[ CAS No. 30148-23-3 ] {[proInfo.proName]}

Name: 30148-23-3|1-Methyl-2-(trichloroacetyl)imidazole|98%
Brand: Ambeed
SKU: A840176
Rating: 93 (32 reviews)

,{[proInfo.pro_purity]}

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

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Quality Control of [ 30148-23-3 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 30148-23-3 ]

Product Details of [ 30148-23-3 ]

CAS No. :	30148-23-3	MDL No. :	MFCD03789113
Formula :	C₆H₅Cl₃N₂O	Boiling Point :	-
Linear Structure Formula :	C₃N₂H₂CH₃COCCl₃	InChI Key :	MODGUAUPMUUXLN-UHFFFAOYSA-N
M.W :	227.48	Pubchem ID :	11299122
Synonyms :

Calculated chemistry of [ 30148-23-3 ] Expand+

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	5
Fraction Csp3 :	0.33
Num. rotatable bonds :	2
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.11
TPSA :	34.89 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.35 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.07
Log Po/w (XLOGP3) :	1.89
Log Po/w (WLOGP) :	1.97
Log Po/w (MLOGP) :	0.35
Log Po/w (SILICOS-IT) :	1.9
Consensus Log Po/w :	1.64

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.62
Solubility :	0.549 mg/ml ; 0.00241 mol/l
Class :	Soluble
Log S (Ali) :	-2.25
Solubility :	1.29 mg/ml ; 0.00569 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-2.65
Solubility :	0.509 mg/ml ; 0.00224 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.67

Safety of [ 30148-23-3 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P264-P280-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P405	UN#:	1759
Hazard Statements:	H314	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 30148-23-3 ]

* 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 [ 30148-23-3 ]
Downstream synthetic route of [ 30148-23-3 ]

[ 30148-23-3 ] Synthesis Path-Upstream 1~6

1
[ 30148-23-3 ]
[ 62366-53-4 ]

Reference： [1] Patent: WO2005/85177, 2005, A2, . Location in patent: Page/Page column 61-62

2
[ 30148-23-3 ]
[ 109012-23-9 ]

Reference： [1] Organic Letters, 2001, vol. 3, # 8, p. 1201 - 1203
[2] Heterocycles, 1988, vol. 27, # 8, p. 1945 - 1952

3
[ 30148-23-3 ]
[ 128293-64-1 ]

Reference： [1] Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8151 - 8153

4
[ 30148-23-3 ]
[ 169770-25-6 ]

Reference： [1] Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8151 - 8153

5
[ 67-56-1 ]
[ 30148-23-3 ]
[ 864076-05-1 ]

Yield	Reaction Conditions	Operation in experiment
15.6%	Stage #1: With N-Bromosuccinimide In tetrahydrofuran at -10 - 20℃; for 14 h; Stage #2: at 75℃; for 1 h;	Step 2To a stirred solution of 2,2,2-trichloro-l-(l-methyl-lH-imidazol-2-yl)ethanone (12.42 g, 54.6 mmol) in THF (40 mL) at -10 ⁰C was added n-bromosuccinimide (6.95 ml, 81.9 mmol). The reaction mixturewas kept at -10 ⁰C for 2 h, warmed to RT with stirring for 12 h and concentrated. The residue was purified with ISCO using straight DCM. The solid obtained was dissolved in MeOH (40 mL), 60percent NaH (80 mg) was added and the reaction mixture heated to 75 ⁰C for 1 h. The reaction mixturewas concentrated and the residue purified with ISCO using 0-10percent EtOAc in DCM to give methyl 4-bromo-l-methyl-lH-imidazole-2- carboxylate (1.86 g, 15.6percent yield).

Reference： [1] Patent: WO2009/75874, 2009, A1, . Location in patent: Page/Page column 132

6
[ 30148-23-3 ]
[ 864076-05-1 ]

Reference： [1] Patent: US2012/295885, 2012, A1,
[2] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 10, p. 2197 - 2200
[3] Patent: WO2017/76852, 2017, A1,

[ 30148-23-3 ] Synthesis Path-Downstream 1~109

1
[ 616-47-7 ]
[ 76-02-8 ]
[ 30148-23-3 ]

Yield	Reaction Conditions	Operation in experiment
91%		To a solution of trichloroacetyl chloride (1.36 mL, 12.2 mmol) in toluene (25 mL) was added dropwise a solution of 1-methyl-1H-imidazole (971 μL, 12.2 mmol) in toluene (25 mL), and the mixture was stirred for 7 hr at room temperature. The reaction mixture was ice-cooled, and triethylamine (1.7 mL, 12.2 mL) was added thereto. The mixture was evaporated under reduced pressure. The residue was suspended in THF-toluene mixed solution, and the suspension was purified by filtration column chromatography using silica gel. The residue was concentrated to give the title compound (2.54 g, yield 91%). 1H-NMR (CDCl3) δ: 4.07 (3 H, s), 7.17 (1 H, s), 7.36 (1 H, d, J = 0.8 Hz).
87.2%		To the 50 L reaction kettle adding trichloro acetyl chloride (1.44 kg, 7.9 µM), dichloromethane (10 L). Temperature control 10 C following slowly dropping (a1) N - methyl imidazole of the dichloromethane solution (10 L), produced in the process of dropping a large amount of white solid. Then completing, after stirring overnight at room temperature, then reducing to -5 C slowly dropping TEA (1.78 kg, 17.5 µM), then completing, -5 C stirring 2 h after natural raised to room temperature.Lowering the temperature to 0 C, slowly dropping water to solution is clarified. Layered, washing the organic phase, saturated salt water washing, dried with anhydrous sodium sulfate. The laying of 5 cm of 200 - 300 mesh silica gel filtered, concentrated to obtain the crude product, in adding ether to the crude product of the pulping, shall be 3.47 kg product b2, yield 87.2%. Rapid column processing is the key step in this embodiment, because this reaction is inevitable in the will of produces a small amount of black tarry impurities, the impurities to the product a great impact on the stability, is easy to make the product is decomposed, fast eluent can better remove this impurity, convenient product storage or further participation in the subsequent reaction.
77.6%		Example 30Synthesis of N-(3-methoxy-4-(4-methyl- 1 H-imidazol- 1 -yl)phenyl)- 1 -methyl -4-phenyl- 1 H- imidazole-2-carboxamideSteplTo a solution of trichloroacetyl chloride (13.6 ml, 122 mmol) in DCM (60 rnL) was added 1-methylimidazole (9.69 ml, 122 mmol) in DCM (60 mL) dropwise for a period of 2 h. The reaction mixture was stirred for 4 h at RT, cooled 0 C, and triethylamine (16.9 ml, 122 mmol) was added dropwise over 1 h. After the addition, the solvent was evaporated in vacuo and the residue purified by ISCO using straight DCM to give 2,2,2-trichloro-l -(I -methyl- IH- imidazol-2-yl)ethanone (21.5 g, 77.6% yield).

56%

To the solution of 1-methyl-1H-imidazole (2 g, 24.4 mmol) in 16 mL of DCM was added dropwise 4.4 g of trichloroacetyl chloride and the resulting mixture was stirred at 25 C. for 6 h. The mixture was cooled to 0 C. and 3.4 mL of triethylamine was added dropwise with stirring. The solvent was evaporated and the residue was purified by flash column chromatography (petroleum ether/DCM=4/1) to give 2,2,2-trichloro-1-(1-methyl-1H-imidazol-2-yl)ethanone (3.1 g, yield 56%). 1H NMR (300 MHz, CDCl3) δ 7.35 (s, 1H), 7.16 (s, 1H), 4.06 (s, 3H).

Reference： [1]Patent: EP2518054,2012,A1 .Location in patent: Page/Page column 50
[2]Organic Preparations and Procedures International,2005,vol. 37,p. 403 - 405
[3]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4325 - 4327
[4]Patent: CN109970617,2019,A .Location in patent: Paragraph 0072; 0096-0100
[5]Organic Letters,2020,vol. 22,p. 533 - 536
[6]Heterocycles,1988,vol. 27,p. 1945 - 1952
[7]Journal of Organic Chemistry,2004,vol. 69,p. 8151 - 8153
[8]Patent: WO2009/75874,2009,A1 .Location in patent: Page/Page column 132
[9]Tetrahedron,2021,vol. 92
[10]Patent: US2012/295885,2012,A1 .Location in patent: Page/Page column 32

2
[ 30148-23-3 ]
[ 120095-64-9 ]
[ 120095-65-0 ]

Reference： [1]Heterocycles,1988,vol. 27,p. 1945 - 1952

3
[ 78486-16-5 ]
[ 30148-23-3 ]
[ 129601-50-9 ]

Reference： [1]Heterocycles,1995,vol. 41,p. 1691 - 1708

4
[ 1026336-75-3 ]
[ 30148-23-3 ]
1,1'-(1,10-decanediyl)bis<N-<5-<<(3,3-dimethylaminopropyl)amino>carbonyl>-1-methyl-1H-pyrrol-3-yl>>-4-<<<1-methyl-1H-imidazol-2-yl>carbonyl>amino>-4'-nitro-bis<1H-pyrrole-2-carboxamide> [ No CAS ]

Reference： [1]Heterocycles,1995,vol. 41,p. 1691 - 1708

5
[ 170997-37-2 ]
[ 30148-23-3 ]
[ 170997-38-3 ]
1,1'-(1,10-decanediyl)bis<N-<5-<<(3,3-dimethylaminopropyl)amino>carbonyl>-1-methyl-1H-pyrrol-3-yl>>-4-<<<1-methyl-1H-imidazol-2-yl>carbonyl>amino>-4'-nitro-bis<1H-pyrrole-2-carboxamide> [ No CAS ]

Reference： [1]Heterocycles,1995,vol. 41,p. 1691 - 1708

7
[ 13138-76-6 ]
[ 30148-23-3 ]
[ 297731-27-2 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536
[2]Journal of Organic Chemistry,2000,vol. 65,p. 5506 - 5513

8
[ 128293-62-9 ]
[ 30148-23-3 ]
1-methyl-4-[(1-methyl-1H-imidazole-2-carbonyl)-amino]-1H-imidazole-2-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 5506 - 5513

9
[ 30148-23-3 ]
[ 120095-64-9 ]

Yield	Reaction Conditions	Operation in experiment
64.3%	With sulfuric acid; nitric acid; acetic anhydride; at 0 - 20℃;Large scale; Green chemistry;	To a 50L reactor, add acetic anhydride (18L), b2 (2.0Kg), cool to 0 C, add concentrated sulfuric acid (1L) dropwiseInto the reaction vessel, concentrated nitric acid (1.760 L) was slowly added dropwise to the reaction vessel at a controlled temperature of 20 C. Reaction to monitoring no raw material remainingI. It was beaten with diethyl ether and filtered to give 1.54 Kg of white solid c2.Yield: 64.3%.

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 8151 - 8153
[2]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186
[3]Patent: CN109970617,2019,A .Location in patent: Paragraph 0072; 0105-0108
[4]Organic Letters,2001,vol. 3,p. 1201 - 1203
[5]Organic Letters,2020,vol. 22,p. 533 - 536

10
[ 30148-23-3 ]
[ 297731-25-0 ]
[ 457641-36-0 ]

Reference： [1]Journal of the Chinese Chemical Society,2002,vol. 49,p. 1073 - 1077

11
[ 30148-23-3 ]
[ 910545-46-9 ]
[ 457641-32-6 ]

Reference： [1]Journal of the Chinese Chemical Society,2002,vol. 49,p. 1073 - 1077

12
[ 30148-23-3 ]
3-({4-[(4-amino-1-methyl-1H-pyrrole-2-carbonyl)-amino]-1-methyl-1H-imidazole-2-carbonyl}-amino)-propionic acid ethyl ester [ No CAS ]
[ 457641-41-7 ]

Reference： [1]Journal of the Chinese Chemical Society,2002,vol. 49,p. 1073 - 1077

13
[ 30148-23-3 ]
3-({4-[(4-amino-1-methyl-1H-imidazole-2-carbonyl)-amino]-1-methyl-1H-imidazole-2-carbonyl}-amino)-propionic acid ethyl ester [ No CAS ]
[ 457641-43-9 ]

Reference： [1]Journal of the Chinese Chemical Society,2002,vol. 49,p. 1073 - 1077

14
[ 128293-64-1 ]
[ 109-55-7 ]
[ 30148-23-3 ]
[ 538372-40-6 ]
Boc-β-alanine-(4-carbonylaminomethyl)benzyl ester copoly(styrene-divinylbenzene)resin [ No CAS ]
4-BocNH-1-methyl-1H-pyrrole 2-carboxylic acid butyl ester [ No CAS ]
C₆₀H₆₇N₂₁O₁₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

15
[ 128293-64-1 ]
[ 109-55-7 ]
[ 30148-23-3 ]
[ 752986-91-7 ]
Boc-β-alanine-(4-carbonylaminomethyl)benzyl ester copoly(styrene-divinylbenzene)resin [ No CAS ]
4-BocNH-1-methyl-1H-pyrrole 2-carboxylic acid butyl ester [ No CAS ]
C₅₈H₆₈N₂₂O₁₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

16
[ 109-55-7 ]
[ 30148-23-3 ]
2-(4-tert-butoxycarbonylamino-1-methyl-1H-imidazol-2-yl)-3H-benzoimidazole-5-carboxylic acid [ No CAS ]
[ 752986-91-7 ]
Boc-β-alanine-(4-carbonylaminomethyl)benzyl ester copoly(styrene-divinylbenzene)resin [ No CAS ]
4-BocNH-1-methyl-1H-pyrrole 2-carboxylic acid butyl ester [ No CAS ]
C₅₉H₆₆N₂₂O₉ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

17
[ 30148-23-3 ]
[ 538372-37-1 ]
methyl 7-methoxy-2-(1-methylimidazol-2-yl)benzimidazole-6-carboxylate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

18
[ 109-55-7 ]
[ 30148-23-3 ]
[ 752986-91-7 ]
H2N-(1-methyl-1H-pyrrole)-(4-aminobutyric acid)-(1-methyl-1H-imidazole)-(1-methyl-1H-pyrrole)3-β-alanine-Pam resin [ No CAS ]
C₅₈H₆₈N₂₂O₁₀ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

19
[ 109-55-7 ]
[ 30148-23-3 ]
2-(4-tert-butoxycarbonylamino-1-methyl-1H-imidazol-2-yl)-3H-benzoimidazole-5-carboxylic acid [ No CAS ]
[ 752986-91-7 ]
NH2-(1-methyl-1H-pyrrole)2-β-alanine-Pam resinBoc-4-aminobutyric acid [ No CAS ]
C₅₉H₆₆N₂₂O₉ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2004,vol. 126,p. 10339 - 10349

20
4-(3-amino-propionylamino)-1-methyl-1H-pyrrole-2-carboxylic acid ethyl ester [ No CAS ]
[ 30148-23-3 ]
[ 865307-77-3 ]

Yield	Reaction Conditions	Operation in experiment
	With diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 2h;	The compound 18 (510 mg, 1.5 mmol) was mixed with 10% trifluoroacetic acid/methylene chloride (24 mL, 30 mmol) and stirred for one hour at a room temperature. The resulting solution was washed with water (15 mL), dehydrated over sodium sulfate, filtered and concentrated. The resulting residue was dissolved in DMF, mixed with N,N'-diisopropylamine (128 µl, 0.75 mmol) and the compound 5 (490 mg, 1.8 mmol) and stirred for two hours at a room temperature. The resulting solution was extracted with chloroform (30ml) and water (20mL), dehydrated over sodium sulfate and concentrated. Re-precipitation of the resulting residue from chloroform and diisopropylether gave the compound 19 (475 mg, 91 %). 1HNMR(DMSO-d6) δ 1.26-1.28 (3H,t,J=7.1Hz), 2.53-2.56(2H,t,J=6.8Hz), 3.45-3.49(2H,m), 3.89(3H,s), 3.92(3H,s), 4.22-4.26(2H,m), 6.94(1H,s), 7.31(1H,s), 7.53(1H,s), 8.34(1H,m), 10.7(1H,s).

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 10311 - 10322
[2]Patent: EP1719777,2006,A1 .Location in patent: Page/Page column 17; 21

21
[ 72083-62-6 ]
[ 30148-23-3 ]
[ 297731-27-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 20℃; for 14h;	Methyl 1 -methyl-4-nitropyrrole-2- carboxylate 31 (6.0 g, 32.6 mmol) was dissolved in EtOAc (100 mL). A slurry of moist 10% Pd/C (600 mg) in EtOAc was added and the contents were stirred vigorously under H2 (70 psi) for 16 h. The reaction mixture was filtered through a bed of Celite. The Celite was washed with MeOH and the combined filtrate was evaporated under reduced pressure to furnish crude amine as dark oil. The crude oil, without any further purification, was taken up in CH3CN (60 mL). Contents were cooled to 0 C and DIPEA (12 mL, 62.4 mmol) was added. A solution of l-methyl-2- trichloroacetylimidazole 24 (8.5 g, 31 mmol) in CH3CN (10 mL) was added and the reaction mixture was allowed to stir at ambient temperature for 14 h. Solvents were removed under reduced pressure and the solid obtained was washed with hexanes and filtered to afford 32. (8.0 g, 94 %). 1H-NMR (CDCl3) 09.08 (s, exch, IH, NH), 7.41 (s, IH, Py-C5H), 7.03 (s, IH, Im-C5H), 6.98 (s, IH, Im-C4H), 6.80 (s, IH, Py-C3H), 4.08 (s, 3H, CH3), 3.90 (s, 3H, CH3), 3.78 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6161.8 (+, s, CO), 157.1 (+, s, CO), 139.1 (+, s, Im-C2), 128.3 (-, d, Im- C4), 127.1 (-, d, Im-C5), 122.6 (+, s, Py-C2), 121.7 (-, d, Py-C5), 119.7 (+, s, Py-C4), 109.5 (-, d, Py-C3), 51.2 (-, q, OCH3), 37.9 (-, q, CH3), 35.5 (-, q, CH3). EI-HRMS: m/z calcd for C12H14N4O3 262.1066, found 262.1056 (M+, 100%), 174.0661 (20%), 109.0407 (40%).

Reference： [1]Journal of Organic Chemistry,2005,vol. 70,p. 10311 - 10322
[2]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 44; 82

22
[ 162085-97-4 ]
[ 30148-23-3 ]
[ 849665-11-8 ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0℃; for 10h;	Methyl l-methyl-4- nitroimidazole-2-carboxylate 40 (3.3 g, 17.8 mmol), dissolved in 1 : 1 MeOH:EtOAc (100 niL), was shaken with hydrogen at 70 psi, for 14 h in presence of Pd/C (400 mg). The reaction mixture was filtered through a bed of celite. The celite was washed with MeOH and the filtrate was concentrated under reduced pressure to furnish crude amine as black oil. The residue was taken up in benzene and concentrated to furnish the amine as black solid, filtered and washed with ether (2.5 g, 88%). The crude amine was dissolved in CH3CN (50 mL) and DIEA (2.3, 18 mmol). A solution of 1- methyl-2-trichloroacetylimidazole 24 (3.6 g, 14.7 mmol) in CH3CN (50 mL) was added to the amine solution at 0 0C. The reaction mixture was allowed to stir for 10 h, solvent was removed and the residue was taken up in MeOH and the product was precipitated by addition Of Et2O to furnish desired compound 41 (2.13 g, 68%). 1H- NMR (DMSO-d6) δlθ.1 1 (s, exch, IH, NH), 7.69 (s, IH, Im'-C5H), 7.43 (s, IH, Im- C5H), 7.07 (s, IH, Im-C4H), 3.99 (s, 3H, CH3), 3.97 (s, 3H, CH3), 3.82 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6159.4 (+, s, CO), 157.2 (+, s, CO), 138.9 (+, s, Im- C2), 137.2 (+, s, Im-C2), 132.4 (+, s, Im-C4), 128.9 (-, d, Im-C4), 127.7 (-, d, Im-C5), 117.3 (-, d, Im-C5), 61.9 (+, t, -OCH2-), 37.6 (-, q, CH3), 35.8 (-, q, CH3), 14.2 (-, q, CH3). EI-HRMS: m/z calcd for C1 1H13N5O3 263.1018; found 263.1016 (M+, 100%), 204.0888 (27%), 182.0573 (27%), 150.0301 (30%), 109.0393 (26%).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 45; 87
[2]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

23
[ 30148-23-3 ]
[ 940931-13-5 ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

24
[ 30148-23-3 ]
C₂₆H₃₀N₁₀O₆ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

25
[ 30148-23-3 ]
[ 940931-15-7 ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

26
[ 30148-23-3 ]
C₅₂H₅₈N₂₀O₁₁ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

27
[ 30148-23-3 ]
C₆₀H₇₄N₂₂O₁₂ [ No CAS ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

28
[ 30148-23-3 ]
[ 464892-44-2 ]

Reference： [1]Chemistry - A European Journal,2007,vol. 13,p. 3177 - 3186

29
[ 30148-23-3 ]
[ 128293-64-1 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 8151 - 8153
[2]Organic Letters,2020,vol. 22,p. 533 - 536

30
[ 30148-23-3 ]
[ 169770-25-6 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 8151 - 8153
[2]Organic Letters,2020,vol. 22,p. 533 - 536

31
[ 30148-23-3 ]
[ 500701-36-0 ]

Reference： [1]Journal of Organic Chemistry,2004,vol. 69,p. 8151 - 8153

32
[ 30148-23-3 ]
[ 109012-23-9 ]

Reference： [1]Organic Letters,2001,vol. 3,p. 1201 - 1203
[2]Heterocycles,1988,vol. 27,p. 1945 - 1952

33
[ 30148-23-3 ]
4-Amino-1-methyl-1H-imidazole-2-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Organic Letters,2001,vol. 3,p. 1201 - 1203
[2]Patent: CN109970617,2019,A

34
[ 30148-23-3 ]
[ 179983-49-4 ]

Reference： [1]Organic Letters,2001,vol. 3,p. 1201 - 1203
[2]Patent: CN109970617,2019,A

35
[ 30148-23-3 ]
[ 62366-53-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide; In tetrahydrofuran; at -10 - 20℃; for 14h;	NBS (N-Bromosuccinimide, 16.2 g, 91.0 mmol, 2.0 Equiv. ) was added to a stirred solution of 2- (trichloroacetyl)-l-methylimidazole (as described by Nishiwaki, E.; Tanaka, S. ; Lee, H. and Shibuya, M. Heterocycles, Vol. 27, No. 8,1988, 1945-1952) (10.35 g, 45.5 mmol, 1.0 Equiv. ) in anhydrous THF (180 mL) at-10C. The reaction mixture was kept at-10C for 2 hours and then left to reach room temperature (ca. 12 h). The THF excess was evaporated in vacuum and the solid was redissolved in chloroform and passed through a pad of Silica Gel (CHC13). The isolated compound was dried and redissolved in dried MeOH (100 mL). To the solution was added through a syringe a solution of sodium methoxide (5 mL). The sodium methoxide solution was prepared from NaH 60% in mineral oil (165 mg, 4.10 mmol, 0.1 Equiv. ), which was previously washed with hexane. The solution was heated to reflux over a period of 30 minutes, when the TLC analysis showed complete consumption of the starting material. The excess of MeOH was evaporated in vacuum and the resulting oil was subject of a flash chromatography (CHC13/Hexane 8: 2) to give a yellow solid 34. (3.62 g, 36. 3%). IR (film, cm-1) 3121,2949, 1718 (C=O), 1442,1414, 1394,1274, 1243, 1190,1147, 1125,1063, 950, 827,804, 662, 631 ; 1H NMR (CDCl3) # 7.05 (1H, s, H-5), 4.01 (3H, s, CH3), 3.94 (3H, s, OCH3) ;"C NMR (CDC13) 8 158.6 (C=O), 136.0 (C2), 125.8 (C5), 115.6 (C4), 52.5 (OCH3) 36.1 (CH3) ; MS (EI) m/z (relative intensity) 219.01 ( [M + H]+ 50%, 220.99 ( [M + H] + 50%).

Reference： [1]Patent: WO2005/85177,2005,A2 .Location in patent: Page/Page column 61-62

36
[ 30148-23-3 ]
[ 500903-70-8 ]
[ 934992-89-9 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 14h;	A solution of 34 (4.6 g, 15 mmol) in 1 :1 MeOH:DMF (100 niL) was stirred with hydrogen at 70 psi in the presence of Pd/C (400 mg) for 14 h. The reaction mixture was filtered through a bed of celite. The celite was washed with MeOH and the filtrate was concentrated under reduced pressure to furnish crude amine as oil. The crude amine without any further purification was taken up in CH3CN (50 rnL) and DIEA (4 mL). A solution of 24 (3.4 g, 15 mmol) in DMF (20 mL) was added and the reaction mixture was allowed to stir at ambient temperature for 14 h during which solid precipitated out. Reaction mixture was filtered and washed with Et2O to furnish 34 (3.6 g). The filtrate was chromatographed to yield additional 1 g of product, (yield 80.7 %). 1H-NMR (CDCl3) 59.53 (s, exch, IH, NH), 8.88 (s, exch, IH), 7.46 (s, IH, Im'-C5H), 7.41 (s, IH, Py-C5H), 7.06 (s, IH, Im-C5H), 7.00 (s, IH, Im-C4H), 6.80 (s, IH, Py-C3H), 4.09 (s, 3H), 4.07 (s, 3H), 3.91 (s, 3H), 3.81 (s, 3H, OCH3). 1H-NMR (DMSO-d6) δlθ.43 (s, exch, IH, NH), 9.72 (s, exch, IH), 7.66 (s, IH, Im'-C5H), 7.55 (s, IH, Py-C5H), 7.43 (s, IH, Im-C5H), 7.06 (s, IH, Im-C4H), 7.01 (s, IH, Py-C3H), 4.00 (s, 3H, CH3), 3.99 (s, 3H, CH3), 3.84 (s, 3H, CH3), 3.73 (s, 3H, OCH3). '3C-NMR (75 MHz, DMSO-d6) 6161.0 (+, s, CO), 155.9 (+, s, CO), 155.8 (+, s, CO), 138.0 (+, s, Im-C2), 134.9 (+, s, Im-C2), 134.4 (+, s, Im- C4), 127.9 (-, d, Im-C4), 127.3 (-, d, Im-C5), 122.3 (+, s, Py-C2), 121.1 (+, s, Py-C4), 1 18.9 (-, d, Py-C5), 1 14.3 (-, d, Im-C5), 108.9 (-, d, Py-C3), 51.2 (-, q, -OCH3), 36.5 (-, q, CH3), 35.4 (-, q, CH3), 35.3 (-, q, CH3). EI-HRMS: m/z calcd for CnH19N7O4 385.1499; found 385.1493 (M+, 100%), 303.0975 (39%), 244.0838 (16%), 205.0961 (6%), 180.0525 (8%), 150.0301 (6%), 109.0396 (15%).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 44; 85

37
[ 126092-99-7 ]
[ 30148-23-3 ]
[ 174223-31-5 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 14h;	A solution of 33 (4.6 g, 15 mmol) in 1 : 1 MeOH:DMF (100 mL) was stirred with hydrogen at 70 psi in the presence of Pd/C (400 mg) for 14 h. The reaction mixture was filtered through a bed of celite. The celite was washed with MeOH and the filtrate was concentrated under reduced pressure to furnish crude amine as oil. The crude amine without any further purification was taken up in DMF (50 mL) and DIEA (4 mL). A solution of 24 (3.4 g, 15 mmol) in DMF (20 mL) was added and the reaction mixture was allowed to stir at ambient temperature for 14 h. Solvents were removed under reduced pressure and the contents were taken up in H2O (100 mL), upon which the product 36 precipitated out, filtered and washed with Et2O (5.2 g, 91%). 1H-NMR (DMSO-d6) 610.47 (s, exch, IH, NH), 9.96 (s, exch, IH, NH), 7.47 (s, IH, Im-C5H), 7.39 (s, IH, Py-C5H), 7.28 (s, IH, Py-C5H), 7.19 (s, IH, Py-C3H), 7.04 (s, IH, Im-C4H), 6.92 (s, IH, Py-C3H), 3.99 (s, 3H, CH3), 3.84 (s, 3H, CH3), 3.83 (s, 3H, CH3), 3.73 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6161.0 (+, s, CO), 158.7 (+, s, CO), 156.3 (+, s, CO), 139.0 (+, s, Im-C2), 127.2 (-, d, Im-C4), 126.6 (-, d, Im-C5), 123.2 (+, s, Py-C2), 123.0 (+, s, Py-C2), 121.7 (+, s, Py-C4), 121.0 (+, s, Py-C4), 119.0 (-, d, Py-C5), 118.7 (-, d, Py-C5), 108.6 (-, d, Py-C3), 105.2 (-, d, Py-C3), 51.1 (-, q, -OCH3), 36.4 (-, q, CH3), 36.3 (-, q, CH3), 35.3 (-, q, CH3). EI- HRMS: m/z calcd for C18H20N6O4 384.1546; found 384.1549 (M+, 100%), 302.0999 (8%), 231.0881 (86%), 149.0355 (55%), 109.0402 (44%).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 44; 84

38
[ 30148-23-3 ]
methyl 2-(4-amino-1-methyl-1H-pyrrol-2-yl)-1H-benzimidazole-5-carboxylate [ No CAS ]
[ 934993-02-9 ]

Yield	Reaction Conditions	Operation in experiment
80%	In acetonitrile; at 30℃; for 2h;	The amine derivative 67 was treated with a 1.5-fold excess of 2-trichloroacetyl-l-methylimidazole dissolved in CH3CN. The mixture was stirred at 30 0C for 2 h, and the resultant suspension filtered to afford a yellow solid which was recrystallized (MeOH) to give the title product (80% yield based on imidazole). 1H-NMR (500 MHz, DMSO-d6) (Mix of tautomers) 612.89 (s, exch, IH, NH), 10-56 (s, exch, IH, NH), 8.19 + 8.01 (split s, IH, Bzi-C4H), 7.83 + 7.78 (split d, IH, Bzi-C6H), 7.68 + 7.52 (split d, IH, Bzi-C7H), 7.43 (d, IH, J = 1.8 Hz, Py-C5H), 7.38 (s, IH, Im-C5H), 7.27 + 7.24 (split d, IH, Py-C3H), 7.07 (s, IH, Im-C4H), 4.07 (s, 3H, CH3), 4.03 (s, 3H, CH3), 3.86 (s, 3H, CH3); 13C-NMR (125 MHz, DMSO-d6) 6167.7, 156.9, 149.1, 139.6, 127.8 (CH), 127.2 (CH), 123.7 (CH), 120.6 (CH), 119.3 (CH), 1 12.9, 1 1 1.4 (CH), 105.4 (CH), 52.8 (CH3), 37.4 (CH3), 35.9 (CH3) (assigned using HMBC); ES-HRMS: m/z calcd for Ci9Hi9N6O3+ (MH+) 379.1513, found 379.1523 (100%), 757.3095 (4%, M2H+), 271.1233 (15%), 190.0797 (17%),

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 51; 98

39
[ 934993-18-7 ]
[ 30148-23-3 ]
[ 934992-92-4 ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 20℃; for 14h;	Methyl l-methyl-[4-(l-methyl-4-nitro-pyrrole-2-carboxamido)]- imidazole-2-carboxylate 42 (6 g, 19.5 mmol) was dissolved in 1 :1 DMF/MeOH. A slurry of moist 10% Pd/C in DMF was added and the contents were stirred vigorously under hydrogen (70 psi) for 14 h. The reaction mixture was filtered through a bed of celite. The celite was washed with MeOH and the filtrate was concentrated under reduced pressure to furnish crude amine as an oil. The oil was taken up in benzene and solvents were removed under reduced pressure. The residue was taken up in EPO <DP n="92"/>CH3CN and the solvents were removed to furnish amine as brown solid, filtered washed with Et2O and set for coupling reaction. To a solution of amine (5.1 g, 95%) in CH3CN (150 mL) and DIEA (5 mL, 27 mmol) was added a solution of l-methyl-2- trichloroacetylimidazole 24 (4.5 g, 20 mmol) in CH3CN (40 mL). The reaction mixture was allowed to stir at ambient temperature for 14 h. Solvents were removed under reduced pressure and the residue was treated with 1 : 1 CH3CN/Et20 during which 45 precipitated out as brown solid (5 g, 70%). 1H-NMR (DMSO-d6) δlθ.71 (s, exch, IH, NH), 10.36 (s, exch, IH, NH), 7.67 (s, IH, Im'-C5H), 7.39 (2 x overlapping s, IH each, Im-C5H + Py-C5H), 7.22 (s, IH, Py-C3H), 7.04 (s, IH, Im-C4H), 3.98 (s, 3H, CH3), 3.93 (s, 3H, CH3), 3.85 (s, 3H, CH3), 3.82 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6159.1 (+, s, CO), 158.9 (+, s, CO), 156.3 (+, s, CO), 139.0 (+, s, Im-C2), 138.0 (+, s, Im-C2), 130.9 (+, s, Im-C4), 127.2 (-, d, Im-C4), 126.5 (-, d, Im- C5), 122.2 (+, s, Py-C2), 121.6 (+, s, Py-C4), 1 19.8 (-, d, Py-C5), 1 15.7 (-, d, Im-C5), 106.3 (-, d, Py-C3), 51.9 (-, q, -OCH3), 36.5 (-, q, CH3), 35.7 (-, q, CH3), 35.3 (-, q, CH3). EI-HRMS: m/z calcd for C17H19N7O4 385.1499; found 385.1506 (M+, 100%), 327.1450 (7%), 303.1014 (4%), 231.0907 (81%), 203.0860 (10%), 149.0426 (40%), 109.0342 (59%).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 45; 89-90

40
[ 162085-98-5 ]
[ 30148-23-3 ]
[ 934992-93-5 ]

Yield	Reaction Conditions	Operation in experiment
31%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; acetonitrile; at 20℃; for 14h;	A solution of methyl l-methyl-4-[(l-methyl-4-nitro-imidazole-2- carboxamido)]-imidazole-2-carboxylate 43 (4 g, 13 mmol) in 1 :1 MeOH/EtOAc (200 mL) was hydrogenated using 5% Pd/C (400 mg) at 70 psi for 18 h. The green reaction mixture was filtered through a bed of celite. The celite bed was washed with MeOH and the filtrate was concentrated to furnish crude amine as an oil. The oil obtained was taken up in benzene, solvents were removed to furnish amine as a green solid (2 g, 60%). To a solution of amine (1.8 g, 6.47 mmol) in CH3CN (50 mL), DMF (10 mL) and DIEA (5 mL), was added a solution of l-methyl-2- trichloroacetylimidazole 24 (1.47 g, 6.47 mmol) in CH3CN (20 mL). The reaction mixture was allowed to stir at ambient temperature for 14 h. Solvents were removed and the residue was taken up in 1PrOH during which solid product precipitated out, filtered washed with ether to furnish crude product 46, which was purified by column EPO <DP n="93"/>chromatography using 1 : 1 MeOH:EtOAc (800 mg, 31%). 1H-NMR (CDCl3) 69.45 (s, exch, IH, NH), 9.41 (s, exch, IH, NH), 7.56 (s, IH, Im'-C5H), 7.49 (s, IH, InV-C5H), 7.09 (s, IH, Im-C5H), 7.01 (s, IH, Im-C4H), 4.08 (s, 3H, CH3), 4.06 (s, 3H, CH3), 4.01 (s, 3H, CH3), 3.94 (s, 3H, CH3), 3.92 (s, 3H, OCH3). 13C-NMR (75 MHz, DMSO-d6) 6160.4 (+, s, CO), 159.2 (+, s, CO), 157.1 (+, s, CO), 138.8 (+, s, Im-C2), 137.0 (+, s, Im-C2), 134.7 (+, s, Im-C2), 134.4 (+, s, Im-C4), 132.2 (+, s, Im-C4), 129.4 (-, d, Im-C4), 127.5 (-, d, Im-C5), 127.1 (-, d, Im-C5), 1 17.3 (-, d, Im-C5), 51.3 (-, q, - OCH3), 37.6 (-, q, CH3), 36.1 (-, q, CH3), 35.8 (-, q, CH3). EI-HRMS: m/z calcd for C16H18N8O4 386.1451; found 385.1456 (M+, 100%), 328.1402 (18%), 304.0920 (10%), 205.0962 (20%), 182.0562 (22%), 150.0308 (24%), 109.0399 (30%).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 45; 90-91

41
[ 30148-23-3 ]
C₆H₃Br₂Cl₃N₂O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4325 - 4327

42
tert-butyl 2-amino-4-(3-aminopropyl)-1H-imidazole-1-carboxylate [ No CAS ]
[ 30148-23-3 ]
[ 1111651-00-3 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 1755 - 1758

43
[ 67-56-1 ]
[ 30148-23-3 ]
[ 864076-05-1 ]

Yield	Reaction Conditions	Operation in experiment
15.6%		Step 2To a stirred solution of 2,2,2-trichloro-l-(l-methyl-lH-imidazol-2-yl)ethanone (12.42 g, 54.6 mmol) in THF (40 mL) at -10 0C was added n-bromosuccinimide (6.95 ml, 81.9 mmol). The reaction mixturewas kept at -10 0C for 2 h, warmed to RT with stirring for 12 h and concentrated. The residue was purified with ISCO using straight DCM. The solid obtained was dissolved in MeOH (40 mL), 60percent NaH (80 mg) was added and the reaction mixture heated to 75 0C for 1 h. The reaction mixturewas concentrated and the residue purified with ISCO using 0-10percent EtOAc in DCM to give methyl 4-bromo-l-methyl-lH-imidazole-2- carboxylate (1.86 g, 15.6percent yield).

Reference： [1]Patent: WO2009/75874,2009,A1 .Location in patent: Page/Page column 132

44
C₅₈H₆₅N₁₈O₁₁Pol [ No CAS ]
[ 30148-23-3 ]
C₆₃H₆₉N₂₀O₁₂Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 40℃; for 4h;	DNA-binding polymer (9), which contains an N-terminal N-methylimidazole (Im) was used as a control polymer. Resin (R1) was treated with 80% TFA in dichloromethane and washed thoroughly. A solution of <strong>[30148-23-3]2-trichloroacetyl-1-methylimidazole</strong> (34 mg, 0.148 mmol) in DMF (0.45 mL) and DIEA (0.5 mL) was poured onto the deprotected resin. The resin slurry was shaken for 4 h at 40 C. and filtered. After washing with DMF and dichloromethane, the resin was cleaved with Dp (1 mL) at 40 C. for 4 h. The crude product was purified by reversed-phase HPLC to afford (9) as a yellow solid upon lyophilization (2.5 mg, 6.9% recovery). MALDI-TOF-MS m/z 1222.03 (1222.58 calcd for M+H).

Reference： [1]Patent: US2009/155202,2009,A1 .Location in patent: Page/Page column 17

45
[ 30148-23-3 ]
methyl 4-[4-(4-amino-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxamido]-1-methyl-1H-pyrrole-2-carboxylate hydrochloride [ No CAS ]
ImPyPyPy-CO₂Me [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2009,vol. 131,p. 7175 - 7181

46
[ 30148-23-3 ]
[ 500701-36-0 ]
[ 849665-11-8 ]

Yield	Reaction Conditions	Operation in experiment
29%		Methyl 4- [ (TERT-BUTOXYCARBONYL) AMINO]-L-METHYLPYRROLE-2-CARBOXYLATE (0.181 g, 0.71 mmol) in TFA/DCM (1 : 1, 4 ml) and H2O (40PL) WAS stirred at room temperature for 30 min. The solvent was removed under reduced pressure and the residue was dissolved in EtOAc (2 ml). Et3N (0.299 ml, 2.13 mmol, 3 equiv) was added followed by N-methylimidazole-2-trichloroacetyl chloride (0.161 g, 0.709 mmol) and the mixture stirred for 2 hr. The solid was collected and air-dried. Yield 0.053 g (29%). H NMR (DMSO) -D6: 8 10.07 (S, 1H), 7.68 (S, 1H), 7.42 (S, 1H), 7.05 (S, 1H), 3.97 (S, 3H), 3.98 (S, 3H), 3.94 (s, 3H), 3.81 (s, 3H).

Reference： [1]Patent: WO2005/33077,2005,A1 .Location in patent: Page/Page column 52

47
[ 934992-95-7 ]
[ 30148-23-3 ]
Mp-Bzi-Py-Im [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General Procedure F. Typically, an acid derivative (1 mmol) was added to DMF (5 mL), to which the following were added in the order as written: HOBt (1.2 mmol), a carbodiimide (either EDCI or DIC, 1.1 mmol), and DIPEA (2 mmol). The resultant suspension was stirred at 45 0C for 3-4 h. After that period, a solution of the amine derivative (1 mmol) in 5 mL DMF was added and the reaction mixture was stirred at 60 0C for an additional 10-16 h. At the end of that period, the mixture was concentrated or evaporated to dryness to remove most of DMF, followed by addition of CH3CN to the contents that resulted in a suspension. Filtration of the material afforded solid residue that was subjected to silica gel column chromatography (eluting the material with a gradient system from 4:1 CHCl3 :MeOH to neat MeOH and finally with 2-4% NH4OH in MeOH). The final products are quite polar and the initial fractions from the column (that were discarded) contained the urea and HOBt. EPO <DP n="106"/>Fractions containing the products were pooled together and evaporated. After an initial characterization and confirming the presence of products, the material was extensively lyophilized to remove traces Of NH3. Final purification of the products entailed conversion to the hydrochloride salt forms by treatment with methanolic HCl and crystallization (MeOH/Et2O or MeOH/acetone binary solvent mixtures). Final product yields are unoptimized since our foremost requirement was recovery of as much material of high purity (by 1H-NMR) as possible. Note: Free base forms were usually dissolved in DMSOd6 or CD3OD for characterization; the former generally gave better resolution spectra but the attendant problems due to mixtures of tautomers for the benzimidazole ring were overcome with fast-exchanging solvent (CD3OD) or by addition of small aliquots of either acid (CF3COOD) or base (1,4- dimethylpiperazine). The C-13 NMR and HMBC/QC experiments were performed only on representative members of each family of compounds due to limited solubility of these compounds and impossible recovery from solution states when dissolved in DMSO-d6. The HCl salt forms were readily soluble in D2O or CD3OD for ease in analysis.The following first series of final products (F1-F4) were all prepared from the same amine (49) and different acid derivatives listed individually for each data set below. Mp-Bzi-Py-Im (F-I) was prepared from 2-trichloroacetyl-l-methylimidazole and amine 49 treated together in CH3CN and according to the isolation methodlogy in general procedure F above. Recovery 56%. 1H-NMR (500 MHz, HCl salt in CD3OD) 67.61 (d, IH, Bzi-C7H), 7.56 (s, 2H, 2 x Im-CH), 7.48 (s, IH, Py-C5H), 7.25 (d, IH, BzI-C6H), 7.23 (s, IH, Bzi-C4H), 7.1 1 (s, IH, Py-C3H), 4.03 (s, 3H, CH3), 3.94 (s, 3H, CH3), 3.82 (m, 2H, CH2), 3.61 (m, 2H, CH2), 3.2 (m, 4H, CH2), 2.93 (s, 3H, CH3). (note the assignment of singlets for Py/Im-CH may be ambiguous). 13C- NMR (125 MHz, HCl salt in CD3OD) 6153.0 (+), 150.3 (+), 142.0 (+), 137.3 (+), 133.6 (+), 127.9, 127.1 (+), 124.0, 123.7 (+), 122.3, 119.2, 115.9 (+), 115.4, 110.0, 101.0, 54.5 (+), 43.9 (-), 37.4 (-), 37.0 (-). ES-HRMS: m/z calcd for C22H26N8O 418.2230, found 418.2981 (M+, 100%), 416.2827 (54%, M-2), 417.2919 (40%, M-I), 419.2964 (50%, M+l), 420.3125 (14%, M+2).

Reference： [1]Patent: WO2007/45096,2007,A1 .Location in patent: Page/Page column 47; 103-104

48
[ 30148-23-3 ]
[ 1260672-33-0 ]

Reference： [1]Patent: EP2518054,2012,A1

49
[ 30148-23-3 ]
[ 1313196-09-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In acetonitrile; at 0 - 20℃; for 20h;	To a stirred solution of 4 (3.41 g, 15 mmol) in CH3CN (30 mL) at 0 C was added DBH (2.58 g, 9.0 mmol).The reaction was gradually warmed up to room temperature and then kept stirring for 20 h at the sametemperature. The reaction was quenched with 5% aq. Na2S2O3 and the mixture was extracted with EtOAc. Thecombined organic layers were washed with brine, dried over Na2SO4, and then concentrated under reducedpressure. The obtained residue was recrystallized from acetone to give the desired product 3 (4.17 g, 91%yield) as white solid.
91%	With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; In acetonitrile; at 0 - 25℃; for 24h;	A solution of the compound 2a-2 (3.41 g, 15 mmol) in MeCN (30 mL) was stirred at 0 C., to which DBH (2.58 g, 9.0 mmol) was added. The reaction was performed by gradually increasing the temperature to room temperature, and then continuously stirring at that temperature for 24 hours. A 5% Na2S2O3 aqueous solution was added to the reaction mixed liquid to terminate the reaction, and the reaction mixed liquid was extracted with ethyl acetate. The mixed organic phase was washed with a brine, dried over Na2S2O3, filtered, and concentrated under reduced pressure. The residue was recrystallized from acetone, so as to provide the target compound 2-4 (4.17 g, 91% yield) as a white solid substance. Melting point (Mp.) 117-118 C.; 1H NMR (400 MHz, CDCl3) δ 4.04 (s, 3H), 7.16 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 37.3, 94.2, 116.4, 128.3, 135.5, 171.3; IR (ATR) ν 1694, 1413, 1377, 954, 818, 750, 721 cm-1
58%	With N-Bromosuccinimide; In tetrahydrofuran; at -10 - 25℃; for 18h;	To the solution of 2,2,2-trichloro-1-(1-methyl-1H-imidazol-2-yl)ethanone (1.5 g, 6.6 mmol) in 26 mL of anhydrous THF was added 2.35 g of NBS at -10 C. The resulting mixture was stirred at -10 C. for 2 h, then 25 C. for 16 h. The solution was evaporated and the residue was purified by silica gel column (DCM as eluent) to give 1-(-4-bromo-1-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone (1.18 g, yield 58%). 1H NMR (300 MHz, CDCl3) δ 7.15 (s, 1H), 4.05 (s, 3H).

25%	With N-Bromosuccinimide; In tetrahydrofuran; at -15 - 20℃; for 20h;	To a solution of 2,2,2-trichloro-l-(l-methyl-1H-imidazol-2-yl)ethanone (0.98 g, 4.31 mmol, Eq: 1) in dry tetrahydrofuran (17.2 ml) was added N-bromosuccinimide (1.53 g, 8.62 mmol, Eq: 2) at -15 C. It was then stirred at room temperature for 20 h and the mixture was concentrated in vacuo. The residue was purified by chromatography on silica gel to afford the desired product as a light yellow solid (331 mg, 25 %).
	With N-Bromosuccinimide; In tetrahydrofuran; at 35℃; for 24h;Cooling with ice;	To a solution of 2,2,2-trichloro-1-(1-methyl-1H-imidazol-2-yl)ethanone obtained in Reference Example 17 (1.0 g, 4.4 mmol) in THF (30 ) was added N-bromosuccinimide (1.56 g, 8.8 mmol) under ice-cooling, and the mixture was stirred for 1 day at room temperature. The reaction mixture was concentrated under reduced pressure to give crude 1-(4-bromo-1-methyl-1H-imidazol-2-yl)-2,2,2-trichloroethanone. To a solution of the obtained crude product in ethanol (40 mL) was added a solution of sodium ethoxide in 20% ethanol (1.0 mL), and the mixture was stirred for 4 hr at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane:ethyl acetate= 33:67→0:100, 90:10→50:50) to give the title compound (181 mg, yield 18%). 1H-NMR (CDCl3) δ : 1.42 (3 H, t, J = 7.1 Hz), 3.39 (3 H, s), 4.41 (2 H, q, J = 7.1 Hz), 7.01 (1 H, s).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1 .Location in patent: Paragraph 0088; 0282; 0283; 0284; 0285; 0286; 0287
[3]Patent: US2012/295885,2012,A1 .Location in patent: Page/Page column 32
[4]Patent: WO2017/76852,2017,A1 .Location in patent: Page/Page column 52-53
[5]Patent: EP2518054,2012,A1 .Location in patent: Page/Page column 50

50
[ 30148-23-3 ]
[ 1313196-10-9 ]

Reference： [1]Patent: EP2518054,2012,A1

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[ 30148-23-3 ]
[ 1313196-96-1 ]

Reference： [1]Patent: EP2518054,2012,A1

52
[ 30148-23-3 ]
[ 1313196-95-0 ]

Reference： [1]Patent: EP2518054,2012,A1

53
[ 30148-23-3 ]
[ 864076-05-1 ]

Reference： [1]Patent: US2012/295885,2012,A1
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[3]Patent: WO2017/76852,2017,A1
[4]Patent: US2019/84928,2019,A1

54
[ 30148-23-3 ]
[ 1413063-58-7 ]

Reference： [1]Patent: US2012/295885,2012,A1

55
[ 30148-23-3 ]
[ 602308-97-4 ]
C₂₂H₂₇N₇O₅ [ No CAS ]

Reference： [1]ChemBioChem,2016,vol. 17,p. 506 - 514

56
[ 30148-23-3 ]
[ 20062-51-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With ammonium hydroxide; In acetonitrile; at 0℃; for 0.25h;	To a stirred solution of 4 (370.1 mg, 1.63 mmol) in MeCN (3.3 mL) at 0 C was added 25% aqueous NH3solution (3.3 mL). After 15 min, the reaction mixture was diluted with EtOAc. The organic layer was washedwith brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was recrystallized fromn-hexane and CHCl3 to give the desired product 5 (173.3 mg, 85% yield) as white solid.
85%	With ammonia; In methanol; water; at 0℃; for 0.25h;	A solution of the compound 2a-2 (370.1 mg, 1.63 mmol) in MeOH (3.3 mL) was stirred at 0 C., to which a 25% NH3 aqueous solution (3.3 mL) was added. After 15 minutes, EtOAc was added to the reaction mixture for diluting. The organic phase was washed with a brine, dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was recrystallized from n-hexane and CHCl3, so as to provide the target compound 1-3 (173.3 mg, 85% yield) as a white solid substance.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1 .Location in patent: Paragraph 0269; 0270; 0271

57
[ 30148-23-3 ]
C₆H₄Cl₃IN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With indium(III) triflate; 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; In acetonitrile; at 0 - 20℃; for 24h;	To a stirred solution of 4 (1.00 g, 4.42 mmol) and In(OTf)3 (247.3 mg, 0.44 mmol) in CH3CN (22.1 mL) at 0C was added DIH (1.80 g, 4.74 mmol). The reaction was gradually warmed up to room temperature and thenkept stirring for 24 h at the same temperature. The reaction was quenched with 5% aq. Na2S2O3 and themixture was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4,and then concentrated under reduced pressure. The obtained residue was purified by silica gel columnchromatography (SiO2, n-hexane/EtOAc = 6/1) to give the desired product SI-3 (700 mg, 45% yield) as paleyellow solid.
45%	With indium(III) triflate; 1,3-Diiodo-5,5-dimethyl-2,4-imidazolidinedione; In acetonitrile; at 0 - 25℃; for 24h;	A solution of the compound 2a-2 (1.00 g, 4.42 mmol) and In(OTf)3 (247.3 mg, 0.44 mmol) in MeCN (22.1 mL) was stirred at 0 C., to which DIH (1.80 g, 4.74 mmol) was added. The reaction was performed by gradually increasing the temperature to room temperature, and then continuously stirring at that temperature for 24 hours. A 5% Na2S2O3 aqueous solution was added to the reaction mixed liquid to terminate the reaction, and the reaction mixed liquid was extracted with ethyl acetate. The mixed organic phase was washed with a brine, dried over Na2S2O3, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (SiO2, n-hexane/EtOAc=6/1), so as to provide the target compound 2-6 (700 mg, 45% yield) as a white solid substance. Melting point (Mp.) 112-113 C.; 1H NMR (400 MHz, CDCl3) δ 4.04 (s, 3H), 7.24 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 37.1, 83.8, 94.3, 134.1, 137.9, 171.2; IR (ATR) ν 1691, 1407, 1367, 942, 852, 815, 741, 703, 612 cm-1

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1 .Location in patent: Paragraph 0088; 0240; 0241; 0242; 0243; 0244; 0245

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[ 30148-23-3 ]
C₆H₇IN₂O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1

59
[ 30148-23-3 ]
[ 297731-27-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1

60
[ 30148-23-3 ]
C₁₂H₁₂BrN₃O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200

61
[ 30148-23-3 ]
C₁₂H₁₂IN₃O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Patent: US2019/84928,2019,A1

62
[ 30148-23-3 ]
C₁₉H₂₀N₄O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200

63
[ 30148-23-3 ]
C₁₈H₁₉N₅O₂ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[3]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200
[4]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 2197 - 2200

64
[ 30148-23-3 ]
4-bromo-N,1-dimethyl-1H-imidazole-2-carboxamide [ No CAS ]

Reference： [1]Patent: WO2017/76852,2017,A1

65
[ 30148-23-3 ]
C₁₈H₁₉N₅O₂ [ No CAS ]

Reference： [1]Patent: US2019/84928,2019,A1

66
[ 30148-23-3 ]
C₁₇H₁₈N₆O₂ [ No CAS ]

Reference： [1]Patent: US2019/84928,2019,A1
[2]Patent: US2019/84928,2019,A1

67
[ 30148-23-3 ]
C₅H₅IN₂O₂ [ No CAS ]

Reference： [1]Patent: US2019/84928,2019,A1

68
[ 30148-23-3 ]
C₁₂H₁₃IN₄O₃ [ No CAS ]

Reference： [1]Patent: US2019/84928,2019,A1

69
[ 30148-23-3 ]
C₁₈H₂₀N₆O₄ [ No CAS ]

Reference： [1]Patent: US2019/84928,2019,A1

70
[ 30148-23-3 ]
tert-butyl 4-[(9-fluorenylmethoxycarbonyl)amino]-N-methyl-1H-imidazole-2-carboxylate [ No CAS ]

Reference： [1]Patent: CN109970617,2019,A

71
[ 30148-23-3 ]
[ 252206-28-3 ]

Reference： [1]Patent: CN109970617,2019,A
[2]Organic Letters,2020,vol. 22,p. 533 - 536

72
[ 30148-23-3 ]
[ 1238706-98-3 ]

Reference： [1]Patent: CN109970617,2019,A
[2]Patent: CN109970617,2019,A

73
[ 30148-23-3 ]
[ 1238707-08-8 ]

Reference： [1]Patent: CN109970617,2019,A
[2]Patent: CN109970617,2019,A

74
[ 13138-76-6 ]
[ 30148-23-3 ]
[ 865307-73-9 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

75
[ 30148-23-3 ]
[ 162085-97-4 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

76
[ 30148-23-3 ]
[ 128293-65-2 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

77
[ 30148-23-3 ]
benzyl 4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-1-methyl-1Himidazole-2-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

78
[ 30148-23-3 ]
4-((diphenyl(p-tolyl)methyl)amino)-1-methyl-1H-imidazole-2-carboxylic acid [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

79
[ 30148-23-3 ]
methyl 4-(4-((diphenyl(p-tolyl)methyl)amino)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

80
[ 30148-23-3 ]
[ 169770-26-7 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

81
[ 30148-23-3 ]
methyl 4-((diphenyl(p-tolyl)methyl)amino)-1-methyl-1H-imidazole-2-carboxylate [ No CAS ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

82
[ 30148-23-3 ]
[ 1040393-13-2 ]

Reference： [1]Organic Letters,2020,vol. 22,p. 533 - 536

83
[ 30148-23-3 ]
[ 100-49-2 ]
cyclohexylmethyl 1-methyl-1H-imidazole-2-carboxylate [ No CAS ]