|
With pyridine at 0 - 20℃; for 13h; |
1.04; 2.07; 3.08; 4.05; 5.01; 6.05; 7.01; 8.08; 9.07; 10.01; 11.01; 12.01; 13.08; 14.08; 15.08; 16.06; 17.05; 18.04; 19.01; 20.05; 21.08; 22.08; 23.08; 24.06
STEP04: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP07: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP08: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP05: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature for 12 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; 3-[4-(5, 7-diethyl-2-oxo-2H-[l, 6] napthyridin-l-ylmethyl)-phenyl]-thiophene-2-sulphonic acid (4,5-dimethyl-isoxazol-3-yl)-amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP05: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; Example 7; 3-[4-(5, 7-diethyl-2-oxo-2H-[l, 6] naphthyridin -l-yl-methyl)-phenyl]-5-methyl-thiophene- 2-sulphonic acid-(4,5 dimethyl-isoxazol-3-yl)-amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP08: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP07: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; Example 10; 3-[4-(2-metiiyl-qumolin-4-yloxymetyl)-phenyl]-thiophene-2-sulphonic acid (4,5-dimethyl- isoxazol-3-yl)-amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; 3-[4-(5, 7-Diethyl-2-oxo-2H-[l,6]naphthyridin-l-ylmethyl)-2-ethoxymethyl-phenyl]-5- methyl-thiophene-2-sulphonic acid-(4,5-dimethyl-isoxazol-3-yl)-amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; Example 12; 3 - [4-(3 - Acetyl-2,6-dimethyl-pyridine-4-yloxymethyl)-2-ethoxymethyl-phenyl] -5-methyl- ihiophene-2-sulphonic acid(4,5-dimethyl-isoxazol-3-yl)-amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP08: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gni) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP08: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl20 dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium 25 sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP08: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3~ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP06: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP05: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature for 12 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; STEP04: Synthesis of (5~methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester.; Example 19; 3-[4-(5,7-Dieyl-2-oxo-2H-[l,6]naphthyridin-l-ylmeyl)-2-methyl-phenyl]-5-methyl- thiophene-2-sulphonic acid(4,5-dimethyl-isoxazol-3yl)-(2-methoxy-ethoxymethyl)amide; STEPOl: Synthesis of (5-methyl-isoxazol-3-yl) carbamic acid tert-butyl ester.; 5-methyl-isoxazol-3-ylamine (100 gm, 1.019 mol) was dissolved in pyridine (200 ml, o 2.545 mol) and then cooled this mixture to 0 C. To this reaction mixture di-tert-butyl dicarbonate (245 gm, 1.12 mol) was added in 1 hr. After the completion of the addition, the reaction mixture was stirred at room temperature forl2 hrs. Then the reaction mixture was o concentrated at 60-70 C under vacuum. The residue thus obtained was dissolved in (500 ml) ethyl acetate. The ethyl acetate layer was washed with dilute hydrochloric acid followed by water and brine washings. Finally organic layer was dried over sodium sulphate and evaporated under vacuum to give crude product. The crude product was dissolved in hot toluene (200 ml) and upon standing for 2 hrs at room temperature the solid crystallized out, which was filtered off, washed with cold toluene(50 ml) and suction dried to give (130 gm) of (5-methyl-isoxazol-3-yl)carbamic acid tert-butyl ester. |