Intermediates useful for making 2,4-pyrimidinediamine compounds

1. A 4-pyrimidineamine compound according to structural formula (II):

including salts, hydrates, solvates and N-oxides thereof, wherein:

X is N;

Y is selected from the group consisting of O, S, SO, SO 2 , SONR 36 , NH, NR 35 and NR 37 ;

Z is selected from the group consisting of O, S, SO, SO 2 , SONR 36 , NH, NR 35 and NR 37 ;

R 5 is selected from the group consisting of R 6 , (C1–C6) alkyl optionally substituted with one or more of the same or different R 8 groups, (C1–C4) alkanyl optionally substituted with one or more of the same or different R 8 groups, (C2–C4) alkenyl optionally substituted with one or more of the same or different R 8 groups and (C2–C4) alkynyl optionally substituted with one or more of the same or different R 8 groups;

R 6 is selected from the group consisting of hydrogen, an electronegative group, —OR d , —SR d , (C1–C3) haloalkyloxy, (C1–C3) perhaloalkyloxy, —NR c R c , halogen, (C1–C3) haloalkyl, (C1–C3) perhaloalkyl, —CF 3 , —CH 2 CF 3 , —CF 2 CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c ; —S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O)NR c R c , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —OC(O)R d , —SC(O)R d , —OC(O)OR d , —SC(O)OR d , —OC(O)NR c R c , —SC(O)NR c R c , —OC(NH)NR c R c , —SC(NH)NR c R c , —[NHC(O)] n R d , —[NHC(O)] n OR d , —[NHC(O)] n NR c R c and —[NHC(NH)] n NR c R c , (C5–C10) aryl optionally substituted with one or more of the same or different R 8 groups, phenyl optionally substituted with one or more of the same or different R 8 groups, (C6–C16) arylalkyl optionally substituted with one or more of the same or different R 8 groups, 5–10 membered heteroaryl optionally substituted with one or more of the same or different R 8 groups and 6–16 membered heteroarylalkyl optionally substituted with one or more of the same or different R 8 groups;

R 8 is selected from the group consisting of R a , R b , R a substituted with one or more of the same or different R a or R b , —OR a substituted with one or more of the same or different R a or R b , —B(OR a ) 2 , —B(NR c R c ) 2 , —(CH 2 ) m —R b , —(CHR a ) m —R b , —O—(CH 2 ) m —R b , —S—(CH 2 ) m —R b , —O—CHR a R b , —O—CR a (R b ) 2 , —O—(CHR a ) m —R b , —O—(CH 2 ) m —CH[(CH 2 ) m R b ]R b , —S—(CHR a ) m —R b , —C(O)NH—(CH 2 ) m —R b , —C(O)NH—(CHR a ) m —R b , —O—(CH 2 ) m —C(O)NH—(CH 2 ) m —R b , —S—(CH 2 ) m —C(O)NH—(CH 2 ) m —R b , —O—(CHR a ) m —C(O)NH—(CHR a ) m —R b , —S—(CHR a ) m —C(O)NH—(CHR a ) m —R b , —NH—(CH 2 ) m —R b , —NH—(CHR a ) m —R b , —NH[(CH 2 ) m R b ], —N[(CH 2 ) m R b ] 2 , —NH—C(O)—NH—(CH 2 ) m —R b , —NH—C(O)—(CH 2 ) m —CHR b R b and —NH—(CH 2 ) m —C(O)—NH—(CH 2 ) m —R b ;

each R 35 is, independently of the others, selected from the group consisting of hydrogen and R 8 , or, alternatively, two R 35 bonded to the same carbon atom are taken together to form an oxo (═O), NH or NR 38 group and the other two R 35 are each, independently of one another, selected from the group consisting of hydrogen and R 8 ;

each R 36 is independently selected from the group consisting of hydrogen and (C1–C6) alkyl;

each R 37 is independently selected from the group consisting of hydrogen and a progroup;

R 38 is selected from the group consisting of (C1–C6) alkyl and (C5–C14) aryl;

each R a is independently selected from the group consisting of hydrogen, (C1–C6) alkyl, (C3–C8) cycloalkyl, cyclohexyl, (C4–C11) cycloalkylalkyl, (C5–C10) aryl, phenyl, (C6–C16) arylalkyl, benzyl, 2–6 membered heteroalkyl, 3–8 membered cycloheteroalkyl, morpholinyl, piperazinyl, homopiperazinyl, piperidinyl, 4–11 membered cycloheteroalkylalkyl, 5–10 membered heteroaryl and 6–16 membered heteroarylalkyl;

each R b is a suitable group independently selected from the group consisting of ═O, —OR d , (C1–C3) haloalkyloxy, —OCF 3 , ═S, —SR d , ═NR d , ═NOR d , —NR c R c , halogen, —CF 3 , —CN, —NC, —OCN, —SCN, —NO, —NO 2 , ═N 2 , —N 3 , —S(O)R d , —S(O) 2 R d , —S(O) 2 OR d , —S(O)NR c R c , —S(O) 2 NR c R c , —OS(O)R d , —OS(O) 2 R d , —OS(O) 2 OR d , —OS(O) 2 NR c R c , —C(O)R d , —C(O)OR d , —C(O)NR c R c , —C(NH)NR c R c , —C(NR a )NR c R c , —C(NOH)R a , —C(NOH)NR c R c , —OC(O)R d , —OC(O)OR d , —OC(O)NR c R c , —OC(NH)NR c R c , —OC(NR a )NR c R c , —[NHC(O)] n R d , —[NR a C(O)] n R d , —[NHC(O)] n OR d , —[NR a C(O)] n OR d , —[NHC(O)] n NR c R c , —[NR a C(O)] n NR c R c , —[NHC(NH)] n NR c R c and —[NR a C(NR a )] n NR c R c ;

each R c is independently a protecting group or R a , or, alternatively, each R c is taken together with the nitrogen atom to which it is bonded to form a 5 to 8-membered cycloheteroalkyl or heteroaryl which may optionally include one or more of the same or different additional heteroatoms and which may optionally be substituted with one or more of the same or different R a or suitable R b groups;

each R d is independently a protecting group or R a ;

each m is independently an integer from 1 to 3;

each n is independently an integer from 0 to 3; and

LG is a leaving group.

2. The compound of claim 1 in which LG is chloro.

3. The compound of claim 2 in which R 5 is fluoro.

4. The compound of claim 3 in which R 6 is hydrogen.

5. The compound of claim 1 in which Y and Z are each, independently of one another, selected from the group consisting of O and NH.

6. The compound of claim 5 in which Y and Z are each O.

7. The compound of claim 6 in which each R 35 is hydrogen.

8. The compound of claim 5 in which Y is O and Z is NH.

9. The compound of claim 8 in which two R 35 bonded to the same carbon atom are taken together to form an oxo group.

10. The compound of claim 9 in which the other two R 35 are each hydrogen, methyl or fluoro.

11. The compound of claim 1 which is selected from the group consisting of compounds (IIf), (IIg), (IIh), (Iii), (IIj), (IIl), (IIm) and (IIn):