Sulfamoylating reagents

Patent metadata

Field	Value
Publication number	US-9802938-B2
Application number	US-201414552883-A
Country	US
Kind code	B2
Filing date	Nov 25, 2014
Priority date	Aug 2, 2007
Publication date	Oct 31, 2017
Grant date	Oct 31, 2017

Abstract

The present invention provides sulfamoylating reagents of formula R u N − —S(O) 2 X + , wherein X is a cyclic tertiary amine or a nitrogen-containing heteroaryl and R u is an amine protecting group or hydrogen.

First claim

What is claimed is:

1. A compound of formula R u N − —S(O) 2 X + , wherein X is a cyclic tertiary amine which is triethylenediamine, diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicycle[4.3.0]non-5-ene, sparteine, N,N′-dimethylpiperazine, or N-ethylmorpholine and R u is an amine protecting group or hydrogen.

2. The compound according to claim 1 , wherein R u is —C(O)OC(R v ) 2 (R w ), wherein:
each R v is independently optionally substituted C 1-10 aliphatic, optionally substituted aryl, or hydrogen;
R w is optionally substituted C 1-10 aliphatic or optionally substituted aryl;
or one R v is optionally substituted C 1-10 aliphatic; and the other R v is taken together with R w to form an optionally substituted C 3-6 cycloaliphatic ring.

3. The compound according to claim 2 , wherein R w is methyl or phenyl.

4. The compound according to claim 2 , wherein each R v independently is methyl, ethyl, butyl, hexyl, octyl, or phenyl.

5. The compound according to claim 2 , wherein R u is —C(O)OC(R v ) 2 (R w ), wherein one R v is optionally substituted C 1-10 aliphatic, and the other R v is taken together with R w to form cyclopropyl, or cyclohexyl.

6. The compound according to claim 1 , wherein R u is —C(O)OCMe 3 , —C(O)OCH 2 Ph, —C(O)N(Ph) 2 , —C(O)OC(Me) 2 Ph, —C(O)OCH(Me)Ph, C(O)OC(Me) 2 Et, —C(O)OC(Et) 2 Ph, —C(O)OC(octyl) 2 Ph,

7. The compound according to claim 6 , wherein R u is —C(O)OCMe 3 .

8. The compound according to claim 1 , wherein R u is —C(O)ON(Ph) 2 .

9. A compound according to claim 1 , wherein X is triethylenediamine.

10. A complex comprising a compound of formula R u N − —S(O) 2 X + and the hydrochloride salt of X, wherein X is a cyclic tertiary amine which is triethylenediamine, diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicycle[4.3.0]non-5-ene, sparteine, N,N′-dimethylpiperazine, or N-ethylmorpholine and R u is an amine protecting group or hydrogen.

11. The complex of claim 10 , wherein the ratio of the compound of formula R u N − —S(O) 2 X + to the hydrochloride salt of X in the complex is less than one.

12. A process for the formation of a compound of formula R u N − —S(O) 2 X + , wherein R u is —C(O)OC(R v ) 2 (R w ), comprising:
I-E) treating (R w )(R v ) 2 C—OH with chlorosulfonylisocyanate;
II-E) treating the reaction mixture formed in step I-E) with X; and
III-E) isolating the sulfamoylating reagent R u N − —S(O) 2 X + formed in step II-E);

wherein
X is a cyclic tertiary amine which is triethylenediamine, diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicycle[4.3.0]non-5-ene, sparteine, N,N′-dimethylpiperazine, or N-ethylmorpholine,
each R v is independently optionally substituted C 1-10 aliphatic, optionally substituted aryl, or hydrogen;
R w is optionally substituted C 1-10 aliphatic or optionally substituted aryl;
or one R v is optionally substituted C 1-10 aliphatic; and the other R v is taken together with R w to form an optionally substituted C 3-6 cycloaliphatic ring.

13. A compound according to claim 9 , wherein R u is —C(O)OCMe 3 .

14. The complex of claim 10 , wherein the ratio of the compound of formula R u N − —S(O) 2 X + to the hydrochloride salt of X in the complex is about one.

15. The complex of claim 10 , wherein the ratio of the compound of formula R u N − —S(O) 2 X + to the hydrochloride salt of X in the complex is more than one.

16. The complex of claim 14 , wherein
X is triethylenediamine and
R u is —C(O)OCMe 3 .

17. The process according to claim 12 , wherein
X is triethylenediamine and
R u is —C(O)OCMe 3 .

18. The compound according to claim 2 , wherein each R v independently is hydrogen, methyl, or ethyl.

Assignees

• Millennium Pharm Inc

Inventors

• ARMITAGE Ian
• Elliott Eric L
• Langston Marianne
• Langston Steven P
• Mccubbin Quentin J
• Mizutani Hiro
• Stirling Matthew
• Zhu Lei

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C07D295/22

  with hetero atoms directly attached to ring nitrogen atoms · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07D305/08

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms · CPC title