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Preparation method of Idelalisib intermediate

A technology for idelaris and intermediates, which is applied in the field of preparation of idelaris intermediates, can solve the problems of low yield, cumbersome preparation methods, and low optical purity, and achieve high yield and simple post-processing Ease of application and high optical purity

Active Publication Date: 2017-06-16
山东轩德医药科技有限公司
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In the current prior art, such as WO2005 / 113554, the preparation method of idelaris is introduced, and WO2015095601A1 introduces the preparation method of idelaris and its intermediates, but the preparation method is cumbersome and the yield is low , and low optical purity

Method used

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  • Preparation method of Idelalisib intermediate
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  • Preparation method of Idelalisib intermediate

Examples

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Embodiment 1

[0029] Example 1 (S)-(1-(5-fluoro-4-carbonyl-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamic acid tertiary Preparation of butyl ester

[0030]

[0031] Add N,N-dimethylformamide (720ml) into the reaction flask, add N-Boc-L-2-aminobutyric acid (A, 203g, 1mol), stir and cool to 0-10°C; at this temperature, Add N-methylmorphine (151g, 1.5mol) dropwise; then add isopropyl chloroformate (122.5g, 1mol) dropwise, stir for 1h after the addition is complete; finally add 2-amino-6-fluorobenzoic acid dropwise (155g, 1mol) of N,N-dimethylformamide (120ml) mixed solution, stirred for 5h, added aniline (139.5g, 1.5mol), heated to 50°C, reacted for 14h, after the reaction was completed, added water (5000ml ), the crude product was precipitated and recrystallized with isopropanol to obtain off-white solid (S)-(1-(5-fluoro-4-carbonyl-3-phenyl-3,4-dihydroquinazolin-2-yl ) Propyl) tert-butyl carbamate 365.2 g (92%), EE value: 99.7%.

[0032] 1H NMR (400MHz, 25℃, DMSO-d6): 7.83(td, J=...

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Abstract

The invention relates to a preparation method of an Idelalisib intermediate. The method is a novel method for preparing a tert-butyl (S)-(1-(5-fluoro-4-carbonyl-3-phenyl-3, 4-dihydroquinazolin-2-yl)propyl)carbamate. The preparation method has the advantages of simple reaction steps, high yield, high optical purity and mass production.

Description

[0001] 1. Technical field [0002] The present invention relates to a preparation method of an intermediate of Idelaris, namely (S)-(1-(5-fluoro-4-carbonyl-3-phenyl-3,4-dihydroquinazoline-2 -A new preparation method of propyl) tert-butyl carbamate. [0003] 2. Background technology [0004] The chemical name of Idelaris is 5-fluoro-3-phenyl-2-[(1S)-1-(9H-purin-6-ylamino)propyl]-4(3H)-quinazolinone , is a highly selective oral PI3Kδ inhibitor developed by Gilead Sciences (Gilead Sciences), which can be used to treat chronic lymphocytic leukemia and non-Hodgkin's lymphoma. [0005] In chronic lymphocytic leukemia (CLL), a slow-growing cancer, the buildup of too many mature white blood cells can lead to fatal complications, including serious infections. Currently, the first-line therapy for this disease is rituximab combined with one or more chemotherapy drugs. Most patients will relapse after initial chemoimmunotherapy, and about 20% of patients are refractory. The efficacy o...

Claims

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Application Information

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IPC IPC(8): C07D239/90
CPCC07D239/90
Inventor 董岩岩
Owner 山东轩德医药科技有限公司
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