| Identification | Back Directory | [Name]
3-Cyclopropylmethoxy-4-difluoromethoxy-benzoic acid | [CAS]
162401-62-9 | [Synonyms]
RofluM
Roflumilast Impurity J
Roflumilast Acid Impurity
Roflumilast intermediate B
RofluMilast InterMediate II
Roflumilast Carboxylic Acid Impurity
CYCLOPROPYL DIFLUOROMETHOXYBENOZOIC ACID
3-CyclopropylMethoxy-4-isopropoxy-benzoic acid
3-CyclopropyMethoxy-4-difluoroMethoxy benzoic acid
3-Cyclopropylmethoxy-4-difluoromethoxy-benzoic acid
Benzoic acid, 3-(cyclopropylMethoxy)-4-(difluoroMethoxy)-
3-Cyclopropylmethoxy-4-difluoromethoxybenzoic acid, >=98%
Roflumilast intermediate (3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid) | [EINECS(EC#)]
605-288-7 | [Molecular Formula]
C12H12F2O4 | [MDL Number]
MFCD04621687 | [MOL File]
162401-62-9.mol | [Molecular Weight]
258.219 |
| Chemical Properties | Back Directory | [Melting point ]
118-120℃ | [Boiling point ]
356.4±37.0 °C(Predicted) | [density ]
1.355±0.06 g/cm3(Predicted) | [storage temp. ]
Sealed in dry,Room Temperature | [solubility ]
DMSO (Slightly), Methanol (Slightly) | [form ]
Solid | [pka]
3.87±0.10(Predicted) | [color ]
White to Off-White | [InChI]
InChI=1S/C12H12F2O4/c13-12(14)18-9-4-3-8(11(15)16)5-10(9)17-6-7-1-2-7/h3-5,7,12H,1-2,6H2,(H,15,16) | [InChIKey]
IGFDIFLMMLWKKY-UHFFFAOYSA-N | [SMILES]
C(O)(=O)C1=CC=C(OC(F)F)C(OCC2CC2)=C1 | [CAS DataBase Reference]
162401-62-9 |
| Hazard Information | Back Directory | [Description]
3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid (DGM,162401-62-9) is a pharmaceutical intermediate ingredient used in the preparation of Roflumilast, a selective phosphodiesterase-4 (PDE4) inhibitor approved for the treatment of chronic bronchitis and to reduce the risk of exacerbations in patients with severe chronic obstructive pulmonary disease (COPD).
| [Uses]
An impurity and intermediate in the preparation of selective phosphodiesterase 4 (PDE4) inhibitor, Roflumilast (R639700). | [Biological Activity]
It was shown that 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid (DGM,162401-62-9) attenuated transforming growth factor-β1 (TGF-β1)-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in rats. DGM treatment suppressed the expression of proteins such as α-SMA, waveform protein and collagen I and other proteins and increased the expression of E-cadherin. Correspondingly, the phosphorylation level of Smad2/3 was significantly reduced after DGM treatment[1].
| [Synthesis]
3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic Acid(162401-62-9) is synthesised using 3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde as raw material by chemical reaction. The specific synthesis steps are as follows:
3-cyclopropylmethoxy-4-difluoromethoxybenzaldehyde (12 g, 50 mmol) and sulfamic acid (7.3 g, 75 mmol) were dissolved in glacial acetic acid (50 ml) and the solution added with a solution of sodium chlorite (8.2 g, 75 mmol) in water (15 ml).
The reaction mixture was stirred at room temperature for 1 hr then water (300 ml) was added so obtaining the precipitation of a solid that was filtered and dried at 40° C. under vacuum (12 g, 48 mmol, 97percent yield).
| [References]
[1] TIANXIAO SUN. Inhibitory Effects of 3-Cyclopropylmethoxy-4-(difluoromethoxy) Benzoic Acid on TGF-β1-Induced Epithelial-Mesenchymal Transformation of In Vitro and Bleomycin-Induced Pulmonary Fibrosis In Vivo.[J]. International Journal of Molecular Sciences, 2023. DOI:10.3390/ijms24076172. |
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