# US 2014/0194622 A1 · Methods for the synthesis of polycyclic guanidine compounds

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- Number: US 2014/0194622 A1
- Document ID: US20140194622A1
- Status: Published application
- Kind: A1
- Application number: 14/148,455
- Filed: 2014-01-06
- Published: 2014-07-10
- Earliest claimed: 2009-12-24
- Assignees: Novomer, Inc.
- Applicants: Novomer, Inc.
- Inventors: Alexei Gridnev
- Web page: https://patentgrep.com/patent/US20140194622A1

## CPC

- C07D 487/04: Ortho-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The present invention provides methods for the synthesis of polycyclic guanidine compounds. In certain embodiments, provided methods include the step of contacting a described reagent with a triamine compound to provide a polycyclic guanidine compound.

## Claims

### Claim 1

A method for the preparation of a polycyclic guanidine compound comprising the step of contacting a triamine compound with a reagent selected from the group consisting of guanidine, acyclic guanidine compounds, cyanamide, cyanimide compounds, melamine and melamine derivatives.

### Claim 2 (depends on 1)

The method of claim 1, wherein a polycyclic guanidine compound of Formula V is prepared by contacting a triamine compound of Formula IV with an acyclic guanidine compound of Formula I:
wherein:
Ra is selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl;
Rc is optionally present, wherein each occurrence of Rc is independently selected from the group consisting of halogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl, wherein two or more Rc groups can optionally be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one to three heteroatoms selected from oxygen, nitrogen, or sulfur;
n is an integer from 1 to 4 inclusive;
m is an integer from 1 to 4 inclusive; and
each occurrence of Rb is independently selected from the group consisting of hydrogen, optionally substituted C1-20 aliphatic, optionally substituted aryl and nitrile.

### Claim 3 (depends on 2)

The method of claim 2, wherein each occurrence of Rb is hydrogen or an alkyl group.

### Claim 4 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is guanidine.

### Claim 5 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is tetraalkyl guanidine.

### Claim 6 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is tetramethyl guanidine.

### Claim 7 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is in the form of a salt or adduct.

### Claim 8 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is selected from the group consisting of:
guanidine carbonate; guanidine sulfate; guanidine acetate; guanidine nitrate; guanidine p-toluene sulfonate; guanidine hydrochloride; and guanidine phosphate.

### Claim at position 9

9-15. (canceled)

### Claim 16 (depends on 2)

The method of claim 2, wherein at least one occurrence of Rb is nitrile.

### Claim 17

(canceled)

### Claim 18 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is of Formula Ia:

### Claim 19 (depends on 2)

The method of claim 2, wherein the acyclic guanidine compound of Formula I is cyanoguanidine.

### Claim 20 (depends on 1)

The method of claim 1, wherein a polycyclic guanidine compound of Formula V is prepared by contacting a triamine compound of Formula IV with a cyanimide compound of Formula II:
wherein:
Ra is selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl;
Rc is optionally present, wherein each occurrence of Rc is independently selected from the group consisting of halogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl, wherein two or more Rc groups can optionally be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one to three heteroatoms selected from oxygen, nitrogen, or sulfur;
n is an integer from 1 to 4 inclusive;
m is an integer from 1 to 4 inclusive; and
each occurrence of Rb is independently selected from the group consisting of hydrogen, optionally substituted C1-20 aliphatic, and optionally substituted aryl.

### Claim 21 (depends on 20)

The method of claim 20, wherein each occurrence of Rb is hydrogen.

### Claim 22 (depends on 20)

The method of claim 20, wherein each occurrence of Rb is hydrogen or an alkyl group.

### Claim 23 (depends on 1)

The method of claim 1, wherein a polycyclic guanidine compound of Formula V is prepared by contacting a triamine compound of Formula IV with melamine or a melamine derivative of Formula III:
wherein:
Ra is selected from the group consisting of hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl;
Rc is optionally present, wherein each occurrence of Rc is independently selected from the group consisting of halogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl, wherein two or more Rc groups can optionally be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one to three heteroatoms selected from oxygen, nitrogen, or sulfur;
n is an integer from 1 to 4 inclusive;
m is an integer from 1 to 4 inclusive; and
each occurrence of Rx and Ry is independently selected from the group consisting of hydrogen, optionally substituted C1-20 aliphatic, and optionally substituted aryl.

### Claim 24 (depends on 23)

The method of claim 23, wherein each occurrence of Rx and Ry is independently hydrogen or an alkyl group.

### Claim 25 (depends on 23)

The method of claim 23, wherein the polycyclic guanidine compound of Formula V is prepared by contacting a triamine compound of Formula IV with melamine.

### Claim 26 (depends on 2)

The method of claim 2, wherein the triamine compound of Formula IV is of Formula IVa:

### Claim 27 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted bis(aminopropyl)amine.

### Claim 28 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted bis(aminoethyl)amine.

### Claim 29 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted 2,6-bis(aminomethyl)piperidine.

### Claim 30 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted 2,6-bis(aminoethyl)piperidine.

### Claim 31 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted 2,5-bis(aminomethyl)pyrrolidine.

### Claim 32 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted 2,5-bis(aminoethyl) pyrrolidine.

### Claim 33 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted N-(2-aminoethyl)-1,3-propanediamine.

### Claim 34 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted N-(2-aminoethyl)-1,4-butanediamine.

### Claim 35 (depends on 1)

The method of claim 1, wherein the triamine compound is an optionally substituted N-(2-aminopropyl)-1,4-butanediamine.

### Claim 36 (depends on 1)

The method of claim 1, wherein the triamine compound is selected from the group consisting of:
where Rc is optionally present, and if present is independently selected from the group consisting of halogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl, wherein two or more Rc groups can optionally be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one to three heteroatoms selected from oxygen, nitrogen, or sulfur.

### Claim 37 (depends on 1)

The method of claim 1, wherein the triamine compound is of the following structure:

### Claim 38 (depends on 1)

The method of claim 1, wherein the triamine compound is of the following structure:

### Claim 39 (depends on 1)

The method of claim 1, wherein the triamine compound is of the following structure

### Claim 40 (depends on 1)

The method of claim 1, wherein the triamine compound and the reagent are contacted in the presence of a solvent.

### Claim 41 (depends on 1)

The method of claim 1, wherein the triamine compound and the reagent are contacted in the absence of a solvent.

### Claim 42 (depends on 1)

The method of claim 1, further comprising a step of heating a mixture of the triamine compound and the reagent.

### Claim 43 (depends on 42)

The method of claim 42, wherein the mixture is heated to a temperature between about 50° C. and about 250° C.

### Claim 44 (depends on 42)

The method of claim 42, wherein the mixture is heated to a temperature between about 80° C. and about 200° C.

### Claim 45 (depends on 42)

The method of claim 42, wherein the mixture is heated to a temperature between about 100° C. and about 180° C.

### Claim 46 (depends on 42)

The method of claim 42, wherein the mixture is heated to a temperature between about 140° C. and about 160° C.

### Claim 47 (depends on 1)

The method of claim 1, wherein the triamine compound and the reagent are contacted in the presence of a promoter.

### Claim 48 (depends on 47)

The method of claim 47, wherein the promoter is an acid.

### Claim 49 (depends on 48)

The method of claim 48, wherein the acid is selected from the group consisting of mineral acids and sulfonic acids.

### Claim 50 (depends on 49)

The method of claim 49, wherein the promoter is a sulfonic acid.

### Claim 51 (depends on 48)

The method of claim 48, wherein the acid is phosphoric acid.

### Claim 52 (depends on 48)

The method of claim 48, wherein the acid is sulfuric acid.

### Claim 53 (depends on 50)

The method of claim 50, wherein the sulfonic acid is selected from the group consisting of methane sulfonic acid, ethane sulfonic acid, p-toluene sulfonic acid, and trifluormethyl sulfonic acid.

### Claim 54 (depends on 48)

The method of claim 48, further comprising a step of treating a crude product generated from reaction of the reagent and the triamine compound with a strong base.

### Claim 55 (depends on 54)

The method of claim 54, wherein the strong base is a metal alkoxide.

### Claim 56 (depends on 48)

The method of claim 48, wherein the molar ratio of acid promoter to reagent is from about 10:1 to about 1:10.

### Claim 57 (depends on 48)

The method of claim 48, wherein the molar ratio of acid promoter to reagent is about 1:1.

### Claim 58 (depends on 1)

The method of claim 1, wherein the molar ratio of triamine compound to reagent is from about 2:1 to about 1:2.

### Claim 59 (depends on 58)

The method of claim 58, wherein the molar ratio of triamine compound to reagent is about 1:1.

### Claim at position 54

60-69. (canceled)