| 主权项 |
1. A process for preparing a compound of formula (Ib) or (IIIa)or salt thereof, wherein
R1g, at each occurrence, is each independently chosen from the group consisting of G1d, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, halogen, C1-C4 haloalkyl, —CN, —ORf, —OC(O)Rf, —OC(O)N(Rf)2, —S(O)2Re, —S(O)2N(Rf)2, —C(O)Rf, —C(O)ORf, —C(O)N(Rf)2, —N(Rf)2, —N(Rf)C(O)Rf, —N(Rf)S(O)2Re, —N(Rf)C(O)O(Re), —N(Rf)C(O)N(Rf)2, —(CR1cR1d)q3—ORf, —(CR1cR1d)q3—OC(O)Rf, —(CR1cR1d)q3—OC(O)N(Rf)2, —(CR1cR1d)q3—S(O)2Re, —(CR1cR1d)q3—S(O)2N(O2, —(CR1cR1d)q3—C(O)Rf, —(CR1cR1d)q3—C(O)ORf, —(CR1cR1d)q3—C(O)N(Rf)2, —(CR1cR1d)q3—N(Rf)2, —(CR1cR1d)q3—N(Rf)C(O)Rf, —(CR1cR1d)q3—N(Rf)S(O)2Re, —(CR1cR1d)q3—N(Rf)C(O)O(Re), —(CR1cR1d)q3—N(Rf)C(O)N(Rf)2, and —(CR1cR1d)q3—CN; Re, at each occurrence, is independently C1-C4 alkyl, C1-C4 haloalkyl, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl); Rf, at each occurrence, is independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, —(CR1cR1d)q3—ORg, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl); Rg, at each occurrence, is independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl); A2 is N(Rb)(Rc), G1c, or —(CR1aR1b)q-G1c; G1c is a monocyclic heterocycle or a monocyclic cycloalkyl wherein each ring is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of oxo, alkyl, alkenyl, alkynyl, halogen, haloalkyl, —CN, alkoxy, haloalkoxy, —C(O)OH, and —C(O)O(alkyl); R2 is C2-C10 alkyl, alkenyl, alkynyl, haloalkyl, —(CR2aR2b)q4—O—Ra, —(CR2aR2b)q4—O G2a, —(CR2aR2b)q4—O(CR2cR2d)q5-G2a, —(CR2aR2b)q5—C(O)—Ra, —(CR2aR2b)q5—C(═N—ORe)Ra, —(CR2aR2b)q5—SO2—Rd, —(CR2aR2b)q5-G2a, —(CR2aR2b)q5—C(O)N(Rb)(Rc), —(CR2aR2b)q4—OC(O)N(Rb)(Rc), or —(CR2aR2b)q5—CN; G2a, at each occurrence, is independently cycloalkyl, cycloalkenyl, heterocycle, aryl, or heteroaryl; wherein each of the rings as represented by G2a is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo, alkyl, halogen, hydroxy, alkoxy, haloalkoxy, and haloalkyl; Ra and Rc, at each occurrence, are each independently hydrogen, alkyl, haloalkyl, —(CR1aR1b)q2—ORh, —(CR1aR1b)q2—N(Rh)2, G1d, or —(CR1aR1b)q2G1d; Rb, at each occurrence, is independently hydrogen, alkyl, haloalkyl, alkoxyalkyl, monocyclic cycloalkyl, —(CR1cR1d)q2-(monocyclic cycloalkyl), or haloalkoxyalkyl; Rd, at each occurrence, is independently alkyl, haloalkyl, —(CR1aR1b)q2—ORh, —(CR1aR1b)q2—N(Rh)2, G1d, or —(CR1aR1b)q2-G1d; G1d, at each occurrence, is independently a monocyclic heterocycle, a monocyclic heteroaryl, a phenyl, a monocyclic cycloalkyl, or a monocyclic cycloalkenyl; each of which is optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of —N(R)2, —CN, oxo, alkyl, haloalkyl, alkoxy, haloalkoxy, halogen, and hydroxy; Rh, at each occurrence, is independently hydrogen, C1-C4 alkyl, C1-C4 haloalkyl, monocyclic cycloalkyl, or —(CR1cR1d)q3-(monocyclic cycloalkyl) wherein the monocyclic cycloalkyl, as a substituent or part of a substituent, of Rb, Re, Rf, Rg, and Rh, at each occurrence, is independently unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of C1-C4 alkyl, halogen, oxo, hydroxy, C1-C4 alkoxy, C1-C4 haloalkoxy, and C1-C4 haloalkyl; q, q1, and q2, at each occurrence, are each independently 1, 2, 3, or 4; R1a, R1b, R1c, R1d, R2a, R2b, R2c, and R2d, at each occurrence, are each independently hydrogen, halogen, C1-C4 alkyl, or C1-C4 haloalkyl; q3, at each occurrence, is independently 1, 2 or, 3; q4, at each occurrence, is independently 2, 3, 4, or 5; q5, at each occurrence, is independently 1, 2, 3, 4, 5, or 6; z is 0, 1, 2, 3, or 4; one of X1, X2, X3, and X4 is N and the others are CH; u is 0, 1, 2, or 3; and each Rx is an optional substituent on any substitutable carbon atom, and is independently selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, haloalkoxy, and haloalkyl; comprising the steps of (1a) treating a compound of formula (IV) wherein R2v is halogen or sulfonate; and R3v is halogen or OH; with a thiocyanate source to produce a compound of formula (V) (1b) reacting a compound of formula (V) with a compound of formula (VI) wherein R4v is halogen or sulfonate to produce a compound of formula (II) or a salt thereof (2a) treating a compound of formula (II) or a salt thereof with a compound of formula HO—(CR1aR1b)q1—O—Rp or HO-A2, or a salt thereof, wherein Rp is hydrogen or a hydroxy-protecting group; to produce a compound of formula (IIIa) or (IIIb), or a salt thereof (2b) deprotect a compound of formula (IIIb) or a salt thereof wherein Rp is a hydroxy-protecting group to form a compound of formula (Ib) or a salt thereof |
