Purified cenicriviroc and purified intermediates for making cenicriviroc
AssigneeTobira Therapeutics, Inc.
InventorsNicholas MORRA, Pasit PHIASIVONGSA
Life of this patent
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Abstract
The disclosure includes high purity compounds having CCR5 and/or CCR2 antagonism, or salts thereof, high purity intermediates thereto and processes for synthesizing the same.
Claims37
A compound, 8-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound II-OH), that comprises one or more of the following:
- (a) about ≦0.50% to about ≧0.30% or about ≦0.01% of 8-(4-(2-ethoxyethoxy)phenyl)-1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound II-OH-A);
- (b) about ≦0.50% to about ≧0.30% or about ≦0.01% of 1-isobutyl-8-(4-(2-propoxyethoxy)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound II-OH-B);
- (c) about ≦0.50% to about ≧0.30% of 4,4′-bis(2-butoxyethoxy)biphenyl (Compound VII);
- and
- (d) about ≦0.50% to about ≧0.30% or about ≦0.01% of 8,8′-(4-(2-butoxyethoxy)-1,3-phenylene)bis(1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid) (Compound VIII);
- and optionally further comprises one or both of
- about ≦0.50% of 8-(4-butoxyphenyl)-1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound II-OH-C);
- and
- about ≦0.50% of 8-(4-(2-butoxyethoxy)phenyl)-1-butyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound IX).
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A compound, 8-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound II-OH), with about ≧95.0% to about ≦96.0% purity.
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A compound, 8-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-N-(4-(2-(1-propyl-1H-imidazol-5-yl)acetyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH), or an enantiomer, a stereoisomer, or a combination thereof, with a purity of ≧96.0% or ≧98.5% or higher, wherein said compound comprises one or more of the following:
- (a) about ≦0.50% to about ≧0.30% of 8,8′-(4-(2-butoxyethoxy)-1,3-phenylene)bis(1-isobutyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid) (Compound VIII);
- (b) about ≦0.50% to about ≧0.30% of 8-(4-(2-butoxyethoxy)phenyl)-1-butyl-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxylic acid (Compound IX);
- (c) about ≦0.50% to about ≧0.30% of 8-(4-(2-ethoxyethoxy)phenyl)-1-isobutyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH-A);
- (d) about ≦0.50% to about ≧0.30% of 1-isobutyl-8-(4-(2-propoxyethoxy)phenyl)-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH-B);
- (e) about ≦0.50% to about ≧0.45% of 8-(4-butoxyphenyl)-1-isobutyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH-C);
- (f) about ≦0.50% to about ≧0.45% of 8-(4-(2-butoxyethoxy)phenyl)-1-isobutyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)thio)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH-E);
- (g) about ≦0.50% to about ≧0.45% of 8-(4-(2-butoxyethoxy)phenyl)-1-butyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl) 1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide methanesulfonate (Compound I-MsOH-F);
- and
- (h) about ≦0.50% to about ≧0.45% of 8,8′-(4-(2-butoxyethoxy)-1,3-phenylene)bis(1-isobutyl-N-(4-(((1-propyl-1H-imidazol-5-yl)methyl)sulfinyl)phenyl)-1,2,3,4-tetrahydrobenzo[b]azocine-5-carboxamide) dimethanesulfonate (Compound I-MsOH-G).
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Dependencies are inferred from the claim text.