1. A method for producing a particulate catalyst with a cross-sectional size in the range 1-50 mm and an aspect ratio in the range 0.5 to 5 using a 3D printing additive layer method comprising:
(i) forming a layer of a powdered catalyst support material comprising an alumina, metal-aluminate, silica, alumino-silicate, titania, zirconia, zinc oxide, or a mixture thereof,
(ii) binding the powder in said layer according to a predetermined pattern,
(iii) repeating (i) and (ii) layer upon layer to form a shaped unit, and
(iv) applying a catalytic material to said shaped unit.
2. A method according to claim 1 wherein the catalytic material applied to the shaped unit comprises a metal, metal compound or a zeolite.
3. A method according to claim 2 wherein the metal, metal compound or zeolite is applied to the shaped unit from a solution or dispersion of the metal, metal compound or zeolite.
4. A method according to claim 3 wherein the metal or metal compound comprises one or more metals selected from the group consisting of Na, K, Mg, Ca, Ba, Al, Si, Ti V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Nb, Mo, Ru, Rh, Pd, Ag, Sn, Sb, La, Hf, W, Re, Ir, Pt, Au, Pb, or Ce.
5. A method according to claim 1 wherein the powdered material has an average particle size, D50, in the range 1 to 200 micrometers.
6. A method according to claim 1 wherein the powder in each layer is bound together with a binder.
7. A method according to claim 6 wherein a burnout additive is included in the catalyst powder or binder to control the porosity of the resulting shaped unit.
8. A method according to claim 1 wherein the shaped unit is subjected to a heating step.
9. A method according to claim 1 wherein the shaped unit, comprising one or more reducible metal compounds, is subjected to a reduction step.
10. A method according to claim 1 wherein the shaped unit is a wire-frame structure or a skeletal framework containing a void space within which may have multiple internal strengthening rods.
11. A catalyst obtained by the method of claim 1.
12. A method according to claim 1 wherein the shaped unit is a solid unit, comprising through holes.
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. An aryl-isoxazol-4-yl-imidazo1,2-apyridine derivative of formula I
wherein
R1 is hydrogen, halogen, hydroxy, lower alkyl, benzyloxy or \u2014O\u2014(CH2)\u2014(CO)-5 or 6 membered heteroaryl optionally substituted by aryl or by lower alkyl;
R2 is hydrogen, halogen, lower alkyl, lower alkynyl, amino, \u2014NHC(O)\u2014Ra or \u2014(CO)\u2014Ra;
R3 is hydrogen, halogen, cyano, lower alkyl, lower alkynyl, amino, \u2014NHC(O)\u2014Ra, \u2014(CO)\u2014Ra, -5 or 6-membered heterocycloalkyl in the 1-position, optionally substituted by \u2550O or is a -5 or 6-membered heteroaryl in the 1-position;
R4 is hydrogen or -5 or 6-membered heteroaryl;
R5 is lower alkyl or cycloalkyl;
Ra is lower alkoxy or NR\u2032R\u2033, wherein R\u2032 and R\u2033 are each independently hydrogen, lower alkyl optionally substituted by hydroxy, lower alkynyl, \u2014(CH2)n-cycloalkyl, \u2014(CH2)n-5 or 6-membered heterocycloalkyl or \u2014(CH2)n-5 or 6-membered heteroaryl; and
n is 0 to 3;
or a pharmaceutically acceptable acid addition salt thereof.
2. The compound of claim 1, wherein R3 is hydrogen.
3. The compound of claim 2, selected from the group consisting of
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
8-methyl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
8-chloro-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
8-bromo-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-8-ol;
8-benzyloxy-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
1-(5-methyl-3-phenyl-isoxazol-4-yl)-2-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-8-yloxy-ethanone;
7-methyl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
7-ethyl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine; and
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid methyl ester.
4. The compound of claim 2, selected from the group consisting of
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid cyclopropylmethyl-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid prop-2-ynylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid cyclopropylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid cyclobutylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid cyclopentylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (2-hydroxy-ethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (tetrahydro-pyran-4-yl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (2-morpholin-4-yl-ethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (3-morpholin-4-yl-propyl)-amide; and
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (pyridin-2-ylmethyl)-amide.
5. The compound of claim 2, selected from the group consisting of
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (pyridin-3-ylmethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (pyridin-4-ylmethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-7-carboxylic acid (furan-2-ylmethyl)-amide;
7-bromo-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
7-ethynyl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-ylamine;
N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-yl-2-pyridin-3-yl-acetamide;
cyclopropanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-yl-amide;
cyclobutanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-yl-amide;
cyclopentanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-yl-amide and
N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-7-yl-nicotinamide.
6. The compound of claim 1, wherein R3 is halogen.
7. The compound of claim 6, selected from the group consisting of
6-fluoro-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
6-chloro-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
6-bromo-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine;
6-Iodo-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine and
6-bromo-2-(5-cyclopropyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine.
8. The compound of claim 1, wherein R3 is cyano.
9. The compound of claim 8, which is 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carbonitrile.
10. The compound of claim 1, wherein R3 is lower alkyl.
11. The compound of claim 10, which is 6-methyl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine.
12. The compound of claim 1, wherein R3 is \u2014C(O)\u2014Ra, wherein Ra is lower alkoxy or NR\u2032R\u2033, wherein R\u2032 and R\u2033 are each independently hydrogen, lower alkyl optionally substituted by hydroxy, lower alkynyl, \u2014(CH2)n-cycloalkyl, \u2014(CH2)n-5 or 6-membered heterocycloalkyl or \u2014(CH2)n-5 or 6-membered heteroaryl; and n is 0 to 3.
13. The compound of claim 12, selected from the group consisting of:
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid methyl ester;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid ethyl ester;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid cyclopropylmethyl-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid prop-2-ynylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid cyclopropylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid cyclobutylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid cyclopentylamide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (2-hydroxy -ethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (tetrahydro-pyran-4-yl)-amide; and
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (2-morpholin-4-yl-ethyl)-amide.
14. The compound of claim 12, selected from the group consisting of:
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (3-morpholin-4-yl-propyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (pyridin-2-ylmethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (pyridin-3-ylmethyl)-amide;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (pyridin-4-ylmethyl)-amide; and
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine-6-carboxylic acid (furan-2-ylmethyl)-amide.
15. The compound of claim 1, wherein R3 is amino, \u2014NHC(O)\u2014Ra, -5 or 6-membered heterocycloalkyl in the 1-position, optionally substituted by \u2550O or is -5 or 6-membered heteroaryl in the 1-position.
16. The compound of claim 15, selected from the group consisting of:
2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-ylamine;
2-cyclopropyl-N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-acetamide;
N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-2-pyridin-3-yl-acetamide;
cyclopropanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-amide;
cyclobutanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-amide;
cyclopentanecarboxylic acid 2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-amide;
N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-benzamide;
N-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-nicotinamide;
1-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-azetidin-2-one;
1-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridin-6-yl-pyrrolidin-2-one;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-6-pyrrol-1-yl-imidazo1,2-apyridine;
2-(5-methyl-3-phenyl-isoxazol-4-yl)-6-pyrazol-1-yl-imidazo1,2-apyridine and
6-imidazol-1-yl-2-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazo1,2-apyridine.