| 主权项 |
1. A process for generating a compound of Formula (II)or a pharmaceutically acceptable salt thereof, wherein
A is 0, 1, or 2; P is Rc—C(O)—; Rc is RD; RD is substituted or unsubstituted mono- or bicyclic ring system selected from the group consisting of phenyl, pyridinyl, pyrimidinyl, naphthyl, benzimidazolyl, quinolinyl, isoquinolinyl, quinoxalinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, tetrahydroquinoxalinyl, and dihydrobenzoxazinyl; Ra is hydrogen, C1-6 aliphatic, C1-6 fluoroaliphatic, —(CH2)m—CH2—RB, —(CH2)m—CH2—NHC(═NR4)NH—Y, —(CH2)m—CH2—CON(R4)2, —(CH2)m—CH2—N(R4)CON(R4)2, —(CH2)m—CH(R6)N(R4)2, —(CH2)m—CH(R5a)—OR5b, or —(CH2)m—CH(R5)—SR5; Ra1 is hydrogen, C1-6 aliphatic, C1-6 fluoroaliphatic, —(CH2)m—CH2—RB, —(CH2)m—CH2—NHC(═NR4)NH—Y, —(CH2)m—CH2—CON(R4)2, —(CH2)m—CH2—N(R4)CON(R4)2, —(CH2)m—CH(R6)N(R4)2, —(CH2)m—CH(R5a)—OR5b, or —(CH2)m—CH(R5)—SR5; each Ra2 independently is hydrogen, C1-6 aliphatic, C1-6 fluoroaliphatic, —(CH2)m—CH2—RB, —(CH2)m—CH2—NHC(═NR4)NH—Y, —(CH2)m—CH2—CON(R4)2, —(CH2)m—CH2—N(R4)CON(R4)2, —(CH2)m—CH(R6)N(R4)2, —(CH2)m—CH(R5a)—OR5b, or —(CH2)m—CH(R5)—SR5; each RB independently is a substituted or unsubstituted mono- or bicyclic ring system; each R4 independently is hydrogen or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group; or two R4 on the same nitrogen atom, taken together with the nitrogen atom, form a substituted or unsubstituted 4- to 8-membered heterocyclyl ring having, in addition to the nitrogen atom, 0-2 ring heteroatoms independently selected from N, O, and S; each R5 independently is hydrogen or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group; each R5a independently is hydrogen or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group; each R5b independently is hydrogen or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group; each R6 independently is a substituted or unsubstituted aliphatic, aryl, or heteroaryl group; Y is hydrogen, —CN, or —NO2; m is 0, 1, or 2;
each of Rb1 and Rb2 independently is hydrogen, —CO2H, —OH, or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group;each of Rb3 and Rb4 independently is hydrogen, —CO2H, or a substituted or unsubstituted aliphatic, aryl, heteroaryl, or heterocyclyl group;or Rb2 and Rb4 are each independently hydrogen, and Rb1 and Rb3, taken together with the carbon atoms to which they are attached, form an unsubstituted or substituted fused 4- to 8-membered non-aromatic ring having 0-3 ring heteroatoms selected from the group consisting of O, N, and S, wherein said ring may be optionally fused to an unsubstituted or substituted 4- to 8-membered non-aromatic ring, or 5- to 6-membered aromatic ring having 0-3 ring heteroatoms selected from the group consisting of O, N, and S;or Rb2 and Rb4 are absent, and Rb1 and Rb3, taken together with the carbon atoms to which they are attached, form an unsubstituted or substituted fused 5- to 6-membered aromatic ring having 0-3 ring heteroatoms selected from the group consisting of O, N, and S, wherein said ring may be optionally fused to an unsubstituted or substituted 4- to 8-membered non-aromatic ring, or 5- to 6-membered aromatic ring having 0-3 ring heteroatoms selected from the group consisting of O, N, and S; and n is 0 or 1; the process comprising:
(1) coupling a compound of Formula (i) with a compound of Formula (ii) to form a compound of Formula (iii) wherein X− is a counter anion; and PG is hydrogen or a protecting group;(2) deprotecting the compound of Formula (iii) to form a compound of Formula (iiia) (3) coupling the compound of Formula (iiia) with a compound, P-LG, to form a compound of Formula (iv) wherein LG is a leaving group;(4) deprotecting the compound of Formula (iv) to form the compound of Formula (v) and
(5) reacting the compound of Formula (v) with an alpha hydroxy carboxylic acid or a beta hydroxy carboxylic acid to form a compound of Formula (II). |
