[ CAS No. 32955-21-8 ] {[proInfo.proName]}

Name: 32955-21-8|Ethyl 2-aminothiazole-5-carboxylate|95%
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Product Details of [ 32955-21-8 ]

CAS No. :	32955-21-8	MDL No. :	MFCD00602139
Formula :	C₆H₈N₂O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VNZXERIGKZNEKB-UHFFFAOYSA-N
M.W :	172.20	Pubchem ID :	314628
Synonyms :

Calculated chemistry of [ 32955-21-8 ]

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 :	1.0
Molar Refractivity :	42.6
TPSA :	93.45 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.53 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.66
Log Po/w (XLOGP3) :	1.16
Log Po/w (WLOGP) :	0.91
Log Po/w (MLOGP) :	-0.16
Log Po/w (SILICOS-IT) :	1.5
Consensus Log Po/w :	1.01

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.78
Solubility :	2.88 mg/ml ; 0.0167 mol/l
Class :	Very soluble
Log S (Ali) :	-2.72
Solubility :	0.33 mg/ml ; 0.00192 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.41
Solubility :	6.67 mg/ml ; 0.0387 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.44

Safety of [ 32955-21-8 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 32955-21-8 ]

* 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 [ 32955-21-8 ]
Downstream synthetic route of [ 32955-21-8 ]

[ 32955-21-8 ] Synthesis Path-Upstream 1~19

1
[ 32955-21-8 ]
[ 110-46-3 ]
[ 32955-22-9 ]

Reference： [1] Patent: US5484801, 1996, A,
[2] Patent: US5559158, 1996, A,

2
[ 32955-21-8 ]
[ 40283-46-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydroxide In tetrahydrofuran; waterReflux	To the solution of the thiazole ethyl ester (0.80 g, 4.32 mmol) in THF/water (2:1), NaOH was added (0.65 g, 16.3 mmol), and the reaction mixture was refluxed overnight. THF was removed under reduced pressure and afterward the reaction mixture was neutralized with 1 M HCl. The resulting precipitate 1 was filtered, washed with diethyl ether and dried overnight at 60 °C. Yield: 86percent;off-white crystals, mp 168-171 C (lit. [32] 172e173 °C). 1H NMR(400 MHz, DMSO-d6): d 7.81 (s, 1H, oxazol-H), 8.99 (br s, 2H, NH2)ppm. HRMS (ESI): m/z [M H] calcd for C4H5N2O2S 145.1475;found 145.1502.

Reference： [1] European Journal of Medicinal Chemistry, 2013, vol. 67, p. 208 - 220
[2] Recueil des Travaux Chimiques des Pays-Bas, 1944, vol. 63, p. 226
[3] Yakugaku Zasshi, 1948, vol. 68, p. 101[4] Chem.Abstr., 1953, p. 7452
[5] Chemische Berichte, 1943, vol. 76, p. 419,428
[6] Journal of Medicinal Chemistry, 1972, vol. 15, p. 1310 - 1312

3
[ 1001-26-9 ]
[ 17356-08-0 ]
[ 32955-21-8 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: With N-Bromosuccinimide In 1,4-dioxane; water at -10 - 20℃; for 1 h; Stage #2: at 80℃; for 1 h;	[0096] At -10°C, a solution of ethyl 3-ethoxyacrylate (14.4 g, 0.1 mol) in water/dioxane (1:1) (100 mL) is treated withN-bromo-succinimide (19.6 g, 0.11 mol). The reaction mixture is stirred at room temperature for 1 hour, then thiourea(7.6 g, 0.1 mol) is added and the reaction mixture is heated to 80 °C for 1 hour. After the reaction solution is cooled toroom temperature, aqueous ammonia (20 mL) is added therein. The paste produced is stirred at room temperature for10 minutes, and filtered. The resultant filter cake is washed with water and dried under vacuum to give compound (2-1)(12.1 g, 70percent).
66%	Stage #1: With N-Bromosuccinimide In 1,4-dioxane; water at -10 - 20℃; for 1 h; Stage #2: at 80℃; for 1 h; Stage #3: With ammonium chloride In 1,4-dioxane; water at 20℃; for 0.166667 h;	Example 4: 6-phenylimidazo[2,l-b][l,3]thiazole-2-carboxylic acid; Step 1: ethyl 2-amino-l,3-thiazole-5-carboxvlate; A solution (1 M) of ethyl 3-ethoxyacrylate in water/dioxane (1:1) at -10°C was treated with NBS (1.1 eq.). The reaction mixture was stirred at RT for 1 hour, then thiourea (1 eq.) was added and the reaction was heated at 80°C for 1 h. After cooling at RT aqueous NH4OH (saturated solution) was added. The resulting slurry was stirred at RT for 10 min and filtered. The resulting cake was washed with water and dried to afford the title compound (66percent) as a pale yellow solid. ^.H NMR (400 MHz, DMSO,300 K) 8 1.23 (t, J6.8 Hz, 3H), 4.17 (q, J6.S Hz, 2H), 7.66 (s, 1H), 7.83 (s, 2H); MS (ES⁺) m/z 173 (M+H)⁺.

Reference： [1] Patent: EP2615092, 2013, A1, . Location in patent: Paragraph 0095; 0096
[2] Patent: WO2006/8556, 2006, A1, . Location in patent: Page/Page column 20-21

4
[ 1001-26-9 ]
[ 57-13-6 ]
[ 32955-21-8 ]

Yield	Reaction Conditions	Operation in experiment
95.7%	With potassium sulfide; copper In tetrahydrofuran; water at 55℃; for 1.5 h; Inert atmosphere	A method for the synthesis of an intermediate of dasatinib,The method comprises: under nitrogen protection,Ethyl 3-ethoxyacrylate (14.4 g, 100 mmol)And urea 12 g (200 mmol)And potassium sulfide 33. lg (300 mmol) of nano-copper powder 1.4 g (10percent1 OOnm) under the catalytic 55 ° C contact reaction 1.5 hours,The solvent for the contact reaction was 100 ml of a 6: 1 by volume mixture of THF and H20,Cooled to room temperature,Poured into ice water,Dichloromethane extraction,The organic phase was concentrated,Washed,Then recrystallized from ethanol,Amino-thiazole-5-carboxylic acid ethyl ester of dasatinib as an intermediate, 16.5 g,The yield was 95.7percentPurity 99.34percent.

Reference： [1] Patent: CN106008393, 2016, A, . Location in patent: Paragraph 0034; 0035

5
[ 17356-08-0 ]
[ 32955-21-8 ]

Yield	Reaction Conditions	Operation in experiment
1.4 g	at 80℃; for 1 h;	2.2 g, 15.2 mmol 3- ethyl acrylate XIV was added to a mixed solvent of 7.5 ml of water and 7.5 ml of dioxane, cooledlarge -10 degrees Celsius, was slowly added 2.97 g, 16.72 mmol of NBS after, room temperature 1 hour, then 1.15 g, 15.2mmol) of thiourea was added, the reaction after 1 hour at 80 ° C, ice-cooling, after addition of an excess of ammonia appearedbrown solid, leaching after the obtained solid was washed with water and drying give 1.4 g of 2-amino-5-carboxylic acid ethylester XV of, in a yield of 53.8percent.

Reference： [1] Tetrahedron Letters, 2001, vol. 42, # 11, p. 2101 - 2102
[2] Tetrahedron Letters, 2010, vol. 51, # 27, p. 3528 - 3530
[3] Patent: CN102942565, 2016, B, . Location in patent: Paragraph 0036-0039; 0091-0092

6
[ 105-39-5 ]
[ 17356-08-0 ]
[ 109-94-4 ]
[ 32955-21-8 ]

Reference： [1] Patent: WO2004/80996, 2004, A1, . Location in patent: Page 26; 46-47

7
[ 1001-26-9 ]
[ 32955-21-8 ]

Reference： [1] Arkivoc, 2010, vol. 2010, # 6, p. 32 - 38
[2] Patent: US2003/119811, 2003, A1,

8
[ 111603-56-6 ]
[ 32955-21-8 ]

Reference： [1] Tetrahedron, 1994, vol. 50, # 24, p. 7253 - 7264

9
[ 33142-21-1 ]
[ 17356-08-0 ]
[ 32955-21-8 ]

Reference： [1] Heterocycles, 1991, vol. 32, # 4, p. 693 - 701

10
[ 5941-55-9 ]
[ 32955-21-8 ]

Reference： [1] Tetrahedron Letters, 2001, vol. 42, # 11, p. 2101 - 2102

11
[ 99903-61-4 ]
[ 32955-21-8 ]

Reference： [1] Recueil des Travaux Chimiques des Pays-Bas, 1944, vol. 63, p. 226

12
[ 10601-80-6 ]
[ 32955-21-8 ]

Reference： [1] Patent: CN102942565, 2016, B,

13
[ 32955-21-8 ]
[ 81449-93-6 ]

Yield	Reaction Conditions	Operation in experiment
40%	With tert.-butylnitrite; copper dichloride In tetrahydrofuran; acetonitrile at 23 - 65℃;	[0097] At 23°C, a solution of ethyl 2-aminothiazole-4-formate (1.0 g, 6.35 mmol) in acetonitrile (10 mL) and tetrahydrofuran(10 mL) is added to a solution (10 mL) of t-butyl nitrite (1.3 mL, 9.52 mmol) and cuprous chloride (1.0 g, 7.6mmol) in acetonitrile (10 mL) and tetrahydrofuran (10 mL). The reaction mixture is required to be heated at 65 °C untilcomplete consumption of the starting materials as shown by thin-layer chromatography (40percent ethyl acetate-hexane).Then, the mixture is cooled to room temperature and partitioned between water and ethyl acetate. The organic layer isconcentrated under vacuum and purified by flash silica gel column chromatography eluted with 20percent ethyl acetate-hexaneto give ethyl 2-chloro-thiazole-4-formate (compound (2-2)) (0.49 g, 40percent).

Reference： [1] Patent: EP2615092, 2013, A1, . Location in patent: Paragraph 0095; 0097
[2] Helvetica Chimica Acta, 1954, vol. 37, p. 2057,2064
[3] Helvetica Chimica Acta, 1944, vol. 27, p. 1432,1433
[4] Patent: WO2004/80996, 2004, A1, . Location in patent: Page 26-27; 47

14
[ 32955-21-8 ]
[ 81449-93-6 ]

Yield	Reaction Conditions	Operation in experiment
97%	With hydrogenchloride; tert.-butylnitrite In acetonitrile	Example 27A Ethyl 2-chlorothiazole-5-carboxylate To a solution of tert-butyl nitrite (9.3 g, 90 mmol) and cupric chloride (9.7 g, 72 mmol) in 150 mL of acetonitrile at 65° C. was added portionwise ethyl 2-aminothiazole-5-carboxylate (10.3 g, 60 mmol) (prepared by the method of Dann, O. Chem Ber 76 419 (1943)) resulting in vigorous gas evolution. After the addition was complete, the solution was stirred until gas evolution ceased (30 minutes). The solution was cooled and poured into 250 mL of cold 20percent v/v aqueous HCl. The aqueous solution was extracted 3 times with 200 mL of EtOAc. The organics were combined, washed once with 100 mL of 20percent aqueous HCl and 2 times with 100 mL saturated brine and dried over magnesium sulfate. Concentration in vacuo gave 11.1 g (97percent yield) of a brown oil which required no purification.

Reference： [1] Patent: US5326776, 1994, A,

15
[ 32955-21-8 ]
[ 41731-83-3 ]

Yield	Reaction Conditions	Operation in experiment
50%	Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; Stage #2: With hydrogen bromide; copper(I) bromide In water at 0 - 20℃;	To a stirred solution of ethyl-2-amino thiazole-5-carboxylate (10.0 g, 46.45 mmol, Combi block) in 48percent HBr (75 mL), sodium nitrite (4.80 g, 69.68 mmol) dissolved in water (50 mL) was added drop wise at 0°C and the reaction mixture was stirred at O 'C for 15 min. Then copper(l)bromide (6.66 g, 46.45 mmol) in 48percent HBr (75 mL) was added drop wise at 0°C and the resulting reaction mixture was stirred at rt for 4 h. The reaction mixture was diluted with DCM (200 mL) and washed with water (50 mL), brine (50 mL), dried over Na₂S0₄ and concentrated under reduced pressure. The resulting crude was purified by flash chromatography (100percent CHCI₃) to give ethyl 2-bromothiazole-5-carboxylate as a yellow liquid. Yield: 50percent (5.5 g). LCMS: (Method A) 235.9 (M+H), RT. 3.85 min, 98.6percent (Max). H NMR (400 MHz, DMSO-d₆): δ 8.16 (s, 1 H), 4.38 (q, J = 7.1 Hz, 2H), 1 .39 (t, J = 7.1 Hz, 3H).
50.18%	Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; for 0.25 h; Stage #2: With hydrogen bromide; copper(I) bromide In water at 0 - 20℃; for 4 h;	To a stirred solution of ethyl-2-amino thiazole-5-carboxylate (10.0 g, 46.45 mmol, Combi block) in 48percent HBr (75 mL), sodium nitrite (4.80 g, 69.68 mmol) in water (50 mL) was added dropwise at 0 °C and the reaction mixture was stirred at 0 °C for 15 min. Copper (l)bromide (6.66 g, 46.45 mmol) in 48percent HBr (75 ml.) was added dropwise at 0 °C and the reaction mixture was stirred at rt for 4h. The reaction mixture was diluted with DCM (200 mL) and washed with water (50 mL,), brine (50 mL,), dried over Na₂SO₄ and concentrated under reduced pressure. The crude product was purified by flash chromatography (100percent CHCl₃) to afford the title compound. Yield: 50.18percent (5.5 g, yellow liquid). ¹H NMR (400 MHz, DMSO-d₆): 5 8.16 (s, 1H), 4.38 (q, J = 7.16 Hz, 2H), 1.40 (t, J = 7.12 Hz, 3H). LCMS: (Method A) 235.9 (M+H), Rt. 3.85 min, 98.6percent (Max).
50.18%	Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; for 0.25 h; Stage #2: With copper(I) bromide In water at 0 - 20℃; for 4 h;	To a stirred solution of ethyl-2-amino thiazole-5-carboxylate (10.0 g, 46.45 mmol,Combi block) in 48percent HBr (75 mL), sodium nitrite (4.80 g, 69.68 mmol) in water (50 mL) was added dropwise at 0 °C and the reaction mixture was stirred at 0 °C for 15 mm. Copper (l)bromide (6.66 g, 46.45 mmol) in 48percent HBr (75 mL) was added dropwise at 0°C and the reaction mixture was stirred at rt for 4h. The reaction mixture was diluted with DCM (200 mL) and washed with water (50 mL), brine (50 mL), dried over Na2SO4 To a stirred solution of ethyl-2-amino thiazole-5-carboxylate (10.0 g, 46.45 mmol,Combi block) in 48percent HBr (75 mL), sodium nitrite (4.80 g, 69.68 mmol) in water (50 mL) was added dropwise at 0 °C and the reaction mixture was stirred at 0 °C for 15 mm. Copper (l)bromide (6.66 g, 46.45 mmol) in 48percent HBr (75 mL) was added dropwise at 0°C and the reaction mixture was stirred at rt for 4h. The reaction mixture was diluted with DCM (200 mL) and washed with water (50 mL), brine (50 mL), dried over Na2SO4

50.18%

Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; for 0.25 h;
Stage #2: With copper(I) bromide In water at 0 - 20℃; for 4 h;

To a stirred solution of ethyl 2-aminothiazole-5-carboxylate (10.0 g, 46.45 mmol, Combi block) in 48percent HBr (75 mL), sodium nitrite (4.80 g, 69.68 mmol) in water (50mL) was added dropwise at 0 °C and the reaction mixture was stirred at 0 °C for 15 mm. Copper(l) bromide (6.66 g, 46.45 mmol) in 48percent HBr (75 mL) was added dropwise at 0 °C and the reaction mixture was stirred at rt for 4h. The reaction mixture was diluted with DCM (200 mL) and washed with water (50 mL), brine (50mL), dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by flash chromatography (100percent CHCl3) to afford the title compound. Yield: 50.18percent (5.5 g, yellow liquid). 1H NMR (400 MHz, DMSO-d6): δ 8.16 (s, 1H), 4.38 (q, J= 7.16 Hz, 2H), 1.40 (t, J= 7.12 Hz, 3H). LCMS: (Method A) 235.9 (M+H), Rt. 3.85 min, 98.6percent (Max).

Reference： [1] Patent: WO2014/159234, 2014, A1, . Location in patent: Page/Page column 87; 88
[2] Patent: WO2016/30443, 2016, A1, . Location in patent: Page/Page column 118-119
[3] Patent: WO2017/144637, 2017, A1, . Location in patent: Page/Page column 52; 53
[4] Patent: WO2017/144635, 2017, A1, . Location in patent: Page/Page column 46; 47
[5] Journal of the American Chemical Society, 2008, vol. 130, # 28, p. 9089 - 9098
[6] Proceedings - Indian Academy of Sciences, Section A, 1945, # 22, p. 362,376
[7] Helvetica Chimica Acta, 1954, vol. 37, p. 2057,2064
[8] Helvetica Chimica Acta, 1952, vol. 35, p. 187,192
[9] Helvetica Chimica Acta, 1976, vol. 59, p. 155 - 164

16
[ 32955-21-8 ]
[ 12775-96-1 ]
[ 41731-83-3 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium hydroxide; sodium carbonate; sodium nitrite In concentrated phosphoric acid; water; hydrogen bromide; nitric acid	The starting material can be prepared as follows: To a 500 mL 24/40 3-neck round bottom flask equiped with a mechanical stirrer, was charged 3.4 g (19.7 mmol) of 2-amino-5-thiazolecarboxylic acid ethyl ester (Ber., 1888, 21, 938), partially dissolved in 30 mL of concentrated phosphoric acid. The stirring mixture was cooled in an ice bath and then 9 mL of concentrated nitric acid was added slowly, followed by the dropwise addition of 2.85 g (41.3 mmol) of sodium nitrite in 5 mL of water. The mixture was stirred in the cold for 35 minutes, and then added dropwise was 3.0 g (47.2 mmol) of copper powder in 75 mL of 48percent hydrobromic acid cooled to -10° C. After the evolution of nitrogen gas ceased, the thick reaction mixture was removed from the ice bath and neutralized to pH 8, first using 5N sodium hydroxide and then sodium carbonate. The aqueous was then extracted with 400 mL ether. The insoluble material was filtered away and the filtrate was washed with 5percent sodium bicarbonate, water, dried over sodium sulfate, and removed in vacuo. The crude residue was then purified using silica gel flash chromatography eluding with 1:1 ether/hexanes to give 2.4 g (52percent) of 2-bromo-5-thiazolecarboxylic acid ethyl ester as a yellow oil. R_f =0.62 (1:1 ether/hexanes). 1H NMR (300 MHz, DMSO d₆) δ 1.26 (t, J=7.0 Hz, 3H), 4.29 (q, J=7.1 Hz, 2H), 8.28 (s, 1H). Anal. Cal'd for C₆ H₆ BrNO₂ S: C, 30.53; H, 2.56; N, 5.93. Found: C, 30.78; H, 2.62; N, 5.98.

Reference： [1] Patent: US6066639, 2000, A,

17
[ 32955-21-8 ]
[ 131184-73-1 ]

Yield	Reaction Conditions	Operation in experiment
225 mg	With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2.25 h; Inert atmosphere; Reflux	[00363] A suspension of ethyl 2-amino-1,3-thiazole-5-carboxylate (1.72 g, 10 mmol) in anhydrous THF (100 mL) was cooled in an ice bath and treated with LiAIH4 (0.76 g, 20 mmol) portionwise, under nitrogen. The reaction mixture was warmed to room temperature and stirred for 90 minutes. After this time, additional LiAIH4 (0.76 g, 20 mmol) was added and thesuspension was heated to reflux for 45 minutes. After this time, the suspension was cooled in an ice bath and cautiously treated with ice chips, followed by concentrated aqueous ammonium hydroxide solution (10 mL) and stirred for 60 hours. The orange suspension was filtered through CeliteTM, washing with MeOH. The filtrate was evaporated under reduced pressure, adsorbed onto silica and purified by flash column chromatography, eluting with MeOH/DCM (5-10percent), with the desired fractions combined and concentrated under reduced pressure to afford the title compound (225 mg). LCMS method: Method 5, RT: 0.55 mm, Ml: 131 [M+1]

Reference： [1] Patent: WO2016/124938, 2016, A1, . Location in patent: Paragraph 00363-00364

18
[ 32955-21-8 ]
[ 24424-99-5 ]
[ 302964-02-9 ]

Reference： [1] Patent: US2003/119811, 2003, A1,

19
[ 32955-21-8 ]
[ 87-63-8 ]
[ 302964-24-5 ]

Reference： [1] Patent: WO2014/102759, 2014, A2, . Location in patent: Page/Page column 17

[ 32955-21-8 ] Synthesis Path-Downstream 1~88

1
[ 32955-21-8 ]
[ 79-03-8 ]
[ 103860-40-8 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1959,vol. 79,p. 920,923
Chem.Abstr.,1959,p. 21888

2
[ 32955-21-8 ]
[ 108-24-7 ]
[ 106840-37-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With pyridine; dmap; In dichloromethane; at 0℃; for 2h;Reflux;	To a stirred solution of ethyl-2-amino thiazole-5-carboxylate (10.0 g, 58.1 mmol), pyridine (9.47 mL, 1 16.27 mmol) and DMAP (200 mg, 1 .6 mmol) in DCM (100 mL), acetic anhydride (8.89 g, 87.20 mmol) was added at 0C and refluxed for 2 h. The reaction mixture was concentrated under reduced pressure and HCI (1 .5 N in water, 50 mL) was added. The mixture was stirred for 1 0 min. The resulting precipitate was filtered and washed with water (250 mL) and hexane (50 mL) to give ethyl 2-acetamidothiazole-5- carboxylate as an off-white solid. Yield: 98% (1 2.1 g). LC/MS: (Method C) 215.0 (M+H), RT. 2.77 min, 97.1 1 % (Max). H NMR (300 MHz, DMSO-d6): delta 8.10 (s, 1 H), 4.24 (q, J = 6.2, 2H), 2.17 (s, 3H), 1 .26 (t, J = 6.2 Hz, 3H).
95%	With pyridine; dmap; In dichloromethane; at 0℃; for 2h;Reflux;	To a stirred solution of ethyl 2-aminothiazole-5- carboxylate (10.00 g, 58.1 mmol), pyridine (9.47 mL, 117.3 mmol) and 4- dimethylaminopyridine (200.0 mg, 1.64 mmol) in dichloromethane (100. mL), was added acetic anhydride (8.23 mL, 87.1 mmol) at 0 C. The reaction was heated to reflux for 2 hours. The reaction mixture was concentrated under reduced pressure and then hydrochloric acid solution (1.5 N in water, 50 mL) was added. The mixture was stirred for 10 min. The resulting precipitate was filtered and washed with water (250 mL) and heptanes (50 mL) and then dried under high vacuum to give the title compound (11.82 g, 95.0% yield). LCMS: [M+H] 215.0. 1H NMR: (400 MHz, DMSO-d6) d 12.55 (s, 1H), 8.12 (s, 1H), 4.27 (q, 7=7.11 Hz, 2H), 2.19 (s, 3H), 1.28 (t, 7=7.15 Hz, 3H).

Reference： [1]Patent: WO2014/159234,2014,A1 .Location in patent: Page/Page column 85; 86
[2]Patent: WO2019/178191,2019,A1 .Location in patent: Paragraph 00213
[3]Chemische Berichte,1943,vol. 76,p. 419,428

3
[ 32955-21-8 ]
[ 98-60-2 ]
[ 859486-36-5 ]

Reference： [1]Journal of the American Chemical Society,1951,vol. 73,p. 2558,2560

5
[ 32955-21-8 ]
[ 598-21-0 ]
[ 99768-16-8 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1957,vol. 77,p. 649,651
Chem.Abstr.,1957,p. 16435

6
[ 32955-21-8 ]
[ 121-60-8 ]
2-[(N-acetyl-sulfanilyl)-amino]-thiazole-5-carboxylic acid [ No CAS ]
3-(N-acetyl-sulfanilyl)-2-(N-acetyl-sulfanilylimino)-2,3-dihydro-thiazole-5-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1948,vol. 68,p. 101
Chem.Abstr.,1953,p. 7452

7
[ 32955-21-8 ]
[ 121-60-8 ]
2-[(N-acetyl-sulfanilyl)-amino]-thiazole-5-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1942,vol. 61,p. 463,465
[2]Patent: DE752870,1940,
DRP/DRBP Org.Chem.,

8
[ 32955-21-8 ]
[ 40283-46-3 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydroxide; In tetrahydrofuran; water;Reflux;	To the solution of the thiazole ethyl ester (0.80 g, 4.32 mmol) in THF/water (2:1), NaOH was added (0.65 g, 16.3 mmol), and the reaction mixture was refluxed overnight. THF was removed under reduced pressure and afterward the reaction mixture was neutralized with 1 M HCl. The resulting precipitate 1 was filtered, washed with diethyl ether and dried overnight at 60 C. Yield: 86%;off-white crystals, mp 168-171 C (lit. [32] 172e173 C). 1H NMR(400 MHz, DMSO-d6): d 7.81 (s, 1H, oxazol-H), 8.99 (br s, 2H, NH2)ppm. HRMS (ESI): m/z [M H] calcd for C4H5N2O2S 145.1475;found 145.1502.

Reference： [1]European Journal of Medicinal Chemistry,2013,vol. 67,p. 208 - 220
[2]Recueil des Travaux Chimiques des Pays-Bas,1944,vol. 63,p. 226
[3]Chemische Berichte,1943,vol. 76,p. 419,428
[4]Journal of Medicinal Chemistry,1972,vol. 15,p. 1310 - 1312

9
[ 32955-21-8 ]
2-amino-thiazole-5-carboxylic acid hydrazide [ No CAS ]

Reference： [1]Proceedings - Indian Academy of Sciences, Section A,1945,p. 362,376

12
[ 32955-21-8 ]
[ 71079-18-0 ]
[ 71079-23-7 ]

Reference： [1]Journal of Medicinal Chemistry,1980,vol. 23,p. 13 - 20

13
[ 32955-21-8 ]
[ 127942-25-0 ]
[ 135999-95-0 ]

Reference： [1]Heterocycles,1991,vol. 32,p. 693 - 701

14
[ 32955-21-8 ]
[ 71079-33-9 ]
[ 71132-06-4 ]

Reference： [1]Journal of Medicinal Chemistry,1980,vol. 23,p. 13 - 20

15
N'-[2-cyano-4-methoxy-5-(3-morpholin-4-ylpropoxy)phenyl]-N,N-dimethylimidoformamido [ No CAS ]
[ 32955-21-8 ]
[ 385780-23-4 ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 955 - 970

16
[ 32955-21-8 ]
[ 827038-84-6 ]