CAS No. : | 241479-67-4 | MDL No. : | |
Formula : | C22H17F2N5OS | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DDFOUSQFMYRUQK-RCDICMHDSA-N |
M.W : | 437.47 | Pubchem ID : | 6918485 |
Synonyms : |
BAL-4815;RO-0094815;trade name Cresemba.;BAL-8557-002
| Chemical Name : | 4-[2-[(1R,2R)-2-(2,5-Difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]-4-thiazolyl]benzonitrile |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
63% | sodium iodide; In acetonitrile; at 20 - 80℃; for 9h; | A solution of 1-[3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2-(2,5-difluoro-phenyl)-2-hydroxy-butyl-1H-[1,2,4]triazol (200 mg, 0.457 mmol), sodium iodide (6.8 mg 0.045 mmol) and acetic acid 2-(chloromethoxycarbonyl-methyl-amino)-benzyl ester 150 mg, 0.552 mmol) was stirred for 6 h at ambient temperature and then at 80° C. for 3 h under Ar atmosphere. The reaction mixture was concentrated under reduced pressure and the resulting material was eluted on a column of silica gel (Kusano Si-5, eluent dichloromethane:methanol=20:1). The fractions containing the product were concentrated under reduced pressure giving the title compound a) as colorless amorphous (204.5 mg, 63percent). 1H-NMR (270 MHz, DMSO-d6): delta 1.20 (3H, d, J=6.9), 1.99 (3H, s), 3.12 (2.4H, s), 3.15 (0.6H, s), 4.15 (1H, q, J=7.3), 4.79-4.91 (3H, m), 5.09 (1H, d, J=14.8), 5.76 (1H, s), 5.90-6.10 (1.6H, m), 6.17 (0.4H, br.s), 6.61-6.66 (1H, m), 7.05-7.15 (1H, m), 7.26-7.44 (6H, m), 7.91-7.96 (2H, m), 8.20-8.24 (2H, m),8.49 (1H, s), 9.01 (0.8H, br.d, J=3.6), 9.12 (0.2H, br.s), 10.16 (0.8H, br.d, J=4.9), 10.27 (0.2H, br.s); FAB-MS: 673 (M-Cl)+; Ratio of Retention Time in HPLC: 1.79 (see Example D). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
51% | sodium iodide; In acetonitrile; at 70℃; | To a solution of [N-methyl-N-2-((tert-butoxycarbonylisopropylamino)methyl)phenyl]carbamic acid 1-chloro-ethyl ester (143 mg, 0.342 mmol) in acetonitrile (1 ml) was added the azole compound (163 mg, 0.372 mmol) and catalytic amount of sodium iodide at 70° C. After stirring overnight, the solvent was removed and extracted with ethyl acetate. The organic phase was washed with water and brine. The solvent was removed in vacuo. The residue was purified by column chromatography (ethyl acetate to 10percent methanel-dichloromethane) to afford 1-[[N-methyl-N-2-(t-butoxycarbonyl-isopropylaminomethyl)phenyl]carbamoyloxy]ethyl-1-[(2R,3R)-2-(2,5-difluorophenyl)-2-hydroxy-3-[4-(4-cyano-phenyl)thiazol-2-yl]butyl]-1H-[1,2,4]triazol-4-ium chloride (155 mg, 0.189 mmol, 51percent) as off-white amorphous. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.4% | With sodium iodide; In acetonitrile; at 45 - 50℃; for 15h; | [N-methyl-N-3-((tert-butoxycarbonylmethylamino)acetoxymethyl)pyridin-2-yl]carbamic acid 1-chloro-ethyl ester(q) (55 g, 0.132 mol, 1.4 eq) and the azole compound of Example 5a) (41.2 g, 0.0944 mol) was dissolved in CH3CN(350 mL) and warmed to 45-50 C. To the solution was added NaI(19.7 g, 0.131 mol, 1.4 eq) and stirred for 15 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The obtained residue was purified by silicagel columnchromatography((eluent: fromAcOEt to AcOEt/MeOH (10/1,v/v) gradient) to give the product as its iodide form(78.7 g, 88.4% yield). [00418] The iodide (66.5 g, 0.07 mol) was dissolved in MeOH(300 mL) and distilled water(200 mL) at 0 C. and strong anion exchange resin[Dia Ion SA10A(200 g)]was added to the solution. The mixture was stirred using an evaporator. After 1 h, the mixture was filtered, washed with methanol and the filtrate was evaporated. The obtained residue was diluted with water(200 mL), brine(200 mL) and ethyl acetate(500 mL). The organic layer was extracted with ethyl acetate and combined ethyl acetate layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silicagel column chromatography((eluent:DCM/MeOH(10/1, v/v)) to give the product (52.1 g, 86.7% yield). |
83% | With sodium iodide; In acetonitrile; at 50 - 60℃; for 12h;Inert atmosphere; | Adding a compound of formula 1 (50 g) to a 500 ml single-mouth round bottom reaction flask,Compound of formula 2 (67 g), NaI (24 g) and anhydrous MeCN (250 ml),Nitrogen replacement, nitrogen protection; heating to 60 C oil temperature, internal temperature 50 C,Stirring for 12 hours; cooling to below 20 C, filtering, filter cake washed with EA;EA (200 ml) and purified water (500 ml) were added to the filtrate, and the mixture was stirred and extracted;Separate, the upper EA phase is wine red; the lower aqueous phase is extracted twice with EA (50 ml).The organic phases were combined and washed with aq. NaCI (50 mL).Dryed by adding 20 g of anhydrous sodium sulfate and concentrated under reduced pressure to give a foamy solid.Used directly in the next reaction;The yield was 83% and the HPLC purity was >90%. |
With potassium iodide; In acetonitrile; at 47 - 50℃; | <strong>[241479-67-4]Isavuconazole</strong> (20 g) and [N-methyl-N-3((tert-butoxycarbonylmethylamino)acetoxy methyl)pyridine-2-yl]carbamic acid 1 -chloro-ethyl ester (24.7 g) were dissolved in acetonitrile (200ml). The reaction mixture was stirred to add potassium iodide (9.9 g). The reaction mixture was stirred at 47-50C for 10-13 hour. The reaction mixture was cooled to room temperature. The reaction mass was filtered through celite bed and washed acetonitrile. Residue was concentrated under reduced pressure to give the crude solid product (47.7 g). The crude product was purified by column chromatography to get its pure iodide form (36.5 g). Yield: 84.5 % HPLC Purity: 87% Mass: m/z 817.4 (M-I)+ |