Synthesis of n-(heteroaryl)-pyrrolo[3,2-d]pyrimidin-2-amines

A process to prepare a 2′-(heteroaryl)-lactam-pyrrolo[3,2-d]pyrimidine comprising:

• reacting a 2′-(alkylsulfonyl or alkylsulfinyl)-lactam-pyrrolo[3,2-d]pyrimidine with a heteroaryl amine, wherein the ratio of heteroaryl amine to 2′-(alkylsulfonyl or alkylsulfinyl)-lactam-pyrrolo[3,2-d]pyrimidine is at least about 2 to 1 and the yield of the reaction is over about 50%, to afford the 2′-(heteroaryl)-lactam-pyrrolo[3,2-d]pyrimidine,
• wherein the 2′-(heteroaryl)-lactam-pyrrolo[3,2-d]pyrimidine is a compound of Formula:
• wherein:
• Z is —(CH2)x—, wherein x is 1, 2, 3 or 4;
• or —O—(CH2)z— wherein z is 2, 3 or 4;
• R2 is independently selected from the group consisting of hydrogen, carbamate, aryl, alkyl, allyl, and arylalkyl;
• each R6 is independently aryl, alkyl, cycloalkyl or haloalkyl, wherein each of said alkyl, cycloalkyl and haloalkyl groups optionally includes O or N heteroatoms in place of a carbon in the chain and two R6's on adjacent ring atoms or on the same ring atom together with the ring atom(s) to which they are attached optionally form a 3-8-membered cycle;
• y is 0, 1, 2, 3 or 4;
• R12 is
• R7 is -(alkylene)m-heterocyclo, -(alkylene)m-heteroaryl, -(alkylene)m-NR8R9, -(alkylene)m-C(O)—NR8R9;
• -(alkylene)m-C(O)—O-alkyl;
• -(alkylene)m-O—R10, -(alkylene)m-S(O)n—R10, or -(alkylene)m-S(O)n—NR8R9;
• any of which ma be optionally independently substituted with one or more R′ groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atom may optionally combine to form a ring;
• R8 and R9 at each occurrence are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, and heteroarylalkyl, any of which may be optionally independently substituted with one or more Rx groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atom may optionally combine to form a ring;
• or
• R8 and R9 together with the nitrogen atom to which they are attached may combine to form a heterocyclo ring optionally independently substituted with one or more Rx groups as allowed by valance, and wherein two Rx groups bound to the same or adjacent atom may optionally combine to form a ring;
• R10 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, cycloalkylalkyl, heterocycloalkyl, arylalkyl, or heteroarylalkyl, any of which may be optionally independently substituted with one or more Rx groups as allowed by valance;
• Rx at each occurrence is independently halo, cyano, nitro, oxo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, heterocyclo, aryl, heteroaryl, arylalkyl, heteroarylalkyl, cycloalkylalkyl, or heterocycloalkyl;
• n is 0, 1, or 2;
• and
• m is 0 or 1.