78441-69-7

Usage

Uses

Used in Pharmaceutical Industry:
2-(DIMETHYLAMINOMETHYL)-4-THIAZOLEMETHANOL is used as an impurity in the histamine H2-receptor antagonist Nizatidine (N598500) for the treatment of conditions such as peptic ulcers, gastroesophageal reflux disease (GERD), and other acid-related disorders. Its presence as an impurity is significant because it can affect the safety, efficacy, and quality of the final drug product. Ensuring the control and removal of this impurity is crucial for maintaining the therapeutic benefits and minimizing potential side effects of Nizatidine.

InChI:InChI=1/C7H12N2OS/c1-9(2)3-7-8-6(4-10)5-11-7/h5,10H,3-4H2,1-2H3

Upstream product

• 82586-66-1 ethyl 2-(dimethylaminomethyl)-4-thiazolecarboxylate 
• 92759-37-0 4-Hydroxy-4-(chloromethyl)-2-<(dimethylamino)methyl>thiazoline 

Downstream Products

• 78441-62-0 4-[[(2-aminoethyl)thio]-methyl]-N,N-dimethyl-2-thiazolemethanamine 
• 199599-68-3 2-dimethylaminomethylthiazole-4-carboxaldehyde 

Relevant academic research and scientific papers

Clean preparation method of 4-hydroxymethylthiazole and its intermediate

The invention discloses a clean preparation method of 4-hydroxymethylthiazole and its intermediate. The clean preparation method includes, taking compound I as an example, the steps of in a solvent, subjecting compound IV and an alkali metal hypohalite to

Preparation method of nizatidine bulk drug

The invention discloses a preparation method of a nizatidine bulk drug. The preparation method comprises the following steps: (1) preparing 2-(N,N-dimethylamino)-4-chloromethyl-4-hydroxy-4,5-dihydrothiazole (III); (2) preparing 2-(N,N-dimethylamino)-4-thiazolemethanol (IV); (3) preparing 2-(dimethylaminomethyl)-4-(2-aminoethylthiomethyl) thiazole (V); and (4) preparing nizatidine. The preparation method has the beneficial effects that the cost is low, the preparation process is simple, the yield is high, and the prepared nizatidine is high in purity.

HYDRAZONE DERIVATIVE

A compound represented by the following formula (I): wherein R1 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R2 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R3 represents hydrogen, etc.; Ar represents a divalent group derived from aromatic hydrocarbon, etc.; X represents a single bond, linear or branched alkylene having from 1 to 3 carbon atoms which may have a substituent, etc.; and G represents halogen, a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc., a salt thereof or a solvate thereof; and an agent for inhibiting aggregation and/or deposition of an amyloid protein or an amyloid-like protein, which comprises the compound, a salt thereof or a solvate thereof

Atropisomers of 2,3-disubstituted-(5.6)-heteroaryl fused-pyrimidin-4-ones

The present invention relates to novel atropisomers of 2,3-disubstituted-(5,6)-heteroarylfused-pyrimidin-4-ones, pharmaceutical compositions containing such compounds the use of such compounds to treat neurodegenerative, psychotropic, and drug and alcohol induced central and peripheral nervous system disorders.

2,3 Disubstituted- (5,6)-heteroarylfused-pyrimidine-4-ones

The present invention relates to novel compounds of the formula I, described above, and their pharmaceutically acceptable salts, and pharmaceutical compositions and methods of treating neurodegenerative and CNS-trauma related conditions.

Novel 2,3-disubstituted-(5,6)- heteroarylfused-pyrimidine-4-ones

From EXEMP_CLAIMS : 1. A bicyclic compound of the formula wherein ring positions ""F"" and ""G"" may be independently selected from carbon, nitrogen, oxygen or sulfur, and J is independently selected from carbon, nitrogen or oxygen with the proviso that: i) if more than two of ""F"", ""G"" or ""J"" is a heteroatom then said 5 membered heteroaromatic ring is selected from the group consisting of (1,2,3)-triazole, (1,2,3)-thiadiazole, (1,2,5)-thiadiazole, and (1,2,5)-oxadiazole; and ii) if two of ""F"", ""G"" or ""J"" are heteroatoms, one of said heteroatoms may be oxygen or sulfur; wherein said fused heteroaromatic rings may optionally be independently substituted on any of the carbon or nitrogen atoms capable of forming an additional bond with a substituent selected from hydrogen, (C1-C6)alkyl, halogen, trifluoromethyl, amino-(CH2)n-, (C1-C6)alkylamino-(CH2)p-, di(C1-C6)alkyl-amino-(CH2)n-, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl-, -CN, hydroxy,-NO2, R3-C(=O)-, R4-O-C(=O)-, di(C1-C6)alkyl-N-C(=O)-, (C1-C6)cycloalkyl, and R4-NH-C(=O)-, and phenyl optionally substituted with halo, (C1-C6) alkyl, -CN, or -CF3; R1 is substituted phenyl of the formula Ph1 or heteroaryl wherein said heteroaryl is selected from the group consisting of pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, wherein said heteroaryl may optionally be substituted on any of the atoms capable of forming an additional bond, up to a maximum of three substituents, with a substituent selected from hydrogen, (C1-C6)alkyl, halogen, trifluoromethyl, amino-(CH2)n-, (C1-C6)alkylamino-(CH2)n-, di(C1-C6)alkyl-amino-(CH2)n-, (C1-C6)alkoxy, hydroxy(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl-, -CN, hydroxy, H-C(=O)-, (C1-C6)alkyl-C(=O)-, HO-C(=O)-, (C1-C6)alkyl-O-C(=O)-, NH2-C(=O)-, (C1-C6)alkyl-NH-C(=O)-, (=O)-, and di(C1-C6)alkyl-NH-C(=O)-; wherein said Ph1 is a group of the formula R2 is disubstituted phenyl of the formula Ph2 or a five or six membered heterocycle, wherein said 6-membered heterocycle has the formula wherein ""N"" is nitrogen; wherein said ring positions ""K"", ""L"" and ""M"" may be independently selected from carbon or nitrogen, with the proviso that only one of ""K"", ""L"" or ""M"" can be nitrogen; wherein said five membered heterocycle has the formula wherein said ring positions ""P,"" ""Q"" and ""T"" may be independently selected from carbon, nitrogen, oxygen or sulfur; with the proviso that only one of ""P,"" ""Q"" or T can be oxygen or sulfur and at least one of ""P,"" ""Q"" or ""T"" must be a heteroatom; wherein said Ph2 is a disubstituted group of the formula R3 is hydrogen or (C1-C6) alkyl; R4 is hydrogen or (C1-C6) alkyl; R5 is hydrogen (C1-C6)alkyl, halo, CF3, (C1-C6)alkoxy or (C1-C6)alkylthiol; R6 is hydrogen or halo; R7 is hydrogen or halo; R8 is hydrogen or halo; R9 is hydrogen, (C1-C6)alkyl optionally substituted with one to three halogen atoms, halo, CF3, [C1-C6)alkoxy optionally substituted with one to three halogen atoms, (C1-C6)alkylthiol, R13O-(CH2)p-, (C1-C6)alkyl-NH-(CH2)p-, di(C1-C6)alkyl-N-(CH2)n-, (C1-C5)cycloalkyl-NH-(CH2)p-, H2N-(C=O)-(CH2)p-, (C1-C6)alkyl-HN-(C=O)-(CH2)p-, di(C1-C6)alkyl-N-(C=O)-(CH2)p-, (C1-C5)cycloalkyl-NH-(C=O)-(CH2)p-R13O-(C=O)-(CH2)p-(C1-C6)alkyl-(O=C)-O-(C1-C6)-alkyl-, (C1-C6)alkyl-O-(O=C)-O-(C1-C6)-alkyl-, (C1-C6)alkyl(O=C)-O-, (C1-C6)alkyl-(O=C)-NH-(CH2)p-, H(O=C)-NH-(CH2)p-, hydroxy, H-C(=O)-(CH2)p-, (C1-C6)alkyl-C(=O)-, (C1-C6)alkyl-O-C(=O)-, R4-(CH2)p-O-C(=O)-, amino-(CH2)p-, hydroxy-(C1-C6)alkyl-, (C1-C6)alkyl-O-(C1-C6)alkyl-, and -CN; R10 and R14 are hydrogen, (C1-C6)alkyl optionally substituted with one to three halogen atoms, halo, CF3, (C1-C6)alkoxy optionally substituted with one to three halogen atoms, (C1-C6)alkyl-NH-(CH2)p-, (C1-C6)alkyl-NH-(CH2)p-, di(C1-C6)alkyl-N-(CH2)p-, (C1-C5)cycloalkyl-NH-(CH2)p-, H2N-(C=O)-(CH2)p-, (C1-C6)alkyl-HN-(C=O)-(CH2)p-, di(C1-C6)alkyl-N-(C=O)-(CH2)p-, (C1-C5)cycloalkyl-NH-(C=O)-(CH2)p-, R13O-(C=O)-(CH2)p-, (C1-C6)alkyl-(O=C)-O-(C1-C6)alkyl-, (C1-C6)alkyl-O-(O=C)-O-(C1-C6)-alkyl-, (C1-C6)alkyl-(O=C)-O-, (C1-C6)alkyl-(O=C)-NH-(CH2)p-, H(O=C)-NH-(CH2)p-, hydroxy, H-C(=O)-(CH2)p-, (C1-C6)alkyl-C(=O)-, (C1-C6)alkyl-O-C(=O)-, R4-(CH2)p-O-C(=O)-, amino-(CH2)p-, hydroxy-(C1-C6)alkyl, (C1-C6)alkyl-O-(C1-C6)alkyl. -CHO and -CN; R11 is hydrogen or halo; R12 is hydrogen or halo; R13 is hydrogen, (C1-C6)alkyl, (C1-C6)alkyl-(C=O)-, (C1-C6)alkyl-O-(C=O)-, (C1-C6)alkyl-O-(C=O)-, or di(C1-C6)alkyl-N-(C=O)-; R15 is hydrogen, -CN, (C1-C6) alkyl, halo, CF3, -CHO or (C1-C6)alkoxy; R16 is hydrogen, -CN, (C1-C6)alkyl, halo, CF3, -CHO or (C1-C6)alkoxy; R17 is hydrogen, -CN, (C1-C6)alkyl, halo, CF3, CHO or (C1-C6)alkoxy; n is an integer from zero to 3; p is an integer from zero to 3; wherein the dashed bond represented an optional double bond; with the proviso that when R9 is hydrogen, then one of R11 and R12 is other than hydrogen; and the pharmaceutically acceptable salts of such compounds.

Spectroscopic Evidence for a Spirooxirane Intermediate in the Synthesis of 4-(Hydroxymethyl)-2-thiazole

The synthesis of 4-(hydroxymethyl)thiazole derivatives from the corresponding 4-(chloromethyl)-4-hydroxythiazole derivatives have been speculated to proceed through spirooxirane intermediates.NMR spectroscopy was used to provide evidence for the existence of such an intermediate in the synthesis of 4-(hydroxymethyl)-2-thiazole.Experimental conditions for the optimum formation and stabilization of a suspect intermediate were determined and spectral data obtained to support the speculated structure.Comparison were made between couplings constants predicted in molecular models and the experimental data.

C-2 basically substituted thiazoles with H2-antagonistic activity/21st Comm.: H2-antihistamines

In studies on structure-activity relationships of histamine H2-receptor antagonists, C-2 basically substituted thiazoles were prepared and tested for their H2-antihistaminic activity on the isolated guinea-pig atrium and on the histamine stimulated acid secretion of the anaesthetized rat. As a basic substituent the dimethylaminomethyl group is especially suitable, while cyclic guanidines lead to lower H2-antagonistic activity.

THIADIAZOLE HISTAMINE H2-ANTAGONISTS

Histamine H 2-antagonists of the formula STR1 wherein p is 1 or 2; R 1 is hydroxy, amino, substituted amino or a 5-to 9-membered fully saturated nitrogen-containing heterocyclic ring attached via its nitrogen atom; m is an integer of from 0 to 2; n is an integer of from 2 to 4; Z is sulfur, oxygen or methylene; and A is an optionally substituted phenyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, thiadiazolyl, oxadiazolyl, furyl, thienyl or pyridyl ring; and nontoxic pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof are novel anti-ulcer agents. Intermediates and processes for their preparation are disclosed.

2-[2-(2-AMINOALKYL-4-THIAZOLYLMETHYLTHIO)ALKYL]-AMINO-5-SUBSTITUTED-4-PYRIMIDONES

2-2-(2-aminoalkyl-4-thiazolylmethylthio)-alkylene!amino-5-aromatic-substitute d alkylene-4-pyrimidones and related compounds, H. sub.2 receptor antagonists, useful in inhibiting gastric acid secretion in mammals.