1-amino-3-tert-butylurea

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

实验步骤: To a solution of 30 g of hydrazine hydrate (80%) in 100 ml of ethanol was added dropwise 34 ml of t-butyl isocyanate under ice-cooling, followed by stirring for 1 hour. After stirring at room temperature for an additional 3 hours, a saturated aqueous solution of sodium chloride was added to the reaction solution. The mixture was extracted three ,times with ethyl acetate, and the organic layer was distilled under reduced pressure. To the residue was added 65 ml of a 10% hydrochloric acid aqueous solution. After washing with chloroform, 16 ml of a 50% aqueous solution of sodium hydroxide was added thereto, and sodium chloride was further added thereto The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. Recrystallization of the residue from n-hexane/ethyl acetate (9:1 by volume) to obtain 36 g of 4-t-butylsemicarbazide (melting point:109 -110 ° C.). cooling After stirring at room temperature for an additional 3 hours The mixture was extracted three with ethyl acetate, and the organic layer was distilled under reduced pressure To the residue was added 65 ml of a 10% hydrochloric acid aqueous solution After washing with chloroform, 16 ml of a 50% aqueous solution of sodium hydroxide was added sodium chloride was further added The mixture was extracted with ethyl acetate the organic layer was dried over anhydrous sodium sulfate The solvent was removed by distillation under reduced pressure Recrystallization of the residue from n-hexane/ethyl acetate (9:1 by volume)

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

实验步骤: To a vigorously stirred mixture of 0.33 g (0.0103 mol) of anhydrous hydrazine in 50 ml of dry ether was added 1 g (0.01 mol) of t-butyl isocyanate. The resulting mixture was stirred for 2 hr. at room temperature then was kept overnight at 4° C. The crystals formed were filtered off, washed with a small portion of ether and dried to give 0.94 g (72% yield) of (t-butylamino)carbonylhydrazine melting at 192-193° C. When this was substituted for t-butyl carbazate in Step A of Example 1, the identical process afforded 1-(t-butylamino)carbonyl-2-isopropylhydrazine in 58% yield as a white solid; NMR (CDCl3): 1.03 (d, 6H, isopropyl CH3); 1.33 (s, 9H, t-butyl CH3); 3.9 (broad s. 1H, NH); 6.02 (broad s, 2H, NH amide). When this was substituted for t-butyl 3-isopropylcarbazate in Step B of Example 19 the identical process afforded 1-(t-butylamino)carbonyl-2-[(2S,3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]-2-isopropylhydrazine in 68% yield, as a white solid; NMR (CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.3 (s, 9H, t-butyl CH3); 2.33-4.22 (m, BH, butyl CH2 -1,4, CH-2,3, OH, isopropyl CH); 5.05 (s, 2H, methoxy CH2); 5.3 (m, 2H, NH); 5.91(m 1H, NH); 7.2, 7.35 (m, s, 5H, 5H, aromatic). When this was substituted for t-butyl 3-isopropyl-[(2R, 3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]carbazate in Example 3, the identical process afforded the title compound in 67% yield; melting point=119-125° C.; Rf (C)=0.06; Rf (D)=0.43; NMR(CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.32 (s, 9H, t-butyl CH3); 2.24-3.38 (m, 7H, butyl CH2 -1,4, CH-3, asn CH2); 3.38-4.63 (m, 3H, butyl CH-2, OH, isopropyl CH); 5.09 (m, 1H, asn CH); 5.63-8.4 (m, 16H, aromatic, NH); 9.0 (d, 1H, asn NH). at room temperature then was kept overnight at 4° C The crystals formed were filtered off washed with a small portion of ether dried

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

实验步骤: To a vigorously stirred mixture of 0.33 g (0.0103 mol) of anhydrous hydrazine in 50 ml of dry ether was added 1 g (0.01 mol) of t-butyl isocyanate. The resulting mixture was stirred for 2 hr. at room temperature then was kept overnight at 4° C. The crystals formed were filtered off, washed with a small portion of ether and dried to give 0.94 g (72% yield) of (t-butylamino)carbonylhydrazine melting at 192°-193° C. When this was substituted for t-butyl carbazate in Step A of Example 1, the identical process afforded 1-(t-butylamino)carbonyl-2-isopropylhydrazine in 58% yield as a white solid; NMR (CDCl3): 1.03 (d, 6H, isopropyl CH3); 1.33 (s, 9H, t-butyl CH3); 3.9 (broad s, 1 H, NH); 6.02 (broad s, 2H, NH amide). When this was substituted for t-butyl 3-isopropylcarbazate in step B of Example 19 the identical process afforded 1-(t-butylamino)carbonyl-2-[(2S,3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]-2-isopropylhydrazine in 68 % yield, as a white solid; NMR (CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.3 (s, 9H, t-butyl CH3); 2.33-4.22 (m, 8H, butyl CH2 -1,4, CH-2,3, OH, isopropyl CH); 5.05 (s, 2H, methoxy CH2); 5.3 (m, 2H, NH); 5.91 (m 1H, NH); 7.2, 7.35 (m, s, 5H, 5H, aromatic). When this was substituted for t-butyl 3-isopropyl-[(2R, 3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]carbazate in Example 3, the identical process afforded the title compound in 67% yield; melting point=119°-125° C.; Rf (C)=0.06; Rf =0.43; NMR(CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.32 (s, 9H, t-butyl CH3); 2.24-3.38 (m, 7H, butyl CH2 -1,4, CH-3, asn CH2); 3.38-4.63 (m, 3H, butyl CH-2, OH, isopropyl CH); 5.09 (m, 1 H, asn CH); 5.63-8.4 (m, 16H, aromatic, NH); 9.0 (d, 1H, asn NH). at room temperature then was kept overnight at 4° C The crystals formed were filtered off washed with a small portion of ether dried

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

实验步骤: To a vigorously stirred mixture of 0.33 g (0.0103 mol) of anhydrous hydrazine in 50 ml of dry ether was added 1 g (0.01 mol) of t-butyl isocyanate. The resulting mixture was stirred for 2 hr. at room temperature then was kept overnight at 4° C. The crystals formed were filtered off, washed with a small portion of ether and dried to give 0.94 g (72% yield) of (t-butylamino)carbonylhydrazine melting at 192-193° C. When this was substituted for t-butyl carbazate in Step A of Example 1, the identical process afforded 1-(t-butylamino)carbonyl-2-isopropylhydrazine in 58% yield as a white solid; NMR (CDCl3): 1.03 (d, 6H, isopropyl CH3); 1.33 (s, 9H, t-butyl CH3); 3.9 (broad s. 1H, NH); 6.02 (broad s, 2H, NH amide). When this was substituted for t-butyl 3-isopropylcarbazate in Step B of Example 19 the identical process afforded 1-(t-butylamino)carbonyl-2-[(2S,3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]-2-isopropylhydrazine in 68%, yield, as a white solid; NMR (CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.3 (s, 9H, t-butyl CH3); 2.33-4.22 (m, 8H, butyl CH2-1,4, CH-2,3, OH, isopropyl CH); 5.05 (s, 2H, methoxy CH2); 5.3 (m, 2H, NH); 5.91(m 1H, NH); 7.2, 7.35 (m, s, 5H, 5H, aromatic). When this was substituted for t-butyl 3-isopropryl[(2R, 3S)-2-hydroxy-3-(phenylmethoxycarbonyl)amino-4-phenylbutyl]carbazate in Example 3, the identical process afforded the title compound in 67% yield; melting point=119-125° C.; Rf (C)=0.06; Rf (D)=0.43; NMR(CDCl3): 1.0 (m, 6H, isopropyl CH3); 1.32 (s, 9H, t-butyl CH3); 2.24-3.38 (m, 7H, butyl CH2-1,4, CH-3, asn CH2); 3.38-4.63 (m, 3H, butyl CH-2, OH, isopropyl CH); 5.09 (m, 1H, asn CH); 5.63-8.4 (m, 16H, aromatic, NH); 9.0 (d, 1H, asn NH). at room temperature then was kept overnight at 4° C The crystals formed were filtered off washed with a small portion of ether dried

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

实验步骤: To a solution of 30 g of hydrazine hydrate (80%) in 100 ml of ethanol was added dropwise 34 ml of t-butyl isocyanate under ice-cooling, followed by stirring for 1 hour. After stirring at room temperature for an additional 3 hours, a saturated aqueous solution of sodium chloride was added to the reaction solution. The mixture was extracted three ,times with ethyl acetate, and the organic layer was distilled under reduced pressure. To the residue was added 65 ml of a 10% hydrochloric acid aqueous solution. After washing with chloroform, 16 ml of a 50% aqueous solution of sodium hydroxide was added thereto, and sodium chloride was further added thereto The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. Recrystallization of the residue from n-hexane/ethyl acetate (9:1 by volume) to obtain 36 g of 4-t-butylsemicarbazide (melting point:109 -110 ° C.). cooling After stirring at room temperature for an additional 3 hours The mixture was extracted three with ethyl acetate, and the organic layer was distilled under reduced pressure To the residue was added 65 ml of a 10% hydrochloric acid aqueous solution After washing with chloroform, 16 ml of a 50% aqueous solution of sodium hydroxide was added sodium chloride was further added The mixture was extracted with ethyl acetate the organic layer was dried over anhydrous sodium sulfate The solvent was removed by distillation under reduced pressure Recrystallization of the residue from n-hexane/ethyl acetate (9:1 by volume)