6633-61-0|Methyl 2-aminothiazole-5-carboxylate| Ambeed

Structure of 6633-61-0

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 6633-61-0 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 6633-61-0 ]

CAS No. :	6633-61-0
Formula :	C₅H₆N₂O₂S
M.W :	158.18
SMILES Code :	C1=C(C(OC)=O)SC(=N1)N
MDL No. :	MFCD03788562
InChI Key :	UJNNCGWBDJHCEM-UHFFFAOYSA-N
Pubchem ID :	238005

Safety of [ 6633-61-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 6633-61-0 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	5
Fraction Csp3	0.2
Num. rotatable bonds	2
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	37.8
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	93.45 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.4
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.79
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.52
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	-0.54
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.23
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.68

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.56
Solubility	4.39 mg/ml ; 0.0278 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-2.33
Solubility	0.734 mg/ml ; 0.00464 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-1.0
Solubility	15.9 mg/ml ; 0.1 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.7 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.37

Application In Synthesis of [ 6633-61-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 6633-61-0 ]

[ 6633-61-0 ] Synthesis Path-Downstream 1~35

1
[ 6633-61-0 ]
[ 52499-04-4 ]

Yield	Reaction Conditions	Operation in experiment
49%	With ammonia; In water; at 50℃; for 72h;	Example 12 (E)-2-[2-(3-Chloro-4-methanesulfonyl-phenyl)-2-cyclohexyloxyimino-acetylamino]-thiazole-5-carboxylic acid amide 2-Amino-thiazole-5-carboxylic acid methyl ester (333 mg, 2.11 mmol) and a solution of concentrated ammonium hydroxide (4.2 mL) were combined and heated to 50 C. After stirring 72 h, the mixture was cooled, filtered and the filtrate was concentrated in vacuo to half the original volume. The precipitate was collected by filtration in vacuo and washed with water. Drying in vacuo afforded the desired product, 2-amino-thiazole-5-carboxylic acid amide (148 mg, 49%) as a tan solid that was used without further purification: LC-MS (ESI) m/e calcd for C4H5N3OS [M+] 103.02, found 286.9 [2M+H+]; H1-NMR (400 MHz, CD3OD) delta=7.59 (1H, s).

References: [1]Patent: US2008/146625,2008,A1 .Location in patent: Page/Page column 12.
[2]Journal of the American Chemical Society,1952,vol. 74,p. 5799.

2
[ 20656-61-5 ]
[ 17356-08-0 ]
[ 6633-61-0 ]

Yield	Reaction Conditions	Operation in experiment
44%		A mixture of 2. 4g of g-2, water 20ml and 1.75g of thiourea was refluxed for 2 hours. The mixture was cooled to room temperature and 0.25g of norit was added and filtered. A solution of 2. 5N sodium hydroxide was added to the filtrate until neutral pH. The filtration yielded 1.23g (44%) of 2-aminothiazole-5-carboxylic acid methyl ester (g-3).

References: [1]Journal of the Chemical Society. Perkin transactions II,1991,p. 349 - 352.
[2]Patent: WO2003/97616,2003,A1 .Location in patent: Page/Page column 26.
[3]Journal of the American Chemical Society,1952,vol. 74,p. 5799.
[4]Patent: US2405820,1944, .

3
[ 6633-61-0 ]
[ 18926-24-4 ]
[ 36324-81-9 ]

References: [1]Journal of medicinal chemistry,1972,vol. 15,p. 101 - 103.

4
[ 6633-61-0 ]
[ 4461-30-7 ]
[ 36324-80-8 ]

References: [1]Journal of medicinal chemistry,1972,vol. 15,p. 101 - 103.

5
[ 6633-61-0 ]
[ 40283-46-3 ]

References: [1]Journal of the Chemical Society. Perkin transactions II,1991,p. 349 - 352.

6
[ 6633-61-0 ]
[ 275-51-4 ]
methyl 2-(azulen-1-yldiazenyl)-1,3-thiazole-5-carboxylate [ No CAS ]

References: [1]Journal of Heterocyclic Chemistry,2003,vol. 40,p. 995 - 1004.

7
[ 6633-61-0 ]
[ 98-88-4 ]
2-benzoylaminothiazole-5-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With pyridine; dmap; In N,N-dimethyl-formamide; at 20℃; for 12h;	A. Benzoyl chloride (0.44 g, 0.37 mL) was added to a mixture of 2- aminothiazole-5-carboxylic acid methyl ester (0.50 g, 3.16 mmol), 4- dimethylaminopyridine (0.050 g, 0.41 mmol) and pyridine (2.5 mL, 31.60 mmol) in N, N- dimethylformamide (20 mL) at ambient temperature. The reaction mixture was stirred at ambient temperature for 12 h, and concentrated in vacuo. The residue was purified by column chromatography to yield 2-benzoylaminothiazole~5-carboxylic acid methyl ester in 78% yield (0.654 g); MS (ES+) m/z 263.2 (M + 1).

References: [1]Patent: WO2007/130075,2007,A1 .Location in patent: Page/Page column 74.

8
[ 6633-61-0 ]
[ 24424-99-5 ]
[ 745078-03-9 ]

Yield	Reaction Conditions	Operation in experiment
100%	With dmap; triethylamine; In tetrahydrofuran; at 20℃; for 16h;	2-Amino-thiazole-5-carboxylic acid methyl ester (4.0 g, 25.28 mmol) was suspended in THF (100 ml). Di-tert-butyl dicarbonate (6.63 g, 30.34 mmol) was added to the reaction vessel and the mixture was stirred vigorously. Next, Triethylamine (7.05 mL, 50.57 mmol) and 4-Dimethylaminopyridine (316 mg, 2.53 mmol) were added to the reaction. The reaction was stirred at room temperature for 16 hours. A brown precipitate was present upon completion of the reaction. The reaction mixture was concentrated down in vacuo and dried in a vacuum oven to afford the crude product, 2-tert-Butoxycarbonylamino-thiazole-5- carboxylic acid methyl ester (6.5 g, 100% yield), which was then taken on to subsequent reaction. LCMS [M+H] 258.9.
38%	With triethylamine;dmap; In tetrahydrofuran; at 0 - 20℃; for 20h;	A solution of di-tert-butyl dicarbonate (1.66 g; 7.59 mmol) in THF (10 mL) was added to a 0 C. solution of <strong>[6633-61-0]methyl 2-aminothiazole-5-carboxylate</strong> (1.20 g; 7.59 mmol) in THF (20 mL). TEA (1.11 mL; 7.97 mmol) was added followed by a catalytic amount of 4-DMAP (10 mg). The reaction mixture was then stirred at RT for 20 h, then was concentrated in vacuo. The residue was partitioned between EtOAc (80 mL) and 0.2 N aqueous HCl (40 mL). The organic phase was washed with brine (40 mL), dried (MgSO4) and concentrated in vacuo to give Part A compound (1.70 g; yield given below in Part B). The crude product was taken forward without further purification.
		Intermediate 4[00176] A solution of di-tert-butyl dicarbonate (1.66 g; 7.59 mmol) in THF (10 mL) was added to a 0C solution of <strong>[6633-61-0]methyl 2-aminothiazole-5-carboxylate</strong> (1.20 g; 7.59 mmol) in THF (20 mL). TEA (1.1 1 mL; 7.97 mmol) was added followed by a catalytic amount of 4-DMAP (10 mg). The reaction mixture was then stirred at RT for 20 h, then was concentrated in vacuo. The residue was partitioned between EtOAc (80 mL) and 0.2 N aqueous HC1 (40 mL). The organic phase was washed with brine (40 mL), dried (MgS04) and concentrated in vacuo to give Part A compound (1.70 g; yield given below in Part B). The crude product was taken forward without further purification.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 8.
[2]Patent: US2008/9465,2008,A1 .Location in patent: Page/Page column 42.
[3]Patent: WO2011/130459,2011,A1 .Location in patent: Page/Page column 64.

9
[ 916520-71-3 ]
[ 6633-61-0 ]
C₁₈H₁₆N₄O₄S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 4664 - 4669.

10
[ 6633-61-0 ]
[ 72605-86-8 ]

Yield	Reaction Conditions	Operation in experiment
	With n-Amyl nitrite; copper dichloride; In acetonitrile; at 50℃; for 2h;	To a preheated (50 C.) slurry of copper (II) chloride (932 mg), 10 mL of acetonitrile was added, along with the thiazole aminoester (1 g) and amyl nitrite (737 mg). The mixture was heated at 50 C. for 2 h. The resulting mixture was concentrated and purified by Biotage (5-10% ethyl acetate in hexane) to give the chloride as a brown solid.
	With sodium nitrite; In hydrogenchloride; water; Petroleum ether;	EXAMPLE I Preparation of Methyl 2-chlorothiazole-5-carboxylate To 5.0 g of <strong>[6633-61-0]methyl 2-aminothiazole-5-carboxylate</strong> [H. E. Faith, U.S. Pat. No. 2,405,820(1946)] suspended in 54 ml of 6 N hydrochloric acid stirred at-5-0 was added dropwise over 15 minutes 3.7 g of sodium nitrite dissolved in 10 ml of water. After stirring 5 minutes, the brown suspension was added in one portion to a rapidly stirred suspension of 10.6 g of cupric sulfate and 10.6 g of sodium chloride cooled at 5. The cooling bath was removed and stirring was continued for 30 minutes. The pH was adjusted to 7.3 with 6 N sodium hydroxide and the green suspension was filtered through Celite. The solid was washed with three portions of ethyl acetate and the extract was combined with the ethyl acetate extract of the original filtrate. After drying the combined extract over magnesium sulfate, concentration in vacuo gave a brown solid. Trituration with four portions of hot petroleum ether (35-60) served to separate the soluble product from some starting material. Concentration in vacuo of the petroleum ether solution gave 3.9 g. of pure methyl 2-chlorothiazole-5-carboxylate having a melting point of 41-46.

References: [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6303 - 6306.
[2]Patent: US2006/293364,2006,A1 .Location in patent: Page/Page column 26; 46.
[3]Patent: US4168380,1979,A .

11
[ 6633-61-0 ]
[ 36324-91-1 ]

References: [1]Journal of medicinal chemistry,1972,vol. 15,p. 101 - 103.

12
[ 6633-61-0 ]
[ 14527-44-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With isopentyl nitrite; In tetrahydrofuran; at 120℃; for 0.333333h;	General procedure: A solution of the selected heterocyclic starting material (1.00 mmol) in THF (10 mL) and a solutionof isopentyl nitrite (141 mg, 1.20 mmol) in THF (10 mL) were both pumped at a flow rate of 0.25 mLmin1 with a Vapourtech ?Easy MedChem V3? system, meeting at a PTFE T-piece and the outputflowing through a 10.0 mL coil reactor maintained at 120 C, giving a residence time of 20 min.The pressure of the system was maintained at 7 bar with a back-pressure regulator. For compoundswhere an isolated yield was reported: the output mixture was concentrated under reduced pressureto give an oil (or powder). The oil (or powder) was purified using column chromatography withvarious mixtures of ethyl acetate and hexane as the eluent, or by recrystallisation using methanol, togive isolated compounds that showed no impurities by NMR spectroscopy. For compounds where aconversion was reported (due to volatility of products), the output mixture was carefully concentratedunder a reduced pressure of 100 mbar for 10 min and the conversion was calculated by integration ofproduct peaks to a quantified internal standard (nitrobenzene).
48%	With isopentyl nitrite; In 1,4-dioxane; at 80℃; for 2h;Heating / reflux;	The mixture of 2. 15g of isoamyl nitrite and 10ml of dioxane was stirred at 80C under a nitrogen atmosphere. A solution of 1.23g of g-3 in 20ml of dioxane was added drop wise. The mixture was refluxed for 2 hours. After cooling to room temperature 30ml of ethyl acetate was added. The mixture was washed with brine and dried and the solvent evaporated under reduced pressure. The crude product is purified on silica, yielding 0.54g (48%) of thiazol 5-carboxylic acid methyl ester (g-4).

References: [1]Molecules,2019,vol. 24.
[2]Patent: WO2003/97616,2003,A1 .Location in patent: Page/Page column 26.

13
[ 1780-26-3 ]
[ 6633-61-0 ]
methyl 2-(6-chloro-2-methylpyrimidin-4-yl-amino)thiazol-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h;	To a suspension of <strong>[6633-61-0]methyl 2-aminothiazole-5-carboxylate</strong> (4.90 g, 31.0 mmol) and NaH (60% dispersion in mineral oil, 1.36 g, 34.1 mmol) in DMF at O0C is added 4,6-dichloro-2-methyl-pyrimidine (5.05 g, 31.0 mmol) in DMF and the mixture is stirred for 2 hours at room temperature. The reaction mixture is diluted with EtOAc and washed with 10% aqueous sodium thiosulfate solution. The organic layer is dried over MgSO4, and concentrated in reduced pressure. The crude product is crystallized from MeOH to give methyl 2-(6-chloro-2-methyl-pyrimidin-4-ylamino)-thiazole-5-carboxylate as a white solid. [0065] To a stirred solution of methyl 2-(6-chloro-2-methyl-pyrimidin-4- ylamino)-thiazole-5-carboxylate (3.97 g, 14.0 mmol) in MeOH is added 4 N NaOH (15 mL) and the mixture is stirred for 12 hours at 6O0C. The reaction mixture is neutralized with 1 N HCl and the resulting precipitate is filtered and washed with MeOH to give 2-(6-chloro-2- methyl-pyrimidin-4-ylamino)-thiazole-5-carboxylic acid in a white solid. [0066] To a solution of 2-(6-chloro-2-methyl-pyrimidin-4-ylamino)-thiazole-5- carboxylic acid (230 mg, 0.85 mmol), N-(3-Amino-4-methyl-phenyl)-3- trifluoromethylbenzamide (250 mg, 0.85 mmol), and diisopropylethylamine (0.59 mL, 3.4 mmol) in DMF is added O-(7-azabenzotriazol-l-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (355 mg, 0.93 mmol), and the mixture is stirred for 12 hours at room temperature. The reaction mixture is diluted with EtOAc and washed with 10% aqueous sodium thiosulfate solution. The organic layer is dried over MgSO4 and concentrated in reduced pressure. The crude product is purified by preparative HPLC to give 2-(6-chloro-2- methyl-pyrimidin-4-ylamino)-thiazole-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl- benzoylamino)-phenyl] -amide as a white solid.[0067] To a stirred solution of 2-(6-chloro-2-methyl-pyrimidin-4-ylamino)- thiazole-5-carboxylic acid [2-methyl-5-(3-trifluoromethyl-benzoylamino)-phenyl]-amide (25 EPO <DP n="27"/>mg, 46 mumol) in l,3-dimethyl-2-imidazolidinone (0.2 mL) is added excess 2-piperazin-l-yl- ethanol (100 mg) in l,3-dimethyl-2-imidazolidinone (0.2 mL) and the mixture is stirred for 4 hours at 60 C . The crude product is diluted with DMSO (1 mL) and purified by preparative HPLC to give 2-{6-[4-(2-Hydroxyethyl)-piperazin-l-yl]-2-methylpyrimidin-4-ylamino}- thiazole-5-carboxylic acid [2-methyl-5-(3-trifluoromethylbenzoylamino)-phenyl]-amide in a TFA salt form: 1H NMR 400 MHz (MeOH-d_0 delta 8.26 (s, IH), 8.20 (d, IH), 8.15 (s, IH), 7.90 (d, IH), 7.83 (s, IH), 7.74 (t, IH), 7.55 (d, IH), 7.31 (d, IH), 6.20 (br, IH), 3.93 (dd, 2H), 3.50 (br, 8H), 3.35 (dd, 2H), 2.53 (s, 3H), 2.31 (s, 3H); MS m/z 641.5(M + 1).
62.89 g	With sodium hydride; In tetrahydrofuran; N,N-dimethyl acetamide; at -5℃; for 3h;	In a reaction flask, 49.49 g 4,6-dichloro-2-methylpyrimidine (0.303 mol), 40.00 g methyl 2-aminothiazol-5-carboxylic acid (0.253 mol), and 200 ml N,N-dimethylacetamide were charged, the temperature was brought to -5 C. and 18.20 g sodium hydride (0.455 mol) in 90 ml tetrahydrofuran were added dropwise and the reaction mixture was kept under these conditions for about three hours. At the end of the reaction, 250 ml of a solution of hydrochloric acid 2N were added, the temperature was brought to the room value, the formed solid was filtered and washed with water (4×200 ml) and dried in oven under vacuum at a temperature of 55 C. for about eight hours, to give 62.89 g methyl 2-(6-chloro-2-methylpyrimidin-4-yl-amino)thiazol-5-carboxylic acid.1H-NMR (DMSO, 300 MHz): delta 8.13 (1H, s), 6.97 (1H, s), 3.82 (3H, s), 2.59 (3H, s)

References: [1]Patent: WO2006/81172,2006,A2 .Location in patent: Page/Page column 24-26.
[2]Patent: US9115124,2015,B1 .Location in patent: Page/Page column 16.

14
[ 107-31-3 ]
[ 96-34-4 ]
[ 6633-61-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium methylate; In water; thiourea; toluene;	Part A Preparation of Methyl 2-aminothiazole-5-carboxylate Methyl chloroacetate 190 g (1.75 mol) and methyl formate 111 g (1.80 mol), were added dropwise to a suspension of 100 g (1.8 moL) of sodium methoxide in 450 mL of dry toluene at 5 C. over 2 hours. After an additional 2.5 hours at 0 C. The contents were diluted with 600 mL of water and the layers separated. The aqueous phase was acidified with 113 mL of concentrated hydrochloric acid. The aqueous solution was placed in a 2 liter flask and 175 grams of thiourea was added and to solution was heated to reflux for 1.45 hours. To the cooled solution was added 25 g of DARCO activated charcoal and filtered through filter paper. The crude dark yellow solution was neutralized with 2.5 N sodium hydroxide upon which time an amber solid precipitated which was filtered and air dried to yield 147 g of desired methyl 2-aminothiazole-5-carboxylate. m/e=159(M+H).

References: [1]Patent: US6046190,2000,A .

15
[ 6633-61-0 ]
[ 110-46-3 ]
[ 14527-44-7 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane; hexane; ethyl acetate;	Part B Preparation of Methyl 5-thiazolecarboxylate To a solution of 35 mL (30.5 g, 260 mmol) of isoamyl nitrite in 120 mL of dioxane at 80 C. under nitrogen, was slowly added a slurry of 20.0 g (126 mmol) of <strong>[6633-61-0]methyl 2-amino-5-thiazolecarboxylate</strong> over a 45 minute period. After refluxing for a further 1 hour, the solution was cooled, concentrated, dissolved in ethyl acetate, washed with saturated sodium bicarbonate, brine, dried over magnesium sulfate, filtered and concentrated to afford 28 g of the crude product. This was chromatographed on 400 g of silica gel using 20% ethyl acetate/hexane to afford 9.07 g of purified material, which was crystallized from methylene chloride/hexane to yield 7.64 g of pure methyl 5-thiazolylcarboxylate, m/e=144(M+H).

References: [1]Patent: US6046190,2000,A .

16
[ 609-14-3 ]
[ 6633-61-0 ]
P₂ O₅ [ No CAS ]
[ 86119-84-8 ]
[ 93465-51-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In PPA;	EXAMPLE 1 2-amino-thiazole-5-carboxylic acid, methyl ester (5 g) was reacted with ethyl 2-methyl-acetoacetate (9.11 g) in polyphosphoric acid (25 g:13.3 g of H3 PO4 and 11.7 g of P2 O5) under stirring at 100 C. for three hours. After cooling, dilution with ice water and neutralization with 20% NaOH, the precipitate was filtered, washed with water and crystallized from CH2 Cl2 -hexane to give 6,7-dimethyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxylic acid, methyl ester, m.p. 158-159 C. (5.46 g), which was reacted with benzaldehyde (3.52 g) in methanol (120 ml) in the presence of sodium methylate (2.7 g) under stirring at reflux temperature for 120 hours.

References: [1]Patent: US4558046,1985,A .

17
[ 6633-61-0 ]
[ 463-04-7 ]
[ 14527-44-7 ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-dioxane;	(A) Preparation of methyl thiazole-5-carboxylate Methyl 2-aminothiazole-5-carboxylate (79 g, 0.5 mol) was added over a period of 2 hours to a boiling solution of amyl nitrite (117.0 g, 1.0 mol) in dioxan (1 liter). After refluxing for a further half hour, the solvent was removed under reduced pressure and the residue was steam distilled to give a yellow oil which, on trituration with petroleum ether, gave the desired product as a white solid (32.0 g), m.pt. 68 C.

References: [1]Patent: US4877802,1989,A .

18
[ 6633-61-0 ]
[ 881384-29-8 ]
[ 881384-32-3 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; sodium iodide; In 1,2-dimethoxyethane; for 24h;Heating / reflux;	EXAMPLE 7 SYNTHESIS OF 2-[4-(2-TRIFLUOROMETHYLBENZOYL)PIPERAZIN-1-YL]-THIAZOLE-5-CARBOXYLIC ACID PENTYLAMIDE A reaction mixture of 2-aminothiazole-2-carboxylic acid methyl ester (0.790 g, 5.0 mmol), N,N-bis(2-chloroethyl)-2-trifluoromethylbenzamide (1.880 g, 6 mmol), K2CO3 (1.0 g, 7.2 mmol), and NaI (0.2 g) in 1,2-dimethoxyethane (20 mL) was heated to reflux for 24 hours. The solvent was removed by evaporation, and the residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous Na2SO4 and concentrated. The residue was purified by column chromatography to give 2-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]thiazole-5-carboxylic acid methyl ester (0.317 g) which was used for next step without further purification.

References: [1]Patent: US2008/108629,2008,A1 .Location in patent: Page/Page column 22-23.

19
[ 6633-61-0 ]
[ 403-29-2 ]
[ 1082605-11-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5263 - 5267.

20
[ 6633-61-0 ]
[ 1111881-85-6 ]
[ 1151240-82-2 ]

Yield	Reaction Conditions	Operation in experiment
44%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 40℃; for 72h;	Intermediate 12: Methyl 2-[({1 -[(3,4-dichlorophenyl)methyl]-1 H-1 ,2,3-triazol-4- yl}carbonyl)amino]-1 ,3-thiazole-5-carboxylateA mixture of 1-[(3,4-dichlorophenyl)methyl]-1 H-1 ,2,3-triazole-4-carboxylic acid (Intermediate 11 ) (1 g, 3.6 mmol), methyl 2-amino-1 ,3-thiazole-5-carboxylate (0.58 g, 3.6 mmol), HATU (1.82 g, 1.3 eq) and DIPEA (0.9 mL, 1.3 eq) in DMF (50 ml.) was stirred at400C for 3 days. The solvent was evaporated and the residue was washed with water and extracted with DCM. A precipitate was formed, filtered and triturated with a mixture of methanol/acetonitrile. After filtration, the yellow solid was dried to give the title compound as a pale yellow solid (644 mg, 44%). LC/MS: m/z 412 (M+H)+. Rt: 3.21 min.

References: [1]Patent: WO2009/60054,2009,A1 .Location in patent: Page/Page column 38.

21
[ 6633-61-0 ]
[ 1196875-69-0 ]
[ 1196873-67-2 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 6: Methyl 2-(3-cyclopentyl-2-(4-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)propanamido)thiazole-5-carboxylate; Compound 6A (1.663 g, 5.1 mmol), which was generated according to the procedure described in connection with Compound 1, was dissolved in dioxane (15 ml). 2 M LiOH (5.1 ml, 10.2 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated, poured to water, acidified with 20% HCl, extracted with ethyl acetate, dried over Na2SO4, concentrated by vacuum to crude compound 6B (1.494 g). [M+H] calc'd for C14H20N2O4S 313.38; found 313.Compound 6B (200 mg, 0.64 mmol) was dissolved in NMP (5 ml). Methyl 2-aminothioazole-5-carboxylate (184 mg, 1.282 mmol) was added, followed by 2-chloro-1-methylpyridinium iodide (360 mg, 1.41 mmol), diisopropylethylamine (0.25 ml, 1.41 mmol). The reaction mixture was heated at 90 C. in sealed vial overnight. After cooling to room temperature, the reaction solution poured to water, extracted with ethyl acetate, concentrated. Residue was purified with HPLC to yield compound 6 (85 mg). [M+H] calc'd for C19H24N4O5S2 453.55; found 453. 1H NMR (400 MHz, MeOD). delta ppm 1.23 (m, 6H) 1.60 (m, 6H) 1.82 (m, 1H) 2.20 (m, 1H) 2.34 (m, 1H) 2.75 (m, 1H), 3.86 (s, 3H) 5.34 (m, 1H) 7.90 (s, 1H) 8.10 (s, 1H) 8.47 (s, 1H)

References: [1]Patent: US2009/286800,2009,A1 .Location in patent: Page/Page column 101.

22
[ 6633-61-0 ]
[ 536-38-9 ]
[ 1228304-55-9 ]

Yield	Reaction Conditions	Operation in experiment
	In acetone; for 72h;Reflux;	EXAMPLE 104; Methyl 6-(4-chlorophenyl)-5-(hydroxymethyl)imidazo[2,l-b][l,3]thiazole-2- carboxylate; A solution of methyl-2-aminothiazole-5-carboxylate (1.0 g, 7.8 mmol) and 2-bromo-4'- chloroacetophenone (1.8 g, 7.8 mmol) in acetone (200 mL) was heated at reflux for 72 h. The remaining intermediate was filtered off and the filtrate was collected. The solvent was removed under reduced pressure to afford the intermediate compound methyl 6-(4- chlorophenyl)imidazo[2,l-b][l,3]thiazole-2-carboxylate as a yellow solid (1.5 g).

References: [1]Patent: WO2010/64020,2010,A1 .Location in patent: Page/Page column 85.

23
[ 34846-90-7 ]
[ 17356-08-0 ]
[ 6633-61-0 ]

Yield	Reaction Conditions	Operation in experiment
		Example 5.1 methyl 2-tert-butoxycarbonylaminothiazole-5-carboxylate 17.42 g of methyl 3-methoxyacrylate are dissolved in 200 ml of a 1/1 1,4-dioxane/water mixture and the solution is cooled to 0° C. before 29.37 g of N-bromosuccinimide are added. After 1 h at 0° C. 11.42 g of thiourea are added and then the mixture is heated at 80° C. for 2 hours. The reaction mixture is subsequently evaporated and the residue is taken up in ethyl acetate and then washed twice with 10percent aqueous sodium hydroxide solution and then with saturated sodium chloride solution. The organic phase is dried over anhydrous magnesium sulphate and then concentrated. This gives 19.17 g of a beige solid. LC/MS: MH+=159

References: [1]Patent: US2006/293366,2006,A1 .Location in patent: Page/Page column 13-14.
[2]Journal of Medicinal Chemistry,2011,vol. 54,p. 4119 - 4132.

24
[ 6633-61-0 ]
[ 108-24-7 ]
[ 1174534-36-1 ]

Yield	Reaction Conditions	Operation in experiment
90%	With triethylamine; In tetrahydrofuran;	Preparation 6[0046] Methyl 2-acetamidothiazole-5-carboxylateMethyl 2-aminothiazole-5-carboxylate, 1.58 g, 10 mmol, was added to a 50 mL, 3-necked round-bottomed flask fitted with a mechanical agitator. Tetrahydrofuran, 15 mL, was added followed by triethylamine, 2.1 mL, 1.5 eq. Acetic anhydride, 1.3 mL, 1.4 eq., was added. After stirring overnight, 20 mL of water and 5 mL of methanol was added and the mixture was stirred at ambient temperature for two hours. The product was isolated by filtration, was rinsed with aqueous methanol and then water. Drying in the air provided 1.81 g, 90%, of an off-white solid, LC/MS: 201.1; NMR: 12.6 (s, 1H), 8.15 (s, 1H), 3.81 (s, 3H), 2.19 (s, 3H); HPLC: RT 5.83 min, 99.5%.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 10-11.

25
[ 6633-61-0 ]
[ 98-59-9 ]
[ 777897-18-4 ]

Yield	Reaction Conditions	Operation in experiment
42%	With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20℃; for 120h;	Preparation 80048] Methyl 2-(4-methylphenylsulfonamido)thiazole-5-carboxylateMethyl 2-aminothiazole-5-carboxylate, 1.00 g, 6.3 mmol, was added to a 50 mL, 3-necked round-bottomed flask fitted with a mechanical agitator. Tetrahydrofuran, 10 mL, was added followed by 4-methylbenzenesulfonyl chloride, 1.81 g, 1.5 eq., then diisopropyl ethylamine, 2.0 mL, 1.8 eq. 4-Dimethylaminopyridine, 0.08 g, 0.1 eq., was added and the mixture was stirred at ambient temperature for five days. After evaporation of most of the solvent at ambient temperature, 20 mL of methanol was added followed by 15 mL of water, and the mixture was stirred at ambient temperature for one hour. The product was isolated by filtration and was rinsed with water. Drying under high vacuum at ambient temperature provided 0.82 g, 42%, of an off-white solid, LC/MS: 313.0, NMR: 8.16 (s, 1H), 7.72 (d, 2H), 7.37 (d, 2H), 3.79 (s, 3H), 2.36 (s, 3H); HPLC: RT 8.38 min, 99.0%.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 11.

26
[ 6633-61-0 ]
[ 501-53-1 ]
[ 778600-83-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran;	Preparation 20042] Methyl 2-(benzyloxycarbonylamino)thiazole-5-carboxylateMethyl 2-aminothiazole-5-carboxylate, 1.00 g, 6.3 mmol, was added to a 50 mL, 3-necked round-bottomed flask fitted with a mechanical agitator. Tetrahydrofuran, 15 mL, was added followed by diisopropyl ethylamine, 1.7 mL, 1.5 eq. Benzyl chloroformate, 1.1 mL, 1.25 eq., was added which caused the temperature to rise to about 45 C. After stirring overnight, 10 mL of water and 5 mL of methanol was added and the mixture was stirred at ambient temperature for two hours. The product was isolated by filtration, was rinsed with aqueous methanol and then water. Drying in the air provided 1.79 g, 97%, of an off-white solid, LC/MS: 293.2, NMR: 12.2 (s, 1H), 8.08 (s, 1H), 7.45-7.35 (m, 5H), 5.27 (s, 2H), 3.80 (s, 3H); HPLC: RT 9.83 min, 100%.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 9.

27
[ 67-56-1 ]
[ 6633-61-0 ]
[ 88-95-9 ]
[ 1334496-16-0 ]

Yield	Reaction Conditions	Operation in experiment
		Preparation 10-(2-(methoxycarbonyl)benzamido)thiazole-5-carboxylateMethyl 2-aminothiazole-5-carboxylate, 1.00 g, 6.3 mmol, was added to a 50 mL, 3-necked round-bottomed flask fitted with a mechanical agitator. Tetrahydrofuran, 15 mL, was added followed by diisopropyl ethylamine, 2.8 mL, 2.5 eq. o-Phthaloyl dichloride, 1.1 mL, 1.2 eq., was added which caused the temperature to rise to about 55 C. After stirring at ambient temperature for an hour, 5 mL of methanol and 10 mL of water was added and the mixture was stirred at ambient temperature for an hour. The product was isolated by filtration, was rinsed with aqueous methanol and then water. A second crop was collected from the mother liquor; it was filtered off and rinsed with water. The combined solids were dried under high vacuum to provide 1.36 g of an off- white solid. LC/MS showed two peaks, m/z = 321.2 and 162.9 for the first and 293.2 for the second. NMR: 13.1 (s, 1H), 8.22 (s, 1H), 7.94 (m, 1H), 7.70 (m, 3H), 3.84 (s, 3H), 3.76 (s, 3H); HPLC: RT 8.42 min, 99%.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 12.

28
[ 6633-61-0 ]
[ 2524-64-3 ]
[ 1334496-13-7 ]

Yield	Reaction Conditions	Operation in experiment
65%	In 4-methyl-morpholine; at 20℃;Cooling with ice;	Preparation 4[0044] Methyl 2-(diphenoxyphosphorylamino)thiazole-5-carboxylate Methyl 2-aminothiazole-5-carboxylate, 1.0 g, 6.20 mmol, was dissolved in 4- methylmorpholine, 20 mL, and cooled in an ice bath for 15 minutes. Diphenylchlorophosphate, 4 mL, 18.6 mmol, was added dropwise. The ice bath was removed and the reaction was allowed to stir at room temperature overnight. The reaction mixture was concentrated in vacuo and the residue was dissolved in methylene chloride, 50 mL. The solution was washed with saturated aqueous aHC03, 1M HC1, and brine, respectively. During the brine wash, a precipitate began to form in the organic layer. The organic layer was separated and its volume was reduced in half. The solid was filtered off and dried in vacuo to afford the white product, 1.6 g, 65%, LC/MS 391.1; NMR 13.0 (broad s, 1H), 8.01 (s, 1H), 7.38 (m, 4H), 7.21 (m, 6H), 3.77 (s, 3H); HPLC: RT 9.64 min, 98.7%.

References: [1]Patent: WO2011/115758,2011,A1 .Location in patent: Page/Page column 9-10.

29
[ 6633-61-0 ]
[ 1416811-33-0 ]