Process for preparing benzimidazole compounds

A process for the preparation of a compound of Formula Ib-1

• and salts and solvates thereof, wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2b is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl;
• X1 and X2 are independently selected from hydrogen, F, Cl, Br, I, OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl and C1-C10 thioalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl and thioalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy and azido;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl or heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and —OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring;
• said method comprising:
• nitrating a compound having the Formula
• wherein X3 and X4 are independently F, Cl, Br, I, or a sulfonate ester, to provide a compound of Formula II
• reacting said compound of Formula II with (i) a reagent that contains or generates ammonia, (ii) a primary or secondary amine other than an aromatic amine or (iii) a reagent that delivers a group that can subsequently be converted into an amine, under conditions that allow selective displacement of X4, to provide a compound of Formula III-11 wherein A is NR2R2a, or reacting said compound of Formula II with (iv) a metal azide under conditions that allow selective displacement of X4 to provide a compound of Formula III-12 wherein A is N3
• and R2 and R2a are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl, and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• reacting said compound of Formula III-11 or III-12, optionally at elevated temperatures, with (i) a reagent that contains or generates ammonia, (ii) a primary or secondary amine other than an aromatic amine or (iii) a reagent that delivers a group that can subsequently be converted into an amine to provide a compound having Formula Vb-11 wherein B is NR2bR2c, and A is —NR2R2a or N3, or reacting said compound of Formula III-11 or III-12 with (iv) a metal azide, optionally at elevated temperatures, to provide a compound of Formula Vb-12 wherein B is N3 and A is —NR2R2a or N3,
• wherein R2c is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• reducing said compound of Formula Vb-11 or Vb-12 to provide a compound of Formula VIIb-1
• wherein when A and/or B of Formula Vb-11 or Vb-12 is —NH-benzyl, N3, —NHOR1 or —NHNHR1, then R2 and R2a and/or R2b and R2c, respectively, of Formula VIIb-1 are hydrogen;
• when R2a of Formula VIIb-1 is hydrogen, cyclizing said compound of Formula VIIb-1 to provide a compound of Formula VIIIb-1
• when R2c of Formula VIIIb-1 is hydrogen, coupling said compound of Formula VIIIb-1 with a compound having the formula
• wherein X6 is F, Cl, Br, I, —OSO2CF3, alkyl sulfonate, aryl sulfonate, alkylaryl sulfonate, —B(OR8)2, —BF3 or —Bi(R1)2, optionally either (i) at elevated temperature and optionally in the presence of a base, or (ii) in the presence of a metal-based catalyst and a base, to provide said compound of Formula Ib-1.

A process for the preparation of a compound of Formula VIIIb-1

• and salts and solvates thereof, wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2b and R2c are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, and C2-C4 alkynyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring;
• said method comprising cyclizing a compound of Formula VIIb-1
• wherein R2 hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl, and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, and C2-C4 alkynyl, and
• R2a is hydrogen,
• to provide said compound of Formula VIIIb-1.

A process for the preparation of a compound of Formula VIIIb-1

• and salts and solvates thereof, wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2b is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2c is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring;
• said method comprising:
• providing a compound of Formula Vb-11 wherein B is NR2bR2c and A is NR2R2a or N3, or a compound of Formula Vb-12 wherein B is N3 and A is NR2R2a or N3,
• wherein R2 is hydrogen, substituted or unsubstituted benzyl, allyl or —C(O)OR6 and R2a is hydrogen;
• reducing said compound of Formula Vb-11 or Vb-12 to provide a compound of Formula VIIb-1
• wherein when A and/or B of Formula Vb-11 or Vb-12 is N3, then R2 and R2a and/or R2b and R2c, respectively, of Formula VIIb-1 are hydrogen;
• and
• when R2a is hydrogen, cyclizing said compound of Formula VIIb-1 to provide said compound of Formula VIIIb-1.

A compound, including salts and solvates thereof, having the Formula VIIb-1

• wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that may be transformed into any of one said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 and R2b are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl, and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2a and R2c are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• or
• —NR2R2a and/or —NR2bR2c is N3;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring.

A compound having the Formula VIIIa-1

• and salts and solvates thereof, wherein
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl, or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 and R2a are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, and C2-C4 alkynyl;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said allyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring.

A compound having the Formula VI

• wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• A is N3 or NR2R2a;
• B is N3 or NR2bR2c;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10) cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 and R2b are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl, and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2a and R2c are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X5 is H, F, Cl, Br, I, or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring.

A compound having the Formula XIb-1

• wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2b and R2c are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring.

A compound of the Formula III

• wherein:
• A is N3 or NR2R2a;
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• X3 is F, Cl, Br, I, NO2 or a sulfonate ester;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2a is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6, —C(O)NR6R7, —OR1 or —NHR1, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl and heteroarylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring.

A method of preparing a compound of Formula XIb-1

• wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl, and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2b and R2c are independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring,
• said method comprising:
• (a) providing a compound of Formula VIIb-1
• wherein R2a is hydrogen;
• and
• (b) reacting said compound of Formula VIIb-1 with (i) formic acid, optionally in the presence of an additional acid, (ii) a formic acid derivative in the presence of an acid, or (iii) two or more equivalents of formaldehyde or a formaldehyde derivative in the presence of an acid, to provide said compound of Formula XIb-1.

A method of preparing a compound of Formula Ic-1

• wherein:
• Z is —C(═O)OR1, —C(═O)NR6R7, CN, —C(═O)H, or
• or a moiety that can be transformed into any one of said Z groups;
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• R2b is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, benzyl, allyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl, benzyl, allyl and arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X1 and X2 are independently selected from hydrogen, F, Cl, Br, I, OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl and C1-C10 thioalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl and thioalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy and azido;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and —O—(C1-C10-alkenyl);
• and
• R12a and R12b are independently selected from hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl,
• or R12a and R12b together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring,
• said method comprising:
• (a) providing a compound of Formula VIIb-1
• wherein R2a and R2c are hydrogen;
• (b) reacting said compound of Formula VIIb-1 with (i) formic acid optionally in the presence of an additional acid, (ii) a formic acid derivative in the presence of an acid, or (iii) two or more equivalents of formaldehyde or a formaldehyde derivative in the presence of an acid, to provide a compound of Formula XIb-1
• (c) coupling said compound of Formula XIb-1 with a reagent having the Formula
• wherein X6 is F, Cl, Br, I, —OSO2CF3, alkyl sulfonate, aryl sulfonate, alkylaryl sulfonate, —B(OR8)2, —BF3 or —Bi(R1)2, optionally either (i) at elevated temperature and optionally in the presence of a base, or (ii) in the presence of a metal-based catalyst and a base, to provide said compound of Formula Ic-1.

A process for preparing a compound of Formula Ia-1

• and salts and solvates thereof, wherein:
• Z is —C(═O)OR1;
• R1 is C1-C10 alkyl;
• R2 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl or arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X1 and X2 are independently selected from hydrogen, F, Cl, Br, I, OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl and C1-C10 thioalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl and thioalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, azido, trifluoromethyl, difluoromethoxy and trifluoromethoxy;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and O—(C1-C10-alkenyl);
• and
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• said method comprising:
• i) nitrating a compound having the Formula
• wherein X3 and X4 are independently F, Cl, Br, I, or a sulfonate ester to provide a compound of Formula II
• ii) reacting the compound of Formula II with a compound of formula R1OH, to form the corresponding ester having the formula
• iii) reacting the ester with two or more equivalents of a reagent that generates ammonia to form a compound of Formula VI-11
• wherein R2a is hydrogen;
• iv) reducing said compound of Formula VI-11 to provide a compound of Formula VIIa-1
• v) cyclizing said compound of Formula VIIa-1 to provide a compound of Formula VIIIa-1
• vi) coupling said compound of Formula VIIIa-1 with a reagent having the Formula
• wherein X6 is F, Cl, Br, I, —OSO2CF3, alkyl sulfonate, aryl sulfonate, alkylaryl sulfonate, —B(OR8)2, —BF3 or —Bi(R1)2 to provide said compound of Formula Ia-1.

A process for preparing a compound of Formula Ia-1

• and salts and solvates thereof, wherein:
• R1 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, trialkylsilyl or dialkylarylsilyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl;
• R2 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, arylalkyl, trialkylsilyl, dialkylarylsilyl, —COR6, —C(O)OR6 or —C(O)NR6R7, wherein said alkyl, alkenyl, alkynyl or arylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl;
• X1 and X2 are independently selected from hydrogen, F, Cl, Br, I, OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl and C1-C10 thioalkyl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl and thioalkyl portions are optionally substituted with one or more groups independently selected from oxo, halogen, cyano, nitro, azido, trifluoromethyl, difluoromethoxy and trifluoromethoxy;
• X5 is H, F, Cl, Br, I or C1-C6 alkyl;
• R6 and R7 are independently hydrogen, trifluoromethyl, —OR8, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl,
• or R6 and R7 together with the atom to which they are attached form a 4 to 10 membered heteroaryl or heterocyclic ring, wherein said heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, trifluoromethyl, difluoromethoxy, trifluoromethoxy and OR8;
• R8 is hydrogen, C1-C10 alkyl, C2-C10 alkenyl, aryl or arylalkyl, wherein said alkyl, alkenyl, aryl and arylalkyl are optionally substituted with one or more groups independently selected from OH, —O—(C1-C10-alkyl) and O—(C1-C10-alkenyl);
• and
• R10 is hydrogen, C1-C10 alkyl, C3-C10 cycloalkylalkyl, arylalkyl, heteroarylalkyl or heterocyclylalkyl, wherein said alkyl, cycloalkylalkyl, arylalkyl, heteroarylalkyl and heterocyclylalkyl portions are optionally substituted with one or more groups independently selected from halogen, hydroxyl, cyano, nitro, azido, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, —NR6R7 and —OR8;
• said method comprising:
• coupling a compound of Formula VIIIa-1,
• where R2a is hydrogen, with a reagent having the Formula X
• wherein X6 is F, Cl, Br, I, —OSO2CF3, alkyl sulfonate, aryl sulfonate, alkylaryl sulfonate, —B(O—R8)2, —BF3 or —Bi(R1)2, in the presence of a suitable metal-based catalyst and a base in an appropriate solvent.