Multicomponent Reaction for the Synthesis of 5,6-Dihydropyrrolo[2,1- a]isoquinolines

Aritra Ghosh; Shivalinga Kolle; Dinesh S Barak; Ruchir Kant; Sanjay Batra

doi:10.1021/acsomega.9b03546

Multicomponent Reaction for the Synthesis of 5,6-Dihydropyrrolo[2,1- a]isoquinolines

ACS Omega. 2019 Nov 27;4(24):20854-20867. doi: 10.1021/acsomega.9b03546. eCollection 2019 Dec 10.

Authors

Aritra Ghosh^{1

2}, Shivalinga Kolle¹, Dinesh S Barak¹, Ruchir Kant¹, Sanjay Batra^{1

2}

Affiliations

¹ Medicinal and Process Chemistry Division and Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
² Academy of Scientific and Innovative Research, CSIR- Human Resource Development Centre, (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad, Uttar Pradesh 201002, India.

Abstract

A multicomponent reaction between isatin, tetrahydroisoquinoline, and terminal alkyne in the presence of benzoic acid for the synthesis of N-(substituted-2-(2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl)phenyl)-3,4-dihydroisoquinoline-2(1H)-carboxamides is described. This three-component reaction proceeds via sequential formation of spirooxindole, generation of isocyanate functionality via cleavage of the C2-C3 bond in the isatin subunit of spirooxindole, and addition of the second molecule of tetrahydroisoquinoline to the isocyanate group to offer title compounds. Expansion of the protocol to four-component by including an additional primary amine affords 1-substituted-3-(2-(2-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinolin-3-yl)phenyl)urea in low to moderate yields. However, the reaction of intermediate spirooxindole with tetrahydroisoquinoline or any primary or secondary amine produced the title compound in excellent yields.