Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. Results Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine ...

/pdf/phase-iii-study-comparing-cisplatin-plus-gemcitabine-with-4aed40upa0.pdf

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. Patients and Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. Results: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.7...

https://www.rmaoem.org/Pdf%20docs/Malignant%20mesothelioma%20treatments.pdf

Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

4.2.8. Reductive Coupling 3109 5. Reaction of Aromatic Compounds 3110 5.1. Electrophilic Substitutions 3110 5.2. Radical Substitution 3111 5.3. Oxidative Coupling 3111 5.4. Photochemical Reactions 3111 6. Reaction of Carbonyl Compounds 3111 6.1. Nucleophilic Additions 3111 6.1.1. Allylation 3111 6.1.2. Propargylation 3120 6.1.3. Benzylation 3121 6.1.4. Arylation/Vinylation 3121 6.1.5. Alkynylation 3121 6.1.6. Alkylation 3121 6.1.7. Reformatsky-Type Reaction 3122 6.1.8. Direct Aldol Reaction 3122 6.1.9. Mukaiyama Aldol Reaction 3124 6.1.10. Hydrogen Cyanide Addition 3125 6.2. Pinacol Coupling 3126 6.3. Wittig Reactions 3126 7. Reaction of R,â-Unsaturated Carbonyl Compounds 3127

Organic Reactions in Aqueous Media with a Focus on Carbon−Carbon Bond Formations: A Decade Update

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

Two independent routes to N-(4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2, 3-d]pyrimidin-6-yl)ethyl]benzoyl)-L-glutamic acid, a regioisomer of the potent TS inhibitor and antitumor agent LY231514, are described. Preliminary in vitro cell culture evaluation has shown that attachment of the ethanobenzoylglutamate moiety of LY2 31514 to position 6 of the pyrrolopyrimidine ring system rather than to position 5 results in complete loss of biological activity

Syntheses of a Regioisomer of N‐(4‐(2‐(2‐Amino‐4(3H)‐oxo‐7H‐pyrrolo(2, 3‐d)pyrimidin‐5‐yl)ethyl)benzoyl)‐L ‐glutamic Acid (LY231514), an Active Thymidylate Synthase Inhibitor and Antitumor Agent.

4,4′-Dimethyl-1,1′-biphenyl



reactant: 42.7 g. (30.5 ml., 0.250 mole) of 4-bromotoluene




intermediate: (4-methylphenyl)magnesium bromide




product: 4,4′-dimethyl-1,1′-biphenyl




product: biphenyl




product: 4,4′-dimethoxy-1,1′-biphenyl




product: 3,3′-dimethyl-1,1′-biphenyl




product: 3,3′,4,4′-tetramethyl-1,1′-biphenyl




product: 4,4′-dichloro-1,1′-biphenyl




product: 4,4′-difluoro-1,1′-biphenyl





Keywords:

coupling;
Grignard and related reactions;
assay methods, for (4-methylphenyl)magnesium bromide;
nitrogen, drying of;
stirrers, mercury-sealed

4,4′‐Dimethyl‐1,1′‐Biphenyl

A new and extremely efficient synthesis of DDATHF from 4-vinylbenzoic acid and bromomalondialdehyde as precursors has been developed which proceeds in 48% overall yield.

A simplified and efficient synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

Unexpected and facile bridgehead substitution in 5,6,7,8,9,10-hexahydro-5,9-methano-pyrimido[4,5-]azocin-4(3)-ones

Improved supported thallium(III) reagents are provided which significantly improve reaction rates and product selectivity of oxythallation reactions. The present reagents have a thallium(III) salt of an acid on the surface and within montmorillonite clay minerals.

Edward C. Taylor

Papers

Syntheses of a Regioisomer of N‐(4‐(2‐(2‐Amino‐4(3H)‐oxo‐7H‐pyrrolo(2, 3‐d)pyrimidin‐5‐yl)ethyl)benzoyl)‐L ‐glutamic Acid (LY231514), an Active Thymidylate Synthase Inhibitor and Antitumor Agent.

4,4′‐Dimethyl‐1,1′‐Biphenyl

A simplified and efficient synthesis of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF).

Unexpected and facile bridgehead substitution in 5,6,7,8,9,10-hexahydro-5,9-methano-pyrimido[4,5-]azocin-4(3)-ones

Thallium(III) reagents supported on montmorillonite clay minerals and oxythallation processes for utilizing same