J=6.4 Hz, 2H), 9.37 (s, 1H), 10.63 (s, 1H), 11.07 (s, 1H).

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

実験手順: The title compound was prepared as described in Example 6, substituting furan-2-carbonyl chloride for 3-phenylpropanoyl chloride in Example 6B, 2′-methyl-2′,3′-dihydro-1′H-spiro[cyclopropane-1,4′-isoquinolin]-7′-amine (Furukawa, S.; Ikeno, T.; Kato, S.; Kawasaki, M.; Kojima, H.; Minagawa, W.; Sawada, N.; Yamamoto, F.; Lohani, S.; Wang, Y. Process for preparation of a 3,4-dihydro-4-imino-pyrimido[4,5-d]pyrimidin-2(1H)-one derivative. WO 2009151997) for 4-(4-methylpiperazin-1-yl)aniline in Example 6C, and allylhydrazine for methylhydrazine in Example 6D. MS (DCI/NH3) m/z 441 (M+H)+; 1H NMR (400 MHz, CDCl3): δ ppm 1.04-1.09 (m, 4H), 2.97 (s, 3H), 3.24-3.31 (m, 2H), 4.44 (s, 2H), 4.77 (d, J=5.6 Hz, 2H), 5.16-5.24 (m, 2H), 5.97-6.06 (m, 1H), 6.78 (s, 1H), 6.93 (d, J=8.8 Hz, 1H), 7.51 (s, 1H), 7.57 (d, J=8.4 Hz, 1H), 7.64 (s, 1H), 7.91 (s, 1H), 9.34 (s, 1H).