α,α‐Dimethyl‐β‐Phenethylamine

Ritter, John J.; Kalish, Joseph

doi:10.1002/0471264180.os044.14

Cited by 4 publications

(6 citation statements)

References 3 publications

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“…A similar synthetic strategy was employed for the formation of 2-phenyl[1,2,4]triazolo[1,5-a]pyridine-8-carboxamide (30), in which case the N-aminopyridinium salt was condensed with benzaldehyde to elaborate the key heterocyclic intermediate 29 that was subsequently transformed to 30. 30 Substituted 2-arylindazole-7-carboxamides were prepared using the previously described route from the appropriately Ritter rearrangement to yield the corresponding formamide, 31 which was in turn reduced to give 50. Homologation to the corresponding phenethylamine 52 was achieve by treating aldehyde 35 with methoxymethyltriphenylphosphonium chloride and KO t Bu followed by mild acid treatment to yield phenacetaldehyde 51, followed by reductive amination.…”

Section: Resultsmentioning

confidence: 99%

“…Preparation of Methyl 2-(4-Formylphenyl)-2H-indazole-7carboxylate 32 (Method D). To a solution of methyl 2H-indazole-7-carboxylate (31) (1.0 equiv) in DMF (0.8 M) were added K 2 CO 3 (1.1 equiv) and 4-fluorobenzaldehyde (1.3 equiv), and the reaction mixture was heated under microwave conditions at 200 °C for 10 min. The reaction mixture was cooled to room temperature and diluted with EtOAc.…”

Section: Methodsmentioning

confidence: 99%

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Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors

et al. 2009

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We disclose the development of a novel series of 2-phenyl-2H-indazole-7-carboxamides as poly(ADP-ribose)polymerase (PARP) 1 and 2 inhibitors. This series was optimized to improve enzyme and cellular activity, and the resulting PARP inhibitors display antiproliferation activities against BRCA-1 and BRCA-2 deficient cancer cells, with high selectivity over BRCA proficient cells. Extrahepatic oxidation by CYP450 1A1 and 1A2 was identified as a metabolic concern, and strategies to improve pharmacokinetic properties are reported. These efforts culminated in the identification of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide 56 (MK-4827), which displays good pharmacokinetic properties and is currently in phase I clinical trials. This compound displays excellent PARP 1 and 2 inhibition with IC(50) = 3.8 and 2.1 nM, respectively, and in a whole cell assay, it inhibited PARP activity with EC(50) = 4 nM and inhibited proliferation of cancer cells with mutant BRCA-1 and BRCA-2 with CC(50) in the 10-100 nM range. Compound 56 was well tolerated in vivo and demonstrated efficacy as a single agent in a xenograft model of BRCA-1 deficient cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors

et al. 2009

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“…Its purity was checked by NMR and HPLC and estimated to be better than 98%. Cumylamine was prepared according to [14]. 1-Nitronaphthalene and all the solvents were purchased from Fluka or Aldrich in their purest commercially available forms and were used without further puri®cation.…”

Section: Methodsmentioning

confidence: 99%

Magnetic field dependence of the deactivation rates of triplet azocumene in solution

et al. 2002

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The triplet sensitized photo-decomposition of azocumene into nitrogen and cumyl radicals is investigated by time resolved EPR and optical absorption spectroscopy. It is found that the cumyl radicals carry an initial spin polarization and are formed with a yield that depends on both the solution viscosity and the strength of an external magnetic ®eld. The phenomenon is interpreted in terms of a depopulation-type triplet mechanism, i.e. a competition between decay into radicals and fast, triplet sublevel selective intersystem crossing (ISC) back to the azocumene ground state. Analysis of the data yields relative rate constants for the ISC processes and the cleavage reaction of triplet azocumene. The energetically lower zero ®eld triplet substate is depopulated by ISC about seven times faster than the upper one and about two orders of magnitude faster than depopulation by cleavage occurs. Cleavage probably takes place on the nanosecond time scale, while the ISC must proceed on the picosecond scale, as at elevated viscosity it becomes faster than the rotational Brownian motion of the molecule.

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“…Literature reports that photo-oxidised products of this compound showed a marked increase in the antifeedant activity than compared to the parent compound 5,6 which gave impetus for performing the semi synthetic modification of the compound to introduce the nitrogen functionality through C-N bond formation. Hence Ritter reaction [7][8][9][10] was attempted to introduce the amide group across the olefinic double bound in ring C in nimbin.…”

Section: Introductionmentioning

confidence: 99%

Acid Catalysed Isomerization of Nimbin to Isonimbin

Narasimhan¹,

Mohankumar²,

Santhanakrishnan³

et al. 2012

AJOC

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α,α‐Dimethyl‐β‐Phenethylamine

Abstract: α,α‐Dimethyl‐β‐phenethylamine intermediate: N‐Formyl‐α,α‐dimethyl‐β‐phenethylamine . product: α,α‐dimethyl‐β‐phenethylamine

Cited by 4 publications

References 3 publications

Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors

Discovery of 2-{4-[(3S)-Piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): A Novel Oral Poly(ADP-ribose)polymerase (PARP) Inhibitor Efficacious in BRCA-1 and -2 Mutant Tumors

Magnetic field dependence of the deactivation rates of triplet azocumene in solution

Acid Catalysed Isomerization of Nimbin to Isonimbin

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