- Selective α-Methylation of Ketones
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The convenient and scalable preparative approach for the two-step α-methylation of ketones is described. The optimized protocols for regioselective preparation of enaminones with further diastereoselective and functional groups tolerant hydrogenation to α-methylketones are developed. The scope and limitations of the proposed methodology are discussed. The advantages compared to known procedures are demonstrated. The unexpected role of acetone in the hydrogenation is suggested. The evaluation of the method for both early building block synthesis and late-stage CH-functionalization is shown. The elaborate procedures' preparability and scalability are demonstrated by the synthesis of several α-methyl ketones up to 100 g amount.
- Frolov, Andriy I.,Ostapchuk, Eugeniy N.,Pashenko, Alexander E.,Chuchvera, Yaroslav O.,Rusanov, Eduard B.,Volochnyuk, Dmitriy M.,Ryabukhin, Sergey V.
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p. 7333 - 7346
(2021/06/28)
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- Aminopyridyloxypyrazole derivative and preparation method and application thereof
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The invention relates to an aminopyridyloxypyrazole derivative and a preparation method and application thereof. The structure of the aminopyridyloxypyrazole derivative is shown as a formula (I). The invention provides a brand-new aminopyridyloxypyrazole derivative which has obvious effects of inhibiting TGF [beta] R1 (ALK5) kinase activity and treating cancer or fibrosis related diseases, and the preparation method of the derivative is simple and easy to operate.
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Paragraph 0075; 0382-0387
(2021/05/19)
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- Chemoselective Oxidation of Equatorial Alcohols with N-Ligated λ3-Iodanes
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The site-selective and chemoselective functionalization of alcohols in complex polyols remains a formidable synthetic challenge. Whereas significant advancements have been made in selective derivatization at the oxygen center, chemoselective oxidation to the corresponding carbonyls is less developed. In cyclic systems, whereas the selective oxidation of axial alcohols is well known, a complementary equatorial selective process has not yet been reported. Herein we report the utility of nitrogen-ligated (bis)cationic λ3-iodanes (N-HVIs) for alcohol oxidation and their unprecedented levels of selectivity for the oxidation of equatorial over axial alcohols. The conditions are mild, and the simple pyridine-ligated reagent (Py-HVI) is readily synthesized from commercial PhI(OAc)2 and can be either isolated or generated in situ. Conformational selectivity is demonstrated in both flexible 1,2-substituted cyclohexanols and rigid polyol scaffolds, providing chemists with a novel tool for chemoselective oxidation.
- Mikhael, Myriam,Adler, Sophia A.,Wengryniuk, Sarah E.
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supporting information
p. 5889 - 5893
(2019/08/26)
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- Preparation method and application of key intermediate of non-opioid analgesic
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Dihydro-4-acetal-2H-pyran-3(4H)-one (compound II) is used as a raw material, and the raw material and methyltriphenylphosphine bromide are subjected to a Wittig reaction to obtain a compound III; thedouble bond of the compound III is subjected to a reduction reaction to obtain a compound IV; the compound IV is subjected to acetal hydrolysis under the action of a dilute acid to generate a compoundV; the compound V and benzylamine are subjected to nucleophilic addition reaction to generate a compound VI; and finally, debenzylating and hydrochloride forming are carried out, so that a non-opioidanalgesic key intermediate is obtained, namely cis-3-methyl-4-aminotetrahydropyran hydrochloride (compound I). The method is easy and convenient to operate and high in yield, the total yield can reach 40%, and rapid preparation in a laboratory can be achieved.
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Paragraph 0054; 0055; 0064; 0065; 0090; 0091
(2019/08/01)
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- AMINO-QUINOLINES AS KINASE INHIBITORS
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Disclosed are compounds having the formula:wherein R 1 , R 2 , R 3 and Z are as defined herein, and methods of making and using the same.
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Page/Page column 60; 61
(2018/06/22)
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- NRF2 ACTIVATOR
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Provided are compounds of Formula I, or pharmaceutically acceptable salts thereof, and methods for their use and production.
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Page/Page column 120
(2018/07/29)
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- AMINO-QUINOLINES AS KINASE INHIBITORS
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Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
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Page/Page column 70; 71
(2018/05/15)
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- ANTI-BACTERIAL COMPOUNDS
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A compound of Formula (II): for use in the prevention or treatment of a bacterial infection.
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Page/Page column 115
(2017/06/28)
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- AMINO-QUINOLINES AS KINASE INHIBITORS
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Disclosed are compounds having the formula: wherein R1, R2, R3 and Z are as defined herein, and methods of making and using the same.
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Paragraph 0129
(2016/10/31)
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- TBK/IKK INHIBITOR COMPOUNDS AND USES THEREOF
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The present invention relates to compounds of Formula I and pharmaceutically acceptable compositions thereof, useful as TBK/IKKε inhibitors.
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Paragraph 0330; 0331
(2017/01/23)
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- SUBSTITUTED AMINOPURINE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are Aminopurine Compounds having the following structures: wherein R1, R2, and R3 are as defined herein, compositions comprising an effective amount of an Aminopurine Compound, and methods for treating or preventing a cancer, for example, melanoma.
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Paragraph 0430
(2016/05/02)
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- CHEMOKINE RECEPTOR ANTAGONISTS
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Disclosed herein are chemokine receptor antagonists of formula (I) wherein R1, R2, and R3 are as defined in the specification. Compositions comprising such compounds; and methods for treating conditions and disorders using
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Paragraph 0370
(2013/10/08)
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- CHEMOKINE RECEPTOR ANTAGONISTS
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Disclosed herein are chemokine receptor antagonists of formula (I) wherein R1, R2, and R3 are as defined in the specification. Compositions comprising such compounds; and methods for treating conditions and disorders using
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Page/Page column 107-108
(2013/10/22)
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- Pyrrolopyrazinyl Urea Kinase Inhibitors
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The present invention relates to the use of novel pyrrolopyrazinyl urea derivatives of Formula I, wherein the variables R1, R2, R3, R4, and R5 are defined as described herein, which inhibit JAK and are useful for the treatment of auto-immune and inflammatory diseases.
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Page/Page column 40
(2010/06/19)
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- AMINOCYCLOPENTYL PYRIDOPYRAZINONE MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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Compounds of Formula I and Formula II (wherein A, E, j, k, m, n, R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R15, R16, R17, R18, R19, R24, R25, R26, R27, R28, R29, R30, R31, R32, R33, R34, X, Y and Z are as defined herein) which are modulators of chemokine receptor activity and are useful in the prevention or treatment of certain inflammatory and immunoregulatory disorders and diseases, allergic diseases, atopic conditions including allergic rhinitis, dermatitis, conjunctivitis, and asthma, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which chemokine receptors are involved.
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Page/Page column 32
(2010/11/27)
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- 3-AMINOCYCLOPENTANECARBOXAMIDES AS MODULATORS OF CHEMOKINE RECEPTORS
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The present invention is directed to compounds of Formula I: which are modulators of chemokine receptors. The compounds of the invention, and compositions thereof, are useful in the treatment of diseases related to chemokine receptor expression and/or activity.
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Page/Page column 24-25
(2008/06/13)
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- Regiochemical Control of the Ring Opening of 1,2-Epoxides by Means of Chelating Processes. 6. Opening Reactions of 3,4-Epoxytetrahydropyran
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The regiochemical control of the ring opening of epoxides bearing polar remote functionalities, through chelation processes assisted by metal ions, was verified in the title compound (4).The use of metal assisted procedures in several ring opening reactions of 4 leads to a modification of the regiochemical outcome, and the attack of the nucleophile on the C-4 oxirane carbon is highly favored.
- Chini, Marco,Crotti, Paolo,Gardelli, Cristina,Macchia, Franco
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p. 1261 - 1274
(2007/10/02)
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- Total synthesis of (±)-breynolide, an aglycon derivative of the orally active hypocholesterolemic agent breynin A
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The total synthesis of (±)-breynolide (3), an aglycon derivative of the potent, orally active hypocholesterolemic glycoside breynin A, has been achieved via a stereochemically linear strategy. The successful approach entailed union of the anion derived fr
- Smith III, Amos B.,Empfield, James R.,Rivero, Ralph A.,Vaccaro, Henry A.,Duan, James J.-W.,Sulikowski, Michelle M.
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p. 9419 - 9434
(2007/10/02)
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- Phyllanthoside-Phyllanthostatin Synthetic Studies. 7. Total Synthesis of (+)-Phyllanthocin and (+)-Phyllanthocindiol
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A stereochemically linear total synthesis of (+)-phyllanthocin (5a), the aglycon methyl ester of the antineoplastic glycoside (+)-phyllanthoside (1), is described. The synthesis proceeds in 23 steps (4.5% overall yield) and affords (+)-phyllanthocin in high enantiomeric purity. The central features of the strategy include: (a) construction of aldehyde 8 via a stereoselective, intramolecular ene reaction; (b) elaboration of the spiroketal unit by a two-step tactic involving addition of a functionalized dihydropyran anion (i.e., 9) to 8, followed by a highly stereoselective spiroketalization; and (c) chemo- and stereoselective methylenation of the C(7) carbonyl group. In addition, a second-generation approach is presented, wherein an augmented spiroketalization maneuver not only establishes the C(8) spirocenter but also permits the regio- and stereocontrolled introduction of the C(11) methyl group. The latter sequence furnishes (+)-phyllanthocin in 21 steps (5.6% overall yield). Finally, the advanced phyllanthocin intermediate (+)-49 is converted in five steps (42% overall yield) to (+)-phyllanthocindiol (5b), the aglycon of phyllanthostatin 3.
- Smith III, Amos B.,Fukui, Mineo,Vaccaro, Henry A.,Empfield, James R.
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p. 2071 - 2092
(2007/10/02)
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- ACYL RADICAL CYCLIZATIONS IN SYNTHESIS. PART 2. FURTHER SUBSTITUENT EFFECTS ON THE MODE AND EFFICIENCY OF CYCLIZATION OF 6-HEPTENOYL RADICALS.
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In an attempt to determine the factors affecting exo-/endo-selectivity in the cyclization of 6-heptenoyl radicals various heteroatom substituted selenol esters were prepared and reacted with tributyltin hydride.The incorporation of a 7-phenylthio moity re
- Crich, David,Eustace, K. Angeline,Fortt, Simon M.,Ritchie, Timothy J.
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p. 2135 - 2148
(2007/10/02)
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- PHYLLANTHOSIDE-PHYLLANTHOSTATIN SYNTHETIC STUDIES. 6. AN AUGMENTED SPIROKETALIZATION TACTIC FOR THE TOTAL SYNTHESIS OF PHYLLANTHOCIN
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An enhanced spiroketalization maneuver permitting equilibration at both the C(8) and C(11) centers of spiroketals 17a,b leads to a more concise and efficient synthesis of phyllanthocin (i.e., 21 steps, 5.6percent overall yield).
- Smith, Amos B.III,Empfield, James R.,Vaccaro, Henry A.
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p. 7325 - 7328
(2007/10/02)
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- SOME STUDIES ON 6,7-UNSATURATED CARBONYL RADICAL CYCLIZATIONS
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6,7-Unsaturated carbonyl radicals, generated by the action of tri-n-butylstannane on the corresponding selenol esters, cyclize to give either cyclohexanones or cycloheptanones depending on the nature and position of the substituents in the hydrocarbon cha
- Crich, David,Fortt, Simon M.
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p. 2585 - 2588
(2007/10/02)
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