- Cobalt-Catalysed Reductive Etherification Using Phosphine Oxide Promoters under Hydroformylation Conditions
-
A phosphine-oxide-promoted, cobalt-catalysed reductive etherification using syngas as a reductant is reported. This novel methodology was successfully used to prepare a broad range of unsymmetrical ethers from various aldehydes and alcohols containing diverse functional groups, and was scaled-up to multigram scale under comparably mild conditions. Mechanistic experiments support an acetalization–hydrogenation sequence.
- Beller, Matthias,Delolo, Fábio G.,Fessler, Johannes,Gusevskaya, Elena V.,Junge, Kathrin,Neumann, Helfried,dos Santos, Eduardo N.
-
supporting information
(2022/02/19)
-
- PHOSPHOINOSITIDE 3-KINASE INHIBITORS WITH ZINC BINDING MOIETY
-
PROBLEM TO BE SOLVED: To provide phosphoinositide 3-kinase inhibitors with a zinc binding moiety. SOLUTION: There is provided a compound represented by formula (I) in the figure. (X is S, O or the like; Y is CH, N or the like; G1 is optionally substituted N or the like; R1 and R2 are each independently H or the like; C is a substituted heterocycle or the like; B is a linear alkyl or the like; Ra and Rb together with the nitrogen atom coupled to them are morpholino or the like; G2 is an indazole ring or the like; q, r and s are independently from 0 to 1, provided that at least one of them is 1; t is from 0 to 1; n is from 0 to 4; and p is from 0 to 2.) COPYRIGHT: (C)2016,JPOandINPIT
- -
-
Paragraph 0356
(2016/10/07)
-
- TREATMENT OF CANCERS HAVING K-RAS MUTATIONS
-
The present invention provides a method of treating a cancer associated with a K-ras mutation in a subject in need thereof. The method comprises the steps of: (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) administering to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.
- -
-
Paragraph 0411; 0412
(2013/05/08)
-
- New method for the synthesis of benzyl alkyl ethers mediated by FeSO 4
-
The synthesis of benzyl alkyl ethers from benzyl bromides and alcohols using FeSO4 as a recoverable and reusable mediator has been described without use of base and cosolvent under mild conditions.
- Joshi, Girdhar,Adimurthy, Subbarayappa
-
experimental part
p. 720 - 728
(2011/03/22)
-
- TREATMENT OF CANCERS HAVING K-RAS MUTATIONS
-
The present invention provides a method of treating a cancer associated with a K- ras mutation in a subject in need thereof. The method comprises the steps of (1) identifying a subject with a cancer associated with a K-ras mutation; and (2) adminsiterign to the subject (i) an inhibitor of PI3 kinase and (ii) an HDAC inhibitor, wherein the PI3 kinase inhibitor and the HDAC inhibitor are administered in amounts which together are therapeutically effective.
- -
-
Page/Page column 188
(2011/11/01)
-
- An improved synthesis of the selective EP4 receptor agonist ONO-4819
-
(Chemical Equation Presented) An improved synthesis of the highly selective EP4-receptor agonist ONO-4819 has been developed. The previous synthesis suffered from several drawbacks, in which a critical one is the difficulty in the removal of byproducts leading to unsatisfactory quality of the active pharmaceutical ingredient (API). Furthermore, on stereoselective reduction of an enone intermediate by binaphthol-modified lithium aluminum hydride, low concentration of the reaction conditions and tedious purification procedures to remove excess binaphthol were critical issues for the manufacturing process of the API. In the improved process,we have developed improved conditions using γ-thiobutyrolactone as sulfur source instead of potassium thioacetate to introduce the sulfur-containing C4 side chain without formation of byproducts. For stereoselective synthesis of the chiral alcohol, (-)-DIP-chloride reduction is found to be the best method, which can improve not only the enantioselectivity but also the workload for removing the chiral modifier in a purification process. Furthermore, benzoyl and tert-butyldimethylsilyl groups as protecting groups for hydroxyl functions were used for precise process controls of all intermediates. By changing these protecting groups, the purity of ONO-4819 was strictly controlled through crystalline intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity was developed. 2009 American Chemical Society.
- Ohta, Chisa,Kuwabe, Shin-Itsu,Shiraishi, Tai,Shinohara, Ikuo,Araki, Hiroshi,Sakuyama, Shigeru,Makihara, Takayuki,Kawanaka, Yasufumi,Ohuchida, Shuichi,Takuya, Seko
-
experimental part
p. 8298 - 8308
(2010/02/17)
-
- 2-CYANOPYRROLOPYRIMIDINES AND PHARMACEUTICAL USES THEREOF
-
The invention relates to pyrrolo pyrimidines of formula (I), wherein Y represents -(CH2)t-O- or -(CH2)r-S-, p is 1 or 2, r is 1, 2 or 3, t is 1, 2 or 3, or Y is -(CH2)j- or -CH=CH-, j is 1 or 2; p is 1 or 2, or Y is -(CH2)f-, f is 1 or 2, p is 1, and the further radicals and symbols have the meaning as defined herein; their preparation, their use as pharmaceuticals, pharmaceutical compositions containing them, the use of such a compound for the manufacture of a pharmaceutical preparation for the treatment of neuropathic pain and to a method for the treatment of such a disease in animals, especially in humans.
- -
-
Page/Page column 38-39
(2010/02/08)
-
- 5-thia-ω-substituted phenyl-prostaglandin E derivatives, process for producing the same and drugs containing the same as the active ingredient
-
The present invention relates to 5-thia-ω-substituted phenylprostaglandin E derivatives of the formula (I) (wherein, all the symbols are as defined in the specification), process for producing them and pharmaceutical compositions comprising them as active
- -
-
-
- γ(v)-SUBSTITUTED PHENYL-PROSTAGLANDIN E DERIVATIVES AND DRUGS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
-
An ω-substituted phenyl-prostaglandin derivative of formula (I), a process for the preparation thereof, a medicament comprising it as active ingredient (all symbols have the same meaning as described in the specification). The compounds of the formula (I)
- -
-
-
- 3,7-dithiaprostanoic acid derivative
-
A 3,7-dithiaprostanoic acid derivative of the formula (I) STR1 (wherein, R1 is OH, C16 alkyloxy, NR6 R7 (R6, R7 are H, C16 alkyl.); R2 is H, OH; R3 is single bond, C16 alkylene; R4 is (i) C18 alkyl substituted by C16 alkyloxy, halogen etc., (ii) phenyloxy
- -
-
-
- The Effect of Phenyl Ring Torsional Rigidity on the Photophysical Behavior of Tetraphenylethylenes
-
The synthesis and photochemical behavior of several members of the bismetacyclophanylidene series are presented.The properties of these compounds are compared to a model compound, tetra-3-tolylethylene.The photophysical properties of the tethered tet
- Shultz, David A.,Fox, Marye Anne
-
p. 6311 - 6320
(2007/10/02)
-
- THE EFFECT OF ARYL SUBSTITUENTS ON ARYLCARBENE REACTIVITY
-
Substituted (p-MeO, p-Me, H, p-Cl, p-Br, m-Br, m-MeO, 3,4-Cl2, p-CO2Me, m-CN and p-CN) monophenylcarbenes are generated in a binary mixture of substrates (methanol, cis-4-methyl-2-pentene and cyclohexane) and the relative rate of O - H insertion into methanol to stereospecific cyclopropanation of the olefin to C - H insertion into cyclohexane are calculated from the ratios of products and substrates.It is found (i) that the reactivities of the substrates decrease in the order of methanol, olefin and cyclohexane and (ii) that electron-donating substituents generally lead to reaction with the more reactive substrates while the reaction with the less reactive substrates is favoured in the case of electron-withdrawing substituents.These results are interpreted in terms of the change in the electrophilicity of the singlet arylcarbene by the substituents rather than the change in the singlet-triplet equilibrium.
- Tomioka, Hideo,Tabayashi, Kazuo,Ozaki, Yasuji,Izawa, Yasuji
-
p. 1435 - 1440
(2007/10/02)
-
- Host-Guest Complexation. 31. A Transacylase Partial Mimic
-
The first two stages are reported of an incremental approach to the synthesis of hosts that mimic serine transacylases.The hosts are 20-membered macrocycles and are composed by attaching to one another aryloxy, cyclic urea, pyridyl, biphenyl, ethylene, methylene and oxygen units.The structures and points of attachment of all but the latter two units are drawn and are symbolized by capital letters.The structures of the hosts and synthetic intermediates are indicated by line formulas consisting of sequences of letters, which represent sequences of units bonded to one another in the host. A, A', U, B, Py, D, Nap, E.In the first stage of our approach the compound U(A'UCH2)2A' was designed and prepared and its binding properties toward Li+, Na+, K+, Rb+, Cs+, NH4+, CH3NH3+, and t-buNH3+ picrates in CDCl3 at 25 deg C were determined.The free energies of binding (-ΔGdeg values) varied from a low of 12.1 to a high of 15.2 kcal mol-1.A crystal structure of the complex U(A'UCH2)2A'*t-BuNH3ClO4 indicated the substance possessed the expected organization.The complex is held together by the three hydrogen bonds RN+(H...O=C)3 in which the carbonyl groups are parts of the three cyclic urea units (U).The high binding power of U(A'UCH2)2A' is attributed the presence of the three cyclic urea units and particularly to their high degree of preorganization.The key ring-closing reaction involved H-U-A'-U-A'-U-H reacting with BrCH2-A'-CH2Br in tetrahydrofuran-NaH to produce U(A'UCH2)2A'*NaBr (50percent).In the second stage, host U(A'UCH2)2BCH2OH was designed and prepared by similar reaction between H-U-A'-U-A'-U-H with (Br(CH2)2BCH2OCH3 to produce U(A'UCH2)2BCH2OCH3 (36percent), which was converted to U(A'UCH2)2BCH2OH.This compound contains both a binding site complementary to RNH3+ guests and a nucleophilic hydroxyl group complementary to the guest carbonyl group in complexes such as U(A'UCH2)2BCH2OH*CH3CH(CO2C6H4NO2-p)NH3ClO4.The -ΔGdeg values of U(A'UCH2)2BCH2OH binding the above picrate salts series in CDCl3 at 25 deg C varied from a low of 10.6 to a high of 15.4 kcal mol-1.When the alanine complex of this nucleophilic host was dissolved in CH2Cl2-10percent pyridine (by volume) at 25 deg C, transacylation occurred to give U(A'UCH2)2BCH2O2CCh(CH3)NH3ClO4.The kinetics of transacylation were followed in CDCl3 buffered with R3N-R3NHCLO4 (R3N is diisopropylethylamine).Pseudo-first-order (saturation) kinetics were observed under conditions where host concentration greatly exceeded that of guest.The reaction was first order in buffer ratio, and therefore the active nucleophile O-.Under the same reaction conditions, the noncomplexing model compound, H2BCH2OH, underwent no detectable reaction.Upper limits were placed on its rate of acylation.Comparisons of the bimolecular acylation rates by CH3CH(CO2C6H4NO2-p)NH3ClO4 of U(A'UCH2)2BCH2OH and of H2BCH2OH were made to assess all the effects of comlexing.The complexing system has a second-order rate constant that is ca 1011 times greater than the second-order rate constant ...
- Cram, Donald J.,Katz, Howard Edan,Dicker, Ira B.
-
p. 4987 - 5000
(2007/10/02)
-