186390-74-9

Usage

Synthesis

Sodium borohydride (5.06 g, 133 mmol) was added in portions to a solution of ?2-(carboxymethyl)-4-nitrobenzoic acid (10.0 g, 44.4 mmol) in THF (220 mL). The contents were cooled to 0 °C, and boron triflfluoride diethyl etherate (21.3 mL, 133 mmol) was added dropwise over 1 h. The mixture was allowed to warm to 25 °C and stirred for 16 h. The reaction mixture was then cooled to 0 °C and cautiously quenched with aqueous sodium hydroxide (1 N, 178 mL). The contents were stirred for 3 h, and the THF was removed under vacuum. The resulting aqueous suspension was cooled to 0 °C and the product was fifiltered off. After drying, 7.78 g (89%) of the diol was afforded as a white solid.

Upstream product

• 39585-32-5 2-carboxymethyl-4-nitro-benzoic acid 
• 109-99-9 tetrahydrofuran 
• 109-63-7 trifluoroborane diethyl ether 
• 150879-75-7 4-nitrohomophthalic anhydride 
• 186390-71-6 2-(carboxy-5-nitro-phenyl)malonic acid dimethyl ester 
• 1025823-76-0 2-(2-Carboxy-5-nitro-phenyl)-malonic acid 
• 99-60-5 2-chloro-4-nitrobenzoic acid 

Downstream Products

• 208589-95-1 2-Benzyl-6-nitro-1,2,3,4-tetrahydroisoquinoline 
• 186390-77-2 6-nitro-1,2,3,4-tetrahydro-isoquinoline 
• 199014-20-5 6-amino-2-<2-(4-methoxybenzyl)-2H-<1,2,4>triazol-3-ylmethyl>-1,2,3,4-tetrahydro-isoquinoline 
• 199014-17-0 2-<2-(4-methoxybenzyl)-2H-<1,2,4>triazol-3-ylmethyl>-6-nitro-1,2,3,4-tetrahydro-isoquinoline 
• 207804-97-5 6-nitro-3,4-dihydro-1H-isochromene 
• 199014-22-7 [2-[2-[(methylsulfonyl)oxy]ethyl]-4-nitrophenyl]methyl methanesulfonate 

Relevant academic research and scientific papers

INHIBITORS OF CHECKPOINT KINASES

The instant invention provides for compounds which comprise fused pyrazoles that inhibit CHK1 activity. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound

Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (ApoB) secretion

Compositions comprising a lipid lowering agent selected from cholesterol biosynthesis inhibitors, bile acid sequestrants, fibrates, cholesterol absorption inhibitors, and niacin; and an inhibitor of microsomal triglyceride transfer protein for treating atherosclerosis, obesity and related diseases.

Apo B-secretion/MTP inhibitory amides

PCT No. PCT/IB97/01368 Sec. 371 Date Apr. 20, 1999 Sec. 102(e) Date Apr. 20, 1999 PCT Filed Nov. 3, 1997 PCT Pub. No. WO98/23593 PCT Pub. Date Jun. 4, 1998This invention is directed to compounds of formula (I) or the stereoisomers, pharmaceutically accept

Apo B-secretion/MTP inhibitor hydrochloride salt

A hydrochloride salt of an Apo B secretion/MTP inhibitor, methods of making the salt, methods of using the salt and pharmaceutical compositions containing the salt are disclosed.

Biphenyl-2-carboxylic acid-tetrahydro-isoquinolin-6-yl amide derivatives, their preparation and their use as inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion

Compounds of formula (I), STR1 wherin X is CH2, CO, CS or SO2 ; Y is selected from: a direct link, aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substituted by hydroxy, (C1 -C10)alkoxy, (C1 -C10)acyl, (C1 -C10)acyloxy, or (C6 -C10)aryl, NH, and O, provided that if X is CH2,Y is a direct link; Z is selected from the following groups: (1) H, halo, cyano, (2) hydroxy, (C1 -C10)alkoxy, (C1 -C10)a1kylthio, (C1 -C10)acyl, thiophenylcaronyl (C1 -C10)alkoxycarbonyl, (3) (C1 -C10)aklkyammo, di(C1 -C10)alylamino, (C6 -C10)aryl(C1 -C10)alkylamino, provided that Y is not O or NH, (4) unsubstituted vinyl, (C6 -C10)aryl, (C3 -C8)cycloalkyl and fused benz derivatives thereof, (C7 -C10)polycycloalkyl, (C4 -C8)cycloalkenyl, (C7 -C10)polycycloalkenyl, (5) (C6 -C10)aryloxy, (C6 -C10)aryltio, (C6 -C10)aryl(C1 -C10)alkoxy, (C6 -C10)aryl(C1 -C10)alkylthio, (C3 -C8)cycloalkyloxy, (C4 -C8)cycloalkenyloxy, (6) heterocyclyl sclected from the group consisting of monocyclic radicals and fused polycycuic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selocted from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independendy satated, partally unsaturated, or aromatic, provided that if X is CH2, Z is H or is selected from groups (4) and (6), wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C1 -C10)alkyl, (C1 -C10)alkoxy, (C1 -C10)alkoxycarbonyl, (C1 -C10)althyltio, (C1 -C10)altylamino, (C1 -C10)alkylaminocarbonyl, di(C1 -C10)alkylamino, di(C1 -C10)alkylaminocarbonyl, di(C1 -C10)alkyo(C1 -C10)alkoxy, (C1 -C3)perfluoroalkyl, (C1 -C3)perfluoroalkoxy, (C1 -C10)acyl, (C1 -C10)acyloxy, (C1 -C10)acyloxy(C1 -C10)alkyl, and pyrrolidinyl; and pharmaceutically acceptable salts thereof.

4'-trifluoromethylbiphenyl-2-carboxylic acid-[2-(2-acetylaminoethyl)-1,2,3,4-tetrahydroisoquinolin-6-yl]amide hydrochloride as apo B-secretion/MTP inhibitors

A hydrochloride salt of an Apo B secretion/MTP inhibitor, methods of making the salt, methods of using the salt and pharmaceutical compositions containing the salt are disclosed.