Org Prep Daily

November 10, 2006

6-amino-4-chloro-2-methylpyrimidine

Filed under: procedures — milkshake @ 6:03 pm

pyrimid2.gif

A mixture of 2-methyl-4,6-dichloropyrimidine 25.41g (0.1559 mol) and 7M NH3 in anhydrous methanol 260mL was heated in a pressure flask at 110 C for one day. The cooled reaction mixture was evaporated and the obtained solid residue was re-crystallized from water (100mL, at +5C, overnight). The crystallized product (14.587g) was collected by filtration, rinsed with ice-cold water and dried on highvac. A second pure fraction (2.536g) was obtained by concentrating the supernatants to a small volume. Y=17.123g (76.5%) of a white crystalline solid. 1H(d6-DMSO, 400MHz): 7.101(br s, 2H), 6.258(s, 1H), 2.284(s, 3H) 

A mixture of 2-methyl-4-chloro-6-aminopyrimidine 2.532g (17.63 mmol) and N-(2-hydroxyethyl)-piperazine 6.0mL (48.9 mmol) was heated without solvent under Ar at 165 C for 75min. The amine excess was removed on highvac (with heating on oil bath), the solid residue was re-evaporated from a mixture of chloroform-methanol (1:1, 60mL), the oily residue was diluted with chloroform 10mL and allowed to crystallize overnight. The product was collected by quick filtration under Ar blanket, washed with chloroform (2x10mL) and dried on highvac. Y=2.774g (66%) of a white hygroscopic crystalline solid. 1H(d6-DMSO, 400MHz): 6.081(br s, 2H), 5.417(s, 1H), 4.434(br s, 1H), 3.515(app t, 6.0Hz, 2H), 3.380(app br t, 4.8Hz, 4H), 2.413(m, 6H), 2.149(s, 3H)

5 Comments »

  1. […] Milkshake runs a superb blog (Org Prep Daily) which does exactly what it says on the tin. Here is an example of a post (6-amino-4-chloro-2-methylpyrimidine). Take a look – you don’t have to be a chemist to get the idea and the quality. He recently posted: I will run out of procedures to post in about a week or two. Since the chemistry cannot keep up with posting one decent procedure a day, I will have to revert into a more convenient one-post-per-month frequency. (I think I will also rename Org Prep Daily as The Reactionary Organiker and will proceed to expound my entire worpetermr’s blog › Edit — WordPressld-wiew here.) Only you can prevent it – by submitting a good reproducible scalable procedure to appear here. My Scripps address is tomasv{}edu. […]

    Pingback by Unilever Centre for Molecular Informatics, Cambridge - petermr’s blog » Blog Archive » Org Prep Daily - Help! An Open Opportunity for Chemistry — November 11, 2006 @ 8:27 am

  2. This seems really familiar. Did this compound make it into one of the Process Chemistry in the Pharmaceutical Industry books? Maybe the ACS one?

    Comment by Prelim completed — November 13, 2006 @ 10:13 pm

  3. Some nasty herbicide I guess🙂

    Comment by milkshake — November 13, 2006 @ 10:42 pm

  4. Dear MS,

    Thanks for the procedure!!!I would like to know about the regioselective amination of the dichloropyrimidine. Dont you get diaminated compound also?? Forgive me if I am wrong. Could u please explain the formation of monoaminated product.

    Cheers
    Marto

    Comment by marto — May 26, 2008 @ 6:27 am

  5. the second chlorine substitution requires slightly more forcing conditions because the introduced amino substituent is electron donating so it will deactivate the second chlorine aryl nucleophilic substitution. But you can get bis substitution if you push hard enough.

    Comment by milkshake — May 26, 2008 @ 7:12 am


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