[ CAS No. 64987-16-2 ] {[proInfo.proName]}

Name: 64987-16-2|Methyl 2-(2-aminothiazol-4-yl)acetate|95%
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SKU: A300401
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Quality Control of [ 64987-16-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 64987-16-2 ]

Product Details of [ 64987-16-2 ]

CAS No. :	64987-16-2	MDL No. :	MFCD00129969
Formula :	C₆H₈N₂O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XTQKFBGFHDNUFY-UHFFFAOYSA-N
M.W :	172.21	Pubchem ID :	738059
Synonyms :

Calculated chemistry of [ 64987-16-2 ]

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 :	42.38
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) :	-7.05 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.47
Log Po/w (XLOGP3) :	0.43
Log Po/w (WLOGP) :	0.45
Log Po/w (MLOGP) :	-0.43
Log Po/w (SILICOS-IT) :	1.5
Consensus Log Po/w :	0.69

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.32
Solubility :	8.3 mg/ml ; 0.0482 mol/l
Class :	Very soluble
Log S (Ali) :	-1.96
Solubility :	1.89 mg/ml ; 0.011 mol/l
Class :	Very 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 :	2.23

Safety of [ 64987-16-2 ]

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

Application In Synthesis of [ 64987-16-2 ]

* 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 [ 64987-16-2 ]
Downstream synthetic route of [ 64987-16-2 ]

[ 64987-16-2 ] Synthesis Path-Upstream 1~4

1
[ 60032-57-7 ]
[ 64987-16-2 ]
[ 56826-61-0 ]
[ 1421928-97-3 ]

Reference： [1] Patent: WO2013/19621, 2013, A1, . Location in patent: Page/Page column 74

2
[ 67-56-1 ]
[ 29676-71-9 ]
[ 64987-16-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: With sulfuric acid In methanol at 0℃; Reflux	Preparation of methyl(2-amino-1,3-thiazol-4-yl)acetate To a solution of 2-amino-4-thiazole acetic acid (20 g, 0.126 mol) in methanol (100 ml) was added concentrated H₂SO₄ (24 ml) dropwise at 0-5° C. and the reaction mixture was refluxed for 5 hours. Subsequently the reaction mixture was basified to pH of 8-9 with NaHCO₃ solution, to give a colorless precipitate, which was filtered and dried to afford the title compound in 19.5 g (93percent yield).
93%	Stage #1: at 0 - 5℃; for 5 h; Heating / reflux Stage #2: With sodium hydrogencarbonate In water	Example 1; Synthesis of pγridin-3-ylmethyI {4-[2-diydroxyaniino)-2-oxoethyn-l,3-thiazoI-2- yUcarbamate; Step: 1Preparation of methyl (2-amino-l,3-thiazol-4-yl)acetate; To a solution of 2-amino-4-thiazole acetic acid (20 g, 0.126 mol) in methanol(100ml) was added concentrated H₂SO4 (24 ml) dropwise at 0-5 ⁰C and the reaction mixture was refluxed for 5 hours. Subsequently the reaction mixture was basified to pH of 8-9 with NaHCO₃ solution, to give a colorless precipitate, which was filtered and dried to afford the title compound in 19.5 g (93 percent yield).
91%	for 12 h;	Obtained in 91percent yield as a white crystalline solid by treatment of 2-amino-4-thiazolylacetic acid with SOCl₂ in methanol for 12 h; mp 126 °C; ¹H NMR (CDCl₃) δ 6.31 (s, 1H), 5.56 (br s, 2H),3.77 (s, 3H), 3.58 (s, 2H)

89.9%

for 1.5 h; Reflux

Methanol (30 mL) was cooled to 0 °C and thionyl chloride (3.45 mL, 47.6 mmol) was added dropwise. Then 2-(2-aminothiazol-4-yl)acetic acid (9) (3.00 g, 19.0 mmol) was added and reaction mixture stirred under reflux for 1.5 h. The solvent was evaporated and the oily residue triturated with diethyl ether. White precipitate (3.564 g, 89.9percent) was filtered off and dried. ¹H NMR (400 MHz, DMSO-d₆) δ 3.66 (s, 3H, CH₃), 3.77 (s, 2H, CH₂), 6.71 (s, 1H, Ar-H), 9.30 (s, 2H, NH₂) ppm; ¹³C NMR (100 MHz, DMSO-d₆): δ 32.7, 52.1, 105.6, 132.4, 169.0, 169.5 ppm.

Reference： [1] Patent: US2010/152188, 2010, A1, . Location in patent: Page/Page column 6
[2] Patent: WO2007/17728, 2007, A2, . Location in patent: Page/Page column 15
[3] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5408 - 5412
[4] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 1, p. 338 - 349
[5] Synthetic Communications, 2003, vol. 33, # 12, p. 1977 - 1995
[6] Medicinal Chemistry Research, 2014, vol. 23, # 1, p. 259 - 268

3
[ 29676-71-9 ]
[ 18107-18-1 ]
[ 64987-16-2 ]

Reference： [1] Patent: WO2004/33423, 2004, A2, . Location in patent: Page 25-27

4
[ 32807-28-6 ]
[ 17356-08-0 ]
[ 64987-16-2 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1255 - 1257

[ 64987-16-2 ] Synthesis Path-Downstream 1~60

1
[ 32807-28-6 ]
[ 17356-08-0 ]
[ 64987-16-2 ]

Reference： [1]Patent: WO2020/10140,2020,A1 .Location in patent: Page/Page column 371; 372
[2]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1255 - 1257

2
[ 72086-72-7 ]
[ 64987-16-2 ]
(S)-2-tert-Butoxycarbonylamino-4-(4-methoxycarbonylmethyl-thiazol-2-ylcarbamoyl)-butyric acid methyl ester [ No CAS ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1996,vol. 44,p. 1498 - 1509

3
[ 64987-16-2 ]
[ 181517-99-7 ]
(2-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-thiazol-4-yl)-acetic acid methyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2988 - 2993

4
[ 67-56-1 ]
[ 29676-71-9 ]
[ 64987-16-2 ]

Yield	Reaction Conditions	Operation in experiment
93%		Preparation of methyl(2-amino-1,3-thiazol-4-yl)acetate To a solution of 2-amino-4-thiazole acetic acid (20 g, 0.126 mol) in methanol (100 ml) was added concentrated H2SO4 (24 ml) dropwise at 0-5 C. and the reaction mixture was refluxed for 5 hours. Subsequently the reaction mixture was basified to pH of 8-9 with NaHCO3 solution, to give a colorless precipitate, which was filtered and dried to afford the title compound in 19.5 g (93% yield).
93%		Example 1; Synthesis of pgammaridin-3-ylmethyI {4-[2-diydroxyaniino)-2-oxoethyn-l,3-thiazoI-2- yUcarbamate; Step: 1Preparation of methyl (2-amino-l,3-thiazol-4-yl)acetate; To a solution of 2-amino-4-thiazole acetic acid (20 g, 0.126 mol) in methanol(100ml) was added concentrated H2SO4 (24 ml) dropwise at 0-5 0C and the reaction mixture was refluxed for 5 hours. Subsequently the reaction mixture was basified to pH of 8-9 with NaHCO3 solution, to give a colorless precipitate, which was filtered and dried to afford the title compound in 19.5 g (93 % yield).
91%	With thionyl chloride; for 12.0h;	Obtained in 91% yield as a white crystalline solid by treatment of 2-amino-4-thiazolylacetic acid with SOCl2 in methanol for 12 h; mp 126 C; 1H NMR (CDCl3) delta 6.31 (s, 1H), 5.56 (br s, 2H),3.77 (s, 3H), 3.58 (s, 2H)

89.9%

With thionyl chloride; for 1.5h;Reflux;

Methanol (30 mL) was cooled to 0 C and thionyl chloride (3.45 mL, 47.6 mmol) was added dropwise. Then 2-(2-aminothiazol-4-yl)acetic acid (9) (3.00 g, 19.0 mmol) was added and reaction mixture stirred under reflux for 1.5 h. The solvent was evaporated and the oily residue triturated with diethyl ether. White precipitate (3.564 g, 89.9%) was filtered off and dried. 1H NMR (400 MHz, DMSO-d6) delta 3.66 (s, 3H, CH3), 3.77 (s, 2H, CH2), 6.71 (s, 1H, Ar-H), 9.30 (s, 2H, NH2) ppm; 13C NMR (100 MHz, DMSO-d6): delta 32.7, 52.1, 105.6, 132.4, 169.0, 169.5 ppm.

Reference： [1]Patent: US2010/152188,2010,A1 .Location in patent: Page/Page column 6
[2]Patent: WO2007/17728,2007,A2 .Location in patent: Page/Page column 15
[3]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412
[4]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 338 - 349
[5]Synthetic Communications,2003,vol. 33,p. 1977 - 1995
[6]Medicinal Chemistry Research,2014,vol. 23,p. 259 - 268

5
[ 64987-16-2 ]
2-(2-amino-thiazol-4-yl)-N-hydroxy-acetamide [ No CAS ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 1977 - 1995

6
[ 64987-16-2 ]
2-(2-amino-thiazol-4-yl)-N-hydroxy-acetamide; hydrochloride [ No CAS ]

Reference： [1]Synthetic Communications,2003,vol. 33,p. 1977 - 1995

7
[ 64987-16-2 ]
(2-{2-[4-(3-o-tolyl-ureido)-phenyl]-acetylamino}-thiazol-4-yl)-acetic acid [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 2988 - 2993

8
[ 29676-71-9 ]
[ 18107-18-1 ]
[ 64987-16-2 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; benzene; at 20℃;	Each of Compounds 36 and 37 was synthesized as follows. Reaction of an amino substituted heteroaryl with (trimethylsilyl) diazomethane (2.0 M solution in hexanes) in a solvent of methanol and benzene yielded an intermediate. Substitution of the intermediate at C-4 position of DBD gave the desired product. See Scheme 2 below. Analytical data on Compound 36 are shown below. Compound 36, i. e., [4'-O-DEMETHYL-4 - [4"- (METHYL-O-ACETYL)-2"-] thiazolylamino] -4-desoxypodophyllotoxin. Yield 59%; Amorphous, mp [116-120 C] (dec. ); ESI MS: 553 [M-H], 577 [[M+NA]. LH] NMR [(CDC13)] [6] 6.85 (s, 1H, 5-H), 6.52 (s, 1H, 8-H), 6.38 (s, 1H, 5"-H), 6.30 (s, 2H, 2', 6'-H), 5.98 and 5.96 (dd, 2H,- [OCH70-),] 5.16 (br, 1H, 4-H), 4. 59 (br, [1H,] 1-H), 4.40 (t, [1H, 11-H),] 3.95 (t, [1H,] 11- H), 3.79 (s, 6H, 3', 5'-OCH3), 3.73 (s, 3H,-COOCH3), 3.60 (s, [2H,-CHACOOCH3),] 3.00 (m, 2H, 2-H, 2-H). Compounds 6,11, 38-42,77-82, 84,96, 118,126, 128,130-131, 140,145- 146,163, and 165 were synthesized by coupling an appropriate alcohol or amine to an amino substituted heteroaryl followed by conjugation with DBD. Analytical data on a number of compounds are shown below. Compound 39, i. e., [4'-O-DEMETHYL-40- [5"- (ETHOXYCARBONYL)-2"-] pyridylamino)]-4-desoxypodophyllotoxin. Yield 35 %; Amorphous, mp [164-168 C] (dec. ); ESI MS: 547 [M-H], 571 [[M+NA]. LH] NMR [(CDC13)] [S] 8.78 (d, 1H, [J] = 2.2 Hz, 6"-H), 8.04 and 8.01 (dd, J = 2.2 Hz, 1H, 4"-H), 6.79 (s, 1H, 5-H), 6.55 (s, 1H, 8- H), 6.42 (d, [J =] 8.8 Hz, [1H,] 5"-H), 6.33 (s, 2H, 2', 6'-H), 5.99, 5.96 (dd, J = 1. 6 Hz, [2H,-OCHEO-),] 5.46 (br, 2H, 4-H, [NH),] 4.88 (d, J = 5.5 Hz, 1H, 1-H), 4.62 (br, 1H, [11-H),] 4.40 (br, [1H, 11-H),] 4. [36] (q, J = 7.1 Hz, 2H, [CH2CH3),] 3.79 (s, 6H, 3', 5'- OCH3), 3.03 (m, 2H, 2-H, 2-H), 1.36 (t, J = 7.1 Hz, 3H, CH2CH3). Compound 84, i. e., [4'-O-DEMETHYL-40- [4"- (ETHOXYCARBONYL)-3"-] pyrazolylamino] -4-desoxypodophyllotoxin. Yield 40 %; White solid, mp [152-155 C] [(DEC.) ; ESI] MS: 536 [M-H]. 1H NMR [(CDC13)] [8] 7.32 (s, 1H, 5"-H), 6.66 (s, 1H, 5- H), 6.62 (s, [1H,] 8-H), 6.31 (s, 2H, 2', 6'-H), 6.01, 6.00 (dd, J = 1. 1 Hz, [2H,-OCH70-),] 5.45 (s, 1H, NH), 5.43 (d, J = 4.9 Hz, [1H,] 4-H), 4.70 (d, J = 4.9 Hz, [1H,] 1-H), 4.68 (br, 1H, [11-H),] 4.36 (br, [1H,] [11-H),] 4.25 (m, 2H, [CH2CH3),] 3.79 (s, 6H, 3', 5'- [OCH9,] 3.55 (m, 1H, 3-H, ), 3.25 (dd, J = 4.9 Hz, 1H, 2-H, ), 1.35 (t, J = 7.1 Hz, 3H, CH2CH3). Compound 140, i. e., [4'-O-DEMETHYL-4ss-[2"-(3"-(2"'-CHLORO-4"'-] pyridinylamino-carbonyl))-pyridinlylamino]-4-desoxypodophyllotoxin. Amorphous, mp > 240 C (dec); ESI MS: 630.0 [(M-1)] [;'H] NMR 6 (400 MHz, [CDC13)] : 8.65 [(1H,] d, J = 2.3 Hz, 3"'-H of second pyridine), 8.32 [(1H,] d, J = 5.5 Hz, [6"'-H] of second pyridine), 7.95 [(1H,] dd, J = 2.3, 9.0 Hz, 4"-H of first pyridine), 7.76 [(1H,] d, J = 2.0 Hz, 6"-H of first pyridine), 7.48 [(1H,] dd, J = 2.0, 5.9 Hz, 5"'-H of second pyridine), 6.79 [(1H,] s, 5-H), 6.56 [(1H,] s, 8-H), 6.50 [(1H,] d, J = 9.0 Hz, 3"-H of first pyridine), 6.34 (2H, s, 2'-H, 6'-H), 5.98 (2H, d d, J = 1. 2,6. 7 Hz,-OCH20-), 5.44 [(1H,] d. [J =] 5.5 Hz, 4-H), 4.63 (1H, d, J = 3.9 Hz, [1-H),] 4.42 (1H, dd, J = 7.0, 9.4 Hz, 113035-H), 3.80 [(1H,] d, J = 2.2, 8.8 Hz, 2-H), 3.80 (6H, s, 3', 5'-OCH3), 3.50 [(1H,] m, 3-H), 3.03 (1H, br. d, J = 4.7 Hz, 11ss-H).

Reference： [1]Patent: WO2004/33423,2004,A2 .Location in patent: Page 25-27

9
[ 16477-16-0 ]
[ 64987-16-2 ]
[ 681138-10-3 ]

Yield	Reaction Conditions	Operation in experiment
	With barium carbonate; In tetrahydrofuran; 1,2-dichloro-ethane;Heating / reflux;	Each of Compounds 36 and 37 was synthesized as follows. Reaction of an amino substituted heteroaryl with (trimethylsilyl) diazomethane (2.0 M solution in hexanes) in a solvent of methanol and benzene yielded an intermediate. Substitution of the intermediate at C-4 position of DBD gave the desired product. See Scheme 2 below. Analytical data on Compound 36 are shown below. Compound 36, i. e., [4'-O-DEMETHYL-4 - [4"- (METHYL-O-ACETYL)-2"-] thiazolylamino] -4-desoxypodophyllotoxin. Yield 59%; Amorphous, mp [116-120 C] (dec. ); ESI MS: 553 [M-H], 577 [[M+NA]. LH] NMR [(CDC13)] [6] 6.85 (s, 1H, 5-H), 6.52 (s, 1H, 8-H), 6.38 (s, 1H, 5"-H), 6.30 (s, 2H, 2', 6'-H), 5.98 and 5.96 (dd, 2H,- [OCH70-),] 5.16 (br, 1H, 4-H), 4. 59 (br, [1H,] 1-H), 4.40 (t, [1H, 11-H),] 3.95 (t, [1H,] 11- H), 3.79 (s, 6H, 3', 5'-OCH3), 3.73 (s, 3H,-COOCH3), 3.60 (s, [2H,-CHACOOCH3),] 3.00 (m, 2H, 2-H, 2-H). Compounds 6,11, 38-42,77-82, 84,96, 118,126, 128,130-131, 140,145- 146,163, and 165 were synthesized by coupling an appropriate alcohol or amine to an amino substituted heteroaryl followed by conjugation with DBD. Analytical data on a number of compounds are shown below. Compound 39, i. e., [4'-O-DEMETHYL-40- [5"- (ETHOXYCARBONYL)-2"-] pyridylamino)]-4-desoxypodophyllotoxin. Yield 35 %; Amorphous, mp [164-168 C] (dec. ); ESI MS: 547 [M-H], 571 [[M+NA]. LH] NMR [(CDC13)] [S] 8.78 (d, 1H, [J] = 2.2 Hz, 6"-H), 8.04 and 8.01 (dd, J = 2.2 Hz, 1H, 4"-H), 6.79 (s, 1H, 5-H), 6.55 (s, 1H, 8- H), 6.42 (d, [J =] 8.8 Hz, [1H,] 5"-H), 6.33 (s, 2H, 2', 6'-H), 5.99, 5.96 (dd, J = 1. 6 Hz, [2H,-OCHEO-),] 5.46 (br, 2H, 4-H, [NH),] 4.88 (d, J = 5.5 Hz, 1H, 1-H), 4.62 (br, 1H, [11-H),] 4.40 (br, [1H, 11-H),] 4. [36] (q, J = 7.1 Hz, 2H, [CH2CH3),] 3.79 (s, 6H, 3', 5'- OCH3), 3.03 (m, 2H, 2-H, 2-H), 1.36 (t, J = 7.1 Hz, 3H, CH2CH3). Compound 84, i. e., [4'-O-DEMETHYL-40- [4"- (ETHOXYCARBONYL)-3"-] pyrazolylamino] -4-desoxypodophyllotoxin. Yield 40 %; White solid, mp [152-155 C] [(DEC.) ; ESI] MS: 536 [M-H]. 1H NMR [(CDC13)] [8] 7.32 (s, 1H, 5"-H), 6.66 (s, 1H, 5- H), 6.62 (s, [1H,] 8-H), 6.31 (s, 2H, 2', 6'-H), 6.01, 6.00 (dd, J = 1. 1 Hz, [2H,-OCH70-),] 5.45 (s, 1H, NH), 5.43 (d, J = 4.9 Hz, [1H,] 4-H), 4.70 (d, J = 4.9 Hz, [1H,] 1-H), 4.68 (br, 1H, [11-H),] 4.36 (br, [1H,] [11-H),] 4.25 (m, 2H, [CH2CH3),] 3.79 (s, 6H, 3', 5'- [OCH9,] 3.55 (m, 1H, 3-H, ), 3.25 (dd, J = 4.9 Hz, 1H, 2-H, ), 1.35 (t, J = 7.1 Hz, 3H, CH2CH3). Compound 140, i. e., [4'-O-DEMETHYL-4ss-[2"-(3"-(2"'-CHLORO-4"'-] pyridinylamino-carbonyl))-pyridinlylamino]-4-desoxypodophyllotoxin. Amorphous, mp > 240 C (dec); ESI MS: 630.0 [(M-1)] [;'H] NMR 6 (400 MHz, [CDC13)] : 8.65 [(1H,] d, J = 2.3 Hz, 3"'-H of second pyridine), 8.32 [(1H,] d, J = 5.5 Hz, [6"'-H] of second pyridine), 7.95 [(1H,] dd, J = 2.3, 9.0 Hz, 4"-H of first pyridine), 7.76 [(1H,] d, J = 2.0 Hz, 6"-H of first pyridine), 7.48 [(1H,] dd, J = 2.0, 5.9 Hz, 5"'-H of second pyridine), 6.79 [(1H,] s, 5-H), 6.56 [(1H,] s, 8-H), 6.50 [(1H,] d, J = 9.0 Hz, 3"-H of first pyridine), 6.34 (2H, s, 2'-H, 6'-H), 5.98 (2H, d d, J = 1. 2,6. 7 Hz,-OCH20-), 5.44 [(1H,] d. [J =] 5.5 Hz, 4-H), 4.63 (1H, d, J = 3.9 Hz, [1-H),] 4.42 (1H, dd, J = 7.0, 9.4 Hz, 113035-H), 3.80 [(1H,] d, J = 2.2, 8.8 Hz, 2-H), 3.80 (6H, s, 3', 5'-OCH3), 3.50 [(1H,] m, 3-H), 3.03 (1H, br. d, J = 4.7 Hz, 11ss-H).

Reference： [1]Patent: WO2004/33423,2004,A2 .Location in patent: Page 25-27

10
[ 29310-88-1 ]
[ 64987-16-2 ]
[ 1123089-24-6 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2008,vol. 44,p. 360 - 365

11
[ 106578-01-2 ]
[ 64987-16-2 ]
[ 1123089-27-9 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2008,vol. 44,p. 360 - 365

12
[ 88735-43-7 ]
[ 64987-16-2 ]
[ 1123089-31-5 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2008,vol. 44,p. 360 - 365

13
[ 106577-99-5 ]
[ 64987-16-2 ]
[ 1123089-29-1 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2008,vol. 44,p. 360 - 365

14
[ 64987-16-2 ]
[ 106578-20-5 ]
[ 1123089-30-4 ]

Reference： [1]Chemistry of Heterocyclic Compounds,2008,vol. 44,p. 360 - 365

15
[ 100-55-0 ]
[ 64987-16-2 ]
[ 530-62-1 ]
[ 924625-59-2 ]

Yield	Reaction Conditions	Operation in experiment
23%		Preparation of methyl(2-[(pyridin-3-ylmethoxy)carbonyl]amino}-1,3-thiazol-4-yl)acetate To a suspension of 1,1'-carbonylbis(1H-imidazole) (2.43 g, 15 mmol) in THF (12 mL) at 0-5 C. was added pyridine-3-methanol (1.63 g, 15 mmol) in THF (5 mL), and stirred at room temperature for 5 hours. The above reaction mixture was added to a solution of <strong>[64987-16-2]methyl (2-amino-1,3-thiazol-4-yl)acetate</strong> (2.58 g, 15 mmol), DBU (2.28 g, 15 mmol) and triethylamine (1.51 g, 15 mmol) in THF (24 ml) and stirred at room temperature, overnight. The THF was removed under reduced pressure and the crude compound was taken in dichloromethane (100 ml), washed with water, the organic layer dried over anhydrous Na2SO4, concentrated and purified by silica gel column chromatography using EtOAc/hexanes (4:6) to afford the title compound as a pale yellow colored solid (1 g, 23% yield).
23%		Step: 2; Preparation of methyl (2-[(pyridin-3-ylmethoxy)carbonyl]amino}-l,3-thiazol-4- yl)acetate; To a suspension of l,l'-carbonylbis(lH-imidazole) (2.43g, 15 mmol) in THF (12 mL) at 0-5 0C was added pyridine-3 -methanol (1.63 g, 15 mmol) in THF (5 mL), and stirred at room temperature for 5 hours. The above reaction mixture was added to a solution of methyl (2-amino-l,3-thiazol-4-yl)acetate (2.58 g, 15 mmol), DBU (2.28 g, 15mmol) and triethylamine (1.51 g, 15 mmol) in THF (24 ml) and stirred at room temperature, overnight. The THF was removed under reduced pressure and the crude compound was taken in dichloromethane (100 ml), washed with water, the organic layer dried over anhydrous Na2Stheta4, concentrated and purified by silica gel column chromatography using EtOAc/hexanes (4:6) to afford the title compound as a pale yellow colored solid (1 g, 23% yield).

Reference： [1]Patent: US2010/152188,2010,A1 .Location in patent: Page/Page column 6
[2]Patent: WO2007/17728,2007,A2 .Location in patent: Page/Page column 15-16

16
[ 76-83-5 ]
[ 64987-16-2 ]
[ 78287-71-5 ]

Yield	Reaction Conditions	Operation in experiment
96%	With triethylamine; In dichloromethane; for 15.0h;	Obtained in 96% yield as a white crystalline solid by treatment of <strong>[64987-16-2]methyl 2-amino-4-thiazolylacetate</strong> with trityl chloride and TEA in DCM for 15 h and successive crystallization of the crude product from diisopropyl ether; mp 177 C; 1H NMR (CDCl3) delta 7.25-7.34 (m, 15H), 6.22 (s, 1H), 3.76 (s, 3H), 3.66 (s, 2H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412

17
[ 64987-16-2 ]
[ 1334402-16-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412

18
[ 64987-16-2 ]
[ 1334402-04-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412

19
[ 64987-16-2 ]
[ 1351823-25-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412

20
[ 64987-16-2 ]
[ 64220-26-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5408 - 5412

21
[ 1427658-56-7 ]
[ 64987-16-2 ]
[ 1416811-05-6 ]

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 58,p. 624 - 639

22
(S)-3-cyclohexyl-2-(5,6-dichloro-1-oxoisoindolin-2-yl)propanoic acid [ No CAS ]
[ 64987-16-2 ]
[ 1416810-89-3 ]

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 58,p. 624 - 639

23
[ 60032-57-7 ]
[ 64987-16-2 ]
[ 56826-61-0 ]
[ 1421928-97-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tris(acetoxy)borohydride; In 1,2-dichloro-ethane; at 0 - 20℃; for 10.0h;	Methyl-2-amino-4-thiazolacetate (420 mg, 2.5 mmol) was added to a solution of <strong>[60032-57-7]2-methylnicotinaldehyde</strong> (300 mg, 2.5 mmol) in 1,2-dichloroethane (5 mL), followed by sodium triacetoxyborohydride (1.0 g, 5.0 mmol) at 0. The reaction mixture was allowed to come to rt and stirred for 10 h. The reaction mixture was quenched with 10% aqueous NaHCO3 solution and extracted with EtOAc. The combined extracts were dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure and the crude product was purified by column chromatography (silica gel 60-120 mesh, eluent 5-10% MeOH in CH2Cl2) to afford methyl 2-(2-(((2-methylpyridin-3-yl)methyl)amino)thiazol-4-yl)acetate (80 mg) along with (2-methyl-pyridin-3-yl)-methanol as mixture. TLC: 100% EtOAc, Rf = 0.3. LC-MS purity >40%

Reference： [1]Patent: WO2013/19621,2013,A1 .Location in patent: Page/Page column 74

24
[ 622-47-9 ]
[ 64987-16-2 ]
[ 1154358-30-1 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 259 - 268

25
[ 621-36-3 ]
[ 64987-16-2 ]
[ 1390409-52-5 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 259 - 268

26
[ 1798-09-0 ]
[ 64987-16-2 ]
[ 1324935-54-7 ]

Reference： [1]Medicinal Chemistry Research,2014,vol. 23,p. 259 - 268

27
[ 64987-16-2 ]
[ 74-88-4 ]
[ 1586872-68-5 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2908 - 2919

28
[ 64987-16-2 ]
[ 1586872-69-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2908 - 2919

29
[ 64987-16-2 ]
[ 1586872-70-9 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2908 - 2919

30
[ 64987-16-2 ]
[ 1586872-71-0 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 2908 - 2919

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; for 2.0h;	General procedure: Step A: methyl 2-(1H-imidazol-4-yl)acetate hydrochloride To a solution of 2-(1H-imidazol-4-yl)acetic acid hydrochloride (200 mg, 1.23 mmol) in methanol (5 ml) was added SOCl2 (145 mg, 1.23 mmol). The reaction mixture was concentrated after two hours to give the desired product
	With thionyl chloride; for 2.0h;	General procedure: Step A: methyl 2-(lH-imidazol-4-yl)acetate hydrochloride To a solution of 2-(lH-imidazol-4-yl)acetic acid hydrochloride (200mg, 1.23 mmol) in methanol (5ml ) was added SOCl2 (145mg, 1.23 mmol). The reaction mixture was concentrated after two hours to give the desired product. LC-MS : m/z (M+H)= 141.1
	With thionyl chloride; for 2.0h;	General procedure: Step A: methyl 2-(lH-imidazol-4-yl)acetate hydrochloride To a solution of 2-(lH-imidazol-4-yl)acetic acid hydrochloride (200mg, 1.23 mmol) in methanol (5ml ) was added SOCl2 (145mg, 1.23 mmol). The reaction mixture was concentrated after two hours to give the desired product. LC-MS : m/z (M+H)= 141.1

32
[ 24424-99-5 ]
[ 64987-16-2 ]
[ 103053-96-9 ]

Yield	Reaction Conditions	Operation in experiment
79%	With dmap; N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 0 - 90℃;	Boc-anhydride (1 .53 mL, 6.6 mmol) was added to <strong>[64987-16-2]methyl 2-(2-aminothiazol-4-yl)acetate</strong> (1 .08 g, 6.28 mmol), N,N-diisopropylethylamine (1 .21 mL, 6.91 mmol) and DMAP (8 mg, 0.06 mmol) in THF (20 mL) at 0 C. The reaction mixture was warmed to room temperature and stirred overnight, then heated to 90 C. After 2 h the reaction was concentrated, and the residue was purified on silica gel, eluting with a 0%-100% EtOAc-hexanes gradient to give the title compound (1 .35 g, 79%). 1H NMR (400 MHz, CD3SOCD3) delta 1 .44 (s, 9 H), 1 .96 (s, 2 H), 3.62 (s, 3 H), 6.89 (s, 1 H), 1 1 .39 (s, 1 H); LC-MS (LC-ES) M-H = 271 .
	In toluene; at 85℃; for 24.0h;	Step B: methyl 2-(2-(tert-butoxycarbonylamino)thiazol-4-yl)acetate A solution of di-tert-butyl dicarbonate (279 mg, 1.28 mmol) in toluene (3 ml) was added a vessel containing <strong>[64987-16-2]methyl 2-(2-aminothiazol-4-yl)acetate</strong> (200 mg, 1.16 mmol), the reaction mixture was heated at 85 C. for 24 h. LCMS showed that the desired product was detected, the mixture was concentrated to give the residue, the residue was purified by a standard method to give the desired product. LC-MS: m/z (M+H)=273.3
	In toluene; at 85℃; for 24.0h;	A solution of di-tert-butyl dicarbonate (279 mg, 1.28 mmol) in toluene (3 ml) was added a vessel containing <strong>[64987-16-2]methyl 2-(2-aminothiazol-4-yl)acetate</strong> (200 mg, 1.16mmol), the reaction mixture was heated at 85 C for 24h. LCMS showed that the desired product was detected, the mixture was concentrated to give the residue, the residue was purified by a standard method to give the desired product. LC-MS : m/z (M+H)= 273.3

at 85℃; for 24.0h;

Step B: methyl 2-(2-(tert-butoxycarbonylamino)thiazol-4-yl)acetate A solution of di-tert-butyl dicarbonate (279 mg, 1.28 mmol) in toluene (3 ml) was added a vessel containing [64987-16-2]methyl 2-(2-aminothiazol-4-yl)acetate (200 mg, 1.16mmol), the reaction mixture was heated at 85 C for 24h. LCMS showed that the desired product was detected, the mixture was concentrated to give the residue, the residue was purified by a standard method to give the desired product. LC-MS : m/z (M+H)= 273.3

Reference： [1]Patent: WO2018/69863,2018,A1 .Location in patent: Page/Page column 194
[2]Patent: US2014/142081,2014,A1 .Location in patent: Paragraph 0901; 0904; 0905
[3]Patent: WO2014/79136,2014,A1 .Location in patent: Page/Page column 187
[4]Patent: WO2014/79150,2014,A1 .Location in patent: Page/Page column 207

33
[ 64987-16-2 ]
[ 1261589-82-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; tert.-butylnitrite; copper(I) bromide; In acetonitrile; at -20 - 20℃; for 2.0h;Inert atmosphere;	Step A: methyl 2-(2-bromothiazol-4-yl)acetate Methyl 2-(2-aminothiazol-4-yl)acetate (5 g, 26.8 mmol) was added under nitrogen to a solution of copper(11) bromide (6.77 g, 30 mmol) and f-butyl nitrite (4.79 ml, 40 mmol) in acetonitrile (20 ml) at -20 C. The reaction mixture was slowly warmed to room temperature and stirred for two hours. The solution was then diluted with diethyl ether and washed with 25 ml of 10 percent hydrochloric acid solution; the aqueous phase was extracted with 20 ml of diethyl ether. The combined organic phases were dried and evaporated to dryness. The residue was purified by a standard method to yield the title compound. LC-MS: m/z (M+H)==235.9
	With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at -20 - 20℃; for 2.0h;Inert atmosphere;	Step A: methyl 2-(2-bromothiazol-4-yl)acetate Methyl 2-(2-aminothiazol-4-yl)acetate (5g, 26.8mmol) was added under nitrogen to a solution of copper(ll) bromide (6.77g, 30mmol) and f-butyl nitrite (4.79ml, 40mmol) in acetonitrile (20ml) at -20C. The reaction mixture was slowly warmed to room temperature and stirred for two hours. The solution was then diluted with diethyl ether and washed with 25ml of 10 percent hydrochloric acid solution; the aqueous phase was extracted with 20ml of diethyl ether. The combined organic phases were dried and evaporated to dryness. The residue was purified by a standard method to yield the title compound. LC-MS : m/z (M+H) = = 235.9
	With tert.-butylnitrite; copper(ll) bromide; In acetonitrile; at -20 - 20℃; for 2.0h;Inert atmosphere;	thyl 2-(2-bromothiazol-4-yl)acetate Methyl 2-(2-aminothiazol-4-yl)acetate (5g, 26.8mmol) was added under nitrogen to a solution of copper(ll) bromide (6.77g, 30mmol) and f-butyl nitrite (4.79ml, 40mmol) in acetonitrile (20ml) at -20C. The reaction mixture was slowly warmed to room temperature and stirred for two hours. The solution was then diluted with diethyl ether and washed with 25ml of 10 percent hydrochloric acid solution; the aqueous phase was extracted with 20ml of diethyl ether. The combined organic phases were dried and evaporated to dryness. The residue was purified by a standard method to yield the title compound. LC-MS : m/z (M+H) = = 235.9

Reference： [1]Patent: WO2020/10140,2020,A1 .Location in patent: Page/Page column 371; 372
[2]Patent: US2014/142081,2014,A1 .Location in patent: Paragraph 0923-0925
[3]Patent: WO2014/79136,2014,A1 .Location in patent: Page/Page column 190
[4]Patent: WO2014/79150,2014,A1 .Location in patent: Page/Page column 210

34
[ 64987-16-2 ]
[ 1610729-36-6 ]

Reference： [1]Patent: US2014/142081,2014,A1
[2]Patent: WO2014/79136,2014,A1
[3]Patent: WO2014/79150,2014,A1

35
[ 64987-16-2 ]
[ 1610728-72-7 ]

Reference： [1]Patent: US2014/142081,2014,A1
[2]Patent: WO2014/79136,2014,A1
[3]Patent: WO2014/79150,2014,A1

36
[ 24424-99-5 ]
[ 64987-16-2 ]
[ 89336-46-9 ]

Reference： [1]Patent: WO2014/79136,2014,A1
[2]Patent: WO2014/79150,2014,A1

37
[ 64987-16-2 ]
[ 1571213-87-0 ]

Reference： [1]Patent: US2015/152096,2015,A1

38
copper(l) cyanide [ No CAS ]
[ 64987-16-2 ]
methyl 2-(2-cyanothiazol-4-yl)acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With tert.-butylnitrite; In acetonitrile; at 50℃; for 1.0h;	To a mixture of tert-butyl nitrite (10 mL, 80 mmol) and CuCN (7.28 g, 80 mmol) in anhydrous acetonitrile (30 mL) was added a solution of ethyl 2-(2-aminothiazol-4-yl)acetate (7.5 g, 40 mmol) in anhydrous acetonitrile (20 mL) dropwise over a period of 1 hour at 50 C., then the mixture was stirred at the temperature for 2.5 hours. The mixture was concentrated in vacuo and the residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=25/1) to give the title compound as yellowish liquid (2 g, 25%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, DMSO-d6): delta 4.01 (q, 2H), 3.72 (s, 2H), 1.16 (t, 3H).
25%	With tert.-butylnitrite; In acetonitrile; at 50℃; for 3.5h;	In a 250 mL three-neck flask, copper cyanide (7.28 g, 80 mmol) was successively added.Anhydrous acetonitrile (30mL),Tert-butyl nitrite(10 mL, 80 mmol),Raise the temperature to 50CA solution of 2-(2-aminothiazol-4-yl)acetic acid ethyl ester (7.5 g, 40 mmol) in anhydrous acetonitrile (20 mL) was added dropwise, and the addition was completed within 1 h and the reaction was continued for 2.5 h. The solvent is distilled off under reduced pressureThe crude product was purified by column chromatography (petroleum ether/ethyl acetate (V/V) = 25/1) to give a slightly yellow liquid (2 g, 25%).

Reference： [1]Patent: US2015/152096,2015,A1 .Location in patent: Paragraph 0716 - 0717
[2]Patent: CN103664897,2018,B .Location in patent: Paragraph 0369; 0370

39
[ 64987-16-2 ]
2-(2-(4,5-dibromo-1H-pyrrole-2-carboxamido)thiazol-4-yl)acetic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 338 - 349
[2]Bioorganic Chemistry,2019,vol. 91

40
[ 64987-16-2 ]
methyl (2-(2-(4,5-dibromo-1H-pyrrole-2-carboxamido)thiazol-4-yl)acetyl)glycinate [ No CAS ]