Solid Phase Synthesis of Heterocycles

Munoz etaU US Patent 6,362,009 (March 26, 2002) Assignee Merck Co., Inc. 

To a suspension of polystyrene-graft-chloroformate (0.5 g, 0.41 mmol based on loading of 0.81mmol/g) dissolved in 6 ml THF was added 4-methoxypyridine (0.48 mmol) and methylmagnesium chloride (0.81 mmol) dissolved in 3 ml. Thereafter, additional THF was added, the mixture immediately filtered, and the modified graft polymer isolated. FTIR data supplied. 

The product from Step 1 was washed successively with a mixture of 3 M HCl and THF, 1 1, 3M HCl, methyl alcohol, N,N-dimethyl-formamide and diethyl ether, dried, and the modified graft polymer isolated. FTIR data supplied. 

Isopropylmagnesium chloride (0.6 mmol) was added to Cul (0.6 mmol) in 3 ml THF at —25°C for 10 minutes, further cooled to —78°C, BF3 diethyl ether added, and the suspension reacted with the product from product from Step 2 (366 mg, 0.82mmol/g, 

3 mmol) 3 hours at ambient temperature. Thereafter the polymer was isolated by filtration, washed successively with THE and IM HCl, 1 1, IM HCl, methyl alcohol and CH2CI2, and the modified graft polymer isolated. 

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Solid-phase synthesis of heterocycles 98MI37, 980PP489, 98YGK2. 

Cyclative Cleavage Strategies for the Solid-Phase Synthesis of Heterocycles and Natural Products... 

Solid-Phase Synthesis of Heterocyclic Compounds from Resin-Bound Amino Acids, Short Peptides, and Polyamines... 

Fig. 2. Solid-phase synthesis of heterocyclic compounds from resin-bound amino acids.

Nefzi A, Ostresh JM, Meyer JP, Houghten RA, Solid phase synthesis of heterocyclic compounds from linear peptides cyclic ureas and thioureas, Tetrahedron Lett., 38 931-934, 1997. 

Generic solid-phase synthesis of heterocycles was claimed A common precursor to all libraries was described and claimed Several relevant documents found by the International Search Report... 

Pericyclic reactions in the synthesis of heterocycles 87YGK60. Pummerer reaction in the synthesis of heterocycles 89KGS1299. Retro-Diels-Alder strategy in the synthesis of heterocycles 87S207. Solid-phase synthesis of heterocycles 89BSF237. 

Raghavan, S., Anuradha, K. Solid-phase synthesis of heterocycles from 1,4-diketone synthons. Synlett 2003, 711-713. 

The virtue of multifunctional triazene linkers in the efficient solid-phase synthesis of heterocyclic libraries 04ACR805. 

C. Solid-Phase Synthesis of Heterocyclic Compounds Using Amino Acids and Peptides as Templates... 

For a review, see Ganesan, A., Cyclative cleavage strategies for the solid-phase synthesis of heterocycles and natural products, in Methods in Enzymology Combinatorial Chemistry, Part B, Morales, G.B. and Bunin, B.A., Fds., Academic Press, San Diego, CA, 2003, 369, 415. 

Representative examples of the recent applications of controlled microwave heating in solid-phase synthesis of heterocyclic compoimds are summarized. The preparation of monocyclic compounds is presented first, followed by a description of the synthesis of polycyclic structmes. 

RECENT ADVANCES MICROWAVE-ASSISTED SOLID-PHASE SYNTHESIS OF HETEROCYCLES... 

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