(2R,3R,4R,5S)-6-(methylamino)hexane-1,2,3,4,5-pentol

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

Procedure: To a solution of 2.001 g of N-methyl-D-glucamine in 20 ml of water was added 3.194 g of 3-carboxymethyl-5-(2-methylcinnamylidene)rhodanine [prepared as described in Example 1 (35)], and the mixture was heated to dissolve the rhodanine derivative, and then 40 ml of methanol was added to the solution at the same temperature. The mixture was cooled to room temperature and the precipitated crystals were filtered. The resulting crystals were washed with 5 ml of mixture of water and methanol (1:2), and 5 ml of methanol, and dried under reduced pressure to obtain 3.73 g of the titled compound. the mixture was heated the precipitated crystals were filtered The resulting crystals were washed with 5 ml of mixture of water and methanol (1:2), and 5 ml of methanol dried under reduced pressure

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

Procedure: To a solution of 2.001 g of N-methyl-D-glucamine in 20 ml of water was added 3.194 g of 3-carboxymethyl-5-(2-methylcinnamylidene)rhodanine [prepared as described in Example 1 (35)], and the mixture was heated to dissolve the rhodanine derivative, and then 40 ml of methanol was added to the solution at the same temperature. The mixture was cooled to room temperature and the precipitated crystals were filtered. The resulting crystals were washed with 5 ml of mixture of water and methanol (1:2), and 5 ml of methanol, and dried under reduced pressure to obtain 3.73 g of the titled compound. the mixture was heated the precipitated crystals were filtered The resulting crystals were washed with 5 ml of mixture of water and methanol (1:2), and 5 ml of methanol dried under reduced pressure

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

Procedure: 7-Chloro-4-hydroxy-2-(4-methoxy-2-methylphenyl)-1,2,5,10-tetrahydropyridazino[4,5-b]quinoline-1,10-dione (0.45 g, 1.17 mM) was stirred in methanol (20 mL) and N-Methyl-D-Glucamine (0.23 g, 1.17 mM) was added to give a clear yellow solution. This solution was concentrated and the residue was dissolved in water (20 mL) to give a yellow solution. This solution was filtered through a Gellman 0.45 μm Acrodisc and concentrated to give a yellow residue. The residue was triturated with 2-propanol (20 mL) to give a yellow suspension. The solids were collected and washed with 2-propanol to give the title compound (0.20 g, 29%) as a yellow powder, mp 177° C. (decomp.). to give a clear yellow solution This solution was concentrated the residue was dissolved in water (20 mL) to give a yellow solution This solution was filtered through a Gellman 0.45 μm Acrodisc concentrated to give a yellow residue The residue was triturated with 2-propanol (20 mL) to give a yellow suspension The solids were collected washed with 2-propanol

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium lauryl sulphate 90% (w/w) (493.4g, 1.67m), N-methyl-D-glucamine (611.1 g, 3.15 m), and sodium hydroxide (60 g, 1.5 m) in 1055.7 g water were charged into a 5 liter autoclave vessel. After pressure testing with nitrogen at 200 psi the autoclave was then heated for 2 hours at 160° C. (maximum steam pressure generated was 88 psi). The reaction mixture was then cooled to give a white spongy material which was washed with water and methanol to remove impurities, and dried in a desiccator to give a white powder. Base value=96% pure. The reaction mixture was then cooled to give a white spongy material which was washed with water and methanol to remove impurities dried in a desiccator to give a white powder

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium lauryl sulphate 90% (w/w) (493.4g, 1.67m), N-methyl-D-glucamine (611.1 g, 3.15 m), and sodium hydroxide (60 g, 1.5 m) in 1055.7 g water were charged into a 5 liter autoclave vessel. After pressure testing with nitrogen at 200 psi the autoclave was then heated for 2 hours at 160° C. (maximum steam pressure generated was 88 psi). The reaction mixture was then cooled to give a white spongy material which was washed with water and methanol to remove impurities, and dried in a desiccator to give a white powder. Base value=96% pure. The reaction mixture was then cooled to give a white spongy material which was washed with water and methanol to remove impurities dried in a desiccator to give a white powder

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

Procedure: To 1.25 g (4.6 mmol) phenytoin sodium was added 10 ml of a 10% solution of meglumine (1.0 g, 5.1 mmol), and the solution diluted to 25 ml. When 2 drops 10 N sodium hydroxide were added, the cloudy suspension became clear. After 10 minutes stirring, the pH was 11.5-11.7. the solution diluted to 25 ml

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

Procedure: A suspension of 373 mg of (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2-carbamoyl-5-methyl-s-triazolo-[1,5-a]pyrimidin-7-yl)-thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid in 7 ml of water was treated portionwise while stirring with 91 mg of N-methyl-D-glucamine. The resulting clear solution was lyophilized. There was obtained (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2-carbamoyl-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)-thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid N-methyl-D-glucamine salt as a white powder. was treated portionwise

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

Procedure: In another embodiment of the present invention, there is provided a process for preparing the organic amine salt of formula II, comprising: (a) reacting D-isoglutamyl-D-tryptophan in water with an organic amine in water wherein the organic amine is tert-butylamine or N-methylglucamine or tromethamine; and (b) concentrating the solution by co-evaporating with isopropanol; adding of acetone to cause the precipitate of the salt; recovering the precipitate thereof; and vacuum drying the product to obtain the organic ammonium salt of formula III wherein A is tert-butylammonium or tris(hydroxymethyl)methylammonium or methyl-(2,3,4,5,6-pentahydroxy-hexyl)-ammonium. In another embodiment of the present invention, there is provided a process and (b) concentrating the solution by co-evaporating with isopropanol adding of acetone recovering the precipitate and vacuum drying the product

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

Procedure: In another embodiment of the present invention, there is provided a process for preparing the organic amine salt of formula II, comprising: (a) reacting D-isoglutamyl-D-tryptophan in water with an organic amine in water wherein the organic amine is tert-butylamine or N-methylglucamine or tromethamine; and (b) concentrating the solution by co-evaporating with isopropanol; adding of acetone to cause the precipitate of the salt; recovering the precipitate thereof; and vacuum drying the product to obtain the organic ammonium salt of formula III wherein A is tert-butylammonium or tris(hydroxymethyl)methylammonium or methyl-(2,3,4,5,6-pentahydroxy-hexyl)-ammonium. In another embodiment of the present invention, there is provided a process and (b) concentrating the solution by co-evaporating with isopropanol adding of acetone recovering the precipitate and vacuum drying the product

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

Procedure: A suspension of 373 mg of (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2-carbamoyl-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)-thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid in 7 ml of water was treated portionwise while stirring with 91 mg of N-methyl-D-glucamine. The resulting clear solution was lyophilized. There was obtained (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-[[[(3,4-dihydroxyphenyl)sulphonyl]methoxy]imino]acetamido]-3-[[(2-carbamoyl-5-methyl-s-triazolo[1,5-a]pyrimidin-7-yl)-thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid N-methyl-D-glucamine salt as a white powder. was treated portionwise

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a reactor, 117 g (0.6 mol) of N-methyl-D-glucamine were dissolved in a mixture of 800 ml of water and 400 ml of tetrahydrofuran, and 201.6 g (2.4 mol) of sodium hydrogen carbonate were then dispersed. While the temperature of the reaction mixture was maintained at 5° C., 115.6 g (0.6 mol) of 2-ethylhexyl chloroformate were added dropwise, and the mixture was then allowed to react for 3 hours with stirring at 5° C. and left standing overnight at room temperature. The reaction mixture was then filtered and concentrated; the pasty residue obtained was dissolved in 2 liters of acetone and then filtered after cooling to 5° C. The crystallized product collected was dried. 105 g (50% yield) of N-(2-ethylhexyloxycarbonyl)-N-methyl-D-glucamine, the melting point of which is 74° C., were obtained. were then dispersed to react for 3 hours left The reaction mixture was then filtered concentrated the pasty residue obtained filtered after cooling to 5° C The crystallized product collected was dried

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-methyl-D-glucamine (1.42 g; 7.28 mMol) and 40 mL of ethanol were charged to a 100 mL RB flask equipped with a magnetic stirrer. The mixture was stirred and heated to 70° C. 2-{3-[Dimethyl-(2-trimethylsilanyl-ethyl)-silanyl]-propoxymethyl}-oxirane 8 (2 g; 7.28 mMol) mixed with 10 g ethanol was placed in an addition funnel and added dropwise to the flask. The mixture was stirred and maintained at 70° C. for an additional 4 hours. Ethanol was stripped off on the rotovap. The mixture was distilled under vacuum to remove impurities. equipped with a magnetic stirrer was placed in an addition funnel added dropwise to the flask The mixture was stirred maintained at 70° C. for an additional 4 hours The mixture was distilled under vacuum to remove impurities