An ANTIMALARIAL ALKALOID FROM HYDRANGEA. X. SYNTHESIS OF 3-[Β-Keto-Γ-(4-Methyl-2-Pyrrolidyl)propyl]-4-Quinazolone

Baker, B. R.; Schaub, Robert E.; Williams, James H.

doi:10.1021/jo01135a011

Cited by 6 publications

(1 citation statement)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Found: C, 55.1; , 8.21; N, 6.43. 8-{8-Keto-y-(l-carbethoxy-8-methyl-2-pyrrolidyl)propyl]-4-quinazolone (XVII). From 5.6 g. of XVb by conversion to the acid chloride, treatment with diazomethane, then with hydrogen bromide as described for l-carbethoxy-4-methylpyrrolidine-2-acetic acid (11) there was obtained 7.4 g. (97%) of l-carbethoxy-2-(7-bromoacetonyl)-3-methylpyrroIidine. This bromoketone, dissolved in 74 cc.…”

mentioning

confidence: 99%

An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

Baker¹,

Schaub²,

Williams³

1952

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

The two possible hydroxymethylpyrrolidine structures (XLV and XLVI) for the Hydrangea alkaloid (1) have now been synthesized via the requisite 2-pyrrolidineacetic acids, XLIII. It was found that neither of these two compounds . . BAKER, R. . SCHAUB, AND J. H. WILLIAMS tion. Cyclization to the pyrrolinone, XIa, by a one to two day treatment with 40 volumes of aqueous alcoholic ammonia was reported to give an over-all yield of 85%. Duplication of this procedure gave only a 45% yield which could be increased to 61% if the intermediate imine was not distilled.A more rapid and convenient procedure has now been devised. The imine, Xa, was prepared in 30 minutes by constant removal of water from the components in boiling benzene. Cyclization was effected by treating this benzene solution with alcoholic sodium ethoxide for ten minutes. The over-all yield was 91% of crystalline material.Treatment of the pyrrolinone, XIa, with lithium aluminum hydride caused reduction at three sites, the lactam, ester, and pseudo imine double bond with the formation of 1 -benzylpyrrolidine-2-ethanol, b.p. 115°( 0.1 mm.) in 47% yield. The N-benzyl group was readily removed by hydrogenolysis. The resultant pyrrolidine, XHIa, was oxidized with chromic acid in dilute sulfuric acid to the amino acid, XlVa, characterized as its benzoyl derivative, XVa.The same sequence of reactions proceeded smoothly from Vb to XVb with R = CH3. The pyrrolidine acid, XVb, was converted to the bromo ketone, XVI, via the acid chloride and diazoketone, then condensed with 4-quinazolone to give the crystalline carbethoxylated 4-quinazolone, XVII, in 76% over-all yield from XVb. Short 48% hydrobromic acid hydrolysis of the latter gave the desired model compound, XVIII, isolated as the dihydrochloride in 80% yield.Another method for the preparation of the pyrrolidone, XXVI, was also investigated. In this synthesis a ß-amino adipic ester was desired which could be cyclized to XXVI rather than form XXVI by the hydrogenation of the pyrrolinone, XI, which takes place with difficulty (6). In addition methanol might be added to the double bond of the ester of XX in order to obtain an intermediate of the methoxymethyl series. Reaction of methylaniline with itaconic anhydride, XIX, rapidly took place to give an 81% yield of a pure anilide, XX, which was hydrogenated to XXI in 92% yield. The structures of the monoanilides, XX and

show abstract

mentioning

confidence: 99%

An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

Baker¹,

Schaub²,

Williams³

1952

J. Org. Chem.

Self Cite

View full text Add to dashboard Cite

show abstract

Oxoquinazolines and 5‐, 6‐, 7‐, and 8‐Hydroxyquinazolines

1967

Chemistry of Heterocyclic Compounds: A Series of Monographs

View full text Add to dashboard Cite

Reductive Amination/Cyclization of ω‐Trifluoromethyl Keto Esters to Trifluoromethylated δ‐Amino Alcohols and Lactams

et al. 2010

View full text Add to dashboard Cite

Reductive Amination/Cyclization of ω-Trifluoromethyl Keto Esters to Trifluoromethylated δ-Amino Alcohols and Lactams. -A diversity of biologically interesting trifluoromethylated four-to seven-membered lactams (VIII) and (XII) is prepared using an imination-reduction-base-induced cyclization sequence starting from ω-trifluoromethyl keto esters (I) and (IX), respectively. Reduction of tautomeric imine-enamine mixtures (III) -(V) provides δ-trifluoromethyl δ-amino alcohols (VII) as main side products. -(WAN, W.; HOU, J.; JIANG, H.; YUAN, Z.; MA, G.; ZHAO, G.; HAO*, J.; Eur.

show abstract

An ANTIMALARIAL ALKALOID FROM HYDRANGEA. X. SYNTHESIS OF 3-[Β-Keto-Γ-(4-Methyl-2-Pyrrolidyl)propyl]-4-Quinazolone

Cited by 6 publications

References 7 publications

An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

An ANTIMALARIAL ALKALOID FROM HYDRANGEA. XI. SYNTHESIS OF 3-[Β-Keto-Γ-(3- AND 4-Hydroxymethyl-2-Pyrrolidyl)propyl]- 4-Quinazolones

Oxoquinazolines and 5‐, 6‐, 7‐, and 8‐Hydroxyquinazolines

Reductive Amination/Cyclization of ω‐Trifluoromethyl Keto Esters to Trifluoromethylated δ‐Amino Alcohols and Lactams

Contact Info

Product

Resources

About