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N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine Ditosylate

IP.com Disclosure Number: IPCOM000202001D
Publication Date: 2010-Nov-30
Document File: 3 page(s) / 22K

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Page 01 of 3

      N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6- [5-[(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine Ditosylate

N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino) methyl]-2-furyl]quinazolin-4-amine Ditosylate has the following chemical structure:

O

x 2 HO3S CH3

Example 1 - Preparation of N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5- [(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine Ditosylate N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino) methyl]-2-furyl]quinazolin-4-amine Ditosylate, previously isolated as known from the literature solid (wet or dry) Anhydrate (Form A) or any other solid form, can be re- crystallized from 40-100 volumes of aqueous solution of polar organic solvents such as C1-C4 alcohols, acetone, methyl ethyl ketone, DMF, DMA, acetonitrile, THF, Methyl- THF, 1,4-dioxane or mixture thereof and converted into N-[3-Chloro-4-[(3- fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-2-furyl] quinazolin-4-amine Ditosylate Monohydrate (Form M) in high yield and good chemical quality. The procedure contains full or almost full dissolving of the starting material in the organic solvent mixture with water under heating, cooling for precipitation and N-[3- Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino)methyl]-2- furyl]quinazolin-4-amine Ditosylate Monohydrate (Form M) filtration. The level of 3- chloro-4-(3-fluorobenzyloxy)aniline in the final product is less than 0.1 ppm.

S

O

O

Cl

F

HN

HN

N

O

N



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Example 2 - Preparation of N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5- [(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine Ditosylate N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5-[(2-methylsulfonylethylamino) methyl]-2-furyl]quinazolin-4-amine Ditosylate, previously isolated as known from the literature solid (wet or dry) Anhydrate (Form A) or any other solid form, can be triturated in 10-40 volumes of aqueous solution of polar organic solvents such as C1-C4 alcohols, acetone, methyl ethyl ketone, DMF, DMA, acetonitrile, THF, Methyl-THF, 1,4-dioxane or mixture thereof and converted into N-[3-Chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-[5- [(2-methylsulfonylethylamino)methyl]-2-furyl]quinazolin-4-amine Ditosylate Monohydrate (Form M) in high yield and good chemical quality. The procedure contains trituration of the starting material in the organic solvent mixt...