IP Library Granted Patent US 11,697,736
Granted Patent B2
US 11,697,736 · App. 16/415,700 · Granted Jul 11, 2023

Silicon containing detectable compounds

Inventors: Ronald Graham (Carlsbad, CA); Rodrigo Rodriguez (San Diego, CA)
Assignee: SINGULAR GENOMICS SYSTEMS, INC.
C09B11/24C07F7/083C07F7/0803C07F7/0825C09B69/008C07F7/0816C07H23/00
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Quick Facts
Patent No.
US 11,697,736
App. No.
16/415,700
Granted
Jul 11, 2023
Kind
B2
Abstract

Disclosed herein, inter alia, are silicon containing detectable compounds and methods of use thereof.

Claims (42)

1. A method of making a compound, or salt thereof, having the formula:

said method comprising mixing compound A, compound B, and compound C in a reaction vessel, wherein

compound A has the formula:

compound B is a coupling reagent;

compound C has the formula:

wherein

R 1 , R 4 , R 5 , R 6 , and R 7 are independently hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —NH 2 , —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 2 and R 3 are independently substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 8 is hydrogen or a bioconjugate reactive moiety;

R 9 , R 10 , R 11 , R 12 are independently hydrogen, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 13 is a leaving group;

L 1 and L 2 are independently a bond or a covalent linker;

R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 7 and R 10 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl; and

R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl.

2. The method of claim 1 , wherein the compound, or salt thereof, has the formula:

3. The method of claim 1 , wherein compound B is benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), 7-Azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyAOP), 6-Chloro-benzotriazole-1-yloxy-tris-pyrrolidinophosphonium hexafluorophosphate (PyClock), 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU), or 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU).

4. The method of claim 1 , wherein compound B is PyBOP.

5. The method of claim 1 , wherein L 1 or L 2 comprises a cleavable linker.

6. The method of claim 1 , wherein L 1 comprises

wherein n is an integer from 1 to 30; and L 2 is bond, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, substituted or unsubstituted C 1 -C 6 alkylene.

7. The method of claim 1 , wherein L 1 is —C(CH 3 ) 2 CH 2 NHC(O)—,

8. The method of claim 1 , wherein L 2 is —C(CH 3 ) 2 CH 2 NHC(O)—,

9. The method of claim 1 , wherein compound C has the formula

wherein R 1 is hydrogen or substituted or unsubstituted alkyl.

10. The method of claim 1 , wherein compound C is

11. The method of claim 1 , wherein compound C is

12. The method of claim 1 , wherein R 2 and R 3 are each independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.

13. The method of claim 1 , wherein R 4 , R 5 , R 6 , and R 7 are each independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.

14. The method of claim 1 , wherein R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.

15. The method of claim 1 , wherein R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.

16. The method of claim 1 , wherein R 4 , R 5 , R 6 , and R 7 are each independently hydrogen.

17. The method of claim 1 , wherein the compound, or salt thereof, has the formula:

wherein

R 23 , R 24 , R 25 and R 26 are independently oxo, halogen, —CF 3 , —CCl 3 , —CI 3 , —CBr 3 , —CHF 2 , —CHCl 2 , —CHI 2 , —CHBr 2 , —CH 2 F, —CH 2 Cl, —CH 2 I, —CH 2 Br, —OCH 2 F, —OCH 2 Cl, —OCH 2 I, —OCH 2 Br, —OCHF 2 , —OCHCl 2 , —OCHI 2 , —OCHBr 2 , —OCF 3 , —OCCl 3 , —OCI 3 , —OCBr 3 , —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC═(O)NHNH 2 , —NHC═(O)NH 2 , —NHSO 2 H, —NHC═(O)H, —NHC(O)OH, —NHOH, —PO 4 H, —PO 3 H, —N 3 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and

z23, z24, z25, and z16 are independently an integer from 0 to 6.

18. The method of claim 1 , wherein the compound, or salt thereof, has the formula:

19. The method of claim 1 , wherein the compound, or salt thereof, has the formula:

20. The method of claim 1 , wherein R 8 is

Assignments (3)
SECURITY INTEREST Recorded Mar 7, 2025
From: SINGULAR GENOMICS SYSTEMS, INC.
To: FIRST-CITIZENS BANK & TRUST COMPANY
Reel/Frame 070440/0465 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 16, 2021
From: GRAHAM, RONALD
To: SINGULAR GENOMICS SYSTEMS, INC.
Reel/Frame 056885/0886 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 16, 2021
From: RODRIGUEZ, RODRIGO
To: SINGULAR GENOMICS SYSTEMS, INC.
Reel/Frame 056885/0931 →
Continuity (2)
Provisional Application 62673579 · May 18, 2018
Related Publication 20190352508A1 · Nov 21, 2019
Cited By (3)
US 12,331,199 US 12,359,068 US 12,365,801