Crystalline form of a substituted thiazolylacetic acid triethylamine salt
AssigneeTheravance, Inc.
InventorsWeijiang Zhang, Michael R. Tracey, Junning Lee
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Abstract
The invention relates to a crystalline form of a triethylamine salt of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid. The invention also relates to processes and intermediates for preparing the crystalline form. The crystalline form is useful as an intermediate for preparing cross-linked glycopeptide-cephalosporin antibiotics.
Claims14
A crystalline form of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid triethylamine salt;
- wherein the crystalline form is characterized by at least one of the following properties:
- (a) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 5.00±0.20, 12.92±0.20, 15.00±0.20, 16.92±0.20, 22.36±0.20, 23.36±0.20 and 24.54±0.20;
- (b) a melting onset temperature of about 139° C.;
- or
- (c) crystalline parameters at 293 K comprising (i) a monoclinic crystal system, (ii) a P21/c space group, and (iii) unit cell dimensions substantially equal to:
- a=8.587(4) {acute over (Å)}, b=35.594(12) {acute over (Å)}, c=8.308(3) {acute over (Å)} and β=100.63(4)°.
(2Z)-2-(2-Amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid having formula I:
- or a salt thereof.
A process for preparing a crystalline form of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid triethylamine salt, the process comprising the steps of:
- (a) reacting (2Z)-2-(2-aminothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid or a salt thereof with a chlorinating agent to form (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonyl-aminopropoxyimino)acetic acid or a salt thereof;
- and
- (b) contacting (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid or a salt thereof with triethylamine to form a crystalline form of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid triethylamine salt.
A method of forming a crystalline form of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid triethylamine salt, the method comprising the steps of:
- (a) providing a solution of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonylaminopropoxyimino)acetic acid triethylamine salt in methanol;
- and
- (b) contacting the solution from step (a) with isopropyl acetate to form a crystalline form of (2Z)-2-(2-amino-5-chlorothiazol-4-yl)-2-(3-N-tert-butoxycarbonyl-aminopropoxyimino)acetic acid triethylamine salt.
Dependencies are inferred from the claim text.