SYNTHESIS OF BORONATE SALTS AND USES THEREOF

• US 20170057979A1
• Filed: 04/30/2015
• Published: 03/02/2017
• Est. Priority Date: 05/05/2014
• Status: Active Grant

• Current Assignee: Melinta Therapeutics, Inc.
• Original Assignee: Rempex Pharmaceuticals, Inc (Melinta Therapeutics, Inc.)
• Inventors: Hecker, Scott, Boyer, Serge
• Granted Patent: US 10,385,074 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A01N 55/08 containing boron
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

Disclosed herein are boronate intermediates in the synthesis of antimicrobial compounds and the use and preparation thereof. Some embodiments relate to crystalline boronate salt derivatives and their use in the synthesis of therapeutic compounds.

Claims

1. A compound of Formula (I)

4. The compound of claim 1, wherein Y₁ is O.

5. The compound of claim 1, wherein Y₁ is N⁺R₅R₆.

6. The compound of claim 1, wherein Y₂ is O.

8. The compound of claim 1, wherein R₁ and R₂ are both H.

16. The compound of claim 1, wherein R₁ and R₂ together with the atoms to which they are attached, form ═

O and wherein R₃ and R₄ together with the atoms to which they are attached, form ═

O.

17. The compound of claim 1, wherein R₃ and R₄ are both H.

25. The compound of claim 1, wherein R₅ and R₆ are both H.

34. The compound of claim 1, wherein R₉ is optionally substituted C₁-C₁₂ alkyl.

47. The compound of claim 1, having a structure selected from the group consisting of:

2. (canceled)

3. (canceled)

7. (canceled)

9-15. -15. (canceled)

18-24. -24. (canceled)

26-33. -33. (canceled)

35-46. -46. (canceled)

48. A method of making a compound of Formula (I), or a salt thereof, comprising the steps of:

(a) protecting the primary hydroxy group of the compound of Formula (A);

57. The method of claim 48, wherein R₁ and R₂ are both H.

65. The method of claim 48, wherein R₁ and R₂ together with the atoms to which they are attached, form ═

O and wherein R₃ and R₄ together with the atoms to which they are attached, form ═

O.

66. The method of claim 48, wherein R₃ and R₄ are both H.

74. The method of claim 48, wherein R₅ and R₆ are both H.

83. The method of claim 48, wherein R₉ is optionally substituted C₁-C₁₂ alkyl.

49-56. -56. (canceled)

58-64. -64. (canceled)

67-73. -73. (canceled)

75-82. -82. (canceled)

84-122. -122. (canceled)

123. A method of making a compound of Formula (D) comprising the steps of:

reacting a compound of Formula (B);

124. The method of claim 123, wherein PG is a trialkylsilyl group.

126. The method of claim 123, wherein R₉ is optionally substituted C₁-C₁₂ alkyl.

145. The method of claim 123, wherein X is optionally substituted C₁-C₄ alkyl.

125. (canceled)

127-144. -144. (canceled)

146-159. -159. (canceled)

160. A method of making a compound of Formula (I), or a salt thereof, comprising the steps of:

reacting a compound of Formula (E);

162. The method of claim 160, wherein n is 1.

164. The method of claim 160, wherein Y₁ is N⁺R₅R₆.

166. The method of claim 160, wherein Y₂ is NR₁₀.

167. The method of claim 160, wherein R₁ and R₂ are both H.

174. The method of claim 160, wherein R₃ and R₄ are both H.

181. The method of claim 160, wherein R₁ and R₂ together with the atoms to which they are attached, form ═

O and wherein R₃ and R₄ together with the atoms to which they are attached, form ═

O.

182. The method of claim 160, wherein R₅ and R₆ are both H.

191. The method of claim 160, wherein R₉ is optionally substituted C₁-C₁₂ alkyl.

192. The method of claim 160, wherein R₉ is t-butyl.

161. (canceled)

163. (canceled)

165. (canceled)

168-173. -173. (canceled)

175-180. -180. (canceled)

183-190. -190. (canceled)

193-203. -203. (canceled)