Process for making substituted thiazolyl-amino pyrimidinyl

A process for preparing substituted thiazolyl-amino pyrimidinyl piperazines of Formula I:

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• wherein
• R is H, (C1-C6)alkyl, (C0-C6)alkyl-NRaRb, or (C0-C6)alkyl-C(O)N(Re)2;
• R1 is H, or unsubstituted or substituted (C1-C6)alkyl;
• R6 is independently selected from H, phenyl, halogen, CN, and pyridyl, said phenyl and pyridyl optionally substituted with one to three substituents selcted from R7;
• R7 is independently selected from:
• 1) Or(C═O)SNRaRb,
• 2) (C═O)rOsaryl,
• 3) (C═O)rOs-heterocyclyl,
• 4) halogen,
• 5) OH,
• 6) O(C1-C3)perfluoroalkyl,
• 7) (C1-C3)perfluoroalkyl,
• 8) (C═O)rOs(C1 C6)alkyl,
• 9) CO2H,
• 10) CN,
• 11) (C1-C6)alkyl-NRaRb, and
• 12) (C1-C6)alkyl-heterocyclyl, wherein r and s are independently 0 or 1, and said aryl, heterocyclyl and alkyl are optionally substituted with one to three substituents selected from Rd;
• Ra and Rb are independently:
• 1) H,
• 2) (C═O)r(C1-C10)alkyl,
• 3) S(O)2Rc,
• 4) (C═O)rheterocyclyl,
• 5) (C═O)raryl, and
• 6) CO2RC,
• wherein r is 0 or 1 and said alkyl, heterocyclyl, and aryl optionally substituted with one or more substituents selected from Rd;
• Rc is independently selected from (C1-C6)alkyl, aryl, and heterocyclyl;
• Rd is independently selected from:
• 1) (C═O)rOS(C1-C10)alkyl, wherein r and s are independently 0 or 1, optionally substituted with up to three substituents selected from OH, (C1-C6)alkoxy, halogen, heterocyclyl, CN, oxo, N(Re)2 and S(O)2Rc,
• 2) Or(C1-C3)perfluoroalkyl,
• 3) (C0-C6)alkylene-S(O)mRc, wherein m is 0, 1, or 2,
• 4) OH,
• 5) halo,
• 6) CN,
• 7) (C0-C6)alkylene-aryl, optionally substituted with up to three substituents selected from Re,
• 8) (C0-C6)alkylene-heterocyclyl, optionally substituted with up to three substituents selected from Re,
• 9) C(O)Rc,
• 10) CO2Rc,
• 11) C(O)H,
• 12) N(Re)2, and
• 13) CO2H;
• Re is independently selected from:
• 1) H,
• 2) (C1-C6)alkyl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1-C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc,
• 3) aryl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1-C6)alkoxy, halogen, CN, N(Rf)2 and S(O)2Rc,
• 4) heterocyclyl, optionally substituted with one or more substituents selected from OH, heterocyclyl, (C1-C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc, and
• 5) S(O)2Rc;
• said heterocycle optionally substituted with one or more substituents selected from OH, (C1-C6)alkoxy, halogen, CN, oxo, N(Rf)2 and S(O)2Rc;
• and
• Rf is independently selected from H, aryl and (C1-C6)alkyl;
• which comprises the steps of:
• a) reacting a compound of Formula II
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• with a compound of Formula III
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• (wherein X is halo), to provide a compound of Formula IV
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• b) reacting the compound of Formula IV with a compound of Formula V
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• c) isolating the compound of Formula I.