3-[4-(3-aminopropoxy)butoxy]propan-1-amine

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

Procedure: 4,9-Dioxadodecane-1,12-diamine (22.8 g, 0.112 mole) was placed in a 250 ml round bottom flask and glycolic acid (17.0 g, 0.224 mole) added portion-wise with stirring and cooling. The resultant liquid was heated in an oil bath to 185° C. whereupon distillation of water occurred. Heating was continued at 185° to 195° C. for 2 hours after which time distillation of water subsided and the liquid was poured into a crystallization dish. The resultant oil slowly crystallized in the form of large white clusters; yield 35.5 g (99.3%); m.p. 67°-71° C. The solid was recrystallized from cold absolute methanol to give a white, crystalline product; m.p. 74°-77° C.; infrared (Nujol), 1120 cm-1, 1625 cm-1, 3250 cm-1 ; proton nuclear magnetic resonance (CDCl3 /TMS, 100 MHz), δ1.55-1.95 (complex multiplet, 8 protons), δ3.30-3.65 (complex multiplet, 12 protons), δ4.03 (singlet, 4 protons), δ4.98 (broad singlet, 2 protons), δ7.51 (broad triplet, 2 protons). cooling Heating after which time distillation of water the liquid was poured into a crystallization dish The resultant oil slowly crystallized in the form of large white clusters The solid was recrystallized from cold absolute methanol to give a white, crystalline product

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

Procedure: 1,7-diamino-3,5dioxaheptane; 1,10-diamino-4,7-dioxadecane; 1,10-diamino-4,7-dioxa-5-methyldecane; 1,11-diamino-4,9-dioxaundecane; 1,11-diamino-4,8-dioxa-5-methylundecane; 1,11-diamino-4,8-dioxa- 5,6-dimetyl-7-propyonylundecane; 1,14-diamino-4,7,10-trioxatetradecane, 1,13-diamino-4,7,10-trioxa-5,8-dimethyltridecane; 1,16-diamino-4,7,10,13-tetraoxahexadecane; 1,20-diamino-4,17-dioxaeicosane; and especially 1,12-diamino-4,9-dioxadodecane, 1,14-diamino-4,11-dioxatetradecane, 1,14-diamino-6,6,8(6,8,8)-trimethyl-4,11-dioxatetradecane, and 1,11-diamino-6,6-dimethyl-4,8-dioxaundecane and the compounds specificed in formulas (b) and (c) wherein m is 2 to 14 and k is 7 to 11, respectively.

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

Procedure: 1,7-diamino-3,5dioxaheptane; 1,10-diamino-4,7-dioxadecane; 1,10-diamino-4,7-dioxa-5-methyldecane; 1,11-diamino-4,9-dioxaundecane; 1,11-diamino-4,8-dioxa-5-methylundecane; 1,11-diamino-4,8-dioxa- 5,6-dimetyl-7-propyonylundecane; 1,14-diamino-4,7,10-trioxatetradecane, 1,13-diamino-4,7,10-trioxa-5,8-dimethyltridecane; 1,16-diamino-4,7,10,13-tetraoxahexadecane; 1,20-diamino-4,17-dioxaeicosane; and especially 1,12-diamino-4,9-dioxadodecane, 1,14-diamino-4,11-dioxatetradecane, 1,14-diamino-6,6,8(6,8,8)-trimethyl-4,11-dioxatetradecane, and 1,11-diamino-6,6-dimethyl-4,8-dioxaundecane and the compounds specificed in formulas (b) and (c) wherein m is 2 to 14 and k is 7 to 11, respectively.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-(6-chloro-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (280 mg) and 3,3′-(butane-1,4-diylbis(oxy))dipropan-1-amine (1928 mg) was heated at 100° C. for 16 hours. After cooling to room etmperature, the mixture was diluted with EtOAc (200 mL), washed with H2O (100 mL), brine (100 mL), and dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give 6-(6-(3-(4-(3-aminopropoxy)butoxy)propylamino)-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (40 mg). After cooling to room etmperature washed with H2O (100 mL), brine (100 mL) dried over MgSO4 concentrated The residue was purified by preparative HPLC

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-(6-chloro-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (280 mg) and 3,3′-(butane-1,4-diylbis(oxy))dipropan-1-amine (1928 mg) was heated at 100° C. for 16 hours. After cooling to room etmperature, the mixture was diluted with EtOAc (200 mL), washed with H2O (100 mL), brine (100 mL), and dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give 6-(6-(3-(4-(3-aminopropoxy)butoxy)propylamino)-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (40 mg). After cooling to room etmperature washed with H2O (100 mL), brine (100 mL) dried over MgSO4 concentrated The residue was purified by preparative HPLC

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

Procedure: 4,9-Dioxadodecane-1,12-diamine (22.8 g, 0.112 mole) was placed in a 250 ml round bottom flask and glycolic acid (17.0 g, 0.224 mole) added portion-wise with stirring and cooling. The resultant liquid was heated in an oil bath to 185° C. whereupon distillation of water occurred. Heating was continued at 185° to 195° C. for 2 hours after which time distillation of water subsided and the liquid was poured into a crystallization dish. The resultant oil slowly crystallized in the form of large white clusters; yield 35.5 g (99.3%); m.p. 67°-71° C. The solid was recrystallized from cold absolute methanol to give a white, crystalline product; m.p. 74°-77° C.; infrared (Nujol), 1120 cm-1, 1625 cm-1, 3250 cm-1 ; proton nuclear magnetic resonance (CDCl3 /TMS, 100 MHz), δ1.55-1.95 (complex multiplet, 8 protons), δ3.30-3.65 (complex multiplet, 12 protons), δ4.03 (singlet, 4 protons), δ4.98 (broad singlet, 2 protons), δ7.51 (broad triplet, 2 protons). cooling Heating after which time distillation of water the liquid was poured into a crystallization dish The resultant oil slowly crystallized in the form of large white clusters The solid was recrystallized from cold absolute methanol to give a white, crystalline product

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

Procedure: 4,9-Dioxadodecane-1,12-diamine (22.8 g, 0.112 mole) was placed in a 250 ml round bottom flask and glycolic acid (17.0 g, 0.224 mole) added portion-wise with stirring and cooling. The resultant liquid was heated in an oil bath to 185° C. whereupon distillation of water occurred. Heating was continued at 185° to 195° C. for 2 hours after which time distillation of water subsided and the liquid was poured into a crystallization dish. The resultant oil slowly crystallized in the form of large white clusters; yield 35.5 g (99.3%); m.p. 67°-71° C. The solid was recrystallized from cold absolute methanol to give a white, crystalline product; m.p. 74°-77° C.; infrared (Nujol), 1120 cm-1, 1625 cm-1, 3250 cm-1 ; proton nuclear magnetic resonance (CDCl3 /TMS, 100 MHz), δ1.55-1.95 (complex multiplet, 8 protons), δ3.30-3.65 (complex multiplet, 12 protons), δ4.03 (singlet, 4 protons), δ4.98 (broad singlet, 2 protons), δ7.51 (broad triplet, 2 protons). cooling Heating after which time distillation of water the liquid was poured into a crystallization dish The resultant oil slowly crystallized in the form of large white clusters The solid was recrystallized from cold absolute methanol to give a white, crystalline product

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

Procedure: 1,7-diamino-3,5dioxaheptane; 1,10-diamino-4,7-dioxadecane; 1,10-diamino-4,7-dioxa-5-methyldecane; 1,11-diamino-4,9-dioxaundecane; 1,11-diamino-4,8-dioxa-5-methylundecane; 1,11-diamino-4,8-dioxa- 5,6-dimetyl-7-propyonylundecane; 1,14-diamino-4,7,10-trioxatetradecane, 1,13-diamino-4,7,10-trioxa-5,8-dimethyltridecane; 1,16-diamino-4,7,10,13-tetraoxahexadecane; 1,20-diamino-4,17-dioxaeicosane; and especially 1,12-diamino-4,9-dioxadodecane, 1,14-diamino-4,11-dioxatetradecane, 1,14-diamino-6,6,8(6,8,8)-trimethyl-4,11-dioxatetradecane, and 1,11-diamino-6,6-dimethyl-4,8-dioxaundecane and the compounds specificed in formulas (b) and (c) wherein m is 2 to 14 and k is 7 to 11, respectively.

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 6-(6-chloro-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (280 mg) and 3,3′-(butane-1,4-diylbis(oxy))dipropan-1-amine (1928 mg) was heated at 100° C. for 16 hours. After cooling to room etmperature, the mixture was diluted with EtOAc (200 mL), washed with H2O (100 mL), brine (100 mL), and dried over MgSO4 and concentrated. The residue was purified by preparative HPLC to give 6-(6-(3-(4-(3-aminopropoxy)butoxy)propylamino)-2-(methylthio)pyrimidin-4-ylamino)nicotinic acid (40 mg). After cooling to room etmperature washed with H2O (100 mL), brine (100 mL) dried over MgSO4 concentrated The residue was purified by preparative HPLC

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

Procedure: 4,9-Dioxadodecane-1,12-diamine (22.8 g, 0.112 mole) was placed in a 250 ml round bottom flask and glycolic acid (17.0 g, 0.224 mole) added portion-wise with stirring and cooling. The resultant liquid was heated in an oil bath to 185° C. whereupon distillation of water occurred. Heating was continued at 185° to 195° C. for 2 hours after which time distillation of water subsided and the liquid was poured into a crystallization dish. The resultant oil slowly crystallized in the form of large white clusters; yield 35.5 g (99.3%); m.p. 67°-71° C. The solid was recrystallized from cold absolute methanol to give a white, crystalline product; m.p. 74°-77° C.; infrared (Nujol), 1120 cm-1, 1625 cm-1, 3250 cm-1 ; proton nuclear magnetic resonance (CDCl3 /TMS, 100 MHz), δ1.55-1.95 (complex multiplet, 8 protons), δ3.30-3.65 (complex multiplet, 12 protons), δ4.03 (singlet, 4 protons), δ4.98 (broad singlet, 2 protons), δ7.51 (broad triplet, 2 protons). cooling Heating after which time distillation of water the liquid was poured into a crystallization dish The resultant oil slowly crystallized in the form of large white clusters The solid was recrystallized from cold absolute methanol to give a white, crystalline product