286440-92-4

Usage

Uses

Used in Organic Synthesis:
Benzeneethanol, 3,4-difluoro(9CI) is utilized as a reagent in organic synthesis, playing a crucial role in the formation of various complex organic molecules. Its unique chemical structure, featuring fluorinated benzene and an ethanol group, allows it to participate in a range of chemical reactions, making it a valuable component in the synthesis of diverse organic compounds.
Used in Pharmaceutical Production:
As an intermediate in the production of pharmaceuticals, Benzeneethanol, 3,4-difluoro(9CI) contributes to the development of new drugs and medications. Its presence in the synthesis process can influence the properties and effectiveness of the final pharmaceutical product, highlighting its importance in the pharmaceutical industry.
Used in Agrochemical Production:
Benzeneethanol, 3,4-difluoro(9CI) also serves as an intermediate in the production of agrochemicals, which are chemicals used in agricultural practices to protect crops and enhance their growth. Its involvement in the synthesis of these chemicals can lead to the development of more effective and targeted agrochemicals.
Used in Solvent Applications:
Due to its solvent properties, Benzeneethanol, 3,4-difluoro(9CI) is employed in various industrial processes where a solvent is required. Its ability to dissolve a wide range of substances makes it a versatile component in numerous applications, from chemical reactions to cleaning processes.
Used in Cosmetics and Personal Care Products:
Benzeneethanol, 3,4-difluoro(9CI) finds use in the manufacturing of cosmetics and personal care products, where it may contribute to the formulation of fragrances, creams, and other products. Its sweet odor and compatibility with various ingredients make it a suitable component for these applications.

Upstream product

• 658-93-5 (3,4-difluorophenyl)acetic acid 
• 129409-55-8 ethyl 2-(3,4-difluorophenyl)acetate 

Downstream Products

• 731825-97-1 3,4-difluorophenethyl 4-methylbenzenesulfonate 
• 150881-71-3 4-(1-bromoethyl)-1,2-difluorobenzene 
• 109346-84-1 2-(3,4-difluorophenyl)acetaldehyde 
• 731825-98-2 4-[2-(3,4-difluoro-phenyl)-ethyl]-piperazine-1-carboxylic acid tert-butyl ester 
• 179534-91-9 1-[2-(3,4-difluorophenyl)ethyl]piperazine 
• 676601-64-2 1-{4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl}-9H-2,4,9-triazafluoren-6-ylamine 
• 676601-59-5 1-{4-[2-(3,4-difluoro-phenyl)ethyl]-piperazin-1-yl}-6-nitro-9H-2,4,9-triaza-fluorene 
• 1420369-76-1 tert-butyl 8-(3,4-difluorophenethoxy)-6-oxo-2,3,4,6-tetrahydro-1H-pyrimido[1,6-a]pyrimidine-1-carboxylate 
• 175018-77-6 2-(3,4-difluorophenyl)ethyl bromide 

Relevant academic research and scientific papers

Synthesis of trans-2-Substituted Cyclopropylamines from α-Chloroaldehydes

Cyclopropylamines are prevalent in pharmaceuticals and agrochemicals. Herein, we report the synthesis of trans-2-substituted cyclopropylamines in high diastereoselectivity from readily available α-chloroaldehydes. The reaction proceeds via trapping of an electrophilic zinc homoenolate with an amine followed by ring closure to generate the cyclopropylamine. We have also observed that cyclopropylamine cis/trans-isomerization occurs in the presence of zinc halide salts and that this process can be turned off by the addition of a polar aprotic cosolvent.

Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines

Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.

3,3-DIFLUORO-PIPERIDINE DERIVATIVES AS NR2B NMDA RECEPTOR ANTAGONISTS

Disclosed are chemical entities of Formula (I): wherein X, Y, Z, R1, R3, R4 and R5 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinaseγ

The Type 1 PI3Kinases comprise a family of enzymes, which primarily phosphorylate PIP2 to give the second messenger PIP3, a key player in many intracellular signaling processes [Science, 2002, 296, 1655; Trends Pharmacol. Sci. 2003, 24, 366]. Of the four type 1 PI3Ks, the γ-isoform, which is expressed almost exclusively in leukocytes [Curr. Biol., 1997, 7, R470], is of particular interest with respect to its role in inflammatory diseases such as rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD) [Mol. Med. Today, 2000, 6, 347]. Investigation of a series of 4,6-disubstituted-4H-benzo[1,4]oxazin-3-ones has led to the identification of single-digit nanomolar inhibitors of PI3Kγ, several of which had good cell based activity and were shown to be active in vivo in an aspectic peritonitis model of inflammatory cell migration.

PYRROLOPYRIMIDINE DERIVATIVES USEFUL AS MODULATORS OF MULTIDRUG RESISTANCE

A compound which is a pyrrolopyrimidine of formula (I) wherein: R1 is selected from R9 and halogen; R2 is NR6R7; R3 is selected from H, C1-C6 alkyl which is unsubstituted or substituted and -(CH2) nAr; R4 is selected from H, C1-C6 alkyl and -(CH2)? Ar; or R3 and R4 form, together with the N and C atoms to which they are attached, a fused five-, six-, seven- or eight-membered N-containing saturated ring which is unsubstituted or substituted; R5 is selected from CN, C02R9,C(O)NR10R11, -(CH2)nOH, -(CH2)nR10Rn, -C=CH, -C(S)NR10R11, -C(NH2)=NOR9, -C(R9)=NOR9, -C(NH2)NH, -C(O)R9 and an unsaturated 5- or 6-membered heterocyclic group which contains 1, 2 or 3 heteroatoms selected from N, O and S and which is unsubstituted or substituted; R6 and R7, which are the same or different, are selected from C1-C6 alkyl which is unsubstituted or substituted, -(CH2)nX and -(CH2)nAr; or R6 and R7 form, together with the nitrogen atom to which they are attached, a saturated five-, six-, seven- or eight-membered heterocyclic group which contains one nitrogen atom and 0 or from 1 to 3 additional heteroatoms selected from N, O and S, which is unsubstituted or substituted and which optionally contains one or two bridgehead atoms; R10and R11,which are the same or different, are selected from H, C1-C6 alkyl which is unsubstituted or substituted, -(CH2)nC3-C10 cycloalkyl and -(CH2)nAr; or R10 and R11 form, together with the nitrogen atom to which they are attached, a saturated five or six membered heterocyclic group which contains a nitrogen atom and 0 or from to 3 additional heteroatoms selected from O, S and N, which is unsubstituted or substituted and which is optionally fused to a benzene ring which is unsubstituted or substituted; n is the same or different when more than one is present within a given substituent group and is 0 or an integer of from 1 to 6; X is selected from -CN, -C02R9 and -NR10R11; R9 is the same or different when more than one is present within a given substituent group and is selected from -H, -QAr, -(CH2) nAr, C1-C6 alkyl which is unsubstituted or substituted and -(CH2) nC3-C10cycloalkyl, wherein the cycloalkyl moiety is optionally fused to a benzene ring which is unsubstituted or substituted; Q is C2-C6 alkenylene or alkynylene; and Ar is an unsaturated C6-C10 membered carbocyclic group or an unsaturated 5-11 membered heterocyclic group, which groups are unsubstituted or substituted; or a pharmaceutically acceptable salt thereof. These compounds have activity as inhibitors of MRP (multidrug resistant protein) and may thus be used to modulate multidrug resistance, for instance in potentiating the cytotoxicity of a chemotherapeutic agent.

PYRROLOPYRIMIDINE DERIVATIVES AS MODULATORS OF MULTI-DRUG RESISTANCE (MDR)

A compound which is a pyrrolopyrimidine of formula (I) wherein R1 is selected from H, Cl-C6 alkyl which is unsubstituted or substituted, (CH2)nAr1, (CH2)pNR4R5, halogen and (CH2)pX; R2 is CH2)pArl; R3 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)pZ and (CH2)pArl; P is an unsaturated 5, 6, or 7 membered carbocyclic or heterocyclic ring which is unsubstituted or substituted; R4 and R5 which are the same or different are selected from H, Cl -C6 alkyl which is unsubstituted or substituted, (CH2)nC3-C10 cycloalkyl, (CH2)nAr1 , and (CH2)nOR6, or R4 and R5 together with the nitrogen atom to which they are attached, form a saturated five or six membered nitrogen containing heterocyclic ring which may contain one extra heteroatom selected from 0, N and S and which is unsubstituted or substituted; R6 is selected from H, Cl -C6 alkyl which is unsubstituted or substituted, C3-C10 cycloalkyl, (CH2)nOC1-C6alkyl which is unsubstituted or substituted, (CH2)nO(CH2)nAr1 , (CH2)nCO2C1-C6,alkyl which is unsubstituted or substituted and (CH2)nAr1; X is selected from CN, azide, (CH2)nNHSO2R6 and (CH2)nNHCOR6; Z is selected from CN, CO2R6 and CONR4R5; Ar1 is the same or different when more than one is present within a given substituent group and is an unsaturated C6-C10 membered carbocylic group or an unsaturated 5-11 membered heterocycle, either of which is unsubstituted or substituted; p is an integer of 1 to 6; n is the same or different when more than one is present within a given substituent group and is 0 or an integer of 1 to 6; with the proviso that the pyrrolepyrimidine compound of formula (I) is other than 1-(4-benzyl-piperazin-1-yl)-9H-2,4,9-triaza-fluorene; and the pharmaceutically acceptable salts thereof, have activity as inhibitors of MRP (multidrug resistant protein) and may thus be used to modulate multidrug resistance, for instance in potentiating the cytotoxicity of a chemotherapeutic agent.

2-substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1- yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioavailability

In this paper we describe the synthesis of a series of α-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxycyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into an antagonist. All of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. On the basis of the improvement in affinity realized for the α-phenylethyl analogue 3, in this paper we explored the effects of substitution on the aromatic ring as a strategy to increase the affinity of these compounds for group II mGluRs. Affinity for group II mGluRs was measured using [3H]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1- aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. Meta substitution on the aromatic ring of 3 with a variety of substituents, both electron donating (e.g., methyl, hydroxy, amino, methoxy, phenyl, phenoxy) and electron withdrawing (e.g., fluorine, chlorine, bromine, carboxy, trifluoromethyl) gave from 1.5- to 4.5-fold increases in affinity. Substitution with p-fluorine, as in 97 (IC50 = 0.022 ± 0.002), was the exception. Here, a greater increase in affinity was realized than for either the ortho- or meta-substituted analogues; 97 was the most potent compound resulting from monosubstitution of the aromatic. At best, only modest increases in affinity were realized for certain compounds bearing either two chlorines or two fluorines, and two methoxy groups gave no improvement in affinity (all examined in a variety of substitution patterns). Three amino acids, 4, 5, and 104, were resolved into their four constituent isomers, and affinity and functional activity for group II mGluRs was found to reside solely in the S,S,S-isomers of each, consistent with 1. With an IC50 = 2.9 ± 0.6 nM, the resolved xanthylmethyl compound 168 was the most potent compound from this SAR. Amino acid 168 demonstrated high plasma levels following intraperitoneal (ip) administration and readily penetrated into the brain. This compound, however, had only limited (~5%) oral bioavailability. Systemic administration of 168 protected mice from limbic seizures produced by the mGluR agonist 3,5-dihydroxyphenylglycine, with an ED50 = 31 mg/kg (ip, 60 min preinjection). Thus, 168 represents a valuable tool to study the role of group II mGluRs in disease.