KinasePro

Kinase Chemistry – Just a year and a half behind the times.

US20060252782

Posted by kinasepro on November 15, 2006

Hi Schering AG, err Bayer, err, whoever you are these days, TIE2 / VEGF Sulfoximine macrocycles I see. Those 5% cyclizations are going to need a little work… But what I really want to see is you guys resolve the enantiomers!

O=S(C1=CC=CC(NC2=NC3=C(C4=CC=C(NC(NC5=CC(C(F)(F)F)=CC=C5F)=O)C=C4)C=N2)=C1)(CCCCN3)=N

A solution of (RS)-S-(3-aminophenyl)-S-{4-[(5-bromo-2-chloropyrimidin-4-yl) amino]butyl}-N-(ethoxycarbonyl) sulfoximide (160 mg, 0.33 mmol) in acetonitrile (10 mL) was added to a mixture of acetonitrile/water/4 M solution of HCl in 1,4-dioxane (45 mL/5 mL/0.5 mL) at a temperature of 80° C. over a period of 4 h by means of a syringe pump. After 24 h, all volatiles were removed in vacuo and sat. aq. NaHCO3 solution (50 mL) and ethyl acetate (250 mL) were added. The organic Layer was separated and the aqueous layer was extracted with ethyl acetate (4×). The combined organic layers were washed with brine, dried (Na2SO4), filtered and evaporated. The residue was triturated with tert-butyl methyl ether to give the desired compound (135 mg, 0.30 mmol, 90% yield).

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3 Responses to “US20060252782”

  1. You have any idea about the PK properties of sulfoximines in general? HOw do they make these rings?

  2. kinasepro said

    PK: No clue. The cyclization: Well on further inspection some of them actually go quite cleanly. They report a 90% yield on the addition of the tethered aniline to a chloropyrimidine intermediate. Its an interesting reaction, so I’ll update with a scheme tonight.

  3. kinasepro said

    Found a ChemMedChem on this stuff. (published 11/28)

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