[ CAS No. 144-48-9 ]

Name: 144-48-9|2-Iodoacetamide|98%
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SKU: A576369
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{[proInfo.proName]} (Synonyms:2-Iodoacetamide) ,{[proInfo.pro_purity]}

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

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Quality Control of [ 144-48-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 144-48-9 ]

SDS Specification

Alternatived Products of [ 144-48-9 ]

Product Details of [ 144-48-9 ]

CAS No. :	144-48-9	MDL No. :	MFCD00008028
Formula :	C₂H₄INO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PGLTVOMIXTUURA-UHFFFAOYSA-N
M.W :	184.96	Pubchem ID :	3727
Synonyms :	2-Iodoacetamide

Safety of [ 144-48-9 ]

Signal Word:	Danger	Class:	6.1
Precautionary Statements:	P261-P280-P301+P310-P342+P311	UN#:	2811
Hazard Statements:	H301-H317-H334	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 144-48-9 ]

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

Upstream synthesis route of [ 144-48-9 ]
Downstream synthetic route of [ 144-48-9 ]

[ 144-48-9 ] Synthesis Path-Upstream 1~5

1
[ 107-91-5 ]
[ 144-48-9 ]

Reference： [1] Tetrahedron, 2015, vol. 71, # 38, p. 6824 - 6831

2
[ 54907-61-8 ]
[ 144-48-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With triethylamine In chloroform	EXAMPLE 13 Iodoacetamide (Compound 49): To a suspension of 20 mg (0.05 mmol) of Compound 48 in 3 mL of chloroform is added 10 μL of triethylamine, followed by addition of 12 mg (0.05 mmol) of iodoacetic anhydride and the mixture is stirred at room temperature for 2 hours. After evaporation under reduced pressure, it is purified by silica gel column chromatography with 2percent methanol in chloroform as eluant to give 19 mg (67percent) of the iodoacetamide 49. Compound 62 is prepared from Compound 61 by the same method as described in Example 13.

Reference： [1] Patent: US5274113, 1993, A,

3
[ 79-07-2 ]
[ 144-48-9 ]

Reference： [1] Zeitschrift fuer Physikalische Chemie, Abteilung A: Chemische Thermodynamik, Kinetik, Elektrochemie, Eigenschaftslehre, 1931, vol. 157, p. 249,254[2] Zeitschrift fuer Physikalische Chemie, Abteilung A: Chemische Thermodynamik, Kinetik, Elektrochemie, Eigenschaftslehre, 1933, vol. 163, p. 38
[3] Zeitschrift fuer Chemie, 1871, p. 6
[4] Chemische Berichte, 1908, vol. 41, p. 2117[5] Chemische Berichte, 1909, vol. 42, p. 2056
[6] Journal of Medicinal Chemistry, 1982, vol. 25, # 6, p. 735 - 742
[7] Journal of Medicinal Chemistry, 2016, vol. 59, # 10, p. 4985 - 4998

4
[ 54907-61-8 ]
[ 144-48-9 ]

Reference： [1] Patent: US5453517, 1995, A,

5
[ 624-75-9 ]
[ 144-48-9 ]

Reference： [1] Synthesis, 1974, p. 574 - 575

[ 144-48-9 ] Synthesis Path-Downstream 1~68

1
[ 144-48-9 ]
[ 485-71-2 ]
(8<i>S</i>,9<i>R</i>)-1-carbamoylmethyl-9-hydroxy-cinchonanium; chloride [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1919,vol. 41,p. 2102

2
[ 144-48-9 ]
[ 101-06-4 ]
[ 137089-44-2 ]

Reference： [1]Chemical and Pharmaceutical Bulletin,1991,vol. 39,p. 1546 - 1550

3
[ 144-48-9 ]
[ 497-76-7 ]
[ 89790-23-8 ]

Reference： [1]Journal of the American Chemical Society,1984,vol. 106,p. 3344 - 3353

4
[ 144-48-9 ]
[ 107-18-6 ]
[ 10374-51-3 ]

Reference： [1]Tetrahedron Letters,1999,vol. 40,p. 519 - 522

5
[ 120-47-8 ]
[ 144-48-9 ]
ethyl 4-(carbamoylmethoxy)benzoate [ No CAS ]

Reference： [1]Angewandte Chemie - International Edition,2007,vol. 46,p. 4577 - 4580
[2]Journal of the American Chemical Society,2010,vol. 132,p. 11110 - 11118

6
C₁₃H₁₆N₂O₃ [ No CAS ]
[ 144-48-9 ]
(2-carbamoylmethoxy-4-cyano-benzyl)-carbamic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With caesium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 72h;	To a solution of 4-aminomethyl-3-hydroxy-benzonitrile hydrochloride (example 110.2, 2.0 g) and triethylamine (2.19 g) in dichloromethane (20 ML) was added di-tert.- butyldicarbonate (2.41 g). The mixture was stirred at r. t. for 3.5 h. The mixture was washed with water (3x), dried, filtered and concentrated. The crude product was dissolved in DMF (15.5 ml). Cesium carbonate (4.00 g) and <strong>[144-48-9]iodoacetamid</strong>e (2.27 g) were added and the mixture was stirred at r. t. for 3 days. Water was added and the mixture was extracted with EtOAc. The org. phase was washed with water, dried, filtered and concentrated. The crude product was dissolved in MeOH and then concentrated to obtain a thick suspension. The solid was filtered off and washed with a small amount of MeOH. This procedure was repeated with the mother liquor to give (2-carbamoylmethoxy-4-cyano-benzyl)-carbamic acid tert-butyl ester (a total of 1.88 g) as a colorless solid. MS 304.2 ([M-H]-)
	With caesium carbonate; In dichloromethane; at 20℃; for 72h;	To a solution of 4-aminomethyl-3-hydroxy-benzonitrile hydrochloride (2.0 g) and triethylamine (2.19 g) in dichloromethane (20 ml) was added di-tert-butyidicarbonate (2.41 g). The mixture was stirred at r.t. for 3.5 h. The mixture was washed with water (3×), dried, filtered and concentrated. The crude product was dissolved in DMF (15.5 ml). Cesium carbonate (4.00 g) and <strong>[144-48-9]iodoacetamid</strong>e (2.27 g) were added and the mixture was stirred at r.t. for 3 days. Water was added and the mixture was extracted with EtOAc. The organic phase was washed with water, dried, filtered and concentrated. The crude product was dissolved in MeOH and then concentrated to obtain a thick suspension. The solid was filtered off and washed with a small amount of MeOH. This procedure was repeated with the mother liquor to give (2-carbamoylmethoxy-4-cyano-benzyl)-carbamic acid tert-butyl ester (a total of 1.88 g) as a colorless solid. MS 304.2 ([M-H]-)
	With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 72h;	To a solution of 4-aminomethyl-3-hydxoxy-benzonitrile hydrochloride (BB1, 2.0 g) and triethylamine (2.19 g) in dichloromethane (20 ml) was added di-tert-butyldicarbonate (2.41 g). The mixture was stirred at r.t. for 3.5 h. The mixture was washed with water (3x), dried, filtered and concentrated. The crude product was dissolved in DMF (15.5 ml). Cesium carbonate (4.00 g) and <strong>[144-48-9]iodoacetamid</strong>e (2.27 g) were added and the mixture was stirred at r.t. for 3 days. Water was added and the mixture was extracted with EtOAc. The org. phase was washed with water, dried, filtered and concentrated. The crude product was dissolved in MeOH and then concentrated to obtain a thick suspension. The solid was filtered off and washed with a small amount of MeOH. This procedure was repeated with the mother liquor to give (2-carbamoylmethoxy-4-cyano-benzyL)-carbamic acid tert-butyl ester (a total of 1.88 g) as a colorless solid. MS 304.2 ([M-HD The BOC protecting group of (2-carbamoylmethoxy-4-cyano-benzyl)-carbamic acid tert-butyl ester was removed using HC1 in dioxane to give 2-(2-aminomethyl-5-cyano-phenoxy)-acetamide hydrochloride as an off-white powder. MS 206.1 ([M+H]+)

Reference： [1]Patent: WO2004/48335,2004,A2 .Location in patent: Page 100
[2]Patent: US2005/137168,2005,A1 .Location in patent: Page/Page column 19
[3]Patent: WO2006/27135,2006,A1 .Location in patent: Page/Page column 38

7
[ 851577-43-0 ]
[ 144-48-9 ]
[ 851578-23-9 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 20℃; for 0.5h;	1) To a solution (10 mL) of 5- { [ (tert- butoxycarbonyl) amino] methyl}-6-isobutyl-2-methyl-4- (4- methylphenyl) nicotinic acid (500 mg, 1.22 mmol) in N, N- dimethylformamide were added 2-<strong>[144-48-9]iodoacetamid</strong>e (673 mg, 3.64 mmol) and potassium carbonate (337 mg, 2.44 mmol) and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with saturated brine. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give 2-amino-2-oxoethyl 5- { [ (tert-butoxycarbonyl) amino] methyl}-6-isobutyl-2-methyl-4- (4- methylphenyl) nicotinate (570 mg, yield 99%) as an oil. H-NMR (CDCl3) 6 : 0.98 (6H, d, J = 6.8 Hz), 1.39 (9H, s), 2. 17- 2.31 (1H, m), 2.39 (3H, s), 2.57 (3H, s), 2.80 (2H, d, J = 7.2 Hz), 4.13-4. 18 (2H, m), 4.23 (lui, brs), 4.40 (2H, s), 5.12 (2H, brs), 7.12 (2H, d, J = 7.7 Hz), 7.25 (2H, d, J = 7.9 Hz).

Reference： [1]Patent: WO2005/42488,2005,A1 .Location in patent: Page/Page column 116-117

8
[ 5900-58-3 ]
[ 124-09-4 ]
[ 5162-44-7 ]
[ 446-48-0 ]
[ 7209-38-3 ]
[ 74-96-4 ]
[ 4784-77-4 ]
[ 22288-78-4 ]
[ 542-69-8 ]
bromomethyl resin [ No CAS ]
9-fluorenyl-methoxycarbonyl-cyclohexyl alanine [ No CAS ]
[ 462-94-2 ]
[ 1458-98-6 ]
[ 78-77-3 ]
[ 1809-10-5 ]
[ 110-53-2 ]
[ 592-55-2 ]
[ 7328-91-8 ]
[ 871-76-1 ]
[ 105-83-9 ]
[ 144-48-9 ]
[ 929-59-9 ]
[ 107-59-5 ]
[ 5324-30-1 ]
[ 5428-54-6 ]
[ 27129-86-8 ]
[ 2417-72-3 ]
[ 2581-34-2 ]
[ 554-84-7 ]
[ 3385-21-5 ]
[ 126-38-5 ]
[ 636-93-1 ]
[ 88-30-2 ]
[ 620-13-3 ]
[ 823-78-9 ]
[ 5035-82-5 ]
[ 29022-11-5 ]
[ 539-48-0 ]
[ 35661-39-3 ]
[ 26759-46-6 ]
[ 20439-47-8 ]
[ 2615-25-0 ]
[ 6393-01-7 ]
[ 5372-81-6 ]
[ 35661-40-6 ]
[ 100-39-0 ]
[ 611-17-6 ]
[ 23915-07-3 ]
[ 71989-23-6 ]
[ 35737-15-6 ]
[ 2592-95-2 ]
[ 18880-00-7 ]
[ 88681-68-9 ]
[ 100063-22-7 ]
[ 75-03-6 ]
[ 106-94-5 ]
[ 104-81-4 ]
[ 589-10-6 ]
[ 107-15-3 ]
[ 109-76-2 ]
[ 110-60-1 ]
[ 7051-34-5 ]
[ 106-95-6 ]
[ 622-95-7 ]
[ 589-15-1 ]
[ 134-20-3 ]
[ 2550-36-9 ]
[ 89-92-9 ]
[ 456-41-7 ]
[ 766-80-3 ]
[ 459-46-1 ]
[ 874-98-6 ]
[ 402-49-3 ]
[ 870-63-3 ]
[ 85118-01-0 ]
[ 22115-41-9 ]
[ 3958-57-4 ]
[ 100-11-8 ]
[ 107-82-4 ]
[ 6482-24-2 ]
[ 3132-64-7 ]
[ 112883-41-7 ]
[ 3433-80-5 ]
[ 52727-57-8 ]
C₁₈H₁₅N₂O₃PolS [ No CAS ]
C₂₀H₂₀N₃OPolS [ No CAS ]
C₂₃H₁₉N₂O₂PolS [ No CAS ]
C₁₈H₂₃ClN₃OPolS [ No CAS ]
C₂₂H₂₆N₃OPolS [ No CAS ]
C₂₂H₂₃N₂O₅PolS [ No CAS ]
C₂₀H₂₆ClN₂O₃PolS [ No CAS ]
C₂₃H₂₂ClN₂O₃PolS [ No CAS ]
C₂₀H₂₁FN₃O₃PolS [ No CAS ]
C₂₂H₂₉N₂O₃PolS [ No CAS ]
C₂₁H₂₈N₃O₃PolS [ No CAS ]
C₁₉H₂₆N₃O₄PolS₂ [ No CAS ]
C₂₂H₃₀N₃OPolS [ No CAS ]
C₂₁H₂₈N₃O₄PolS [ No CAS ]
C₂₆H₂₆N₃OPolS [ No CAS ]
C₂₃H₁₅ClF₃N₂O₂PolS [ No CAS ]
C₂₄H₂₂N₃O₃PolS [ No CAS ]
C₂₃H₁₆ClF₂N₂O₂PolS [ No CAS ]
C₂₂H₂₂Br₂N₃OPolS [ No CAS ]
C₂₄H₂₆FN₂O₅PolS [ No CAS ]
C₂₅H₂₂FN₂O₄PolS [ No CAS ]
C₂₆H₂₂N₃O₄PolS [ No CAS ]
C₂₅H₂₅ClN₃O₃PolS [ No CAS ]
C₂₅H₁₈ClF₂N₂O₃PolS [ No CAS ]
C₂₉H₂₆N₃O₃PolS [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine; Carbonyldiimidazole; tin-2-ethylhexanoate dihydrate; potassium tert-butylate; water; N-ethyl-N,N-diisopropylamine; trifluoroacetic acid; diisopropyl-carbodiimide; dibromotriphenylphosphorane; In DMF (N,N-dimethyl-formamide); dichloromethane; N,N-dimethyl acetamide; 1,2-dichloro-ethane;Combinatorial reaction / High throughput screening (HTS);	EXAMPLE 1 [0213] This example shows the synthesis of a combinatorial library of thioquinazolinone derivatives. [0214] Step 1a: Preparation of Wang Bromide Resin [0215] 40 tea bags containing 2 g each of Wang resin (80 g, 120 mmol) was taken in a 5 L PP container. A solution of triphenylphosphine dibromide (152 g, 0.15 M, 3 eq., 360 mmol) in 2000 ml DCM was added and the solution was shaken at room temperature overnight. The resin was sequentially washed with DCM (4×, 1.5 L each) and diethylether (6×, 1.5 L each) and dried under vacuum, to give the bromo wang resin. [0216] Step 1b: Loading of the Nitrophenol on Bromo Wang [0217] 20 g of the Bromo wang resin (1.5 meq/g) was taken in a 2 L wide-mouthed glass container and 1000 mL DMA was addded to it followed by the addition of the nitro phenol (10 eq., 0.3M, 300 mmol). Potasium t-butoxide (33.46 g, 10 eq., 300 mmol) was then added to it and the bottles were heated at 50 C. overnight. The bags were washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The tea bags were then dried overnight in air. The following nitrophenols were used: [0218] 2-METHYL-5-NITROPHENOL [0219] 5-HYDROXY-2-NITROBENZOTRIFLUORIDE [0220] 3-METHYL-4-NITROPHENOL [0221] 2-METHOXY-5-NITROPHENOL [0222] M-NITROPHENOL [0223] Step 1c: Reduction of the Nitro Group to Amine [0224] A 2.0 M solution of tin-2-ethylhexanoate dihydrate was prepared in DMF containing 0.5% H2O. The tea bags were added and the solution is heated at 50 C. for 40 hours. After cooling the bags are washed with DMF/10% HOAc (3×), DMF (3×), 5% DIEA/DCM (2×), DCM (2×) and MeOH (2×) and dried in air overnight. [0225] Step 1d: Coupling N-FMOC Protected Amino Acid to Wang Resin. [0226] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL plastic bottle. DMF (300 mL), DCM (300 mL), FMOC-Cyclohexyl alanine (70.82 g, 6 eq., 0.3M, 180 mmol), DIC (22.71 g, 6 eq., 180 mmol), HOBt (24.32 g, 6 eq., 180 mmol) were added sequentially. After shaking for 12 hours, the packet was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried overnight in air. The tea bags containing the amino acids were then treated with 20% piperidine/DMF for 2 h at room temperature to deblock the FMOC group. The following amino acids were used: [0227] FMOC-GLY-OH [0228] FMOC-ALA-OH [0229] FMOC-L-ISOLEUCINE [0230] FMOC-L-PHENYLALANINE [0231] FMOC-D-NLE-OH [0232] FMOC-CHA-OH [0233] FMOC-L-TRYPTOPHAN [0234] Step 1e: Coupling of the Diamines to Wang Resin [0235] 20 g of Wang resin (1.5 meq/g) was placed in a porous polypropylene packet (Tea-bag, 60 mm×60 mm, 65mu) and taken in a 1000 mL Nalgene bottle. 600 mL of DCM was added followed by the addition of the carbonyl diimidazole (29.9 g, 6 eq., 0.3M, 180 mmol) and the flasks were shaken at room temperature for 3 hours after which they were decanted and washed with DCM (2×, 600 mL). To these Nalgene bottles were added the diamines (6 eq., 0.4M, 180 mmol) in 450 mL of DCM (0.4M) and they were shaken at room temperature overnight. The diamines used were as follows: [0236] 2,2-DIMETHYL-1,3-PROPANEDIAMINE [0237] 1,3-CYCLOHEXANEDIAMINE [0238] (1R,2R)-(-)-1,2-DIAMINOCYCLOHEXANE [0239] TRANS-1,4-DIAMINOCYCLOHEXANE [0240] P-XYLYLENEDIAMINE [0241] 1,4-BIS(3-AMINOPROPYL)PIPERAZINE [0242] ETHYLENEDIAMINE [0243] 1,3-DIAMINOPROPANE [0244] 1,8-DIAMINO-3,6-DIOXAOCTANE [0245] 1,4-DIAMINOBUTANE [0246] 1,5-DIAMINOPENTANE [0247] 1,6-HEXANEDIAMINE [0248] N,N-BIS(3-AMINOPROPYL)METHYLAMINE [0249] 2,2'-THIOBIS(ETHYLAMINE) [0250] 2,5-DIMETHYL-1,4-PHENYLENEDIAMINE [0251] After shaking overnight, the packets was washed alternatively with DMF (500 mL) and DCM (500 mL) 3 cycles followed by 6 cycles of MeOH (500 mL). The packet was then dried in air. [0252] Step 2: Formation of the Isothiocyanate [0253] The o-amino benzoate ester (136 g, 10 eq., 900 mmol) was taken in a 5 L wide-mouthed glass bottle and 2.7 L of dichloroethane was added to it (0.3M). The following esters were used: [0254] METHYL ANTHRANILATE [0255] METHYL 2-AMINO-4-CHLOROBENZOATE [0256] 2-AMINO-4,5-DIMETHOXYBENZOIC ACID [0257] METHYL ESTER [0258] METHYL 3,4,5-TRIMETHOXYANTHRANILATE [0259] DIMETHYL AMINOTEREPHTHALATE [0260] METHYL 2-AMINO-5-BROMOBENZOATE [0261] METHYL 3-AMINOTHIOPHENE-2-CARBOXYLATE [0262] METHYL 3-AMINO-5-PHENYLTHIOPHENE-2-CARBOXYLATE [0263] Thiocarbonyl diimidazole (160 g, 10 eq., 900 mmol) was added to it and the solution was heated at 55 C. overnight to form the isothiocyanate. [0264] Step 3: Formation of the Thioquinazolinone [0265] The next day the tea bags containing the amino acids, diamines and the amino phenols on wang resin (90 mmol) was added to the isothiocyanate solution from reaction 2 and the glass bottles were heated at 55 C. overnight. After cooling the bags was washed alternatively with DMF (2000 mL) and DCM (2000 mL) 3 cycles followed by 6 cycles of MeOH...

Reference： [1]Patent: US2004/102629,2004,A1 .Location in patent: Page 16-18

9
[ 865604-30-4 ]
[ 144-48-9 ]
[ 865604-31-5 ]

Yield	Reaction Conditions	Operation in experiment
89%	With N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 23℃; for 24h;	Tosylate 5 (7.05 g, 21.5 mmol) was dissolved in dry dimethyl formamide (120 mL), to this was added diisopropylethylamine (3.06 g, 23.7 mmol) and <strong>[144-48-9]iodoacetamid</strong>e (4. 38 g, 23.7 mmol). The mixture was stirred at 23 C for 24 h. then concentrated under reduced pressure to provide an oil. This oil was diluted with water (300 mL) and the resulting solid collected by filtration and washed with ethyl acetate, providing the desired compound 6 (yield: 7.39 g, 89%) ;'H NMR [400 MHz, (CD3) 2SO] delta 7.96 (d, J = 7.1 Hz, 1 H), 7.74 (s, 1 H), 7.66 (d, J = 8. 2 Hz, 2 H), 7.54 (d, J = 2. 1 Hz, 1 H), 7.35 (s, 1 H), 7.29 (d, J = 8. 0 Hz, 2 H), 7.00 (dd, J = 7. 1,2. 2 Hz, 1 H), 4.78 (s, 2 H), 2.35 (s, 3 H).

Reference： [1]Patent: WO2005/89763,2005,A1 .Location in patent: Page/Page column 39

10
[ 865604-42-8 ]
[ 144-48-9 ]
[ 865604-44-0 ]
[ 865604-43-9 ]

Yield	Reaction Conditions	Operation in experiment
63%	With sodium hydride; In DMF (N,N-dimethyl-formamide); at 23℃; for 16.17h;	Sodium hydride (0.57 g of a 60% dispersion in mineral oil, 0.014 mol) was added in portions at 23 C to a stirred solution of the alcohol (4) (4.22 g, 0.012 mol) in dry dimethyl formamide (60 mL). After 10 min a solution of <strong>[144-48-9]iodoacetamid</strong>e (2. 68 g, 0.014 mol) in dimethyl formamide (10 mL) was added and the solution was stirred at 23 C for 16 h. Silica gel was added and the reaction mixture was adsorbed directly onto it by concentration of the mixture to dryness in vacuo. The product was chromatographed on silica. Elution with ethyl acetate gave isomer (6) as a white solid (3.16 g, 63%). Elution with methanol/ethyl acetate (5: 95) gave the required product (5) as a foamy solid (4.92 g-contains sodium iodide as well). This material was used directly in the next step. APCI-MS Found [M+H] =416,414.

Reference： [1]Patent: WO2005/89763,2005,A1 .Location in patent: Page/Page column 45

11
[ 144-48-9 ]
[ 704-14-3 ]
2-carbamoylmethoxy-4-methoxynitrobenzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;	Reaction of 0.84 g of <strong>[704-14-3]5-methoxy-2-nitrophenol</strong>, 1.66 g of potassium carbonate and 1.84 g of iodoacetamide by the process described in Example 55) gives 2-carbamoylmethoxy-4-methoxynitrobenzene: mp 185-7 C.; Rf (O)=0.58.

Reference： [1]Patent: US5719141,1998,A

12
[ 861359-74-2 ]
[ 144-48-9 ]
[ 60-35-5 ]
1S-(1'R-(3,5-Bistrifluoromethyl)phenyl)ethoxy)-2S-phenyl-3S-(N-N-(aminocarbonylmethyl)-N-(methyl)amino)-cyclohexane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With sodium hydrogencarbonate; In methanol; acetonitrile;	EXAMPLE 160 1S-(1'R-(3,5-Bistrifluoromethyl)phenyl)ethoxy)-2S-phenyl-3S-(N-N-(aminocarbonylmethyl)-N-(methyl)amino)-cyclohexane STR90 To a solution of the amine (11.0 mg, 0.025 mmol) in CH3 CN (1 mL) at room temp was added diisopropylethyl amine (4.8 mg, 0.037 mmol) and <strong>[144-48-9]iodoacetamid</strong>e (5.0 mg, 0.027 mmol). The reaction mixture was heated to 50 C. under Ar for 4 h whereupon it was cooled to room temp and quenched by addition of sat. aq. NaHCO3 (10 mL). The mixture was extracted with EtOAc (3*10 mL) and the combined organic extracts were washed with brine, dried (Na2 SO4), and concentrated in vacuo. The residue was purifed by column chromatography (1.8 g silica gel 60, 8 mm diam. column, 2.5-8.0% MeOH/CH2 Cl2) to afford the acetamide (10.2 mg, 81%) as a colorless solid. ESIMS/CI m/z calcd. for C25 H28 N2 O2 F6 502.50; found 503.2 (18%), 485.2 (20%), 474.2 (16%), 446.2 (100%).

Reference： [1]Patent: US5750549,1998,A

13
[ 144-48-9 ]
[ 7048-04-6 ]
[ 14226-97-2 ]

Yield	Reaction Conditions	Operation in experiment
560 mg (34.8%)	With hydrogenchloride; sodium carbonate; In water;	(1) Synthesis of 3-oxo-5-carboxyperhydro-1,4-thiazine: A solution of 1.75 g (10 mmole) of <strong>[7048-04-6]L-cysteine hydrochloride monohydrate</strong> dissolved in 50 ml of water was adjusted to pH 8.0 with 1M sodium carbonate. Under nitrogen gas stream, 1.85 g (10 mmole) of monoiodoacetamide and 1M sodium carbonate were added alternately while maintaining pH at 8.0. After the reaction was carried out at room temperature for 1 hour, further the reaction was carried out in a sealed tube at 100 C for 2 hours. To the reaction mixture was added 4N HCl to adjust the pH to 3.25, followed by concentration to dryness. The residue was extracted with hot ethanol, and after cooling, the crystals were collected by filtration and recrystallized from hot ethanol. Yield: 560 mg (34.8 %), melting point: 182 to 184 C, Fab mass analysis [M + H]+ = 162.

Reference： [1]Patent: EP370165,1990,A2

14
[ 787542-91-0 ]
[ 144-48-9 ]
C₁₁H₁₄IN₇O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tetra-(n-butyl)ammonium iodide; In N,N-dimethyl-formamide; at 20℃; for 18h;	A mixture of EXAMPLE 52B (0.18 g), <strong>[144-48-9]iodoacetamid</strong>e (0.1 g), K2CO3 (0.35 g) and tetrabutylammonium iodide (0.01 g) in DMF (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine and dried, filtered and concentrated. The concentrate was recrystallized from diethylether.

Reference： [1]Patent: US2007/203143,2007,A1 .Location in patent: Page/Page column 47

15
[ 144-48-9 ]
[ 1032648-21-7 ]
[ 1032648-29-5 ]

Yield	Reaction Conditions	Operation in experiment
38%	With potassium hydroxide; In N,N-dimethyl-formamide; at 0 - 20℃;	Example 14: 2-(7-{2,2,2-Trifluoro-l-[l-(4-fluorophenyl)-lH-indazol-5- yl]ethylamino}indol-l-yl)acetamide; To a chilled (00C) solution of 78 mg (0.18 mmol) of (lH-Indol-7-yl)-{2,2,2-trifluoro-l-[l-(4- fluorophenyl)-lH-indazol-5-yl]ethyl} amine in 5 mL of DMF was added 15 mg (1.09 mmol) of powder KOeta followed by 37 mg (1.09 mmol) of <strong>[144-48-9]iodoacetamid</strong>e. The mixture stirred overnight at room temperature. The mixture was then poured onto ice water and extracted with three 20 mL portions of ethyl acetate. The combined organic layers were washed with brine, saturated aqueous ammonium chloride, brine, and dried over sodium sulfate. The crude material was loaded onto a silica cartridge and purified by Combiflash chromatography using a 0-60% <n="126"/>EtOAc-hexanes (0-60% gradient) to afford 30 mg (38%) of the title compound as a colorless foam, m.p. 1050C

Reference： [1]Patent: WO2008/70507,2008,A2 .Location in patent: Page/Page column 123-124

16
[ 144-48-9 ]
[ 1032648-37-5 ]
[ 1032648-38-6 ]

Yield	Reaction Conditions	Operation in experiment
39%	With potassium hydroxide; In N,N-dimethyl-formamide; at 0 - 20℃;	To a chilled (00C) solution of 45 mg (0.11 mmol) of 2,2,2-trifluoro-l-(lH-indol-3-yl)-l-(l- pyridin-3-yl-lH-indazol-5-yl)ethanol in 5 mL of DMF was added 13 mg (0.17 mmol) of powder KOeta followed by 31 mg (0.17 mmol) of <strong>[144-48-9]iodoacetamid</strong>e. The mixture was stirred over night at room temperature, poured onto ice water and extracted with three 20 mL portions of ethyl acetate. The combined organic layers were dried over sodium sulfate, adsorbed on to silica gel and purified by Combiflash chromatography using EtOAc/hexanes (0-80% gradient, product eluted at 40% EtOAc) to provide a colorless film. The material from the column was crystallized from EtOAc -hexanes to afford 20 mg (39%) of the title compound as a colorless powder.

Reference： [1]Patent: WO2008/70507,2008,A2 .Location in patent: Page/Page column 125-126

17
[ 144-48-9 ]
[ 1058169-30-4 ]
[ 1058168-06-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate; In N,N-dimethyl-formamide; at 40℃; for 18h;	EXAMPLE 1. A solution of (3S,5S)-5-(3-(cyclopentyloxy)-4-methoxyphenyl)-3-(3- hydroxybenzyl)piperidin-2-one (857 mg, 2.17 mmol), <strong>[144-48-9]iodoacetamid</strong>e (802 mg, 4.33 mmol), K2CO3 (898 mg, 6.50 mmol) and DMF (6 mL) was stirred at 40 0C for 18 hours. The reaction mixture was allowed to cool to ambient temperature, then was diluted with water (100 mL) and EtOAc (150 mL). The layers were separated and a white precipitate was filtered from the EtOAc layer. The aqueous layer was extracted with EtOAc and the combined EtOAc solutions were washed with saturated NaHCO3 solution and brine then dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography eluting with 5%, followed by 10% MeOH/EtOAc to afford 455 mg of 2-(3-(((3S,5S)-5-(3- (cyclopentyloxy)-4-methoxyphenyl)-2-oxopiperidin-3-yl)methyl)phenoxy)acet- amide (7). The white precipitate that was isolated by filtration was dissolved in 10% MeOH/CHCI3 and was washed with saturated NaHCO3 solution and brine then dried over MgSO4, filtered and concentrated to give a total of 809 mg (82%) of 2-(3-(((3S,5S)-5-(3-(cyclope?tyloxy)-4-methoxyphenyl)-2-oxopiperidin-3-yl)- methyl)phenoxy)acetamide, MW 452.54.

Reference： [1]Patent: WO2008/110794,2008,A1 .Location in patent: Page/Page column 96-97

18
[ 144-48-9 ]
2S albumin [ No CAS ]
2S albumin, reduced, alkylated [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		Reduction and alkylation of 2S albumin Lyophilized protein (540 mg) was dissolved in 6 M guanidinium, 100 mM NH4HCO3 pH 7.8 (270 mL; 2 mg/mL) and then the solution was warmed to 56 C and dithiotreitol (DTT) (830 mg; 20 mM final concentration) was added. After 60 min. the reduced protein was allowed to cool to room temperature and a freshly prepared <strong>[144-48-9]iodoacetamid</strong>e solution (5.02 g in 27 mL 100 mM NH4HCO3 pH 7.8; 100 mM final concentration) was added to the stirred protein solution. The alkylation was allowed to proceed for 90 min. at room temperature in the dark. The reduced and alkylated protein was dialyzed against demineralized water (3 times 10 L) in Spectro/Por 6 (1 kDa cut off) dialysis tubing at 4 C. As control 2S albumin (110 mg) was dissolved in 6 M guanidinium, 100 mM NH4HCO3 pH 7.8 (50 mL; 2 mg/mL), was heated to 56C, cooled to room temperature and then dialyzed. Both the alkylated 2S albumin and the control were lyophilized. The akylated 2S albumin (524 mg, yielding 97%) was obtained as a crystalline slightly yellow dense powder and the control 25 albumin (110 mg, 100%) was obtained as a white fluffy powder. Both the alkylated and control 2S albumin were dissolved (2 mg/mL) in 100 mM NH4HCO3 pH 7.8. Four hundred muL protein solution and 100 muL DTNB solution (5,5'-dithiobis(2-nitrobenzoic acid) or Ellman's reagent, 50 mM in NH4HCO3 pH 7.8) were mixed and the absorption at 405 nm was measured after 10 min incubation at room temperature. As a blank 400 muL buffer and 100 muL DTNB solution were mixed. The number of free SH groups was calculated using the molar extinction coefficient (A405 = 13260 M-1 cm-1) of the free 5-thio2-nitrobenzoic acid (TNBS) anion. Reduced and alkylated 2S albumin showed 0.01 free SH groups per molecule, and in the control preparation, no free SH groups could be detected. The reduced and alkylated 2S albumin shows a large and small subunit, at approximately 9 and 3 kDa, respectively (Figure 1). This preparation is further denoted as RA-2S albumin. The heavy and light chains of RA-2S albumin were isolated using size exclusion chromatography. The reduced, alkylated and lyophilized 2S albumin was dissolved in 20 mM sodium phosphate buffer containing 100 mM NaCl. The heavy and light chain were separated using an Aekta Explorer FPLC (Amersham Pharmacia Biotech) equipped with a SD-30 peptide gel filtration column (475 mL, Amersham-Pharmacia Biotech), calibrated with a mixture of globular proteins and peptides of known mass according to the instruction of the column manufacturer. Separation was performed batch-wise (4 mL,10 mg/mL portions) with a flow rate of 1 mL/min and proteins were monitored at 214 nm.

Reference： [1]Patent: EP1547610,2005,A1 .Location in patent: Page/Page column 6

19
[ 144-48-9 ]
[ 1076230-22-2 ]
(3S,4S)-1-(2-amino-2-oxoethyl)-N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 16h;	Example 156(3S,4S)-1-(2-amino-2-oxoethyl)-N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamideTo a solution of (3S,4S)-N-{(1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-3-(4-fluoro-2-methylphenyl)-N-methylpiperidine-4-carboxamide monohydrochloride (211 mg) synthesized by a known method (WO2006/004195) and 2-<strong>[144-48-9]iodoacetamid</strong>e (104 mg) in DMF (3 mL) was added Et3N (139 muL) at room temperature, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was poured into water, and the resultant product was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 10?100% ethyl acetate/hexane) to give the title compound (212 mg, 97%) as a white crystal powder.MS (ESI+):548 (M+H)[alpha]D25-43.8 (c 1.00, MeOH)elemental analysis value: C26H28N3O2F7.0.1 hexaneFound C, 57.64; H, 5.60; N, 7.35Calculated C, 57.45; H, 5.33; N, 7.56Melting point: 161-164 C.1H-NMR (300 MHz, CDCl3):delta 1.16-1.47 (3H, m), 1.87-2.08 (2H, m), 2.18-2.36 (2H, m), 2.42 (3H, s), 2.48-2.65 (3H, m), 2.88-3.11 (5H, m), 3.61 (1H, dt, J=11,4 Hz), 5.10-5.92 (2H, m), 6.72-7.03 (3H, m), 7.11 (1H, br), 7.28-7.83 (3H, m)

Reference： [1]Patent: US2008/275085,2008,A1 .Location in patent: Page/Page column 90

20
[ 144-48-9 ]
[ 1092394-88-1 ]
[ 1092394-89-2 ]

Yield	Reaction Conditions	Operation in experiment
61%		(iv) N-{3-[ (l-(2-amino-2-oxoethyl)-6-{ [ (4- methylphenyl) sulfonyl] imino}-l, 6-dihydropyridin-3-yl) oxy] phenyl }- 3- (trifluoromethyl) benzamide; To a solution of N-{3- [ (6-{ [ (4-35 methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl} -3- <n="332"/>(trifluoromethyl)benzamide (2.7 g, 5.12 itimol) in N, N- dimethylformamide (18 itiL) was added N,N-diisopropylethylamine (0.94 mL, 5.38 iranol) , and the mixture was stirred at room temperature for 15 min. 2-Iodoacetamide (995 mg, 5.38 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 18 hr. Water (200 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (300 mL) . The organic layer was washed with water (100 mL) and saturated brine (100 mL) , and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40?0/100) and recrystallized from ethyl acetate and hexane to give the title compound (1.84 g, 61%) as a colorless solid.1H-NMR (DMSO-d6, 300 MHz) delta 2.34 (3H, s) , 4.83 (2H, s) , 6.78 (IH, dd, J = 8.4, 2.7 Hz), 7.28 (2H, d, J = 8.4 Hz), 7.32 - 7.45 (3H, m) , 7.47 (IH, t, J = 2.1 Hz), 7.60 (IH, d, J = 8.4 Hz), 7.68 (2H, d, J = 8.4 Hz), 7.71 - 7.85 (3H, m) , 7.98 (IH, d, J = 7.8 Hz), 8.15 (IH, d, J = 2.7 Hz) , 8.19 - 8.30 (2H, m) , 10.56 (IH, s) .

Reference： [1]Patent: WO2008/150015,2008,A1 .Location in patent: Page/Page column 330-331

21
[ 144-48-9 ]
[ 1092394-00-7 ]
[ 1092393-99-1 ]

Yield	Reaction Conditions	Operation in experiment
99%		A mixture of 4-methyl-N- [5- (3- nitrophenoxy)pyridin-2-yl]benzenesulfonamide (4.15 g, 10.7 mmol) thus-obtained, N,N-diisopropylethylamine (2.44 mL, 14.0 mmol) and N,N-dimethylformamide (20 mL) was stirred at room temperature for 2 hr, <strong>[144-48-9]iodoacetamid</strong>e (2.59 g, 14.0 mmol) was added, and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (x3) . The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (5.28 g, 99%) as a white solid. 1H-NMR (DMSO-d6, 300 MHz) delta 2.34 (3H, s) , 4.82 (2H, s) , 7.29 (2H, d, J = 8.4 Hz), 7.40 (IH, br s) , 7.44 (IH, d, J = 9.6 Hz), 7.51 - 7.55 (IH, m) , 7.65 - 7.71 (3H, m) , 7.77 - 7.82 (3H, m) , 7.98 - 8.02 (IH, m) , 8.21 (IH, d, J = 2.7 Hz).

Reference： [1]Patent: WO2008/150015,2008,A1 .Location in patent: Page/Page column 172

22
[ 144-48-9 ]
[ 1092393-87-7 ]
[ 1092393-88-8 ]

Yield	Reaction Conditions	Operation in experiment
71%		Reference Example 5; N- {3- [ (1- (2-amino-2-oxoethyl) -6-{ [ (4- methylphenyl) sulfonyl] imino}-l, 6-dihydropyridin-3-yl) oxy] phenyl }- 1, 3-dimethyl-lH-pyrazole-5-carboxamide; A mixture of 1, 3-dimethyl-N-{3- [ (6-{ [ (4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl } -lH-pyrazole- 5-carboxamide (1.11 g, 2.32 mmol) , N,N-diisopropylethylamine (424 muL, 2.44 mmol) and N,N-dimethylformamide (7 mL) was stirred at room temperature for 2 hr, <strong>[144-48-9]iodoacetamid</strong>e (451 mg, 2.44 mmol) was added and the mixture was stirred at room temperature for 15 hr. The reaction mixture was diluted with water and extracted with ethyl acetate (x3) . The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was collected by filtration and washed with ethyl acetate-hexane to give the title compound (883 mg, 71%) as a white solid. <n="165"/>1H-NMR (DMSOd6, 300 MHz) delta 2.19 (3H, s) , 2.34 (3H, s) , 3.97 (3H, s)f 4.83 (2H, s), 6.72 - 6.79 (2H, m) , 7.26 - 7.43 (6H, m) , 7.52 - 7.56 (IH, m), 7.66 - 7.77 (4H, m) , 8.12 (IH, d, J = 2.7 Hz), 10.18 (IH, s)

Reference： [1]Patent: WO2008/150015,2008,A1 .Location in patent: Page/Page column 163-164

23
[ 144-48-9 ]
[ 1092394-48-3 ]
[ 1092394-49-4 ]

Yield	Reaction Conditions	Operation in experiment
70%		Reference Example 72; N- (3-{ [1- (2-amino-2-oxoethyl) -6-{ [ (4- methylphenyl) sulfonyl] imino}-l, 6-dihydropyridin-3-yl] oxy}phenyl) - 3-methylpyridine-2-carboxamide; A mixture of 3-methyl-N- { 3- [ ( 6- { [ (4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl }pyridine-2- carboxamide (12.4 g, 26.2 mmol) , N,N-diisoprorhoylethylamine (6.00 mL, 34.4 mmol) and N,N-dimethylformamide (100 mL) was stirred at room temperature for 1 hr. Iodoacetamide (6.29 g, 34.0 mmol) was added, and the mixture was stirred at room temperature for 71 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was recrystallized from ethanol to give the title compound (9.72 g, 70%) as a white solid.1H-NMR (DMSO-de, 400 MHz) delta 2.34 (3H, s) , 2.55 (3H, s) , 4.83 (2H, s), 6.73 (IH, dd, J = 8.2, 2.3 Hz), 7.28 (2H, d, J = 8.3 Hz), 7.34 (IH, t, J = 8.2 Hz), 7.37 - 7.44 (2H, m) , 7.52 (IH, dd, J = 7.8, 4.6 Hz), 7.57 (IH, t, J = 2.1 Hz), 7.64 - 7.70 (3H, m) , 7.71 <n="211"/>- 7.85 (3H, m), 8.13 (IH, d, J = 2.7 Hz), 8.53 (IH, d, J = 3.9 Hz), 10.65 (IH, s).

Reference： [1]Patent: WO2008/150015,2008,A1 .Location in patent: Page/Page column 209-210

24
[ 144-48-9 ]
[ 1092394-51-8 ]
[ 1092394-52-9 ]

Yield	Reaction Conditions	Operation in experiment
88%		Reference Example 75 N- (3-{ [1- (2-amino-2-oxoethyl) -6-{ [ (4- methylphenyl ) sulfonyl] imino} -l, 6-dihydropyridin-3-yl] oxy} phenyl) - 6-methylpyridine-2-carboxanu.de; <n="213"/>A mixture of 6-methyl-N- { 3- [ ( 6- { [ ( 4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl }pyridine-2- carboxamide (14.8 g, 31.2 mmol) , N,N-diisoprorhoylethylamine (7.10 mL, 40.7 mmol) and N,N-dimethylformamide (100 mL) was stirred at room temperature for 20 min. After stirring, <strong>[144-48-9]iodoacetamid</strong>e (7.51 g, 40.6 mmol) was added, and the mixture was stirred at room temperature for 16 hr. The reaction mixture was diluted with , aqueous sodium hydrogen carbonate solution and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography(0%-»100% ethyl acetate-hexane-»10% methanol-ethyl acetate) to give the title compound (14.6 g, 88%) as a pale-yellow oil. 1H-NMR (CDCl3, 400 MHz) delta 2.37 (3H, s) , 2.63 (3H, s) , 4.81 (2H, s) , 5.69 (IH, br s) , 6.73 (IH, dd, J = 8.3, 2.4 Hz), 7.10 (IH, br s) , 7.24 (2H, d, J = 8.3 Hz), 7.30 - 7.36 (2H, m) , 7.39 - 7.49 (3H, m), 7.59 - 7.65 (2H, m) , 7.75 - 7.84 (3H, m) , 8.07 (IH, d, J = 7.8 Hz), 10.13 (IH, s) .

Reference： [1]Patent: WO2008/150015,2008,A1 .Location in patent: Page/Page column 211-212

25
[ 144-48-9 ]
[ 1143522-56-8 ]
[ 1143522-59-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyhdin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5- dimethyl-4,5-dihydro-imidazole-1 -carboxylic acid (1 -carbamoyl methyl-pipehdin-4- yl)-amideChiralTo a mixture of (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyhdin-3-yl)-4,5-bis-(4- chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1 -carboxylic acid piperidin-4-yl amide (50.0 mg, 0.081 mmole, example 205) and potassium carbonate (22.4 mg, 0.162 mmole) in N,N-dimethylformamide (4 ml_) was added <strong>[144-48-9]iodoacetamid</strong>e (29.8 mg, 0.162 mmole, Aldrich). The mixture was stirred at room temperature overnight and diluted with ethyl acetate, washed with water, brine and concentrated. The crude product was purified by flash column chromatography (silica gel, eluting with a gradient of 1-10% methanol in dichloromethane) to give the title compound (40.5 mg, 74% yield). HR-MS (ES, m/z) calculated for C36H45CI2N6O3 [(M+H)+] 679.2925, observed 679.2924.

Reference： [1]Patent: WO2009/47161,2009,A1 .Location in patent: Page/Page column 169

26
[ 144-48-9 ]
[ 91349-44-9 ]
[ 1012343-75-7 ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	Step C. 2-(3-chloro-6-(tosylimino)pyridazin-1(6H)-yl)acetamide N,N-Diisopropylethylamine (10.4 mL, 81 mmol) was added to a suspension of N-(6-chloropyridazin-3-yl)-4-methylbenzenesulfonamide (21 g, 74 mmol) in dry DMF (100 mL) under argon. To the resulting solution was added 2-<strong>[144-48-9]iodoacetamid</strong>e (15 g, 81 mmol, Aldrich, St. Louis, Mo.) and the mixture was stirred for 24 h at rt. The reaction mixture was diluted with water and precipitated solid was filtered off to afford the title compound (17 g, 68%). 1H NMR (DMSO-d6, 300 MHz): delta 2.4 (s, 3H), 4.8 (s, 2H), 7.3 (d, 2H), 7.6-7.8 (m, 4H), 7.95 (d, 1H).
		The crude solid (0.5 g, purity=80% by LCMS at 254 nm) from Example 4, Step 1, was dissolved in DMF (5.0 mL) under an atmosphere of nitrogen. N,N-diisopropylethylamine (0.4 mL, 2.0 mol) was added and the reaction mixture was stirred for 5 minutes. Iodoacetamide (358 mg, 1.9 mmol) was then added at once and the reaction mixture turned from orange to red. After stirring for 3 hours at room temperature, the reaction mixture was poured onto 50 mL of water and stirred for 1 hour. The precipitate was filtered, washed with minimum water and dried with air and under vacuum to give 2-[3-Chloro-6-(toluene-4-sulfonylmethylene)-6H-pyridazin-1-yl]-acetamide as a brownish solid (600 mg, purity=72% by LCMS at 254 nm) which was used in next step without further purification.MS (ESI (+)m/z): 340.95 (M+H+)

Reference： [1]Patent: US2009/163489,2009,A1 .Location in patent: Page/Page column 20
[2]Patent: US2011/21513,2011,A1 .Location in patent: Page/Page column 18

27
[ 4414-84-0 ]
[ 144-48-9 ]
[ 1173929-45-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	In acetone; at 20℃; for 2h;Sonication;	General procedure: Under US irradiation, 5mmol of imidazole derivative (as indicated in Table 2) and 6mmol of activated halogeno-derivative (as indicated in Table 2) in 10mL of acetone, were placed in the reaction vessel and exposed to US irradiation for an appropriate time, as is presented in Table 5. The reaction vessel was cooled to 20C using a circulating bath in order to prevent the acetone evaporation. Once the irradiation cycle was completed, the reaction tube was removed from the reactor, and processed as indicated above for TH.

Reference： [1]Ultrasonics Sonochemistry,2015,vol. 23,p. 376 - 384
[2]Molecules,2009,vol. 14,p. 403 - 411

28
[ 144-48-9 ]
[ 23996-53-4 ]
[ 1173929-42-4 ]

Yield	Reaction Conditions	Operation in experiment
90%	In acetone; at 20℃; for 0.66h;Sonication;	General procedure: Under US irradiation, 5mmol of imidazole derivative (as indicated in Table 2) and 6mmol of activated halogeno-derivative (as indicated in Table 2) in 10mL of acetone, were placed in the reaction vessel and exposed to US irradiation for an appropriate time, as is presented in Table 5. The reaction vessel was cooled to 20C using a circulating bath in order to prevent the acetone evaporation. Once the irradiation cycle was completed, the reaction tube was removed from the reactor, and processed as indicated above for TH.

Reference： [1]Molecules,2009,vol. 14,p. 403 - 411
[2]Ultrasonics Sonochemistry,2015,vol. 23,p. 376 - 384

29
[ 144-48-9 ]
[ 1203605-13-3 ]
[ 1203603-97-7 ]

Yield	Reaction Conditions	Operation in experiment
40%		Under argon, a solution of 2-([5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino}methyl)-1,3-benzothiazol-5-ol (30 mg, 0.074 mmol, prepared as in example 16) and potassium carbonate (20.5 mg, 0.149 mmol) in anhydrous THF (0.3 mL) was stirred at 50C for I hour. Then <strong>[144-48-9]iodoacetamid</strong>e (27.5 mg, 0.15 mmol) was added and the reaction mixture was stirred at 50C overnight. The mixture was then concentrated and the residue was purified by preparative TLC (silica gel, dichloromethane/methanol 95/5) to afford 2-[2-([5-(2,6-dichlorophenyl)-1,2,4-triazin-3-yl]amino}methyl)-1,3-benzothiazol-5-yl]oxy}acetamide (13.6 mg, 40%) as a yellow solid. ESI-MS m/z 461 and 463 (M+H)+. 1H NMR (CDCl3), delta (ppm): 8.70 (s, 1H), 7.74 (d, J = 8.7 Hz, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.42-7.33 (m, 3H), 7.06 (dd, J = 8.7 Hz and J = 2.4 Hz, 1H), 6.60 (br s, 2H), 5.87 (br s, 1H), 5.17 (br s, 2H), 4.57 (s, 2H).

Reference： [1]Patent: EP2141164,2010,A1 .Location in patent: Page/Page column 22
[2]Journal of Medicinal Chemistry,2013,vol. 56,p. 1418 - 1430

30
[ 144-48-9 ]
[ 1195781-09-9 ]
benzyl (4-[1-(2-amino-2-oxoethyl)-6-[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl]oxy}phenyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a solution of benzyl {4-[(6-[(4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl } carbamate (23.8 g, 48.6 mmol) in N, N-dimethylformamide (238 mL) were added N,N-diisopropylethylamine (11.0 mL, 63.2 mmol) and <strong>[144-48-9]iodoacetamid</strong>e (11.7 g, 63.2 mmol), and the mixture was stirred at room temperature for 24 hr. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with <n="135"/>hexane/ethyl acetate and collected by filtration to give the title compound (20.6 g, 78%) .1H-NMR (DMSOd6, 300MHz) delta 2.34 (3H, s) , 4.81 (2H, s) , 5.14 (2H, s), 6.97 (2H, d, J = 9.0 Hz), 7.27 (2H, d, J = 8.1 Hz), 7.31 - 7.48 (9H, m) , 7.63 - 7.68 (3H, m) , 7.74 (IH, br s) , 7.99 (IH, d, J = 3.0 Hz) , 9.76 (IH, br s) .

Reference： [1]Patent: WO2009/136663,2009,A1 .Location in patent: Page/Page column 133-134

31
[ 144-48-9 ]
[ 1195782-14-9 ]
2-[5-[(4-methoxybenzyl)oxy]-2-[(4-methylphenyl)sulfonyl]imino}pyridin-1(2H)-yl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 48h;	To a suspension of 18 (35g, 91mmol) in DMF (300mL) were added iPr2NEt (23.8mL, 136.5mmol) and 2-<strong>[144-48-9]iodoacetamid</strong>e (20.2g, 109mmol), and the mixture was stirred at rt for 2days. EtOAc and water were added to the mixture, and the mixture was extracted with EtOAc. The organic layer was washed with water and brine. The organic layer was holded for 30min. The precipitate was collected by filtration and washed with EtOAc to give 19 (25g) as white solid. The filtrate was concentrated in vacuo. The residue was washed with EtOAc to get 19 (7g) as white solid. The total yield of 19 was 80%. 1H NMR (DMSO-d6) delta 2.33 (3H, s), 3.75 (3H, s), 4.82 (2H, s), 4.89 (2H, s), 6.81-7.03 (2H, m), 7.20-7.41 (6H, m), 7.60-7.69 (3H, m), 7.76 (1H, s), 7.92 (1H, d, J=3.0Hz).
75%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 60℃; for 5h;	To a suspension of N- { 5- [ (4-methoxybenzyl) oxy] pyridin-2- yl } -4-methylbenzenesulfonamide (10.0 g, 26.0 mmol) in N, N- <n="191"/>dimethylformamide (85 mL) were added N, N-diisopropylethylamine (6.8 mL, 39.0 mmol) and <strong>[144-48-9]iodoacetamid</strong>e (5.77 g, 31.0 mmol) , and the mixture was stirred at 60C for 5 hr. After cooling to room temperature, ethyl acetate and water were added, and the mixture was extracted 3 times with a mixed solution of ethyl acetate and tetrahydrofuran. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was washed with ethyl acetate and collected by filtration to give the title compound (34.4 g, 75%) as a white solid.1H-NMR (DMSO-de, 300 MHz) delta 2.33 (3H, s), 3.75 (3H, s) , 4.82 (2H, s), 4.89 (2H, s) , 6.81 - 7.03 (2H, m) , 7.20 - 7.41 (6H, m) , 7.60 - 7.69 (3H, m) , 7.76 (IH, d) , 7.92 (IH, d, J = 3.0 Hz) .

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 7686 - 7698
[2]Patent: WO2009/136663,2009,A1 .Location in patent: Page/Page column 189-190

32
[ 144-48-9 ]
[ 1195781-20-4 ]
[ 1195781-21-5 ]

Yield	Reaction Conditions	Operation in experiment
72%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a solution of benzyl { 3-fluoro-4- [ (6-{ [ (4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl } carbamate <n="140"/>(35.0 g, 69.0 mmol) in N, N-dimethylformamide (350 mL) were added N, N-diisopropylethylamine (15.6 mL, 89.6mmol) and <strong>[144-48-9]iodoacetamid</strong>e (16.6 g, 89.6 mmol), and the mixture was stirred at room temperature for 24 hr. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with hexane/ethyl acetate and collected by filtration to give the title compound (28.0 g, 72%).1H-NMR (DMSOd6, 300MHz) delta 2.34 (3H, s) , 4.80 (2H, s) , 5.16 (2H, s), 7.08 - 7.46 (12H, m) , 7.50 - 7.58 (IH, m) , 7.64 - 7.74 (3H, m) , 7.95 (IH, d, J = 3.0 Hz), 10.03 (IH, s) .

Reference： [1]Patent: WO2009/136663,2009,A1 .Location in patent: Page/Page column 138-139

33
[ 144-48-9 ]
[ 1195781-29-3 ]
[ 1195781-31-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 24h;	To a solution of benzyl { 2-fluoro-4- [ ( 6- { [ (4- methylphenyl) sulfonyl] amino}pyridin-3-yl) oxy] phenyl} carbamate (32.0 g, 63.1 mmol) in N, N-dimethylformamide (320 mL) were added N, N-diisopropylethylamine (14.3 mL, 82.0 mmol) and <strong>[144-48-9]iodoacetamid</strong>e (15.2 g, 82.0 mmol), and the mixture was stirred at room temperature for 24 hr. Water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate/tetrahydrofuran. The combined organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure, and the residue was washed with hexane/ethyl acetate and collected by filtration to give the title compound (34.2 g, 96%).1H-NMR (DMSO-de, 300MHz) delta 2.34 (3H, s) , 4.81 (2H, s) , 5.13 (2H, s), 6.79 - 6.87 (IH, m) , 7.02 (IH, dd, J = 11.7, 2.9 Hz), 7.28(IH, d, J = 7.8 Hz), 7.30 - 7.43 (8H, m) , 7.53 - 7.59 (IH, m) ,7.65 - 7.75 (4H, m) , 8.12 (IH, d, J = 3.0 Hz), 9.38 (IH, br s) .

Reference： [1]Patent: WO2009/136663,2009,A1 .Location in patent: Page/Page column 143-144

34
[ 144-48-9 ]
[ 1221749-05-8 ]
[ 1221748-66-8 ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃;	To a stirred solution of 1'-(3-hydroxybenzyl)-5,6-dihydrospiro[benzo[1 ,2-jb:5,4- £>']difuran-3,3'-indol]-2'(17-/)-one (0.30 g, 0.78 mmol) in Lambda/,Lambda/-dimethylformamide (2 mL) was added potassium carbonate (0.32 g, 2.3 mmol) at ambient temperature and 2- <strong>[144-48-9]iodoacetamid</strong>e (0.29 g, 1.6 mmol). The mixture was stirred at 40 0C for 16 h. Water (20 ml_) and chloroform (80 mL) were added to the mixture. The organic solution was separated and the aqueous layer was extracted with chloroform (2 x 80 mL). The combined organic solution was washed with saturated aqueous sodium bicarbonate solution (60 mL), brine (60 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (hexanes/ethyl acetate from 1 :1 to 1:2 to 0:1) to afford 2-{3-[(2-oxo-5,6- dihydrospiro[benzo[1,2-jb:5,4-iotafciota]difuran-3,3-indol]-1(2/-/)-yl)methyl]phenoxy}acetamide (0.30 g, 87%) as a colorless solid: mp 109-111 0C; 1H NMR (300 MHz, CDCI3) 57.54 (s, 1 H), 7.39 (s, 1 H), 7.33-7.22 (m, 2H), 7.21-7.16 (m, 1H), 7.06-6.92 (m, 4H), 6.89- 6.84 (m, 1 H), 6.46 (s, 1 H), 6.43 (s, 1 H), 5.00-4.81 (m, 3H), 4.77-4.71 (m, 1 H), 4.55- 4.45 (m, 2H), 4.39 (s, 1 H), 3.07-2.87 (m, 2H); 13C NMR (75 MHz, CDCI3) £ 177.1, 169.7, 161.1 , 160.6, 158.0, 142.1 , 137.9, 132.0, 129.8, 128.6, 123.6, 123.1 , 120.4, 119.9 (2C), 118.9, 113.7, 113.5, 109.4, 92.5, 79.8, 72.1 , 66.6, 56.9, 42.9, 28.3; MS (ES+) m/z 443.0 (M + 1 ).

Reference： [1]Patent: WO2010/45197,2010,A1 .Location in patent: Page/Page column 100-101

35
[ 144-48-9 ]
[ 138308-78-8 ]
[ 1146962-11-9 ]

Yield	Reaction Conditions	Operation in experiment
65%		6.2 g (55 mmol) of potassium tert-butoxide is added in portions with ice-cooling to a solution of 7.0 g (42 mmol) of phenol 7 in 50 ml of DMF, and the mixture is stirred for a further 1 hour. 10.2 g (55 mmol) of 2-<strong>[144-48-9]iodoacetamid</strong>e are then slowly added, and the mixture is stirred at room temperature for 16 h. The mixture is subjected to conventional work-up, giving 5.7 g (65%) of oxoacetamide 8 as crystals, m.p. 118-119 C.

Reference： [1]Patent: US2010/249151,2010,A1 .Location in patent: Page/Page column 12; 13

36
[ 144-48-9 ]
[ 1218762-60-7 ]
[ 1218762-90-3 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate; In N,N-dimethyl-formamide; at 45 - 55℃;	Example 334 2-(4-[(3S,4R)-3-[[3,5-bis(trifluoromethyl)phenyl](methyl)carbamoyl}(methyl)amino]-4-(4-fluorophenyl)pyrrolidin-1-yl]carbonyl}piperidin-1-yl)acetamide A mixture of the compound (0.21 g) obtained in Example 304, 2-<strong>[144-48-9]iodoacetamid</strong>e (0.078 g), potassium carbonate (0.12 g) and DMF (5.0 mL) was stirred at 45 to 55C overnight. The mixture was diluted with ethyl acetate, and washed with water (2 times) and saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 0?6% methanol/ethyl acetate) to give the title compound (0.19 g, 85%) as a pale-yellow powder. MS(ESI+): 632(M+H)

Reference： [1]Patent: EP2336105,2011,A1 .Location in patent: Page/Page column 164

37
[ 144-48-9 ]
[ 1218760-13-4 ]
[ 1218760-42-9 ]

Yield	Reaction Conditions	Operation in experiment
89%		Example 79 2-[(3R,4R)-4-[[3,5-bis(trifluoromethyl)phenyl](methyl)carbamoyl}(methyl)amino]-3-(4-fluorophenyl)piperidin-1-yl]acetamide monohydrochloride To a solution of the compound (0.15g) obtained in Example 51 and 2-<strong>[144-48-9]iodoacetamid</strong>e (0.083 g) in DMF (6.0 mL) was added potassium carbonate (0.12 g), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (NH Chromatorex) (solvent gradient; 0?100% ethyl acetate/hexane) and treated with 4N hydrogen chloride/ethyl acetate to give the title compound (0.15 g, 89%) as a white powder. MS(ESI+): 535(M-HCl+H)

Reference： [1]Patent: EP2336105,2011,A1 .Location in patent: Page/Page column 107

38
[ 144-48-9 ]
[ 526-75-0 ]
[ 35368-58-2 ]

Yield	Reaction Conditions	Operation in experiment
83%		19.95 g of 2,3-dimethylphenol 6 are dissolved in 250 ml of DMF, 6.4 g of NaH (60% suspension in paraffin oil) are carefully added with cooling, and the mixture is stirred at RT for 45 min. 31.4 g of 2-<strong>[144-48-9]iodoacetamid</strong>e 2 are then added, and the reaction mixture is stirred overnight. The mixture is subsequently subjected to conventional work-up, giving 23.8 g (83%) of 2-(2,3-dimethylphenoxy)acetamide 7 ; MS-EI (M+)=179

Reference： [1]Patent: US2011/195991,2011,A1 .Location in patent: Page/Page column 12

39
[ 144-48-9 ]
[ 18362-30-6 ]
[ 1000267-52-6 ]

Yield	Reaction Conditions	Operation in experiment
90%		1.0 g of 6-chlorosalicylaldehyde 9 is dissolved in 30 ml of DMF, 0.26 g of NaH (60percent suspension in paraffin oil) is carefully added with cooling, and the mixture is stirred at RT for 45 min. 1.30 g of 2-iodoacetamide 2 are then added, and the reaction mixture is stirred overnight. The mixture is subsequently subjected to conventional work-up, giving 1.28 g (90percent) of 2-(3-chloro-2-formylphenoxy)acetamide 10 ; MS-EI (M+)=213

Reference： [1]Patent: US2011/195991,2011,A1 .Location in patent: Page/Page column 13

40
[ 700-44-7 ]
[ 144-48-9 ]
[ 1000267-50-4 ]

Yield	Reaction Conditions	Operation in experiment
59%		1.1 1.0 g (6.57 mmol) of 2-hydroxy-6-methoxybenzaldehyde 1 is dissolved in 30 ml of DMF, 0.29 g of NaH (60% suspension in paraffin oil) is carefully added with cooling, and the mixture is stirred at RT for 45 min. 1.34 g of 2-<strong>[144-48-9]iodoacetamid</strong>e 2 are then added, and the reaction mixture is stirred overnight. The mixture is subsequently subjected to conventional work-up, giving 0.81 g (59%) of 2-(2-formyl-3-methoxyphenoxy)acetamide 3 as solid. MS-EI (M+)=209.

Reference： [1]Patent: US2011/195991,2011,A1 .Location in patent: Page/Page column 11

41
[ 144-48-9 ]
[ 447424-19-3 ]
[ 447424-20-6 ]

Yield	Reaction Conditions	Operation in experiment
44%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 80℃; for 10h;	A solution of 33a (0.63 g, 1.5 mmol), 2-<strong>[144-48-9]iodoacetamid</strong>e (0.43 g, 2.3 mmol) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.34 mL, 2.3 mmol) in N,N-dimethylformamide (10 mL) was stirred at 80 C for 10 h. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/AcOEt = 50/50) to give 34a (0.32 g, 44%) as crystals. 1H NMR (300 MHz, DMSO-d6) delta 0.89 (6H, d, J = 6.6 Hz), 1.38 (9H, s), 2.07-2.21 (1H, m), 3.88 (2H, d, J = 6.6 Hz), 3.95 (2H, d, J = 4.0 Hz), 4.34 (2H, s), 6.30 (1H, d, J = 2.4 Hz), 7.13 (1H, dd, J = 2.4, 8.8 Hz), 7.34-7.52 (8H, m), 8.24 (1H, d, J = 8.8 Hz). Mp 226-227 C. Anal. Calcd for C27H33N3O5: C, 67.62; H, 6.94; N, 8.76. Found: C, 67.36; H, 6.73; N, 8.60.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 4953 - 4970

42
[ 144-48-9 ]
[ 447425-68-5 ]
[ 447425-71-0 ]

Yield	Reaction Conditions	Operation in experiment
40%	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 80℃; for 10h;	General procedure: A solution of 33a (0.63 g, 1.5 mmol), 2-<strong>[144-48-9]iodoacetamid</strong>e (0.43 g, 2.3 mmol) and 1,8-diazabicyclo[5.4.0]-7-undecene (0.34 mL, 2.3 mmol) in N,N-dimethylformamide (10 mL) was stirred at 80 C for 10 h. The reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified by silica gel column chromatography (hexane/AcOEt = 50/50) to give 34a (0.32 g, 44%) as crystals.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 4953 - 4970

43
[ 209971-43-7 ]
[ 144-48-9 ]
[ 209971-46-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃;	To a suspension of N-(5-Iodopyridin-2-yl)-4-methylbenzenesulfonamide (115.6 g, 309 mmol) and N,N-ethyldiisopropyl amine (39.9 g, 340 mmol) in DMF (1.0 L) was added 2-<strong>[144-48-9]iodoacetamid</strong>e (62.9 g, 340 mmol). The reaction mixture was stirred at room temperature overnight. The mixture was then concentrated and the residue was washed with CH2Cl2 (500 mL) and ethyl acetate (500 mL) to give the title compound as a white solid (114.0 g, 86%): 1H NMR (DMSO-d6) delta 2.35 (s, 3H), 4.76 (s, 2H), 7.16 (d, J = 9.4 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.38 (s, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.78 (s, 1H), 7.91 (dd, J = 9.4, 2.1 Hz, 1H), 8.36 (d, J = 2.1 Hz, 1H).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 7326 - 7329
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6586 - 6590

44
[ 144-48-9 ]
[ 1280210-79-8 ]
[ 1270029-90-7 ]

Yield	Reaction Conditions	Operation in experiment
		INTERMEDIATE 4; Step A: fert-Butyl 2-(2-aniino-2-oxoemyl)-2,6-dihvdropvrrolof3,4-c\|pyrazole-5(4H)- carboxylateA 2 L three neck flask fitted with a thermometer, a mechanical stirrer and an addition funnel was charged with a suspension of tert-butyl 2,6-dihydropyrrolo[3,4-c]pyrazole- 5(4H)-carboxylate (18.01 g, 86.5 mmol) in anhydrous acetonitrile (1.0 L). Sodium hydride (60% dispersion in oil, 4.15 g, 104 mmol) was added to the suspension in one portion under nitrogen. The reaction was stirred at room temperature for 2 h. The resulting white suspension was then cooled in an ice bath and iodoacetamide (31.95 g, 173 mmol) was added. The ice bath was then removed and the mixture was stirred 18 h at room temperature. The mixture was quenched with water (50 mL) and the solvent was removed under reduced pressure. The residue was partitioned between diluted NaCl (50 mL brine and 100 mL water) and 1.0 L EtOAc. The aqueous layer was extracted with 2 1.0L EtOAc. The organic layers were combined and dried over Na2S04 and solvent was evaporated under reduced pressure. Crude material was purified on silica gel eluting with 20-50%EtOAc/CH2Cl2 to wash out excess iodoacetamide, and then with 2- 10%MeOH CH2Cl2 to afford a mixture of the two products which were separated on a chiral AD column by eluting with 30% MeOH/C02 to afford the title compound (less mobile fraction). LC- MS - 267.32 [M+l].
		A 2 L three neck flask fitted with a thermometer, a mechanical stirrer and an addition funnel was charged with a suspension of tert-butyl 2,6-dihydropyrrolo[3,4-c]pyrazole- 5(4H)-carboxylate (18.01 g, 86.5 mmol) in anhydrous acetonitrile (1.0 L). Sodium hydride (60% dispersion in oil, 4.15 g, 104 mmol) was added to the suspension in one portion under nitrogen. The reaction was stirred at room temperature for 2 h. The resulting white suspension was then cooled in an ice bath and iodoacetamide (31.95 g, 173 mmol) was added. The ice bath was then removed and the mixture was stirred 18 h at room temperature. The mixture was quenched with water (50 mL) and the solvent was removed under reduced pressure. The residue was partitioned between diluted NaCl (50 mL brine and 100 mL water) and 1.0 L EtOAc. The aqueous layer was extracted with 2x1.0L EtOAc. The organic layers were combined and dried over Na2SC>4 and solvent was evaporated under reduced pressure. Crude material was purified on silica gel eluting with 20-50%EtOAc/CH2C.2 to wash out excess iodoacetamide, and men with 2- 10%MeOH/CH2C-2 to afford a mixture of the two products which were separated on a chiral AD column by eluting with 30% MeOH/C02 to afford the title compound (less mobile fraction). LC- MS - 267.32 [M+l].

Reference： [1]Patent: WO2011/103256,2011,A1 .Location in patent: Page/Page column 49
[2]Patent: WO2011/146358,2011,A1 .Location in patent: Page/Page column 53

45
[ 144-48-9 ]
[ 1005785-61-4 ]
[ 1352624-97-5 ]

Yield	Reaction Conditions	Operation in experiment
68%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 38h;	b) (E)-2-(5-Fluoro-2-(tosylimino)pyridin-1(2H)-yl)acetamide: Diisopropylethylamine (7.30 mL, 41.8 mmol) and 2-<strong>[144-48-9]iodoacetamid</strong>e (7.70 g, 41.6 mmol) were added to a stirred solution of (E)-N-(5-fluoropyridin-2(1H)-ylidene)-4-methylbenzenesulfonamide (Preparation 83a, 10.07 g, 37.8 mmol) in N,N'-dimethylformamide (65 mL). After stirring for 20 hours at ambient temperature further diisopropylethylamine (1.8 mL) and 2-<strong>[144-48-9]iodoacetamid</strong>e (1.93 g) were added and stirring was continued for a further 18 hours. The mixture was evaporated to dryness and water was added to the residue. After stirring for 1 hour, the precipitate was filtered, washed with water and ethyl acetate and dried to give the title compound (8.25 g, 68%) as a white solid. LRMS (m/z): 324 (M+1)+.1H NMR (300 MHz, DMSO-d6) delta ppm 2.34 (s, 3H), 4.77 (s, 2H), 7.27 (d, 2H), 7.36 (dd, 1H), 7.41 (br s, 1H), 7.66 (d, 2H), 7.79 (br s, 1H), 7.88 (ddd, 1H), 8.33 (dd, 1H).
68%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 38h;	b) (E)-2-(5-Fluoro-2-(tosylimino)pyridin-1(2H)-yl)acetamide: Diisopropylethylamine (7.30 mL, 41.8 mmol) and 2-<strong>[144-48-9]iodoacetamid</strong>e (7.70 g, 41.6 mmol) were added to a stirred solution of (E)-N-(5-fluoropyridin-2(1H)-ylidene)-4-methylbenzenesulfonamide (Preparation 83a, 10.07 g, 37.8 mmol) in N,N'-dimethylformamide (65 mL). After stirring for 20 hours at ambient temperature further diisopropylethylamine (1.8 mL) and 2-<strong>[144-48-9]iodoacetamid</strong>e (1.93 g) were added and stirring was continued for a further 18 hours. The mixture was evaporated to dryness and water was added to the residue. After stirring for 1 hour, the precipitate was filtered, washed with water and ethyl acetate and dried to give the title compound (8.25 g, 68%) as a white solid. LRMS (m/z): 324 (M+1)+.1H NMR (300 MHz, DMSO-d6) delta ppm 2.34 (s, 3H), 4.77 (s, 2H), 7.27 (d, 2H), 7.36 (dd, 1H), 7.41 (br s, 1H), 7.66 (d, 2H), 7.79 (br s, 1H), 7.88 (ddd, 1H), 8.33 (dd, 1H).

Reference： [1]Patent: EP2397482,2011,A1 .Location in patent: Page/Page column 92-93
[2]Patent: WO2011/157397,2011,A1 .Location in patent: Page/Page column 154-155

46
[ 144-48-9 ]
[ 892-48-8 ]
[ 1341220-59-4 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 7734 - 7738

47
[ 553-26-4 ]
[ 144-48-9 ]
C₁₄H₁₆N₄O₂⁽²⁺⁾*2F₆P^(1-) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%		To a solution of 200 mg (1.28 mmol) 4,4'-dipyridyl in 10 ml DMF was added 500 mg (2.69 mmol) <strong>[144-48-9]iodoacetamid</strong>e and refluxed overnight. The precipitated solid was filtered and washed with ether several times. Then the solid was dissolved in 10 ml water. As soon as 5 ml of 1 M NH4PF6 was added to the solution, the receptor 1 was precipitated. Filtration and drying the solid gave 650 mg (97%) of the receptor 1. 1H NMR (DMSO-d6, 500 MHz): 9.26 (d, J = 7.0, 4H), 8.79 (d, J = 7.0, 4H), 8.10 (s, 2H), 7.78 (s, 2H), 5.49 (s, 4H) 13C NMR (DMSO-d6, 500 MHz) 165.86, 149.20, 147.25, 126.07, 61.62 HRMS (ESI): calcd for C14H15N4O2PF6 : 417.0910 m/e; found for 417.0909.

Reference： [1]Tetrahedron Letters,2012,vol. 53,p. 247 - 252

48
[ 144-48-9 ]
[ 1092393-87-7 ]
N-(3-[1-(2-amino-2-oxoethyl)-6-[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl]oxy}phenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%		General procedure: A mixture of 14a (1.11g, 2.32mmol), N,N-diisopropylethylamine (424muL, 2.44mmol), and DMF (7mL) was stirred at room temperature for 2h. Iodoacetamide (451mg, 2.44mmol) was added to the mixture, and the resulting mixture was stirred at room temperature for 15h. The mixture was diluted with water and extracted with AcOEt. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was collected by filtration and washed with AcOEt-hexane to give 15a (883mg, 71%) as a white solid: 1H NMR (DMSO-d6) delta 2.19 (3H, s), 2.34 (3H, s), 3.97 (3H, s), 4.83 (2H, s), 6.72-6.79 (2H, m), 7.26-7.43 (6H, m), 7.52-7.56 (1H, m), 7.66-7.77 (4H, m), 8.12 (1H, d, J=2.7Hz), 10.18 (1H, s).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4714 - 4729

49
[ 144-48-9 ]
[ 1092393-96-8 ]
N-(5-[1-(2-amino-2-oxoethyl)-6-[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl]oxy}-2-methylphenyl)-1,3-dimethyl-1H-pyrazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%		General procedure: A mixture of 14a (1.11g, 2.32mmol), N,N-diisopropylethylamine (424muL, 2.44mmol), and DMF (7mL) was stirred at room temperature for 2h. Iodoacetamide (451mg, 2.44mmol) was added to the mixture, and the resulting mixture was stirred at room temperature for 15h. The mixture was diluted with water and extracted with AcOEt. The extract was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was collected by filtration and washed with AcOEt-hexane to give 15a (883mg, 71%) as a white solid: 1H NMR (DMSO-d6) delta 2.19 (3H, s), 2.34 (3H, s), 3.97 (3H, s), 4.83 (2H, s), 6.72-6.79 (2H, m), 7.26-7.43 (6H, m), 7.52-7.56 (1H, m), 7.66-7.77 (4H, m), 8.12 (1H, d, J=2.7Hz), 10.18 (1H, s).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 4714 - 4729

50
[ 144-48-9 ]
(1S,2S,3R,4R)-3-[6-chloro-2-(4-methyl-2-piperidin-4-ylthiazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-ylamino]bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide [ No CAS ]
(1S,2S,3R,4R)-3-{2-[2-(1-carbamoylmethylpiperidin-4-yl)-4-methylthiazol-5-yl]-6-chloro-3H-imidazo[4,5-b]pyridine-7-ylamino}-bicyclo[2.2.1]hept-5-ene-2-carboxylic acid amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With MP-carbonate; In N,N-dimethyl-formamide; at 40℃;	(lS,2S,3R,4R)-3-[6-Chloro-2-(4-methyl-2- piperidin-4-yl-thiazol-5-yl)-3H-imidazo[4,5-b]pyridine-7-ylamino]-bicyclo[2.2.1]hept-5- ene-2-carboxylic acid amide (Compound LXIV above) (50 mg, 0.103 mmol), <strong>[144-48-9]iodoacetamid</strong>e (19 mg, 0.103 mmol), and MP-carbonate (31.6 mg, 0.100 mmol) were combined in Nu,Nu-dimethylformamide (1 mL) and heated at 40C overnight. Solids were removed by filtration and the filtrate was concentrated. The crude product was purified by reverse phase chromatography (Gilson) to afford, following lyophilization and neutralization, the title compound as a white solid (71%). NMR (d-6 DMSO): 9.69 (br s, 1H), 7.99 (m, 2H), 7.78 (s, 1H), 7.27 (s, 1H), 6.36 (m, 2H), 5.08 (m 1H), 3.60 (m, 2H), 3.37-3.12 (m, 3H), 2.89 (s, 1H), 2.79 (s, 1H), 2.72 (s, 3H), 2.71 (m, 1H), 2.59 (m, 1H), 2.35-2.18 (m, 5H), 2.10(m, 2H), 1.40 (m, 1H). MS: 541.0 (M+H). HPLC retention time: 1.66 minutes (G Method).

Reference： [1]Patent: WO2013/116291,2013,A1 .Location in patent: Page/Page column 100; 101

51
[ 144-48-9 ]
[ 143468-13-7 ]
[ 1584678-97-6 ]

Yield	Reaction Conditions	Operation in experiment
89%		Compound 5 (200mg, 1.01mmol) dissolved in dry DMF (0.61mL) was added dropwise to a suspension of NaH (60% in mineral oil) in dry DMF (0.81mL) and the mixture was stirred for 30min at room temperature. Iodoacetamide (187mg, 1.01mmol) dissolved in DMF (1.01mL) was added dropwise and the reaction was stirred for 3h at room temperature. Iced water was added (20mL) and the mixture was extracted with ethyl acetate (3 ×20mL). The combined organic phases were dried, filtered and the solvent was evaporated to give 229mg (89%) of the desired compound as a white solid; mp 223C; 1H NMR (DMSO-d6) delta 7.94 (1H, d, J=8.8Hz); 7.64 (1H, br s); 7.51 (1H, d, J=3.5Hz); 7.26 (1H, d, J=8.8Hz); 7.25 (1H, br s); 6.51 (1H, d, J=3.5Hz); 4.85 (2H, s). Anal. Calcd for C9H8BrN3O: C, 42.54; H, 3.17; N, 16.54. Found: C, 42.69; H, 3.12; N, 16.36.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1089 - 1103

52
[ 144-48-9 ]
glycine-rich cell wall structural protein from maize [ No CAS ]
glycine-rich cell wall structural protein from maize, Cys and Tyr residues blocked with iodoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To samples of 50mul of either GRP (50muM) or MGRP (50muM) in 0.01M sodium phosphate, pH 7.5 was added 5mul of 2% SDS and 200mM ammonium bicarbonate, (45mul, pH 8.0). To reduce the disulfide bonds, 200mM TCEP (5mul) was added and incubated at 55C for 1h. Then 5mul of freshly prepared 375mM <strong>[144-48-9]iodoacetamid</strong>e in 200mM NH4HCO3, pH 8.0 was added and incubated for 30min. The sample was protected from light during reaction. After reaction, treated protein was desalted on a Sephadex G-25 column in 10mM sodium phosphate, pH 7.5.

Reference： [1]Phytochemistry,2013,vol. 96,p. 449 - 456

53
[ 144-48-9 ]
maize glycine-rich cell wall structural protein E₈C/D₁₆T/D₅₇T/E₆₇C/E₇₀C mutant [ No CAS ]
maize glycine-rich cell wall structural protein E₈C/D₁₆T/D₅₇T/E₆₇C/E₇₀C mutant, Cys and Tyr residues blocked with iodoacetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		General procedure: To samples of 50mul of either GRP (50muM) or MGRP (50muM) in 0.01M sodium phosphate, pH 7.5 was added 5mul of 2% SDS and 200mM ammonium bicarbonate, (45mul, pH 8.0). To reduce the disulfide bonds, 200mM TCEP (5mul) was added and incubated at 55C for 1h. Then 5mul of freshly prepared 375mM <strong>[144-48-9]iodoacetamid</strong>e in 200mM NH4HCO3, pH 8.0 was added and incubated for 30min. The sample was protected from light during reaction. After reaction, treated protein was desalted on a Sephadex G-25 column in 10mM sodium phosphate, pH 7.5.

Reference： [1]Phytochemistry,2013,vol. 96,p. 449 - 456

54
[ 144-48-9 ]
[ 712301-24-1 ]
[ 407-25-0 ]
[ 723286-57-5 ]

Yield	Reaction Conditions	Operation in experiment
65%		[0108] Method D-Step b: Preparation of 2,2,2-trifluoro-N-(imidazo[l,2-a]pyrazin-2- yl)acetamide [0109] To a solution of 4-methyl-N-(pyrazin-2-yl)benzenesulfonamide (8.6 g, 34.5 mmol) in DMF (60 mL) were added <strong>[144-48-9]iodoacetamid</strong>e (7 g, 37.8 mmol) and DIPEA (6.6 mL, 37.9 mmol). The mixture was stirred at room temperature for 28 hours, 40 mL of H20 was added and stirred at room temperature for 100 minutes, filtered. The solid was washed with 200 mL of H20 and 100 mL of diethyl ether to obtain a gray solid which dissolved in the mixture of dichloromethane (110 mL) and trifluoroacetic anhydride (110 mL), the mixture was refluxed for 2 hours. After the mixture was concentrated, the residue was added to ethyl acetate (220 mL) to give a precipitate. The precipitate was washed with ethyl acetate to obtain a gray solid (5.2 g, 65%). 1H NMR (400 MHz, DMSO-d6) delta 12.71 (s, 1H), 8.98 (s, 1H), 8.63 (d, / = 4.8 Hz, 1H), 8.40 (s, 1H), 7.93 (d, / = 4.4 Hz, 1H).

Reference： [1]Patent: WO2014/113191,2014,A1 .Location in patent: Paragraph 0108; 0109

55
[ 144-48-9 ]
3-(2-(3-bromo-5-nitrophenyl)propan-2-yl)phenol [ No CAS ]
2-(3-(2-(3-bromo-5-nitrophenyl)propan-2-yl)phenoxy)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With potassium carbonate; In N,N-dimethyl-formamide; at 30℃; for 76h;	3-(2-(3-Bromo-5-nitrophenyl)propan-2-yl)phenol (123.0 mg, 0.37 mmol) was dissolved in anhydrous DMF (3.5 mL), and K2C03(152.0 mg, 1.10 mmol) and 2- <strong>[144-48-9]iodoacetamid</strong>e (135.0 mg, 0.73 mmol) were added. The reaction mixture was stirred at 30C for 76 hours, water was added, and then extracted with EtOAc. The organic extract was washed with brine, dried over anhydrous Na2S04, concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, n-Hex : EtOAc = 1 : 2) to obtain 2-(3-(2-(3-bromo-5-nitrophenyl)propan-2-yl)phenoxy)acetamide (129.1 mg, 83%) as a white solid.LC/MS ESI (+): 393 (M+l)-NMR (300MHz, DMSO-c: delta 8.22 (m, IH), 7.96 (m, IH), 7.83 (m, IH), 7.51(brs, IH), 7.36 (brs, IH), 7.25 (td, IH, J=8.4, 3.1Hz), 6.78-6.89 (m, 3H), 4.38 (s, 2H), 1.68 (s, 6H)

Reference： [1]Patent: WO2014/196793,2014,A1 .Location in patent: Page/Page column 78

56
[ 144-48-9 ]
[ 1192885-45-2 ]
2-(4-(6-chloropyridin-2-yl)-3-(3-methoxy-5-methylphenyl)-1H-pyrazol-1-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3h;	To a mixture of 3(1 g, 3.34 mmol) and K2CO3 (0.92 g, 6.67 mmol) in DMFsolution (10 mL) was added 2-<strong>[144-48-9]iodoacetamid</strong>e (1.24 g, 6.67mmol). The reaction mixture was stirred at room temperaturefor 3 h and the solvent was evaporated under vacuum. The residuewas partitioned between brine and ethyl acetate. Thecombined organic layers were dried over anhydrous MgSO4and evaporated under vacuum to yield the pure product 4d(1.1 g, 92%);

Reference： [1]Bulletin of the Korean Chemical Society,2015,vol. 36,p. 305 - 311

57
[ 144-48-9 ]
[ 3964-57-6 ]
C₁₀H₁₀ClNO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83.1%	With potassium carbonate; In acetone; at 20℃;	[0495] To a solution of 237-1 (0.93 g. 5 mmol) in acetone (30 mL) was added K2C03 (2.08 g, 15 mmol) and 2-<strong>[144-48-9]iodoacetamid</strong>e ( 1 .39 g. 7.5 mmol). The mixture was stirred at r.t. overnight. The mixture was diluted with water and extracted with EA (4 x 100 mL). The combined organic layers were dried over anhydrous Na SC^ and concentrated in vacuum to give crude 237-2, which was further purified by column chromatography on silica gel (PE:EA= 2: 1) to 237-2 (1.01 g, 83.1 %) as a white solid.

Reference： [1]Patent: WO2015/26792,2015,A1 .Location in patent: Paragraph 0495

58
[ 144-48-9 ]
[ 24215-02-9 ]
3-(2-amino-2-oxoethyl)-1-(3-ethoxy-3-oxopropyl)-1H-3-imidazolium iodide [ No CAS ]