1. A printhead tile comprising:
a printhead integrated circuit incorporating ink ejection nozzles, each nozzle comprising an ink chamber and a thermal bend actuator beam configured to thermally expand upon receipt of an electrical current so as to cause ejection of ink from the chamber;
a channel layer adjacent the printhead integrated circuit and having channel layer slots;
an upper layer having upper layer holes on one side in communication with the channel layer slots and upper layer channels on an opposite side;
a middle layer having middle layer holes in communication with the upper layer channels; and
a lower layer having lower layer channels on one side in communication with the middle layer holes and inlet holes on an opposite side, the inlet holes being arranged to receive ink for supply to the chambers via the channel, upper, middle and lower layers.
2. A printhead tile as claimed in claim 1, wherein an endplate is provided adjacent the channel layer.
3. A printhead tile as claimed in claim 1, wherein the channel layer slots are provided as fingers integrated in the channel layer.
4. A printhead tile as claimed in claim 1, wherein the printhead integrated circuit is bonded onto the upper layer.
5. A printhead tile as claimed in claim 4, wherein the nozzles overlie the upper layer holes.
6. A printhead tile as claimed in claim 1, wherein the diameter of holes decreases from the inlet holes to the upper layer holes.
7. A printhead tile as claimed in claim 1, comprising a nozzle guard adjacent the printhead integrated circuit.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A process for preparing 1,2-diamino compounds of formula
19
and pharmaceutically acceptable addition salts thereof
wherein R1, R1, R2 and R2, independently from each other, are H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-lower alkyl, cycloalkyl-lower alkenyl, cycloalkyl-lower alkynyl, heterocyclyl, heterocyclyl-lower alkyl, heterocyclyl-lower alkenyl, heterocyclyl-lower alkynyl, aryl, aryl-lower alkyl, aryl-lower alkenyl, or aryl-lower alkynyl, or
R1 and R2, R1 and R2, R1 and R2 or R1 and R2 taken together with the two carbon atoms to which they are bound, are a carbocyclic or heterocyclic ring system, or
R1 and R1 or R2 and R2 taken together with the carbon atom to which they are bound, are a carbocyclic or heterocyclic ring system, wherein at least one of R1, R1, R2 and R2 is not H, and
R3 and R4, are independently, a substituent of an amino group, wherein R3 and R4 are not both H,
said process comprising the steps of:
a) reacting a 1,2-epoxide of formula
20
wherein R1, R1, R2 and R2 are as above with an amine of formula R5NH2 wherein R5 is a substituent of an amino group but not H, to form a 2-aminoalcohol of formula
21
wherein R1, R1, R2, R2 and R5 are as above;
b) converting the 2-aminoalcohol of formula (III) to the aziridine of formula
22
wherein R1, R1, R2, R2 and R5 are as above;
c) reacting the aziridine of formula (IV) with an amine of formula R7NHR8, wherein R7 and R8, independently from each other, are a substituent of an amino group, to obtain a 1,2-diamino compound of formula
23
wherein R1, R1, R2, R2, R5, R7and R8 are as above;
d) acylating the secondary amino group in position 1 of the 1,2-diamino compound of formula (V) to form an acylated 1,2-diamino compound of formula
24
wherein R1, R1, R2, R2, R3, R5, R7 and R8 are as above;
e) removing R5 from the acylated 1,2-diamino compound (VI) to produce an acylated 1,2-diamino compound of formula
25
wherein R1, R1, R2, R2, R3, R7and R8 are as above; and
f) deprotecting the amino group in position 2 of the 1,2-diamino compound of formula (VII) to produce the 1,2-diamino compound of formula (I).
2. The process of claim 1 wherein the 1, 2 epoxide is a cyclohexene oxide of formula
26
wherein R11 and R12 are as above.
3. The process of claim 2, wherein the cyclohexene oxide of formula (IX) is (1S,5R,6R)-5-(1-ethyl-propoxy)-7-oxa-bicyclo4.1.0hept-3-ene-3-carboxylic acid ethyl ester.
4. The process of claim 1 wherein the 1,2 diamino compound is a 4,5-diamino-shikimic acid derivative of formula
27
and pharmaceutically acceptable addition salts thereof, wherein
R11 is an alkyl group or a substituted alkyl group, R12 is an alkyl group and R3 and R4 are, independently, H or a substituent of an amino group, wherein R3 and R4 are not both H.
5. The process of claim 4, wherein the 4,5-diamino-shikimic acid derivative of formula (VIII) is selected from the group consisting of ethyl (3R,4R,5S)-4-N-Acetylamino-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate, and ethyl (3R,4R,5S)-4-N-Acetylamino-5-amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate phosphate (1:1).
6. The process of claim 1, wherein R5 in the amine of formula R5NH2 is a straight chain or branched alkyl of 1 to 6 C-atoms
7. The process of claim 6, wherein the amine of formula R5NH2 is tert-butylamine, 2-methylbutylamine, or 2-methylpentylamine.
8. The process of claim 7, wherein the amine of formula R5NH2 is tert-butylamine.
9. The process of claim 1, wherein the reaction of step a) is conducted in the presence of a catalyst.
10. The process of claim 9, wherein the catalyst is a metal catalyst or a magnesium halide catalyst or a magnesium halide derivative catalyst.
11. The process of claim 10, wherein the catalyst is a magnesium halide derivative.
12. The process of claim 10, wherein the catalyst is magnesium chloride.
13. The process of claim 1, wherein the cyclization in step (b) is performed in the presence of a sulfonylating agent.
14. The process of claim 1, wherein R7 and R8 in the amine of formula R7NHR8 are, independently, a straight chain or branched alkenyl of 2 to 6 C-atoms, benzyl, substituted benzyl or heterocyclyl methyl.
15. The process of claim 14, wherein the amine of R7NHR8 is a primary or secondary amine.
16. The process of claim 15, wherein the amine of R7NHR8 is a secondary amine.
17. The process of claim 16, wherein the amine of R7NHR8 is a diallylamine.
18. The process of claim 14, wherein the ring opening is performed in the presence of a catalyst.
19. The process of claim 18, wherein the catalyst is sulfonic acid or a derivative of sulfonic acid or a Lewis acid catalyst.
20. The process of claim 1, wherein the reaction in step (d) is carried out in the presence of acylating agents.
21. The process of claim 20, wherein the acylating agent is acetic anhydride.
22. The process of claim 1, wherein the reaction in step (d) is carried out in the presence of a catalyst.
23. The process of claim 22, wherein the catalyst is pyridine or a derivative of pyridine or an inorganic base.
24. The process of claim 22, wherein the catalyst is pyridine.
25. The process of claim 22, wherein the catalyst is an inorganic base.
26. The process of claim 22, wherein the catalyst is an organic base.
27. The process of claim 26, wherein the catalyst is sodium acetate.
28. The process of claim 1, wherein the reaction in step (d) is carried out at a temperature of from 70 C. to 120 C.
29. The process of claim 1, wherein the removal of the tert-butyl group from the acetamide of formula (VI) in step (e) is carried out by heating in acids.
30. The process of claim 1, wherein the cleavage of the tert-butyl group from the acetamide of formula (VI) is carried out with trifluoroacetic acid (TFA).
31. The process of claim 1, wherein the cleavage of the tert-butyl group from the acetamide of formula (VI) is carried out with hydrogen chloride in ethanol at reflux.
32. The process of claim 1, wherein the reaction in step (e) is carried out either with or without addition of any solvents.
33. The process of claim 1, wherein the conversion step (f) is performed at a temperature of from 20 C. to 70 C.
34. The process of claim 1, wherein the conversion step (f) is an alkenyl cleavage reaction performed in the presence of a metal catalyst wherein R7 and R8 are, independently, a straight chain or branched alkenyl of 2 to 6 C-atoms.
35. The process of claim 34, wherein the catalyst is palladium acetate.
36. The process of claim 34, wherein the catalyst is tetrakis(triphenylphosphine) palladium.
37. A process for preparing an acylated 1,2-diamino compound of formula
28
wherein R1, R1, R2 and R2, independently from each other, are H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkyl-lower alkyl, cycloalkyl-lower alkenyl, cycloalkyl-lower alkynyl, heterocyclyl, heterocyclyl-lower alkyl, heterocyclyl-lower alkenyl, heterocyclyl-lower alkynyl, aryl, aryl-lower alkyl, aryl-lower alkenyl, or aryl-lower alkynyl, or
R1 and R2, R1 and R2, R1 and R2 or R1 and R2 taken together with the two carbon atoms to which they are bound, are a carbocyclic or heterocyclic ring system, or
R1 and R1 or R2 and R2 taken together with the carbon atom to which they are bound, are a carbocyclic or heterocyclic ring system,
wherein at least one of R1, R1, R2 and R2 is not H, and
R3 is a substituent of an amino group and not H
R7 and R8, independently from each other, are H or a substituent of an amino group, wherein R7 and R8 are not both H
comprising removing the alkyl group from position 1 of the acylated 1,2-diamino compound of formula (VI)
29
wherein R1, R1, R2, R2, R3, R5, R7 and R8 are as above.
38. The process of claim 37, wherein R5 is a tert-butyl group.
39. A compound of the formula
30
wherein R11 is an alkyl group or substituted alkyl group and R5 and R12 are independently, an alkyl group
and pharmaceutically acceptable addition salts thereof.
40. The compound of claim 39, wherein the compound is ethyl (3R,4S,5R)-5-N-(1,1-Dimethylethyl)amino-3-(1-ethylpropoxy)-4-hydroxy-cyclohexene-1-carboxylate.
41. A compound of the formula
31
wherein R11 is an alkyl group or substituted alkyl group and R5 and R12 are independently, an alkyl group
and pharmaceutically acceptable addition salts thereof.
42. The compound of claim 41 wherein the compound is ethyl (3R,4S,5R)-4,5-(1,1-Dimethylethyl)imino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.
43. A compound of the formula
32
wherein R11 is an alkyl group, substituted alkyl group and R12 is an alkyl group,
R3 is a substituent of an amino group, R5 is an alkyl group, and
R7 and R8 are, independently, H or a substituent of an amino group, wherein R7 and R8 are not both H,
and pharmaceutically acceptable addition salts thereof.
44. The compound of claim 43, wherein the compound is ethyl (3R,4R,5S)-5-N,N-Diallylamino-4-(1,1-dimethylethyl)amino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.
45. The compound of claim 43, wherein the compound is ethyl (3R,4R,5S)-4-N-Acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.
46. The compound of claim 43, wherein the compound is ethyl (3R,4R,5S)-4-N-Acetyl(1,1-dimethylethyl)amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate hydrochloride.
47. The compound of claim 43 wherein the compound is ethyl (3R,4R,5S)-4-N-Acetyl amino-5-N,N-diallylamino-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate hydrochloride.