1-(1,3-dioxolan-2-yl)-N-methylmethanamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(N,N-Dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl isocyanate dimer (6 grams), N-(1,3-dioxolan-2-ylmethyl)-N-methylamine (6 grams) and ethyl acetate (20 ml) were charged into a glass reaction vessel fitted with a mechanical stirrer. The reaction mixture was heated on a steam bath for a period of about 2 hours. Solvent was then stripped off using a rotary evaporator to yield the desired product N-[5-(N,N-dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl]-N'-(1,3-dioxolan-2-ylmethyl)-N'-methylurea as the residue. Melting point 100°-110° C. fitted with a mechanical stirrer The reaction mixture was heated on a steam bath for a period of about 2 hours a rotary evaporator

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound CC-12 (0.86 g, 2 mmole) was dissolved in anhydrous tetrahydrofuran (30 ml), and to the solution was added successively with DIPEA (1 ml, 6 mmole) and 2-methylaminomethyl-1,3 dioxolane (0.91 ml, 8 mmole) under stirring for 5 to 10 minutes. This mixture was heated under reflux for 16 hours. After the completion of the reaction, the mixture was filtered, and the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator). The residue was extracted with ethyl acetate for several times. The extract was dried on magnesium sulfate, and concentrated under reduced pressure. The crude product was washed with ethyl acetate/hexane. Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36. Mol. Wt.: 513.5412 (C29H27N3O6); Rf: 0.31 (ethyl acetate: n-hexane=1:2); Yield: 43%; Mp.: 156-157° C. (EtOH); HRMS (EI) m/z: calcd [M]+, 513.1900 (C29H27N3O6+). Found, 513.1902. 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 2.18 (s, 3H, —CH3), 2.44 (s, 3H, —CH3), 2.54 (d, J=8.7 Hz, 2H, —NCH2—), 3.26 (s, 2H, —CH2N—), 3.52-3.55 (m, 2H, —OCH2—), 3.72-3.77 (m, 2H, —OCH2—), 4.58 (t, J=4.5 Hz, 1H, —OCHO—), 7.43 (d, J=7.8 Hz, 2H, Ar—H), 7.88-7.92 (m, 2H, Ar—H), 8.04 (d, J=8.1 Hz, 2H, Ar—H), 8.10-8.19 (m, 2H, Ar—H), 8.27 (d, J=8.4 Hz, 1H, Ar—H), 8.70 (d, J=8.7 Hz, 1H, Ar—H), 10.15 (s, 1H, Ar—NH—), 10.53 (s, 1H, Ar—NH—); 13C-NMR (75 MHz, DMSO-d6) δ (ppm): 20.87, 43.49, 59.43, 61.73, 63.91, 102.61, 125.50, 126.31, 126.48, 126.90, 127.89, 128.06, 129.06, 129.31, 130.75, 132.33, 134.16, 134.38, 134.45, 140.42, 142.29, 166.25 (NCO), 169.59 (NCO), 181.46 (CO), 183.70 (CO). This mixture was heated under reflux for 16 hours After the completion of the reaction the mixture was filtered the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator) The residue was extracted with ethyl acetate for several times The extract was dried on magnesium sulfate concentrated under reduced pressure The crude product was washed with ethyl acetate/hexane Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 5-(N,N-Dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl isocyanate dimer (6 grams), N-(1,3-dioxolan-2-ylmethyl)-N-methylamine (6 grams) and ethyl acetate (20 ml) were charged into a glass reaction vessel fitted with a mechanical stirrer. The reaction mixture was heated on a steam bath for a period of about 2 hours. Solvent was then stripped off using a rotary evaporator to yield the desired product N-[5-(N,N-dimethylaminosulfonyl)-1,3,4-thiadiazol-2-yl]-N'-(1,3-dioxolan-2-ylmethyl)-N'-methylurea as the residue. Melting point 100°-110° C. fitted with a mechanical stirrer The reaction mixture was heated on a steam bath for a period of about 2 hours a rotary evaporator

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound CC-12 (0.86 g, 2 mmole) was dissolved in anhydrous tetrahydrofuran (30 ml), and to the solution was added successively with DIPEA (1 ml, 6 mmole) and 2-methylaminomethyl-1,3 dioxolane (0.91 ml, 8 mmole) under stirring for 5 to 10 minutes. This mixture was heated under reflux for 16 hours. After the completion of the reaction, the mixture was filtered, and the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator). The residue was extracted with ethyl acetate for several times. The extract was dried on magnesium sulfate, and concentrated under reduced pressure. The crude product was washed with ethyl acetate/hexane. Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36. Mol. Wt.: 513.5412 (C29H27N3O6); Rf: 0.31 (ethyl acetate: n-hexane=1:2); Yield: 43%; Mp.: 156-157° C. (EtOH); HRMS (EI) m/z: calcd [M]+, 513.1900 (C29H27N3O6+). Found, 513.1902. 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 2.18 (s, 3H, —CH3), 2.44 (s, 3H, —CH3), 2.54 (d, J=8.7 Hz, 2H, —NCH2—), 3.26 (s, 2H, —CH2N—), 3.52-3.55 (m, 2H, —OCH2—), 3.72-3.77 (m, 2H, —OCH2—), 4.58 (t, J=4.5 Hz, 1H, —OCHO—), 7.43 (d, J=7.8 Hz, 2H, Ar—H), 7.88-7.92 (m, 2H, Ar—H), 8.04 (d, J=8.1 Hz, 2H, Ar—H), 8.10-8.19 (m, 2H, Ar—H), 8.27 (d, J=8.4 Hz, 1H, Ar—H), 8.70 (d, J=8.7 Hz, 1H, Ar—H), 10.15 (s, 1H, Ar—NH—), 10.53 (s, 1H, Ar—NH—); 13C-NMR (75 MHz, DMSO-d6) δ (ppm): 20.87, 43.49, 59.43, 61.73, 63.91, 102.61, 125.50, 126.31, 126.48, 126.90, 127.89, 128.06, 129.06, 129.31, 130.75, 132.33, 134.16, 134.38, 134.45, 140.42, 142.29, 166.25 (NCO), 169.59 (NCO), 181.46 (CO), 183.70 (CO). This mixture was heated under reflux for 16 hours After the completion of the reaction the mixture was filtered the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator) The residue was extracted with ethyl acetate for several times The extract was dried on magnesium sulfate concentrated under reduced pressure The crude product was washed with ethyl acetate/hexane Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound CC-12 (0.86 g, 2 mmole) was dissolved in anhydrous tetrahydrofuran (30 ml), and to the solution was added successively with DIPEA (1 ml, 6 mmole) and 2-methylaminomethyl-1, 3 dioxolane (0.91 ml, 8 mmole) under stirring for 5 to 10 minutes. This mixture was heated under reflux for 16 hours. After the completion of the reaction, the mixture was filtered, and the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator). The residue was extracted with ethyl acetate for several times. The extract was dried on magnesium sulfate, and concentrated under reduced pressure. The crude product was washed with ethyl acetate/hexane. Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36. Mol. Wt.: 513.5412 (C29H27N3O6); Rf: 0.31 (ethyl acetate:n-hexane=1:2); Yield: 43%; Mp.: 156-157° C. (EtOH); HRMS (EI) m/z: calcd [M]+, 513.1900 (C29H27N3O6+); found, 513.1902; 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 2.18 (s, 3H, —CH3), 2.44 (s, 3H, —CH3), 2.54 (d, J=8.7 Hz, 2H, —NCH2—), 3.26 (s, 2H, —CH2N—), 3.52-3.55 (m, 2H, —OCH2—), 3.72-3.77 (m, 2H, —OCH2—), 4.58 (t, J=4.5 Hz, 1H, —OCHO—), 7.43 (d, J=7.8 Hz, 2H, Ar—H), 7.88-7.92 (m, 2H, Ar—H), 8.04 (d, J=8.1 Hz, 2H, Ar—H), 8.10-8.19 (m, 2H, Ar—H), 8.27 (d, J=8.4 Hz, 1H, Ar—H), 8.70 (d, J=8.7 Hz, 1H, Ar—H), 10.15 (s, 1H, Ar—NH—), 10.53 (s, 1H, Ar—NH—); 13C-NMR (75 MHz, DMSO-d6) δ (ppm): 20.87, 43.49, 59.43, 61.73, 63.91, 102.61, 125.50, 126.31, 126.48, 126.90, 127.89, 128.06, 129.06, 129.31, 130.75, 132.33, 134.16, 134.38, 134.45, 140.42, 142.29, 166.25 (NCO), 169.59 (NCO), 181.46 (CO), 183.70 (CO). This mixture was heated under reflux for 16 hours After the completion of the reaction the mixture was filtered the filtrate was concentrated by reduced pressure concentrator (such as Vacuum Evaporator) The residue was extracted with ethyl acetate for several times The extract was dried on magnesium sulfate concentrated under reduced pressure The crude product was washed with ethyl acetate/hexane Finally, the crude product was recrystallized in hot ethanol to obtain a kelly green compound CC-36

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound is prepared from 3-fluoro-N-[4-(2-methanesulfonyl-pyrimidin-4-yloxy)-naphthalen-1-yl]-5-piperidin-1-yl-benzamide and [1,3]dioxolan-2-ylmethylmethylamine according to conditions described in general procedure C. Mp: 125-127° C.; 1H NMR (400 MHz, DMSO-d6) δ 1.57-1.61 (m, 6 H), 2.76 (bs, 1 H), 3.04 (bs, 1 H), 3.22-3.32 (m, 7 H), 3.55-3.86 (m, 4 H), 4.74-4.90 (m, 1 H), 6.26 (d, J=5.1 Hz, 1 H), 6.94-6.97 (m, 1 H), 7.15 (d, J=8.8 Hz, 1 H), 7.41 (d, J=8.0 Hz, 1 H), 7.46 (s, 1 H), 7.55-7.60 (m, 3 H), 7.82 (d, J=7.7 Hz, 1 H), 7.96-7.99 (m, 1 H), 8.24 (d, J=5.5 Hz, 1 H), 10.44 (s, 1 H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Compound is prepared from 3-fluoro-N-(4-{[2-(methylsulfonyl)pyrimidin-4-yl]oxy}-1-naphthyl)-5-morpholin-4-ylbenzamide and [1,3]dioxolan-2-ylmethyl-methylamine according to conditions described in general procedure C. Mp: 111-112° C.; 1H NMR (400 MHz, DMSO-d6) δ 2.75-3.96 (m, 8H), 3.27 (m, 4H), 3.80 (m, 4H), 4.75-5.0 (m, 2H), 6.27 (d, J=5.1 Hz, 1H), 7.05 (d, J=12.5 Hz, 1H), 7.28 (d, J=8.8 Hz, 1H), 7.42-7.62 (m, 5H), 7.84 (d, J=7.7 Hz, 1H), 7.99-8.01 (m, 1H), 8.28 (d, J =5.5 Hz, 1H), 10.47 (s, 1H).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared as described for N-({6-[(3-fluorophenyl)sulfonyl]-1,2,3,4-tetrahydro[1]benzofuro[2,3-c]pyridin-1-yl}methyl)acetamide using tert-butyl (2-{5-[(3-fluorophenyl)sulfonyl]-1-benzofuran-3-yl}ethyl)carbamate and N-[1,3]dioxolan-2-ylmethyl-methyl)-acetamide, which was prepared from [1,3]dioxolan-2-ylmethyl-methyl-amine and acetic anhydride. MS m/z 417 [M+H]+. Prepared

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Trifluoromethyl-1,3,4-thiadiazol-5-yl isocyanate dimer (3.1 grams) was added to a solution of N-(1,3-dioxolan-2-ylmethyl)-N-methylamine (2grams) in benzene (10 ml) contained in a glass reaction vessel equipped with a mechanical stirrer and thermometer. The mixture was heated on a steam bath for a period of about 1 hour. The mixture was then stripped of solvent under reduced pressure to yield a solid residue. The residue was recrystallized from an ether-pentane mixture to yield the desired product N-(2-trifluoromethyl-1,3,4-thiadiazol-5-yl)-N'-(1,3-dioxolan-2-ylmethyl)-N'-methylurea having a melting point of 114° to 115°C. contained in a glass reaction vessel equipped with a mechanical stirrer The mixture was heated on a steam bath for a period of about 1 hour to yield a solid residue The residue was recrystallized from an ether-pentane mixture