4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-

Base Information

• Chemical Name: 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-
• CAS No.: 314771-88-5
• Molecular Formula: C18H14ClFN4O4
• Molecular Weight: 404.78000
• Mol file: 314771-88-5.mol

Synonyms:4-[(3-Chloro-4-fluorophenyl)amino]-6-nitro-7-((5)-tetrahydrofuran-3-yloxy)-quinazoline;(S)-N-(3-chloro-4-fluorophenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine;(S)-N-(3-chloro-4-fluorophenyl)-6-nitro-7-((tetrahydrofuran-3-yl)oxy)quinazolin-4-amine;(2Z)-Afatinib intermediate;

Chemical Property of 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-

Chemical Property:

• Boiling Point: 585.0±50.0 °C(Predicted)
• PKA: 5.07±0.70(Predicted)
• PSA: 102.09000
• Density: 1.534±0.06 g/cm3(Predicted)
• LogP: 4.83800
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C

Purity/Quality:

99% ^*data from raw suppliers

(S)-N-(3-Chloro-4-fluorophenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Uses: (S)-N-(3-chloro-4-fluorophenyl)-6-nitro-7-(tetrahydrofuran-3-yloxy)quinazolin-4-amine is a used in the synthetic preparation of 4-anilinoquinazolines with C-6 urea-linked side chains as inhibitors of epidermal growth factor receptor. It is also used in the preparation of (2Z)-Afatinib (A355305) which is used for treating cancer and diseases of the respiratory tract, lungs, gastrointestinal tract, bile duct, and gallbladder.

Technology Process of 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]-

There total 25 articles about 4-QuinazolinaMine, N-(3-chloro-4-fluorophenyl)-6-nitro-7-[[(3S)-tetrahydro-3-furanyl]oxy]- which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 99.5%

(S)-3-hydroxytetyrahydrofurane (86087-23-2,84921-89-1,864447-89-2) + N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine (162012-67-1) → 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline (314771-88-5,402855-07-6)

Guidance literature:

(S)-3-hydroxytetyrahydrofurane; With potassium tert-butylate; In tetrahydrofuran; at 20 ℃; for 1h;

N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine; In tetrahydrofuran; at 20 ℃; for 3h;

DOI:10.1016/j.bmc.2016.02.017

Reference yield: 97.8%

7-chloro-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine (179552-73-9) + (S)-3-hydroxytetyrahydrofurane (86087-23-2,84921-89-1,864447-89-2) → 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline (314771-88-5,402855-07-6)

Guidance literature:

(S)-3-hydroxytetyrahydrofurane; With potassium tert-butylate; In N,N-dimethyl-formamide; at 0 ℃; for 2h;

7-chloro-N-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine; With sodium benzenesulfonate; In N,N-dimethyl-formamide; at 30 - 90 ℃; for 6h;

Reference yield: 89.6%

N-((3-chloro-4-fluorophenyl)-6-nitro-7-phenylsulfonyl)quinazolin-4-one (945553-94-6) + (S)-3-hydroxytetyrahydrofurane (86087-23-2,84921-89-1,864447-89-2) → 4-[(3-chloro-4-fluorophenyl)amino]-6-nitro-7-[(S)-(tetrahydrofuran-3-yl)oxy]quinazoline (314771-88-5,402855-07-6)

Guidance literature:

With potassium tert-butylate; In tetrahydrofuran; N,N-dimethyl-formamide; tert-butyl alcohol; at 20 - 45 ℃; for 8h;

upstream raw materials:

N-((3-chloro-4-fluorophenyl)-6-nitro-7-phenylsulfonyl)quinazolin-4-one

(S)-3-hydroxytetyrahydrofurane

3-chloro-4-fluorophenylamine

N-(3-chloro-4-fluorophenyl)-7-fluoro-6-nitroquinazolin-4-amine

Refernces

• 1、 -. "Afatinib refined product synthetic method". Paragraph 0025; 0036-0038; 0049; 0054; 0059; 0064. . Retrieved 2019/06/12.
• 2、 -. "PROCESS FOR THE PREPARATION OF N-[4-[(3-CHLORO-4-FLUORO PHENYL) AMINO]-7-[[(3s-TETRAHYDRO-3-FURANYL]OXY]-6-QUINAZOLINYL]-4-(DIMETHYL AMINO)-(2E)-2-BUTENAMIDE (2Z)-2-BUTENEDIOATE (1 :2) AND ITS POLYMORPHS THEREOF". . . Retrieved 2018/11/21.