Structure of 494769-44-7
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 494769-44-7 |
Formula : | C9H14N2O3S |
M.W : | 230.28 |
SMILES Code : | OCC1=CSC(NC(OC(C)(C)C)=O)=N1 |
MDL No. : | MFCD08275703 |
InChI Key : | OWLBQQTUOQLZST-UHFFFAOYSA-N |
Pubchem ID : | 22280475 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H332-H335 |
Precautionary Statements: | P261-P280-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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With manganese(IV) oxide; In dichloromethane; for 2h;Heating / reflux; | Step 3: (4-Formyl-thiazol-2-yl)-carbamic acid tert-butyl ester; (4-Hydroxymethyl-thiazol-2-yl)-carbamic acid tert-butyl ester (1.62 g, 6.95 mmol) was dissolved in 30 ml dichloromethane. Mangan(IV)oxid (3.65 g, 41.7 mmol) was added and the reaction mixture stirred at reflux for 2 hrs. The suspension was filtered through a dicalite speed plus pad and washed with dichloromethane. The solvents were evaporated and the desired compound was obtained as a light yellow solid (1.25 g, 78%), MS: m/e=229.2 (M+H+). |
75% | With Dess-Martin periodane; In dichloromethane; for 2h; | (b) To a solution of 42a (10 g, 43.4 mmol) in 500 mL of DCM was added Dess Martin periodinane (30 g, 70.7 mmol) all at once. After 2 h, the reaction was concentrated by rotary evaporator, diluted with 1n NaOH, and extracted 3×EtOAc. The EtOAc extracts were dried over MgSO4. The solution was filtered and concentrated by rotary evaporator to give 7.4 g (75%) of the yellow solid 2-[(tert-butoxycarbonyl)amino]thiazole-4-carboxaldehyde 42b. 1H-NMR (400 MHz, CDCl3): delta 9.81 (s, 1H), 9.80 (bs, 1H), 7.73 (s, 1H), 1.47 (s, 9H). |
75% | With manganese(IV) oxide; In dichloromethane; at 20℃; | (4-Formyl-thiazol-2-yl)-carbamic acid tert-butyl ester A solution of (4-hydroxymethyl-thiazol-2-yl)-carbamic acid tert-butyl ester (0.302 g, 1.31 mmol) in dry DCM (15 mL) is treated with manganese dioxide (1 .14 g, 13.1 mmol). The mixture is stirred at RT overnight. The reaction mixture is filtered over celite. The celite cake is washed with DCM (15 mL) and MeOH (15 ml_). The filtrate is evaporated under reduced pressure and dried under HV for 1 h to deliver the title compound (0.225 g, 75%) as a colorless solid; LC-MS A: tR = 0.71 min; [M+H]+ = 229.12. |
75% | With manganese(IV) oxide; In dichloromethane; at 20℃; | (4-Formyl-thiazol-2-yl)-carbamic acid tert-butyl ester [0579] A solution of (4-hydroxymethyl-thiazol-2-yl)-carbamic acid tert-butyl ester (0.302 g, 1.31 mmol) in dry DCM (15 mL) is treated with manganese dioxide (1.14 g, 13.1 mmol). The mixture is stirred at RT overnight. The reaction mixture is filtered over celite. The celite cake is washed with DCM (15 mL) and MeOH (15 mL). The filtrate is evaporated under reduced pressure and dried under HV for 1 h to deliver the title compound (0.225 g, 75%) as a colorless solid; LC-MS A: tR=0.71 min; [M+H]+=229.12 |
75% | With Dess-Martin periodane; In dichloromethane; at 20℃; for 16h; | A solution of compound 2 (400 mg, 1.7 mmol) in DCM (10 mL) was added Dess-MaRTin (1.44 g, 3.4 mmol), then stirred at RT for 16 h. The resulting reaction mixture was quenched with water and extracted with DCM, dried and evaporated, purified by combiflash (methanol:DCM = 1:20) to give compound 3 (300 mg, 75%). |
70% | With Dess-Martin periodane; In dichloromethane; at 0 - 20℃; for 20h; | A solution of Example 13 Part B compound (0.94 g; 4.08 mmol) in DCM (8 mL) was added dropwise to a 0 C. solution of Dess-Martin periodinane (1.82 g; 4.28 mmol) in DCM (8 mL). After 20 h at RT, the reaction was diluted with DCM (4 mL) and 1.0 N aqueous NaOH (6 mL). After stirring for 10 min, the mixture was filtered through Celite. The organic phase was washed with brine (10 mL), dried (MgSO4) and concentrated in vacuo. The residue was chromatographed (SiO2; continuous gradient from 0 to 50% EtOAc in hexanes over 12 min, hold at 50% EtOAc in hexanes for 8 min) to give Part A compound (0.65 g; 70%) as a white solid. |
7 g | With Dess-Martin periodane; In dichloromethane; at 20℃; for 2h; | To a mixture of Compound AG (14 g, 60.79 mmol) in DCM (200 mL) was added Dess- Martin (30.9 g, 72.95 mmol) at rt. The mixture was kept for 2 hrs. Na2 S203 was added then the mixture was washed with water, aq. NaHC03. The organic layer was dried and concentrated to afford light yellow oil. The residue was purified by column chromatography in silica gel (PE: EA =10: 1) to give Compound AH (7.0 g) as light yellow oil. |
7 g | With Dess-Martin periodane; In dichloromethane; at 20℃; for 2h; | To a mixture of Compound AG (14 g, 60.79 mmol) in DCM (200 mL) was added Dess-Martin (30.9 g, 72.95 mmol) at rt. The mixture was kept for 2 hrs. Na2O3 was added then the mixture was washed with water, aq. NaHCO3. The organic layer was dried and concentrated to afford light yellow oil. The residue was purified by column chromatography in silica gel (PE: EA=10:1) to give Compound AH (7.0 g) as light yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 8h; | General procedure: The intermediate (3) (0.5 g, 0.00217 mol), EDCl (0.622 g, 0.00325 mol), DMAP (0.345 g, 0.0028 mol) were stirred in dichloromethane (6 mL) at 0 C, and the substituted acid (0.00217 mol) were dissolved in (4 mL) of dichloromethane and charged to the reaction mixture and stirred at room temperature for 8 h. The reaction completion was monitored by TLC. Reaction was completed. The reaction mixture was diluted with (10 mL) of dichloromethane, and was washed with 10% NaHCO3 (10 mL). Separated the organic layer and was washed with saturated brine solution (10 mL). The organic layer was dried over sodium sulfate and concentrated the organic layer under reduced pressure to afford compounds 4a-t. The spectral data of compounds 4(a-t) are given below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 20℃; for 8h; | General procedure: The intermediate (3) (0.5 g, 0.00217 mol), EDCl (0.622 g, 0.00325 mol), DMAP (0.345 g, 0.0028 mol) were stirred in dichloromethane (6 mL) at 0 C, and the substituted acid (0.00217 mol) were dissolved in (4 mL) of dichloromethane and charged to the reaction mixture and stirred at room temperature for 8 h. The reaction completion was monitored by TLC. Reaction was completed. The reaction mixture was diluted with (10 mL) of dichloromethane, and was washed with 10% NaHCO3 (10 mL). Separated the organic layer and was washed with saturated brine solution (10 mL). The organic layer was dried over sodium sulfate and concentrated the organic layer under reduced pressure to afford compounds 4a-t. The spectral data of compounds 4(a-t) are given below. |
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