1. A method of synthesizing a 1-(acyloxy)-alkyl N-hydroxysuccinimidyl carbonate compound of Formula (I):
comprising contacting a thiocarbonate compound of Formula (VIII) with an oxidant (IX), in the presence of an N-hydroxysuccinimide compound of Formula (X) to afford the compound of Formula (I);
wherein:
R1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl;
R2 and R3 are independently hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl, or optionally, R2 and R3 together with the atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring;
R4 is C1-4 alkyl, phenyl, substituted phenyl or C7-9 phenylalkyl; and
R5 and R6 are independently hydrogen, acylamino, acyloxy, alkoxycarbonylamino, alkoxycarbonyloxy, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, arylalkyl, carbamoyloxy, dialkylamino, heteroaryl, hydroxy, sulfonamido, or optionally, R5 and R6 together with the atoms to which they are attached form a substituted cycloalkyl, substituted cycloheteroalkyl, or substituted aryl ring.
2. The method of claim 1, wherein R1 is selected from the group consisting of C1-6 alkyl, substituted C1-6 alkyl, C3-6 cycloalkyl, phenyl, substituted phenyl and C7-9 phenylalkyl.
3. The method of claim 2, wherein R1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, neopentyl, 1,1-diethoxyethyl, phenyl or cyclohexyl.
4. The method of claim 1, wherein R2 and R3 are independently selected from the group consisting of hydrogen, C1-4 alkyl, substituted C1-4 alkyl, C1-4 alkoxycarbonyl, C3-6 cycloalkyl, C3-6 cycloalkoxycarbonyl, phenyl, substituted phenyl and C7-9 phenylalkyl.
5. The method of claim 4, wherein R2 is hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, phenyl, cyclohexyl, methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl or cyclohexyloxycarbonyl and R3 is hydrogen or methyl, or R2 and R3 together with the carbon atom to which they are attached form a cyclobutyl, cyclopentyl or cyclohexyl ring.
6. The method of claim 1, wherein R4 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, phenyl, 4-methoxyphenyl, 4-methylphenyl or benzyl.
7. The method of claim 1, wherein R5 and R6 are each hydrogen, acyloxy, alkoxycarbonyloxy, alkoxy, carbamoyloxy, hydroxyl, acetoxy, isobutyroyloxy, pivaloyloxy, benzoyloxy, C1-4 alkyl-substituted benzoyloxy, methoxy, or benzyloxy.
8. The method of claim 1, wherein R1 is isopropyl, R2 is methyl or isopropyl, R3 is hydrogen, R4 is methyl, ethyl or tert-butyl, and R5 and R6 are each hydrogen, benzoyloxy, isobutyroyloxy, pivaloyloxy or C1-4 alkyl-substituted benzoyloxy.
9. The method of claim 1, wherein R2 and R3 in the compound of Formula (I) are different, such that the carbon atom to which R2 and R3 are attached is a stereogenic center.
10. The method of claim 9, wherein the compound of Formula (X) is chiral and non-racemic.
11. The method of claim 10, wherein R5 and R6 in the compound of Formula Formula (X) are each isobutyryloxy or benzoyloxy, and the stereochemistry of the compound is either (1) the stereochemistry at the carbon to which R5 is attached is of the R-configuration, and the stereochemistry at the carbon to which R6 is attached is of the R-configuration; and (2) the stereochemistry at the carbon to which R5 is attached is of the S-configuration, and the stereochemistry at the carbon to which R6 is attached is of the S-configuration.
12. The method of claim 10, wherein the compound of Formula (I) comprises substantially one diastereomer.
13. The method of claim 12, wherein R1 is isopropyl, R2 is isopropyl, R3 is hydrogen, R4 is methyl, ethyl or tert-butyl, R5 and R6 are each benzoyloxy or isobutyroyloxy, and the stereochemistry of the compound is selected from:
(i) the stereochemistry at the carbon to which R2 and R3 are attached is of the S-configuration, the stereochemistry at the carbon to which R5 is attached is of the R-configuration, and the stereochemistry at the carbon to which R6 is attached is of the R-configuration;
(ii) the stereochemistry at the carbon to which R2 and R3 are attached is of the R-configuration, the stereochemistry at the carbon to which R5 is attached is of the S-configuration, and the stereochemistry at the carbon to which R6 is attached is of the S-configuration;
(iii) the stereochemistry at the carbon to which R2 and R3 are attached is of the R-configuration, the stereochemistry at the carbon to which R5 is attached is of the R-configuration, and the stereochemistry at the carbon to which R6 is attached is of the R-configuration; and
(iv) the stereochemistry at the carbon to which R2 and R3 are attached is of the S-configuration, the stereochemistry at the carbon to which R5 is attached is of the S-configuration, and the stereochemistry at the carbon to which R6 is attached is of the S-configuration.
14. The method of claim 1, wherein said contacting is carried out in the presence of a base.
15. The method of claim 1, wherein the oxidant (IX) comprises a composition selected from the group consisting of a peroxy acid, a peroxide, ozone and oxygen.
16. The method of claim 15, wherein the peroxy acid is selected from the group consisting of peroxyacetic acid, m-chloroperoxybenzoic acid, monoperoxy-o-phthalic acid, monoperoxymaleic acid, peroxytrifluoroacetic acid and salts thereof.
17. The method of claim 1, wherein said contacting is carried out in the presence of a solvent selected from the group consisting of acetic acid, dichloromethane, dichloroethane, chloroform, ethyl acetate, toluene, chlorobenzene, xylene, acetonitrile, methyl tert-butyl ether, cyclohexane or combinations thereof.
18. The method of claim 17, wherein said contacting is carried out at a temperature between about \u221220\xb0 C. and about 80\xb0 C.
19. The method of claim 1, wherein said contacting is carried out in the absence of a base.
20. A compound of Formula (I),
and salts thereof, wherein:
R1 is phenyl, substituted phenyl, or styryl;
R2 is methyl or isopropyl;
R3 hydrogen; and
R5 and R6 are each hydrogen, benzoyloxy or isobutyroyloxy.
21. The method of claim 1, further comprising:
contacting the compound of Formula (I) with a primary or secondary amine-containing drug of Formula (II) to afford a compound of Formula (III) or a pharmaceutically acceptable salt, or hydrate thereof;
wherein:
HNR7R8 is a primary or secondary amine-containing drug.
22. The method of claim 21, wherein HNR7R8 is gabapentin.
23. The method of claim 21, wherein said contacting of the compound of Formula (I) with the primary or secondary amine-containing drug of Formula (II) is conducted in the presence of a solvent selected from the group consisting of acetone, acetonitrile, dichloromethane, toluene, tetrahydrofuran, pyridine, methyl tert-butyl ether, methanol, ethanol, isopropanol, water, and combinations thereof.
24. The method of claim 21, wherein said contacting of the compound of Formula (I) with the primary or secondary amine-containing drug of Formula (II) is carried out at a temperature between about \u221220\xb0 C. and about 40\xb0 C.
25. The method of claim 21, wherein said contacting of the compound of Formula (I) with the primary or secondary amine-containing drug of Formula (II) is performed in the absence of a base.
26. The method of claim 21, wherein said contacting of the compound of Formula (I) with the primary or secondary amine-containing drug of Formula (II) is performed in the presence of a base.
27. The method of claim 21, wherein the base is an alkali metal bicarbonate, an alkali metal carbonate salt or an organic base selected from the group consisting of triethylamine, diisopropylethylamine, N-methylmorpholine, and pyridine.
28. The method of claim 21, wherein HNR7R8 is pregabalin.
29. The method of claim 21, wherein HNR7R8 is tranexamic acid.
30. A method of synthesizing a 1-(acyloxy)-alkyl carbamate prodrug of pregabalin or a salt or hydrate thereof, comprising contacting a compound of Formula (I) with pregabalin or a salt, thereof:
wherein R1, R2, R3, R5 and R6 are as defined in claim 1.
31. A method of synthesizing a 1-(acyloxy)-alkyl carbamate prodrug of tranexamic acid or a salt or hydrate thereof, comprising contacting a compound of Formula (I) with tranexamic acid or a salt thereof:
wherein R1, R2, R3, R5 and R6 are as defined in claim 1.
32. The method of claim 21, wherein HNR7R8 is R-baclofen.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
We claim:
1. An integrated circuit configuration, comprising:
a semiconductor body having:
a rear side;
a front side;
a first semiconductor zone of a first conductivity type in a region of said rear side; and
a second semiconductor zone of said first conductivity type adjoining said first semiconductor zone, said second semiconductor zone doped weaker than said first semiconductor zone and disposed in a region of said front side;
a first component region in said semiconductor body having at least one semiconductor zone of a second conductivity type;
a second component region in said semiconductor body having at least one semiconductor zone of said second conductivity type; and
a conversion structure having a first structure semiconductor zone of said second conductivity type and a second structure semiconductor zone of said first conductivity type, said first structure semiconductor zone and said second structure semiconductor zone being short-circuited and respectively disposed at a distance from said first semiconductor zone in said second semiconductor zone between said first and second component regions.
2. The integrated circuit configuration according to claim 1, including a vertical semiconductor component having at least a first and a second terminal electrode, said first terminal electrode connected to said first semiconductor zone and said second terminal electrode connected to said at least one semiconductor zone of said second conductivity type, said at least one semiconductor zone of said second conductivity type in said second semiconductor zone in said first component region being part of said vertical semiconductor component.
3. The integrated circuit configuration according to claim 2, including semiconductor zones of said first conductivity type connected to said first terminal electrode, said semiconductor zones disposed in said at least one semiconductor zone of said second conductivity type in said second semiconductor zone.
4. The integrated circuit configuration according to claim 3, including a control electrode in said first component region insulated from said semiconductor body adjacent said at least one semiconductor zone of said second conductivity type and at least one of said semiconductor zones of said first conductivity type, said at least one semiconductor zone being formed in said at least one semiconductor zone of said second conductivity type.
5. The integrated circuit configuration according to claim 1, including at least one further semiconductor zone of said first conductivity type disposed in said at least one semiconductor zone of said second conductivity type in said second semiconductor zone in said first component region.
6. The integrated circuit configuration according to claim 3, wherein at least two of said semiconductor zones of said first conductivity type are disposed in said at least one semiconductor zone of said second conductivity type in said second semiconductor zone in said first component region.
7. The integrated circuit configuration according to claim 1, wherein said first and second structure zones of said conversion structure directly adjoin one another.
8. The integrated circuit configuration according to claim 1, wherein said conversion structure is a plurality of conversion structures each with a first structure semiconductor zone of said second conductivity type and a second structure semiconductor zone of said first conductivity type disposed next to one another between said first and second component regions.
9. The integrated circuit configuration according to claim 1, wherein said conversion structure is formed annularly around said first component region.