 
                                
                                 
                                
                                
                                    Structure of L(-)-Glyceraldehyde
                                    
                                    
CAS No.: 497-09-6
                                    
                                
 
                                 
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| CAS No. : | 497-09-6 | 
| Formula : | C3H6O3 | 
| M.W : | 90.08 | 
| SMILES Code : | O=C[C@@H](O)CO | 
| MDL No. : | MFCD00006971 | 
| InChI Key : | MNQZXJOMYWMBOU-GSVOUGTGSA-N | 
| Pubchem ID : | 439723 | 
| GHS Pictogram: |   | 
| Signal Word: | Warning | 
| Hazard Statements: | H302-H315-H319-H335 | 
| Precautionary Statements: | P261-P305+P351+P338 | 
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

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                                                    [ 497-09-6 ]| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 98% | Part 1 Ethyl (2E,4R)-4,5-isopropylidenedioxy-2-pentenoate (Scheme XV; 20) A solution of (2S,3R)-1,2-O-isopropylidene-butane-1,2,3,4-tetrol 19 (11.0 g, 68.1 mmol) in CH2Cl2 (120 mL) containing saturated NaHCO3 solution (4.5 mL) was cooled to 0° C., treated with NaIO4 (29.1 g, 136.3 mmol) and allowed to stir at 0° C. to 20° C. After 2 to 3 h (TLC analysis), solid Na2SO4 (6 g) was added and the reaction mixture was stirred further for 15 min. The reaction mixture was filtered and solvent evaporated (below 25° C. bath temperature) to give (S)-glyceraldehyde 19a (8.7 g) in 98percent yield as a colorless liquid. Compound 19 was prepared by procedures described in J. Am. Chem. Soc., 102, 6304 (1980); and J. Org. Chem., 53, 2598 (1988). | |
| 98% | Part 1: Ethyl (2E,4R)-4,5-isopropylidenedioxy-2-pentenoate (Scheme IX; 20): A solution of (2S,3R)- 1,2-O-isopropylidene-butane- 1,2,3,4-tetrol 19 (11.0 g, 68.1 mmol) in CH2Cl2 (120 mL) containing saturated NaHCO3 solution (4.5 mL) was cooled to 0° C., treated with NaIO4 (29.1 g, 136.3 mmol) and allowed to stir at 0° C. to 20° C. After 2 to 3 h (TLC analysis), solid Na2SO4 (6 g) was added and the reaction mixture was stirred further for 15 min. The reaction mixture was filtered and solvent evaporated (below 25° C. bath temperature) to give (S)-glyceraldehyde 19a (8.7 g) in 98percent yield as a colorless liquid. Compound 19 was prepared by procedures described in J Am. Chem. Soc., 102, 6304 (1980); and J Org Chem., 53, 2598 (1988). | 
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| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| Step 1 (S)-(-)-2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde The desired compound was prepared as described in Jackson, Synthetic Commun. 1988, 18(4), 337-341), except starting with L-<strong>[497-09-6](S)-glyceraldehyde</strong>, prepared as described by Hubschwerlen, C. Synthesis, 1986, 962-964, instead of D-(R)-glyceraldehyde. | ||
| Step 1: (S) -(-)2,2-dimethyl-1,3-dioxolane-4-carboxaldehyde. The desired compound was prepared as described in Jackson, Synthetic Commun. 1988, 18(4), 337-341), except starting with L-<strong>[497-09-6](S)-glyceraldehyde</strong>, prepared as described by Hubschwerlen, C. Synthesis, 1986, 962-964, instead of D-(R)-glyceraldehyde. | 
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                                                    [ 497-09-6 ]| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| EXAMPLE 42 (R)-1-tert.butylamino-3-(2-methyltheino[3,2-c]pyridin-4-yloxy)-2-propanol The process is effected in a manner analogous to Example 1, using (R)-4-(3-tert.butyl-2-phenyl-5-oxazolidinylmethoxy)-2-methylthieono[3,2-c]-pyridine [process a)], or in a manner analogous to Example 2, using 4-chloro-2-methylthieno[3,2-c]pyridine and (R)-1-tert.butylamino-2,3-dihydroxypropane [process b)], whereby the title compound is obtained. (M.P. of the hydrogen maleate: 166°-167°); [alpha]20546 ' +12.20° (c = 2.:09; methanol). The starting materials are obtained in a manner analogous to that described in Example 41, using (S)-glyceraldehyde, whereby the following intermediates are isolated: | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 49.4% | 2-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1 ,3,4-thiadiazol-2-yl)-3-methyl-4, 5,6,7- tetrahydro-2H-pyrazolo[4,3-c]pyridine (Example 1 )(150 mg, 0.39 mmol), (2S)-2,3- dihydroxypropanal (139 mg, 1.54 mmol) and sodium triacetoxyborohydride (326 mg, 1.54 mmol) were dissolved in dichloromethane (DCM) (4.5 mL) and Methanol (0.5 mL) at RT under N2 and stirred for 2 days. More aldehyde (70 mg, 2 eq.) and sodium triacetoxyborohydride (163 mg, 2 eq.) were added with more MeOH (1 mL) and DCM (1 mL) and stirring continued for 3 days. The mixture was diluted with DCM (10 mL) and washed with saturated aqueous sodium bicarbonate solution, then the mixture was separated on a phase sep cartridge and the chlorinated phase and evaporated under vacuum to give a dark brown oil which was dissolved in 1 :1 MeOH:DMSO (1 ml.) and purified by Mass Directed AutoPrep (Method Formate). The solvent was evaporated under vacuum to give an off white solid (2R)-3-[2-(5-{3-chloro-4-[(1- methylethyl)oxy]phenyl}-1 ,3,4-thiadiazol-2-yl)-3-methyl-2,4,6,7-tetrahydro-5H- pyrazolo[4,3-c]pyridin-5-yl]-1 ,2-propanediol formic acid salt (97 mg, 49.4percent) LCMS: Retention time 0.82 min; [M+H]+ = 464 | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| In methanol; dichloromethane; | L-Glyceraldehyde (182 mg, 2.02 mmol) as added to a stirred solution of 2-[(1- methylethyl)oxy]-5-[5-(3-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl)- 1 ,3,4-thiadiazol-2-yl]benzonitrile (Example 3) (200 mg, 0.4 mmol) in dichloromethane (5 ml.) and methanol (1 ml_). After stirring for 15 minutes sodium triacetoxyborohydride (429 mg, 2.02 mmol) was added and stirring continued overnight at room temperature. Saturated NaHCObeta (10 ml.) was added and the mixture extracted with ethyl acetate (3x10 ml_). The combined extracts were washed with brine, dried and evaporated. The residue was chromatographed [2-10percent methanol/dichloromethane] twice and pure fractions combined to give 5-(5-{5-[(2R)- 2,3-dihydroxypropyl]-3-methyl-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-2-yl}- 1 ,3,4-thiadiazol-2-yl)-2-[(1-methylethyl)oxy]benzonitrile as a colourless solid (20 mg, 11 percent) LCMS: Retention time 0.77 min; [M+H]+ = 455 | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| L-glyceraldehyde (1.84g, 21 mmol) was added to a stirred solution of 2-[(1- methylethyl)oxy]-5-[3-(5-methyl-1 ,2,3,4-tetrahydro-6-isoquinolinyl)-1 ,2,4-oxadiazol-5- yl]benzonitrile trifluoroacetate (Preparation 25) (2.Og, 4.1 mmol) in DCM (50ml) and methanol (5ml). The mixture was stirred at room temperature for 20min then treated with sodium triacetoxyborohydride (4.34g, 21 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated to approx. half volume and diluted with ethyl acetate (50ml). The mixture was washed with saturated sodium hydrogen carbonate (3x 25ml). The organic phase was separated, washed with brine, dried and evaporated. The residue was chromatographed (methanol / DCM, 5percent). The product was dissolved in DCM (20ml) and treated with hydrogen chloride in diethyl ether (1 M, 5ml). The solvent was evaporated and the residue triturated with diethyl ether to give 5-(3-{2-[(2/?)-2,3- dihydroxypropyl]-5-methyl-1 ,2,3,4-tetrahydro-6-isoquinolinyl}-1 ,2,4-oxadiazol-5-yl)-2- [(1-methylethyl)oxy]benzonitrile hydrochloride as a colourless solid (1.Og). LCMS (Method formate): Retention time 0.84min, MH+ = 449 | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 69% | To a stirred suspension of <strong>[497-09-6]L-(-)-glyceraldehyde</strong> (127mg, 1.4 mmol) and 2-[(1- methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1 H-3-benzazepin-7-yl)-1 ,2,4-oxadiazol-5- yl]benzonitrile hydrochloride (Preparation 43) (187mg, 0.46 mmol) in DCM (10ml) under nitrogen, was added acetic acid (0.039ml, 0.68 mmol) followed by sodium triacetoxyborohydride (436mg, 2.1 mmol). The mixture was stirred at room temperature for 2Oh. Further sodium triacetoxyborohydride (193mg, 0.91 mmol) was added and stirring continued for 72h. Saturated aqueous sodium hydrogen carbonate solution (5ml) was added and the mixture stirred vigorously for 30min. The mixture was evaporated to dryness under a stream of nitrogen and the residue was partitioned between saturated aqueous sodium hydrogen carbonate solution (5ml) and ethyl acetate (5ml). The phases were separated and the aqueous phase extracted with ethyl acetate (3x 4ml). The combined organic phases were dried (hydrophobic frit) and evaporated to dryness under a stream of nitrogen. The residue was purified by MDAP (Method formate). The required fraction was evaporated under a stream of nitrogen to give 5-(3-{3-[(2/?)-2,3-dihydroxypropyl]- 2,3,4,5-tetrahydro-1 H-3-benzazepin-7-yl}-1 ,2,4-oxadiazol-5-yl)-2-[(1 - methylethyl)oxy]benzonitrile as a white crunchy foam (140mg, 69percent). LCMS (Method formate): Retention time 0.87min, MH+ = 449 | 
| Yield | Reaction Conditions | Operation in experiment | 
|---|---|---|
| 28% | To a stirred suspension of <strong>[497-09-6]L-(-)-glyceraldehyde</strong> (270mg, 3.0 mmol) and 2-[(1- methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1 H-3-benzazepin-7-yl)-1 ,2,4-oxadiazol-5- yl]-3-pyridinecarbonitrile trifluoroacetate (Preparation 96) (245mg, 0.5 mmol), in DCM (10 ml) under nitrogen, was added acetic acid (0.043ml, 0.75 mmol) followed by sodium triacetoxyborohydride (689mg, 3.3 mmol). The mixture was stirred at room temperature for 1 15h. Saturated aqueous sodium hydrogen carbonate solution (5ml) was added and the reaction stirred vigorously for 15min. The mixture was evaporated to dryness under a stream of nitrogen and the residue partitioned between saturated aqueous sodium hydrogen carbonate solution (5ml) and ethyl acetate (5ml). The aqueous phase was extracted with ethyl acetate (3x 4ml). The combined organic phases were dried (hydrophobic frit) and evaporated to dryness under a stream of nitrogen. The residue was purified by MDAP (Method formate). The required fraction was evaporated under a stream of nitrogen and the residue further purified by MDAP (Method formate, extended run). The required fraction was evaporated under a stream of nitrogen to give 5-(3-{3-[(2S)-2,3-dihydroxypropyl]- 2,3,4,5-tetrahydro-1 H-3-benzazepin-7-yl}-1 ,2,4-oxadiazol-5-yl)-2-[(1 - methylethyl)oxy]-3-pyridinecarbonitrile as a white solid (63mg, 28percent). LCMS (Method formate): Retention time 0.93min, MH+ = 450 |