Ethyl 2-bromothiazole-4-carboxylate

Cat.NO.:A241927 Purity:97%

Product Details of [ 100367-77-9 ]

CAS No. :	100367-77-9
Formula :	C₆H₆BrNO₂S
M.W :	236.09
SMILES Code :	C1=C(C(OCC)=O)N=C(S1)Br
MDL No. :	MFCD03788564
InChI Key :	CNHISCQPKKGDPO-UHFFFAOYSA-N
Pubchem ID :	353965

Safety of [ 100367-77-9 ]

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

Computational Chemistry of [ 100367-77-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	5
Fraction Csp3	0.33
Num. rotatable bonds	3
Num. H-bond acceptors	3.0
Num. H-bond donors	0.0
Molar Refractivity	45.9
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	67.43 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.22
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	2.53
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.08
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.	0.81
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	2.9
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.11

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.04
Solubility	0.217 mg/ml ; 0.00092 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.59
Solubility	0.0603 mg/ml ; 0.000255 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	-2.63
Solubility	0.547 mg/ml ; 0.00232 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	Yes
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	Yes
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.	-5.94 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	0.0
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)	2.86

Application In Synthesis of [ 100367-77-9 ]

* 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.

Upstream synthesis route of [ 100367-77-9 ]
Downstream synthetic route of [ 100367-77-9 ]

[ 100367-77-9 ] Synthesis Path-Upstream 1~1

1
[ 100367-77-9 ]
[ 5198-86-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium tetrahydroborate; water; lithium chloride In tetrahydrofuran for 2 h;	Preparation of (2-bromothiazol-4-yl)methanol (5) To a solution of ester 4 (10.0 g, 42.4 mmol, 1 equiv) in THF (200 mL) was added NaBH4 (4.81 g, 127 mmol, 3 equiv), LiCl (5.4 g, 130 mmol, 3 equiv) and H₂O (40 mL). The resulting biphasic mixture was vigorously stirred for 2 h, after which TLC (20percent EtOAc:hexanes) showed complete consumption of starting material. The reaction was quenched with saturated aqueous NH₄Cl (200 mL), diluted with EtOAc (200 mL), and the layers were separated. The aqueous layer was extracted with EtOAc (100 mL), and the organic layers were combined, dried (Na₂SO₄), filtered, and concentrated under reduced pressure to give the title compound as a yellow semi-solid (7.82 g, 95percent). R_f= 0.2 (SiO₂, 20percent EtOAcrhexanes); ¹H and ¹³C NMR of the product matched those previously reported (Wipf and Wang 2007).
91%	at 20 – 70℃; for 8 h;	2-Bromothiazol-4-Carboxylic acid ethyl ester (11.8g, 50.0mmol)Was dissolved in absolute ethanol (100 mL)Sodium borohydride (3.8 g, 100 mmol) was added, stirred at room temperature for 4 hours, and then heated to 70 ° C for 4 hours.The solvent was evaporated under reduced pressure and the crude product was purified by column chromatography (ethyl acetate / petroleum ether (v / v) = 1/5) to give a pale yellow oil (8.85 g, 91percent).
87%	With sodium tetrahydroborate In ethanol at 0 – 70℃; for 7.5 h;	At 0 , 2-bromo-thiazole-4-carboxylate (13.30g, 56.33mmol)In ethanol (150 mL) was added portionwiseSodium borohydride (4.263 g, 112.7 mmol),Stirring was continued at 0 0.5 hours.The mixture was stirred at room temperature for 3 hours,And heated to 70 ° C for 4 hours.The solvent was distilled off under reduced pressure,Slowly add water (100 mL)Extracted with ethyl acetate (100 mL x 3).Combine organic phase,Washed with saturated brine (50 mL)Dried over anhydrous sodium sulfate.Filtration, evaporation of the solvent under reduced pressure,The crude product was purified by column chromatography (petroleum ether / ethyl acetate (v / v) = 5/1)To give a colorless oil (9.5 g, 87percent).

87%	With sodium tetrahydroborate In ethanol at 0 – 20℃; for 3 h;	Into a 500-mL round-bottom flask, was placed ethyl 2-bromothiazole-4-carboxylate (14 g, 59.30 mmol) and EtOH (200 mL). This was followed by the addition of NaBH₄ (2.3 g, 60.53 mmol) in portions at 0^oC. The resulting solution was stirred for 3 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 2×200 mL of DCM and the organic layers combined and dried over anhydrous Na₂SO₄, then concentrated under vacuum. This resulted in 10 g (87percent) of the title compound as colorless oil. MS-ESI: 195.9, 193.9 (M+1).
87%	at 0 – 20℃; for 3 h;	Into a 500-mL round-bottom flask was placed a solution of ethyl 2-bromothiazole-4-carboxylate(14 g, 59.3 mmol), EtOH (200 mL). This was followed by the addition of NaBH₄(2.3 g, 60.5 mmol) in portions at 0°C. The resulting solution was stirred for 3 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 2×200 mL of DCM.The organic layers were combined, dried over anhydrous Na₂S04 and then concentrated under vacuum. This resulted in 10.0 g (87percent) of the title compound as colorless oil. MS-ESI: 195.9, 193.9(M+l).
81%	at 20℃; for 3 h; Cooling	Into a 100-mL round-bottom flask was placed a solution of ethyl 2-bromo-1,3-thiazole-4- carboxylate (3 g, 12.71 mmol) in EtOH (30 mL). NaBH4 (1.0 g, 25.41 mmol) was added in portions with an ice/water bath. The resulting solution was stirred for 3 hr at room temperature. The reaction was then quenched by the addition of 100 mL of water in an ice/water bath. The resulting solution was extracted with 3×100 ml of ethyl acetate, and the combined organic layers were concentrated. This resulted in 2 g (81percent) of the title compound as yellow oil. MS-ESI: 196.2, 194.2 (M+1).
68%	With sodium tetrahydroborate; lithium chloride In tetrahydrofuran; water at 0 – 20℃; for 16 h;	NaBH₄ (2.49 g, 0.066 mol, 3 equiv), LiCl (2.79 g, 0.066 mol, 3 equiv) and H₂0 (30 mL) were added to a stirred solution ethyl 2-bromothiazole-4-carboxylate (1) (5.0 g, 0.022 mol, 1 equiv) in THF (50 mL) at 0 °C. The reaction mixture was allowed to warm to ambient temperature and stirred for 16 h. The reaction mixture was quenched with 1.5 M hydrochloric acid and the resulting mixture was extracted with ethyl acetate (2X150 mL). The combined organic layers were washed with water (150 mL), brine (150 mL), dried over Na₂S0₄, filtered through celite bed and concentrated to provide compound 2 as a pale brown liquid (3.0 g, 68percent). LC-MS (ESI⁺): m/z 195.9 (M+H)⁺ 1H-NMR (300 MHz, DMSO-d6): δ 7.48 (s, 1H), 5.43 (t, J = 5.7 Hz, 1H), 4.52 (d, J = 5.7 Hz, 2H).
67%	Stage #1: With lithium borohydride In tetrahydrofuran for 1 h; Cooling with an ice bath Stage #2: With methanol In tetrahydrofuran for 3.5 h;	Step 3 : (2-bromothiazol-4-yl)methanolA solution of ethyl 2-bromothiazole-4-carboxylate (7.821 g, 33.13 mmol) in THF (100 mL) was cooled in an ice-bath and treated portionwise with lithium borohydride (1.083 g, 49.70 mmol). After 1 hour MeOH (1.614 g, 2.040 mL, 50.36 mmol) was added over a period of half an hour. The reaction was allowed to stir for 3 hours and then the solvent was concentrated in vacuo and the resultant residue was dissolved in EtOAc, washed with HCl (2x), saturated sodium bicarbonate, followed by brine, dried (Na₂SO₄), concentrated and purified by column chromatography (EtOAc/Petroleum ether 1: 1) to give the required product as a colorless oil (4.3Og, 67percent Yield). ¹H NMR (CDCl₃, 400 MHz) δ 2.51 (IH, m), 4.75 (2H, m), 7.19 (IH, s); MS (ES⁺) 195.96

References:

[1] Patent: WO2015/57585, 2015, A1, . Location in patent: Page/Page column 27; 28.

[2] Patent: CN104478866, 2017, B, . Location in patent: Paragraph 0281; 0283; 0284.

[3] Patent: CN104478869, 2017, B, . Location in patent: Paragraph 0142; 0143; 0144; 0145.

[4] Patent: WO2017/184624, 2017, A1, . Location in patent: Page/Page column 185; 186.

[5] Patent: WO2019/23147, 2019, A1, . Location in patent: Page/Page column 445.

[6] Journal of Organic Chemistry, 2016, vol. 81, # 21, p. 10302 – 10320.

[7] Patent: WO2019/23145, 2019, A1, . Location in patent: Page/Page column 393.

[8] Russian Journal of General Chemistry, 2017, vol. 87, # 12, p. 2766 – 2775[9] Zh. Obshch. Khim., 2017, vol. 87, # 12, p. 1947 – 1956,10.

[10] Organic Letters, 2007, vol. 9, # 8, p. 1605 – 1607.

[11] Patent: WO2018/200674, 2018, A1, . Location in patent: Page/Page column 72.

[12] Patent: WO2010/129668, 2010, A1, . Location in patent: Page/Page column 48.

[13] Journal of Medicinal Chemistry, 2008, vol. 51, # 6, p. 1530 – 1533.

[14] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 22, p. 5172 – 5177.

[15] Organic Process Research and Development, 2017, vol. 21, # 10, p. 1602 – 1609.

[ 100367-77-9 ] Synthesis Path-Downstream 1~6

1
[ 100367-77-9 ]
[ 3973-08-8 ]

References: [1]Helvetica Chimica Acta,1942,vol. 25,p. 1075.

2
[ 100367-77-9 ]
[ 170017-74-0 ]
[ 1023298-53-4 ]

Yield	Reaction Conditions	Operation in experiment
72%	With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 80℃; for 3h;	Step 1 – Synthesis of Intermediate Compound AATo a solution of 2-bromo-thiazole-4-carboxylic acid (2.0 mmol, 0.42 g), N1N- diisopropylethylamine (3.0 mmol, 0.52 ml_) and HATU (2.0 mmol, 0.76 g) in DMF (10 ml_) was added 4-(2-aminophenyl)-piperazine-1 -carboxylic acid te/t-butyl ester (2.0 mmol, 0.56 g). The reaction mixture was stirred at 80 0C for 3 h, and then concentrated in vacuo. Column chromatography on silica gel using Hexane/EtOAc (4.5/1) provided Compound A as a yellow solid (0.67 g, 72%). 1H NMR (400 MHz, CDCI3) D 10.38 (s, 1 H), 8.49 (dd, J= 8.0, 1.2 Hz, 1 H), 8.14 (s, 1 H), 7.23-7.10 (m, 3 H), 3.72 (br s, 4H), 2.89-2.87 (m, 4H), 1.50 (s, 9H). HPLC-MS RT= 2.39 minutes, mass calculated for formula Ci9H2SBrN4O3S 466.07, observed LCMS m/z 467.05 (M+H).

References: [1]Patent: WO2008/54702,2008,A1 .Location in patent: Page/Page column 122.

3
[ 100367-77-9 ]
[ 22246-66-8 ]
[ 1023298-62-5 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium phosphate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 105℃; for 12h;	Example 39; Preparation of Intermediate Compound 39A; To a pressure tube charged with 2-bromo-4-carboethoxythiazole (2.5 g, 10.6 mmol) and a stir bar was added 6-methoxyisoindolin-1 -one (2.1 g, 12.7 mmol), K3PO4 (4.9 g, 23.3 mmol), Pd2(dba)3 (0.58 g, 0.64 mmol), Xant-Phos (0.62g, 1.1 mmol). Dioxane (20 mL) was added and N2 was bubbled thru the solution for 10 EPO <DP n=”152″/>min before the vessel was capped. The mixture stirred at 105 C for 12h and was cooled to rt. The mixture was filtered thru a pad of Celite and was washed with CH2CI2/Me0H (20:1 ; 2 x 10 mL). The resulting filtrate was concentrated under reduced pressure and place under high vacuum. The crude product was purified using flash chromatography using a gradient from CH2Cb to 97:3 CH2CI2/acetone to provide 3.1 g (91% yield) of compound 39A as a brown solid. LC-MS [M+H] = 400.2; 98% purity.

References: [1]Patent: WO2008/54749,2008,A1 .Location in patent: Page/Page column 149-150.

4
[ 100367-77-9 ]
[ 3347-62-4 ]
C₁₆H₁₅N₃O₂S [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2013,vol. 23,p. 6064 – 6067.

5
[ 100367-77-9 ]
[ 145349-76-4 ]
ethyl 2-(4-(ethylthio)phenyl)thiazole-4-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With dicyclohexyl-(2′,6′-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; In 1,4-dioxane; water; at 60℃; for 18.0h;Schlenk technique; Inert atmosphere;	General procedure: A 15-50 ml Schlenk-tube with magnetic stirring bar was evacuated and purged with Ar (repeated three times). The Schlenk-tube was subsequently charged with 5 mol-% Pd(OAc)2, 10 mol-% SPhos, 1.2 eq boronic acid, 1.0 eq aryl halide (if solid) and 5.0 mL 1 ,4-dioxane. At this point 1.0 eq aryl halide (if liquid) and 1.0 mL of a 3.4 M K3PO4 solution (degassed) was added via Eppendorf pipette in an Ar counterstream. The reaction mixture was degassed by evacuation and purging with Ar (repeated three times) and placed in an oil bath at 60 C. After stirring for 18-22 h (reaction control via TLC and GC/MS) the reaction mixture was cooled to RT, the phases separated and the organic phase filtered through a pad of Celite. The filter cake was washed with an appropriate amount of EtOAc, the volatiles were removed under reduced pressure and the crude residue was died in oil-pump vacuum. Pure product was obtained via flash column chromatography (S1O2, cyclohexan Details Products CAS 37-87-6 Read more Products CAS 53-57-6 Read more Products CAS 50-90-8 Read more Reviews There are no reviews yet. Be the first to review “Ethyl 2-bromothiazole-4-carboxylate” Cancel reply Your email address will not be published. Required fields are marked * Your rating * Your review * Name * Email * Save my name, email, and website in this browser for the next time I comment. Previous 2-Iodo-5-trifluoromethylpyridine Next 3-Amino-4-bromobenzene-1-sulfonamide Easy CDMO Easy CDMO is China TOP100 CDMO company. We believe: Easy CDMO, Medicinal Chemical is Big. More than 100 scientists are serving you. Quick Links About Us Products Blog Contacts Support Links Privacy Policy Term And Condition Locations Office address: Chenxun Technology Building, No. 633, Jinzhong Road, Changning District, Shanghai info@easycdmo.com +8602161734564 © Copyright Easy CDMO 2025. All Rights Reserved.

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