benzyl N-amino-N-methylcarbamate

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO-d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted

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

Procedure: To a solution of the product of Example 2, starting material step (c) (470 mg), HBTU (460 mg) and HOBT (190 mg) in DMF (3 ml) under argon was added diisopropylethylamine (0.63 ml). After 2-3 minutes the resultant pale yellow reaction mixture was added to benzyl 2-methylcarbazate (Dutta, A. S. et al (1975), J. Chem. Soc. Perkin Trans. I, 1712-20) (200 mg). The reaction mixture was stirred at ambient temperature under argon for 3.5 hours then diluted with ethyl acetate (50 ml) and washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water, dried (MgSO4) and evaporated to give benzyl 2-methyl-3-(3,4-di-t-butoxycarbonylmethoxybenzoyl)carbazate (0.61 g) as a glass; NMR Spectrum (DMSO-d6) 1.43 (18H, s), 3.13 (3H, br s), 4.70 (2H, s), 4.75 (2H, s), 5.02-5.20 (2H, br), 6.99 (1H, m), 7.20-7.50 (7H, m), 10.68 (1H, br); Mass Spectrum m/Z 544 (M+). In the ambient temperature NMR spectrum, ancillary signals attributable to rotamers were observed. washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water dried (MgSO4) evaporated

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

Procedure: To a solution of the product of Example 2, starting material step (c) (470 mg), HBTU (460 mg) and HOBT (190 mg) in DMF (3 ml) under argon was added diisopropylethylamine (0.63 ml). After 2-3 minutes the resultant pale yellow reaction mixture was added to benzyl 2-methylcarbazate (Dutta, A. S. et al (1975), J. Chem. Soc. Perkin Trans. I, 1712-20) (200 mg). The reaction mixture was stirred at ambient temperature under argon for 3.5 hours then diluted with ethyl acetate (50 ml) and washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water, dried (MgSO4) and evaporated to give benzyl 2-methyl-3-(3,4-di-t-butoxycarbonylmethoxybenzoyl)carbazate (0.61 g) as a glass; NMR Spectrum (DMSO-d6) 1.43 (18H, s), 3.13 (3H, br s), 4.70 (2H, s), 4.75 (2H, s), 5.02-5.20 (2H, br), 6.99 (1H, m), 7.20-7.50 (7H, m), 10.68 (1H, br); Mass Spectrum m/Z 544 (M+). In the ambient temperature NMR spectrum, ancillary signals attributable to rotamers were observed. washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water dried (MgSO4) evaporated

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO--d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO--d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted

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

Procedure: To a solution of the product of Example 2, starting material step (c) (470 mg), HBTU (460 mg) and HOBT (190 mg) in DMF (3 ml) under argon was added diisopropylethylamine (0.63 ml). After 2-3 minutes the resultant pale yellow reaction mixture was added to benzyl 2-methylcarbazate (Dutta, A.S. et al (1975), J. Chem. Soc. Perkin Trans. I, 1712-20) (200 mg). The reaction mixture was stirred at ambient temperature under argon for 3.5 hours then diluted with ethyl acetate (50 ml) and washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water, dried (MgSO4) and evaporated to give benzyl 2-methyl-3-(3,4-di-t-butoxycarbonylmethoxybenzoyl)carbazate (0.61 g) as a glass; NMR Spectrum (DMSO--d6) 1.43 (18H, s), 3.13 (3H, br s), 4.70 (2H, s), 4.75 (2H, s), 5.02-5.20 (2H, br), 6.99 (1H, m), 7.20-7.50 (7H, m), 10.68 (1H, br); Mass Spectrum m/Z 544 (M+). In the ambient temperature NMR spectrum, ancillary signals attributable to rotamers were observed. washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water dried (MgSO4) evaporated

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

Procedure: To a solution of the product of Example 2, starting material step (c) (470 mg), HBTU (460 mg) and HOBT (190 mg) in DMF (3 ml) under argon was added diisopropylethylamine (0.63 ml). After 2-3 minutes the resultant pale yellow reaction mixture was added to benzyl 2-methylcarbazate (Dutta, A. S. et al (1975), J. Chem. Soc. Perkin Trans. I, 1712-20) (200 mg). The reaction mixture was stirred at ambient temperature under argon for 3.5 hours then diluted with ethyl acetate (50 ml) and washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water, dried (MgSO4) and evaporated to give benzyl 2-methyl-3-(3,4-di-t-butoxycarbonylmethoxybenzoyl)carbazate (0.61 g) as a glass; NMR Spectrum (DMSO-d6) 1.43 (18H, s), 3.13 (3H, br s), 4.70 (2H, s), 4.75 (2H, s), 5.02-5.20 (2H, br), 6.99 (1H, m), 7.20-7.50 (7H, m), 10.68 (1H, br); Mass Spectrum m/Z 544 (M+). In the ambient temperature NMR spectrum, ancillary signals attributable to rotamers were observed. washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water dried (MgSO4) evaporated

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

Procedure: To a solution of the product of Example 2, starting material step (c) (470 mg), HBTU (460 mg) and HOBT (190 mg) in DMF (3 ml) under argon was added diisopropylethylamine (0.63 ml). After 2-3 minutes the resultant pale yellow reaction mixture was added to benzyl 2-methylcarbazate (Dutta, A. S. et al (1975), J. Chem. Soc. Perkin Trans. I, 1712-20) (200 mg). The reaction mixture was stirred at ambient temperature under argon for 3.5 hours then diluted with ethyl acetate (50 ml) and washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water, dried (MgSO4) and evaporated to give benzyl 2-methyl-3-(3,4-di-t-butoxycarbonylmethoxybenzoyl)carbazate (0.61 g) as a glass; NMR Spectrum (DMSO-d6) 1.43 (18H, s), 3.13 (3H, br s), 4.70 (2H, s), 4.75 (2H, s), 5.02-5.20 (2H, br), 6.99 (1H, m), 7.20-7.50 (7H, m), 10.68 (1H, br); Mass Spectrum m/Z 544 (M+). In the ambient temperature NMR spectrum, ancillary signals attributable to rotamers were observed. washed with water, dilute KHSO4 (aq.) and dilute NaOH (aq.) and water dried (MgSO4) evaporated

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO-d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted

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

Procedure: To an ice cold, stirred solution of 36.8 (0.8 mol; 42.49 ml) methylhydrazine and 161.6 g (1.6 mol, 224 ml) triethylamine in 700 ml tetrahydrofuran were added dropwise 136.5 g (0.8 mol, 113.6 ml) benzylchloroformate. After stirring at room temperature overnight, the tetrahydrofuran was evaporated and the residue was worked up with ethylacetate/water (pH=9.0. Insoluble material was removed by filtration and the organic phase was washed (H2O), dried (MgSO4) and evaporated. The oily residue was stirred with 1 1. of ether, the etherial solution was decanted from insoluble material and evaporated to give 61 g of an oil which was dissolved in 200 ml MeOH containing 25 ml conc. HCl. After evaporation to dryness, the residue was recrystallized from EtOH/ ethylacetate to give 22.0 g of the hydrochloride of 2 as colorless crystals. This material was dissolved in water and the pH was adjusted to 9.0. Extraction with ethylacetate, drying of the organic phase (MgSO4) and evaporation yielded 19.0 g of the title compound as a colorless oil. the tetrahydrofuran was evaporated Insoluble material was removed by filtration the organic phase was washed (H2O) dried (MgSO4) evaporated The oily residue was stirred with 1 1 of ether, the etherial solution was decanted from insoluble material evaporated

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO-d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted

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

Procedure: In a similar manner to Example 9, starting material step (a), 4-t-butoxycarbonylaminomethylbenzoic acid (300 mg), HBTU (460 mg), HOBT (190 mg), diisopropylethylamine (0.62 ml), DMF (3 ml) and benzyl 2-methylcarbazate (190 mg) were reacted to give benzyl 2-methyl-3-(4-t-butyoxycarbonylaminomethylbenzoyl)carbazate (440 mg) as a foam; NMR Spectrum (DMSO--d6) 1.39 (9H, s), 3.13 (3H, s), 4.17 (2H, d), 5.08 (2H, s), 7.42 (8H, m), 7.78 (2H, m), 10.73 (1H, br); Mass Spectrum m/Z 414 (M+H)+. In the NMR spectrum, ancillary signals attributable to rotamers were observed. were reacted