[ CAS No. 25900-61-2 ] {[proInfo.proName]}

Name: 25900-61-2|3-Amino-N-methylbenzamide|95%
Brand: Ambeed
SKU: A335836
Price: 16.0 USD
Availability: InStock
Rating: 91 (26 reviews)

,{[proInfo.pro_purity]}

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

DV 2D 3D

3d Animation Molecule Structure of 25900-61-2

Structure of 25900-61-2 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 25900-61-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 25900-61-2 ]

SDS Specification

Alternatived Products of [ 25900-61-2 ]

Product Details of [ 25900-61-2 ]

CAS No. :	25900-61-2	MDL No. :	MFCD00070630
Formula :	C₈H₁₀N₂O	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PYDQTASEULDNRL-UHFFFAOYSA-N
M.W :	150.18	Pubchem ID :	676526
Synonyms :

Calculated chemistry of [ 25900-61-2 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	1.0
Num. H-bond donors :	2.0
Molar Refractivity :	43.84
TPSA :	55.12 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.29 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.16
Log Po/w (XLOGP3) :	-0.11
Log Po/w (WLOGP) :	0.64
Log Po/w (MLOGP) :	0.91
Log Po/w (SILICOS-IT) :	0.65
Consensus Log Po/w :	0.65

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.97
Solubility :	16.0 mg/ml ; 0.106 mol/l
Class :	Very soluble
Log S (Ali) :	-0.59
Solubility :	38.2 mg/ml ; 0.254 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.41
Solubility :	0.588 mg/ml ; 0.00392 mol/l
Class :	Soluble

Medicinal Chemistry

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

Safety of [ 25900-61-2 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P280	UN#:	N/A
Hazard Statements:	H302-H317	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 25900-61-2 ]

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

Upstream synthesis route of [ 25900-61-2 ]
Downstream synthetic route of [ 25900-61-2 ]

[ 25900-61-2 ] Synthesis Path-Upstream 1~6

1
[ 3400-26-8 ]
[ 25900-61-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen In methanol at 20℃;	A mixture of N-methyl-3-nitro-benzamide (2.47 g, 13.71 mmol) and 10percent Pd/C (0.5 g) in methanol (50 ML) was hydrogenated at room temperature and atmospheric pressure overnight.The reaction mixture was filtered through a Celite pad and concentrated.The crude material was used in the next step without further purification. (Yield 2.06 g, 100percent).
87.6%	With ammonium chloride In tetrahydrofuran; methanol; water at 0 - 50℃;	Step 3 Synthesis of 3-Amino-N-methyl-benzamide Ammonium chloride (254 g, 4793 mmol) dissolved in water (1000 mL) was added to a stirred solution of N-Methyl-3-nitro-benzamide (86.3 g, 479 mmol) in THF (700 mL), followed by MeOH (300 mL) to afford a clear solution. This was followed by portion wise addition of Zinc powder (245 g, 3834 mmol) with stirring and temperature while addition of zinc was maintained below 50° C. The reaction mixture was stirred at ambient temperature for 3 hr. filtered the mixture over celite bed, concentrated the filtrate to afford the residue. The residue obtained was extracted with ethyl acetate, washed with brine solution, dried over Na₂SO₄, and concentrated under reduced pressure to afford the crude solid. The crude solid was purified by recrystallisation from ethyl acetate to afford 63 g (87.6percent) of 3-Amino-N-methyl-benzamide. LCMS purity: 96.26percent.

Reference： [1] Patent: US2004/97493, 2004, A1, . Location in patent: Page/Page column 24
[2] Patent: US2010/160323, 2010, A1, . Location in patent: Page/Page column 54
[3] Journal of Chemical Research, 2006, # 4, p. 223 - 224
[4] Patent: US5589489, 1996, A,
[5] Patent: EP2774918, 2014, A1, . Location in patent: Paragraph 0126; 0133
[6] Patent: US2015/159142, 2015, A1, . Location in patent: Page/Page column

2
[ 582-33-2 ]
[ 74-89-5 ]
[ 25900-61-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	With sodium methylate In methanol at 20℃; for 72 h;	[00509] Intermediate 48: 3-amino-N-methyl-benzamide[00510] A solution of ethyl 3-aminobenzoate (0.l8mL, 1.21 mmol), methylamine (0.44mL,12.llmmol) and sodium methoxide (6mg, 0.O3mmol) in MeOH (2mL) was left to stir at room temperature for 3 days. MeOH was removed in vacuo and DCM (5OmL) and water (5OmL) were added to the residue. The organic layer was separated and the aqueous extracted with DCM (3 x 2OmL) The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo togive 3-amino-N-methyl-benzamide (l7Omg,1.l3mmol, 93percent yield) as a yellow oil which was used in the next step without further purification.1H NMR (CDCI3,400MHZ) O/ppm: 7.20 (1H, t, J= 7.8Hz), 7.15 (1H, t, J= 2.0Hz), 7.05 (1H, ddd, J=7.6Hz, 1.6Hz, 1.0Hz), 6.80 (1H, dd, J= 8.0Hz, 2.4Hz), 6.14 (1H, brs), 3.70 (2H, brs), 3.01 (3H, d, J= 4.9Hz).MS Method 2: RT: 0.36 mi mlz 151.0 [M+H]

Reference： [1] Patent: WO2016/51193, 2016, A1, . Location in patent: Paragraph 00508; 00509; 00510

3
[ 99-05-8 ]
[ 74-89-5 ]
[ 25900-61-2 ]

Reference： [1] Bulletin of the Korean Chemical Society, 2011, vol. 32, # 12, p. 4444 - 4446

4
[ 3400-26-8 ]
[ 7291-02-3 ]
[ 25900-61-2 ]

Reference： [1] Patent: US2015/159142, 2015, A1, . Location in patent: Page/Page column

5
[ 121-92-6 ]
[ 25900-61-2 ]

Reference： [1] Patent: EP2774918, 2014, A1,

6
[ 25900-61-2 ]
[ 18759-96-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 2, p. 309 - 312

[ 25900-61-2 ] Synthesis Path-Downstream 1~88

1
[ 14301-31-6 ]
[ 25900-61-2 ]
3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium iodide; sodium chloride; sodium carbonate; calcium carbonate; In N-methyl-acetamide; methanol; diethyl ether; 1,1-dichloroethane; ethanol;	EXAMPLE 1 250 ml of dimethylformamide was added to a mixture of 68.6 g of 2-chloro-N-(2-(3,4-dimethoxyphenyl)ethyl)acetamide, 40.0 g of <strong>[25900-61-2]3-amino-N-methylbenzamide</strong>, 39.9 g of sodium iodide and 53.8 g of calcium carbonate, and the resulting mixture was stirred for 7 hours at 45 to 50 C. After cooling, an insoluble material was removed by filtration, and the filtrate was concentrated in vacuo. The residue was extracted with 600 ml of chloroform and the extract was washed with a 5% sodium sulfite aqueous solution and then a saturated aqueous solution of sodium chloride. The washings were extracted with chloroform, and the extract was added to the above washed chloroform solution. The combined chloroform solution was dried over sodium sulfate, and the solvent was distilled off. The residue was dissolved in 100 ml of methanol, and 50 ml of concentrated hydrochloric acid was added to the methanol solution. The mixture was concentrated in vacuo, and ethanol was added to the residue. The solvent was distilled off to remove the azeotropic water. The residue was dissolved in 100 ml of ethanol, and diethyl ether was added to the solution. The precipitate formed was collected by filtration, washed with a mixture of ethanol and diethyl ether (1:2 by volume) and dried. The precipitate was suspended in 1 liter of dichloroethane, and a 10% sodium carbonate aqueous solution was added to the suspension to make the solution alkaline. The dichloroethane solution was separated and washed with a saturated aqueous solution of sodium chloride. The washings were extracted with 400 ml of dichloroethane, and the extract was added to the above dichloroethane solution. The mixture was dried over sodium sulfate and the solvent was distilled off. A mixture of methanol and diethyl ether was added to the residue, and the precipitate formed was collected by filtration. The precipitate was recrystallized from a mixture of methanol and diethyl ether to give 51.0 g of 3-((2-((2-(3,4-dimethoxyphenyl)ethyl)amino)-2-oxoethyl)amino)-N-methylbenzamide as colorless needles with m.p. 93 to 96.5 C. Analysis for C20 H25 N3 O4: Calcd: C 64.67, H 6.78, N 11.31. Found: C 64.59, H 6.83, N 11.30. NMR (DMSO-d6): delta: 2.60 (2H, t, 7 Hz), 2.72 (3H, d, 5 Hz), 3.27 (2H, q, 7 Hz), 3.63 (2H, d, 6 Hz), 3.69 (6H, s), 5.97 (1H, t, 6 Hz), 6.49-7.22 (7H, m), 7.76 (1H, br), 8.13 (1H, br). IR numaxKBr cm-1: 1650 (C=O), 3320, 3370 (--NH).

Reference： [1]Chemical and Pharmaceutical Bulletin,1992,vol. 40,p. 2712 - 2719
[2]Patent: US4985595,1991,A

2
[ 108-24-7 ]
[ 25900-61-2 ]
3-Acetylamino-N-methylbenzamide [ No CAS ]

Reference： [1]Xenobiotica,1995,vol. 25,p. 501 - 510

3
[ 603-33-8 ]
[ 25900-61-2 ]
3-phenylamino-N-methylbenzamide [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2000,vol. 65,p. 7747 - 7749

4
[ 37859-24-8 ]
[ 25900-61-2 ]
N-(3-methylcarbamoylphenyl)-4-bromophenylacetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

5
[ 5121-00-6 ]
[ 25900-61-2 ]
N-(3-methylcarbamoylphenyl)-2-naphthylacetamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

6
[ 37859-25-9 ]
[ 25900-61-2 ]
N-methyl-3-(2-naphthalen-2-yl-acetylamino)-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

7
[ 50720-05-3 ]
[ 25900-61-2 ]
3-(2-1H-indol-3-yl-acetylamino)-N-methyl-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

8
[ 65853-61-4 ]
[ 25900-61-2 ]
N'-methyl-3-(4-chlorobenzyloxycarbonylamino)benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4468 - 4474

9
[ 25900-61-2 ]
[ 18759-96-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 309 - 312

10
[ 3400-26-8 ]
[ 25900-61-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With hydrogen;palladium 10% on activated carbon; In methanol; at 20℃;	A mixture of N-methyl-3-nitro-benzamide (2.47 g, 13.71 mmol) and 10% Pd/C (0.5 g) in methanol (50 ML) was hydrogenated at room temperature and atmospheric pressure overnight.The reaction mixture was filtered through a Celite pad and concentrated.The crude material was used in the next step without further purification. (Yield 2.06 g, 100%).
87.6%	With ammonium chloride;zinc; In tetrahydrofuran; methanol; water; at 0 - 50℃;	Step 3 Synthesis of 3-Amino-N-methyl-benzamide Ammonium chloride (254 g, 4793 mmol) dissolved in water (1000 mL) was added to a stirred solution of N-Methyl-3-nitro-benzamide (86.3 g, 479 mmol) in THF (700 mL), followed by MeOH (300 mL) to afford a clear solution. This was followed by portion wise addition of Zinc powder (245 g, 3834 mmol) with stirring and temperature while addition of zinc was maintained below 50 C. The reaction mixture was stirred at ambient temperature for 3 hr. filtered the mixture over celite bed, concentrated the filtrate to afford the residue. The residue obtained was extracted with ethyl acetate, washed with brine solution, dried over Na2SO4, and concentrated under reduced pressure to afford the crude solid. The crude solid was purified by recrystallisation from ethyl acetate to afford 63 g (87.6%) of 3-Amino-N-methyl-benzamide. LCMS purity: 96.26%.
	With hydrogen;aluminum nickel; In dichloromethane; water; acetic acid;	b. N-methyl-3-aminobenzamide. A solution of N-methyl-3-nitrobenzamide (20 g) in acetic acid (500 mL) was treated with Raney Nickel catalyst (50 mL of slurry in water) and hydrogenated at 15 psi hydrogen pressure for 1.75 hour. At the end of this period the reaction mixture was filtered to remove the catalyst, evaporated and the residue was dissolved in dichloromethane. The dichloromethane layer was extracted with sodium bicarbonate solution, the aqueous layer was basified with potassium carbonate solution and extracted with two portions of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, and evaporated to obtain a solid, which was crystallized from ethyl acetate to give the amine (12.7 g): mp 115-116 C.; MS: m/z=229(M+1); NMR: 2.97 (d,3 J=9.7), 3.84 (s,2), 6.12 (broad,1), 6.55 (m,1), 6.84 (d,1, J=2.9), 7.27 (d,1, J=8.6).

	With 5%-palladium/activated carbon; hydrogen; In methanol;	Compound 5a or 5b was reduced in the following manner to prepare compound 6c or 6d. Nitrogen-substituted compound 5a or 5b was dissolved in anhydrous MeOH, and 5% palladium carbon was added thereto under an argon atmosphere. The reaction solution was stirred overnight in a hydrogen atmosphere and filtered through a celite pad, and the filtrate was purified without additional purification to obtain a crude product. 1) 3-Amino-N-methylbenzamide (6c) was obtained as a white solid from compound 5a. 1H NMR (DMSO-d6, 400 MHz) delta = 8.13 (d, J = 4.0 Hz, 1H), 6.99-7.05 (m, 2H), 6.89 (d, J = 7.2 Hz, 1H), 6.62-6.65 (m, 1H), 5.17 (s, 2H), 2.71 (d, J = 4.8 Hz, 3H).
		1) 3-Amino-N-methylbenzamide (6c) was obtained as a white solid from compound 5a. 1H NMR (DMSO-d6, 400 MHz) delta=8.13 (d, J=4.0 Hz, 1H), 6.99-7.05 (m, 2H), 6.89 (d, J=7.2 Hz, 1H), 6.62-6.65 (m, 1H), 5.17 (s, 2H), 2.71 (d, J=4.8 Hz, 3H).

Reference： [1]Patent: US2004/97493,2004,A1 .Location in patent: Page/Page column 24
[2]Patent: US2010/160323,2010,A1 .Location in patent: Page/Page column 54
[3]Journal of Chemical Research,2006,p. 223 - 224
[4]Patent: US5589489,1996,A
[5]Patent: EP2774918,2014,A1 .Location in patent: Paragraph 0126; 0133
[6]Patent: US2015/159142,2015,A1 .Location in patent: Page/Page column

11
[ 639858-43-8 ]
[ 25900-61-2 ]
N-Methyl-3-[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 3766 - 3769

12
[ 639858-56-3 ]
[ 25900-61-2 ]
N-Methyl-3-[2-(pyridin-2-ylamino)-thiazol-5-ylmethyl]-amino}benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	In N,N-dimethyl-formamide; at 20℃; for 2.5h;	Step B A mixture of compound 10A (16 mg, 71 mumol) and <strong>[25900-61-2]3-amino-N-methyl-benzamide</strong> (12 mg, 78 mumol) in DMF (0.7 mL) was stirred at RT for 2.5 h, diluted with 10% of lithium chloride solution and extracted with ethyl acetate (4*5 mL). The combined organic layer was washed with 10% lithium chloride solution, dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel eluding with 2 to 5% methanol in chloroform to provide N-methyl-3-[2-(pyridin-2-ylamino)thiazol-5-ylmethyl]amino}benzamide (2.5 mg, 10%). MS: [M+H]+=440.

Reference： [1]Patent: US2004/77696,2004,A1 .Location in patent: Page/Page column 12

13
[ 691864-10-5 ]
[ 25900-61-2 ]
[ 691864-23-0 ]

Yield	Reaction Conditions	Operation in experiment
28%	With toluene-4-sulfonic acid; In isopropyl alcohol; at 170℃; for 1h;Microwave reactor;	A solution of 7-methanesulfinyl-3-(2,6-dichloro-phenyl)-1-methyl-1H-pyrimido[4,5-e][1,3,4]oxadiazine (0.10 g, 0.28 mmol), N-methyl-3-amino-benzamide (84 mg, 0.56 mmol) and p-toluenesulfonic acid monohydrate (53.3 mg, 0.28 mmol) (Aldrich) in isopropanol (4 ML) was placed in a microwave reactor (SmithSynthesizer).The reaction mixture was heated at 170 C. for 1 h.The reaction mixture was concentrated and purified by RP-HPLC (C-18, eluding with MeCN/H2O) to obtain a solid which was recrystallized from methanol to afford the product. (Yield 34 mg, 28%). HRMS m/z Calculated for C20H16Cl2N6O2 [(M+H)+]: 443.0785. Found: 443.0791.

Reference： [1]Patent: US2004/97493,2004,A1 .Location in patent: Page/Page column 24

14
[ 284462-97-1 ]
[ 25900-61-2 ]
N-(4-chloro-3-((trifluoromethyl)phenyl))-N'-(4-(3-methylcarbamoylphenyl)carbamoylphenyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 0 - 20℃;	D1b. Conversion of omega-Carboxyphenyl Ureas into omega-(Arylcarbamoyl)phenyl Ureas. Synthesis of N-(4-Chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl)carbamoylphenyl) Urea To a solution of N-(4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl) carboxyaminophenyl) urea (0.14 g, 0.48 mmol), 3-methylcarbamoylaniline (0.080 g, 0.53 mmol), HOBT.H2O (0.14 g, 1.07 mmol), and N-methylmorpholine (0.5 mL, 1.07 mmol) in DMF (3 mL) at 0 C. was added EDCI.HCl (0.10 g, 0.53 mmol). The resulting mixture was allowed to warm to room temp. and was stirred overnight. The resulting mixture was treated with water- (10 mL), and extracted with EtOAc (25 mL). The organic phase was concentrated under reduced pressure. The resulting yellow solids were dissolved in EtOAc (3 mL) then filtered through a pad of silica gel (17 g, gradient from 70% EtOAc/30% hexane to 10% MeOH/90% EtOAc) to give N-(4-chloro-3-((trifluoromethyl)phenyl)-N'-(4-(3-methylcarbamoylphenyl)carbamoylphenyl) urea as a white solid (0.097 g, 41%): mp 225-229; TLC (100% EtOAc) Rf 0.23.

Reference： [1]Patent: US2003/207872,2003,A1 .Location in patent: Page/Page column 21

15
[ 25900-61-2 ]
[ 49845-33-2 ]
C₁₂H₁₀ClN₅O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With cesium bicarbonate; In tetrahydrofuran; water; N,N-dimethyl-formamide; isopropyl alcohol; at 20℃; for 1.5h;	EXAMPLE 9; N-(2-Diethylamino-ethyl)-4-(3-indan-5-yl-3H-[1 ,2,3]triazolo[4,5-d]- pyrimidin-5-ylamino)-benzamide (7); To a solution of 2,4-dichloro-5-nitropyrimidine (25.0 mg, 0.13 mmol) in THF (0.2 mL) was added a solution of <strong>[25900-61-2]3-amino-N-methyl-benzamide</strong> (19.5 mg, 0.13 mmol) in isopropyl alcohol (0.5 mL)/dimethylformarnide (0.3 mL), and CsHCO3 (25.2 mg, 0.13 mmol) in water (0.016 mL total volume). The mixture was stirred at rt for 1.5 hr at which time 4-amino-N-(2-diethylamino-ethyl)-benzamideEtaCl (procainamide hydrochloride) (38.9 mg, 0.14 mmol) in isopropyl alcohol (0.5 mL)/dimethylformamide (0.3 mL) was added. The mixture was stirred at 50C for 20 hr, cooled to rt, and acetic acid (0.1 mL) was added. To the resulting slurry was added Zn dust (45 mg, 0.69 mmol); after stirring for 15 min at rt, the reaction solution was loaded onto a 1 g silica gel SPE cartridge and eluted with 6 mL of MeOH. The eluent was concentrated at reduced pressure, dried at approximately 1 mm Hg for 18 hr, and re-suspended in MeOH (1.0 mL). To this slurry was added HOAc (0.05 mL) and sodium nitrite (0.09 g, 1.3 mmol) in water (total volume 0.2 mL). The mixture was stirred at rt for 11 hr, loaded onto a 1 g C-18 SPE cartridge, and eluted with 6 mL of MeOH. The eluent was concentrated and the resulting residue was purified by reverse-phase liquid chromatography using a gradient of 90:10 (water:acetonitrile, with 0.1% TFA) to 10:90 (wateracetonitrile, with 0.1% TFA) to furnish (7) (0.0128 g, 0.018 mmol) as the bis TFA salt. HRMS (ES-TOF) calcd. for C25H30N9O2 m/z 488.2522 (M+H),+ found: 488.2514

Reference： [1]Patent: WO2006/76442,2006,A2 .Location in patent: Page/Page column 50-51

16
[ 103-71-9 ]
[ 25900-61-2 ]
1-(3-methylcarbamoylphenyl)-3-phenylurea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride; In N-methyl-acetamide; ethyl acetate;	Example 69 Preparation of 1-(3-Methylcarbamoylphenyl)-3-phenylurea(Compound No. 182 in Table 2) Phenylisocyanate (209 mg) and 3-aminobenzoylmethylamide (239 mg) were dissolved in dimethylformamide (2 ml). After starring for 6 hours at room temperature, dilute hydrochloric acid (15 ml) was added. The obtained crystals were filtered and washed with water to obtain crude crystals. The crude crystals were dried under reduced pressure and added to ethyl acetate (8 ml), and the mixture was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain the desired compound (386 mg, yield 90%). Melting Point: 209-210 C.; IR(KBr, cm-1): 3328, 3279, 1699, 1626, 1557; NMR(DMSO-d6, delta): 2.75(d, J=4.1 Hz, 3H), 6.95(dd, J-7.3 Hz, 7.3 Hz, 1H), 7.20-7.45(m, 6H), 7.57(d, J=7.7 Hz, 1H), 7.86(s, 1H), 8.37(d, J=4.1 Hz, 1H), 8.67(s, 1H), 8.79(s, 1H).
90%	With hydrogenchloride; In N-methyl-acetamide; ethyl acetate;	Example 19 Preparation of 1-(3-methylcarbamoylphenyl)-3-phenylurea (Compound No.182 in Table 1) After dissolving 209 mg of phenylisocyanate and 239 mg of 3-aminobenzoylmethylamide in 2 ml of dimethylformamide and stirring for 6 hours at room temperature, 15 ml of dilute hydrochloric acid was added. The obtained crystals were filtered and washed with water to obtain crude crystals. The crude crystals were dried under reduced pressure and added to 8 ml of ethyl acetate, and the mixture was heated under reflux for 10 minutes. The mixture was cooled to room temperature, and the crystals were collected by filtration and washed with ethyl acetate to obtain 386 mg of the target compound (90% yield). Melting point: 209-210C IR (KBr, cm-1): 3328, 3279, 1699, 1626, 1557. NMR (DMSO - d6, delta): 2.75 (d, J = 4.1Hz, 3H), 6.95 (dd, J = 7.3Hz, 7.3Hz, 1H), 7.20 - 7.45 (m, 6H), 7.57 (d, J = 7.7Hz, 1H), 7.86 (s, 1H), 8.37 (d, J= 4.1Hz, 1H), 8.67 (s, 1H), 8.79 (s, 1H).

Reference： [1]Patent: US6444849,2002,B1
[2]Patent: EP1142868,2001,A1

17
sodium thiomethoxide [ No CAS ]
[ 25900-61-2 ]
N-methyl-3-methylthiobenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium nitrite; In water;	c. N-methyl-3-methylthiobenzamide. To water (50 mL) containing concentrated hydrochloric acid (12.7 mL) was added <strong>[25900-61-2]N-methyl-3-aminobenzamide</strong> (12.7 g), the resulting suspension was stirred for 15 minutes and treated with sodium nitrite (3/75 g) in water (75 mL). The temperature of the reaction mixture was maintained below 5 C. and added to a solution of sodium thiomethoxide (8.93 g) in water (100 mL) kept at 5 C. Upon the addition was complete the reaction mixture was stirred at 0 C. for 1 hour and then allowed to warm to 15 C. The resulting precipitate was filtered and washed (water). Upon drying in vacuum, the solid was crystallized from ethyl acetate to afford the desired N-methyl-3-methylthiobenzamide (10.2 g); MS: m/z=260(M+1); NMR: 2.47 (s,3), 3.00 (d,3, J=3), 6.06 (broad,1), 7.19 (m,3).

Reference： [1]Patent: US5589489,1996,A

18
[ 25900-61-2 ]
[ 815-17-8 ]
[ 1028252-99-4 ]

Yield	Reaction Conditions	Operation in experiment
		Compound 202 Isomers; 3-methyl-N-(3-(methylcarbamoyl)phenyl)-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide and3-methyl-N-(3-(methylcarbamoyl)phenyl)-D-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N-((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide; Example 202; Preparation of Compounds 202A and 202B; Step 1:; To a mixture of <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (230 mg, 1.532 mmol) and 3,3-dimethyl-2-oxobutanoic acid (199 mg, 1.532 mmol) in a 100 mL RBF at RT was added tetraisopropoxytitanium (2 ml,) via a pipet, The color of the mixture soon changed into a characteristic canary color. The solution was warmed to 75 C. for about 15 minutes and the color remained the same. The solution was diluted with absolute ethanol (8 ml) at RT, followed by the addition of 1.5× of sodium cyanotrihydroborate (245 mg, 3.90 mmol), and the remaining half after the bubbling and sizzling was over. The color of the solution became lighter. The solution was mixed with 4 mL of water, forming a suspension, the white PPT was removed by centrifuge, organic was extracted into ethyl acetate, dried over Na2SO4. Evaporated into dryness, white foam was obtained and used in the next step without further purification. LC-MS, MS m/z 265 (M++H).

Reference： [1]Patent: US2008/119461,2008,A1 .Location in patent: Page/Page column 86-87

19
[ 1045859-52-6 ]
[ 25900-61-2 ]
[ 1045859-54-8 ]

Yield	Reaction Conditions	Operation in experiment
		To 2-chloro-N-(5-chloroisoquinolin-6-yl) acetamide in MeOH is added KI and the solution is heated to 60 C. for 40 minutes. The mixture is cooled to 45 C. and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> is added and stirred at 45 C. After 2-4 hours or when TLC indicates completion of the reaction, the solvents are evaporated and the residue is taken up in EtOAc and extracted with NaHCO3 (sat). The organics are dried (Na2SO4), filtered and evaporated. Flash chromatography (SiO2, NH3(2M) in MeOH/3% MeOH/CH2Cl2) gives pure 3-(2-(5-chloroisoquinolin-6-ylamino)-2-oxoethylamino)-N-methylbenzamide. Using the general procedure shown for example 119b, the following compounds can be synthesised from the corresponding 6-aminoisoquinoline.

Reference： [1]Patent: US2008/167340,2008,A1 .Location in patent: Page/Page column 19

20
[ 1045859-71-9 ]
[ 25900-61-2 ]
[ 1045860-35-2 ]

Yield	Reaction Conditions	Operation in experiment
		To 1-chloro-N-(isoquinolin-6-yl) methanesulfonamide in MeOH is added KI and the solution is heated to 60 C. for 40 minutes. The mixture is cooled to 45 C. and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> is added and stirred at 45 C. After 2-4 hours or when TLC indicated completion of the reaction, the solvents are evaporated and the residue is taken up in EtOAc and extracted with NaHCO3 (sat). The organics are dried (Na2SO4), filtered and evaporated. Flash chromatography (SiO2, 2% NH3(2M) in MeOH/3% MeOH/CH2Cl2) gives 3-((N-isoquinolin-6-ylsulfamoyl)methylamino)-N-methylbenzamide.

Reference： [1]Patent: US2008/167340,2008,A1 .Location in patent: Page/Page column 20

21
[ 515140-23-5 ]
[ 25900-61-2 ]
[ 515153-37-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 324 - 328

22
[ 32315-10-9 ]
[ 25900-61-2 ]
[ 1009296-67-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 4298 - 4302

23
[ 1232028-64-6 ]
[ 25900-61-2 ]
[ 1232028-66-8 ]

Yield	Reaction Conditions	Operation in experiment
51.09%	With triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	Step 4 Synthesis of 3-{2-[4-(5-Fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-acetylamino}-N-methyl-benzamide [4-(5-Fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-oxo-acetyl chloride (105 mg, 0.286 mmol) (prepared by the similar method described in example 57, Step-2 using 5-Fluoro-2-trifluoromethyl-phenyl)-piperazin-1-yl-methanone hydrochloride salt as starting material which is being prepared by the general method mentioned in the earlier examples using 5-fluoro-2-trifluoromethyl benzoic acid as starting material, Aldrich, St. Louis, Mo.) in DCM (2.5 mL) was added to cold(0 C.) solution of 3-Amino-N-methyl-benzamide (43 mg, 0.28 mmol), Et3N (86 mg, 0.12 mL, 0.86 mmol) in DCM (2.5 mL) and stirring was continued at ambient temperature for 2 hr. The reaction mixture was diluted with DCM, washed with cold water, followed by 2N HCl and brine solution. The organic layer thus collected was dried over sodium sulphate, concentrated under reduced pressure to afford the residue. The residue obtained was purified by recrystallisation from a mixture of ethyl acetate and hexane to afford 70 mg (51.09%) of 3-{2-[4-(5-Fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-acetylamino}-N-methyl-benzamide. LCMS Purity: 99.7%. 1H NMR (DMSO-d6): delta 10.95 (d, 1H), 8.4 (m, 1H), 8.2-8.0 (d, 1H), 8.6-7.9 (m, 1H), 7.8-7.6 (m, 1H), 7.6-7.4 (m, 4H), 3.9-3.4 (m, 6H), 3.3-3.1 (m, 2H), 2.8 (m, 3H).

Reference： [1]Patent: US2010/160323,2010,A1 .Location in patent: Page/Page column 54-55

24
[ 1009827-36-4 ]
[ 25900-61-2 ]
C₂₁H₁₇N₃O₃S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 635 - 654

25
[ 1313039-28-9 ]
[ 25900-61-2 ]
[ 1313038-33-3 ]

Yield	Reaction Conditions	Operation in experiment
46%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃; for 18h;	To a solution of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine-5-yl)(4-chlorophenyl)methanone (500 mg, 1.72 mmol) in DMF (6 mL) were added <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (516 mg, 3.44 mmol) and DIPEA (899 muL, 5.16 mmol). The reaction was heated at 120 C. for 18 hours. After cooling down to room temperature, 20 mL of DCM was added to the mixture. The precipitates were collected, washed with DCM, and dried on high vacuum to give a yellow solid (320 mg, 46%). M.p.>300 C.; 400 MHz 1HNMR (DMSO-d6) delta 13.06 (s, 1H), 11.33 (s, 1H), 8.48 (s, 1H), 8.21 (d, J=7.6 Hz, 1H), 8.03 (s, 1H), 7.89 (d, J=8.4 Hz, 2H), 7.65 (d, J=8.0 Hz, 2H), 7.52-7.46 (m, 2H), 2.80 (d, J=4.0 Hz, 3H); LCMS [M+H] 406.

Reference： [1]Patent: US2011/160203,2011,A1 .Location in patent: Page/Page column 67

26
[ 3934-20-1 ]
[ 25900-61-2 ]
[ 1332302-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 20 - 80℃; for 117h;Sealed tube;	Step 1To 2,4-dichloropyrimidine (250.0 mg, 1.678 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (252 mg, 1.678 mmol) in 2-propanol (8390 mu) in a disposable sealed tube at RT was added N- ethyl-N-isopropylpropan-2-amine (585 mu, 3.36 mmol). The resulting reaction mixture was heated at 60 C for 22 h, then to 70 C for 23 h, then 80 C for 3 days, cooled to RT, concentrated, purified using MPLC (5 g cartridge, 12 g column, 0 to 60%> 90/10 CH2C12- MeOH in CH2C12) giving 3-(2-chloropyrimidin-4-ylamino)-N-methylbenzamide (389.0 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 100

27
[ 25900-61-2 ]
[ 1332301-99-1 ]

Reference： [1]Patent: WO2011/103196,2011,A1

28
[ 25900-61-2 ]
[ 1332298-32-4 ]

Reference： [1]Patent: WO2011/103196,2011,A1

29
[ 25900-61-2 ]
[ 1332298-99-3 ]

Reference： [1]Patent: WO2011/103196,2011,A1

30
[ 25900-61-2 ]
[ 1332302-08-5 ]

Reference： [1]Patent: WO2011/103196,2011,A1

31
[ 2831-66-5 ]
[ 25900-61-2 ]
[ 1332301-67-3 ]

Yield	Reaction Conditions	Operation in experiment
78%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 4h;Product distribution / selectivity;	Reference CSynthesis of 3-(4-chloro-l ,3,5-triazin-2-ylamino)-N-methylbenzamide2,4-Dichloro-l,3,5-triazine (6.99 g, 46.6 mmol) was dissolved in DMF (56.5 mL, 46.6 mmol) and the solution was cooled to 0 C. To this solution was added N-ethyl-N- isopropylpropan-2-amine (8.93 mL, 51.3 mmol) followed by the portionwise addition of 3- amino-N-methylbenzamide (7.00 g, 46.6 mmol). The resulting reaction mixture was allowed to slowly warm to room temperature and stirredfor 4 hours. Water (about 800 mL) was added to the reaction mixture. A small amount of solid precipitated out of the solution at which point 100 mL of CH2C12 was added. The product was filtered off through a coarse Buchner funnel with the aid of water. After drying under vacuum, batch No.1 of 3-(4-chloro-l,3,5-triazin-2- ylamino)-N-methylbenzamide was obtained (7.15 g, 58% yield) as a yellow solid. The filtrate was extracted with CH2CI2 (3 x 100 mL). The organic layer was separated, dried over MgSC^, filtered and concentrated, providing an additional batch of material (2.4 g, 20%) as yellow solid.

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 74-75

32
[ 1193-21-1 ]
[ 25900-61-2 ]
[ 1332302-07-4 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 72h;	Step 1To 4,6-dichloropyrimidine (500.0 mg, 3.36 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (504 mg, 3.36 mmol) in 2-propanol (5.00 mL) at RT was added N,N-diisopropylethylamine (0.877 mL, 5.03 mmol). The resulting reaction mixture was heated at 80 C for 3 days, cooled to RT, concentrated, purified using MPLC (25 g cartridge, 40 g column, 0 to 100% EtOAc- hexanes then 30-100% 90: 10 CH2Cl2-MeOH in CH2C12). Fractions with product were combined and concentrated giving 3-(6-chloropyrimidin-4-ylamino)-N-methylbenzamide (815.2 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 100

33
[ 3177-24-0 ]
[ 25900-61-2 ]
[ 1332302-03-0 ]
[ 1332302-04-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; at 0 - 20℃; for 3h;	Step 1To 3-amino-N-methylbenzamide (353 mg, 2.351 mmol) in DME (8 mL) at 0 °C was added N-ethyl-N-isopropylpropan-2-amine (1.024 mL, 5.88 mmol) followed by 2,4- dichloropyrimidine-5-carbonitrile (450.0 mg, 2.59 mmol). The resulting reaction mixture was allowed to warm to RT (ice melt) over 3 h, concentrated, purified using MPLC (25 g cartridge, 40 g column, 0 to 100percent EtOAc-hexanes). Separation of 2- and 4-substitution products was not achieved. Fractions with both products were combined and concentrated giving about a 3 : 1 mixture of 3 -(2-chloro-5 -cyanopyrimidin-4-ylamino)-N-methylbenzamide and 3 -(4-chloro-5 - cyanopyrimidin-2-ylamino)-N-methylbenzamide (172.7 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 98

34
[ 3177-24-0 ]
[ 25900-61-2 ]
[ 1332300-63-6 ]

Reference： [1]Patent: WO2011/103196,2011,A1

35
[ 25900-61-2 ]
[ 2927-71-1 ]
[ 1332302-45-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 7h;	Step 1To a solution of 2, 4-dichloro-5-fluoropyrimidine (1 g, 5.98 mmol) in isopropanol (18 mL, 3 mL/mmol) was added DIPEA (1.6 mL, 8.9 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (900 mg, 5.98 mmol) and the mixture was heated at 80 C for 7 h. The reaction mixture was concentrated under reduced pressure and extracted with EtOAc (2 x 40mL) and water (2 x 40mL). The organic extracts were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography provided 3-((2- chloro-5-fluoropyrimidin-4-yl)amino)-N-methylbenzamide (800 mg, 50%) as a solid.Observed mass (M+l): 281.1

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 115-116

36
[ 1332302-00-7 ]
[ 25900-61-2 ]
[ 1332296-80-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In tert-butyl alcohol; at 100℃; for 7h;Inert atmosphere; Sealed tube;	Step 2To a disposable sealed tube was charged 2-bromo-6-(3-(4-fluorophenoxy)azetidin-l- yl)pyridine (100.0 mg, 0.309 mmol), <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (69.7 mg, 0.464 mmol), potassium carbonate (59.9 mg, 0.433 mmol) followed by X-Phos (2.95 mg, 6.19 muiotaetaomicron) and Pd2(dba)3 (1.417 mg, 1.547 muiotaetaomicron). The tube was fitted with a septum with an argon inlet for 5- 10 min, when t-BuOH (1.0 mL) was added. The reaction mixture was then heated to 100 C for 7 h, cooled to RT, diluted with EtOAc, and filtered through Celite (diatomaceous earth) with EtOAc. The filtrate was concentrated and purified using MPLC (5 g cartridge, 12 g column, 0 to 75 %> EtOAc-hexanes) giving 3-(6-(3-(4-fluorophenoxy)azetidin-l-yl)pyridin-2- ylamino)-N-methylbenzamide (112.8 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 96

37
[ 1332302-01-8 ]
[ 25900-61-2 ]
[ 1332298-61-9 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In isopropyl alcohol; at 84 - 92℃; for 600h;Sealed tube;	Step 2 To 2-chloro-4-(3-(4-fluorophenoxy)azetidin-l-yl)pyridine (90 mg, 0.323 mmol) and 3- amino-N-methylbenzamide (72.7 mg, 0.484 mmol) in 2-propanol (3.00 mL) in a disposable sealed tube at RT was added trifluoroacetic acid, (0.075 mL, 0.969 mmol). The resulting reaction mixture was heated at 84 C for 5 days and 92 C for 20 days, cooled to RT, concentrated, purified using MPLC (5 g cartridge, 12 g column, 0 to 100% 90/10 CH2CI2- MeOH in CH2CI2) giving 3-(4-(3-(4-fluorophenoxy)azetidin-l-yl)pyridin-2-ylamino)-N- methylbenzamide (73.6 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 96-97

38
[ 1332302-02-9 ]
[ 25900-61-2 ]
[ 1332295-66-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In isopropyl alcohol; at 84℃; for 18h;Sealed tube;	Step 2To 2-chloro-4-(3-(4-fluorophenoxy)azetidin-l-yl)pyrimidine (90.0 mg, 0.322 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (53.2 mg, 0.354 mmol) in a disposable sealed tube in 2- propanol (2.50 mL) was added trifluoroacetic acid (0.074 mL, 0.965 mmol). The resulting reaction mixture was heated at 84 C for 18 h, cooled to RT, concentrated, taken up in MeOH- DCM, filtered through an SCX-2 column with MeOH. The product was eluted with 2.0 M NH3 in MeOH. Fractions containing the product were concentrated to afford 3-(4-(3-(4- fluorophenoxy)azetidin- 1 -yl)pyrimidin-2-ylamino)-N-methy lbenzamide (123.9 mg) .

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 97

39
[ 1332302-05-2 ]
[ 25900-61-2 ]
[ 1332299-65-6 ]

Yield	Reaction Conditions	Operation in experiment
	With trifluoroacetic acid; In isopropyl alcohol; at 84℃; for 72h;Sealed tube;	Step 2To 2-chloro-5-fluoro-4-(3-(4-fluorophenoxy)azetidin-l-yl)pyrimidine (90.0 mg, 0.302 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (49.9 mg, 0.333 mmol) in a disposable sealed tube in 2-propanol (2.50 mL) was added trifluoroacetic acid (0.070 mL, 0.907 mmol). The resulting reaction mixture was heated at 84 C for 3 d, cooled to RT and concentrated. The residue was stirred in EtOAc and saturated aqueous NaHC03 for 10 min and transferred to a separatory funnel. The organic layer was washed with brine, dried and concentrated giving 3-(5-fluoro-4- (3 -(4-fluorophenoxy)azetidin- 1 -yl)pyrimidin-2-ylamino)-N-methylbenzamide ( 124.8 mg).

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 99

40
[ 1332302-22-3 ]
[ 25900-61-2 ]
[ 1332295-95-0 ]

Yield	Reaction Conditions	Operation in experiment
53%	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 24h;	Step 2To a solution of 2-chloro-4-(3-(4-chloro-2-fluorophenoxy)azetidin-l-yl)-l,3,5-triazine (0.800 g, 2.54 mmol) in Isopropanol (8 mL) was added DIPEA (0.7 mL, 3.81 mmol) and 3- amino-N-methylbenzamide (0.382 g, 2.54 mmol) and the reaction mixture was stirred at 80 C for 24 h. The mixture was concentrated under reduced pressure and extracted with EtOAc (2 X 40 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography to obtain 3-(4-(3-(4-chloro-2-fluorophenoxy)azetidin-l-yl)-l,3,5-triazin-2-ylamino)-N- methylbenzamide (0.527 g, 53%) as a solid. Observed mass (M+l): 428.9

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 105

41
[ 1332302-28-9 ]
[ 25900-61-2 ]
[ 1332302-27-8 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃; for 24h;	Step 3To a solution of 2-chloro-4-(3-(4-chloro-2-fluorophenoxy)azetidin-l-yl)-6-methyl- 1,3,5-triazine (1.0 g, 3.04 mmol) in Isopropanol (10 mL) was added DIPEA (0.8 mL) and 3- amino-N-methylbenzamide (0.460 g, 3.04 mmol) and the reaction mixture was stirred at 80 C for 24 h. The reaction mixture was concentrated under reduced pressure and extracted with EtOAc (2 X 40 mL) and water (2 x 40 mL). The organic extracts were washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography provided 3-((4-(3-(4-chloro-2-fluorophenoxy) azetidin-1- yl)-6-methyl-l, 3, 5-triazin-2-yl) amino)-N-methylbenzamide (0.057 g, 6%) as a solid.Observed mass (M+l): 443.1.

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 109

42
[ 1332302-42-7 ]
[ 25900-61-2 ]
[ 1332302-41-6 ]

Yield	Reaction Conditions	Operation in experiment
23%	With caesium carbonate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 0.5h;Microwave irradiation;	Step 2To a solution of l-(3-bromophenyl)-3-(4-fluorophenoxy)azetidine (400 mg, 1.24 mmol) and <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (187 mg, 1.24 mmol) in toluene (4 mL, 3 mmoL) was added cesium carbonate (180 mg, 1.86 mmol) and degassed for 15 min. Pd2(dba)3 (56 mg, 0.062 mmol) and BINAP (38 mg, 0.062 mmol) were added and the mixture was heated in the microwave for 30 min at 100 C. The reaction mixture was concentrated under reduced pressure and extracted with EtOAc (2 x 30mL) and water (2 x 30mL). The organic extracts were washed with brine, dried over sodium sulfate and concentrated under reduced pressure then purified by silica gel column chromatography to provide 3-((3-(3-(4- fluorophenoxy)azetidin-l-yl)phenyl)amino)-N-methylbenzamide (113 mg, 23%) as a solid. Observed mass (M+l): 393.1

Reference： [1]Patent: WO2011/103196,2011,A1 .Location in patent: Page/Page column 115

43
[ 1333238-86-0 ]
[ 25900-61-2 ]
[ 1333239-00-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 5224 - 5229

44
[ 25900-61-2 ]
[ 2882-19-1 ]
[ 1333902-92-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With DIPEA; In acetonitrile;	Preparation of ethyl 2-(3-(methylcarbamoyl)phenylamino)-2-phenylacetate (I8) 3-Amino-N-methylbenzamide (371 mg, 2.47 mmol), ethyl 2-bromo-2-phenylacetate (0.29 ml, 1.64 mmol), and DIPEA (0.43 ml, 2.47 mmol) were dissolved in acetonitrile (5 ml) and stirred under microwave irradiation into a sealed vial at 100 C. for 60 minutes (UPLC-MS: complete conversion). Acetonitrile was evaporated, and the crude residue was purified by flash chromatography (DCM/EtOAc=8/2) to obtain ethyl 2-(3-(methylcarbamoyl)phenylamino)-2-phenylacetate (475 mg, 92% yield).
92%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 100℃; for 1h;microwave irradiation;	3-Amino-N-methylbenzamide (371 mg, 2.47 mmol), ethyl 2-bromo-2- phenylacetate (0.29 ml, 1.64 mmol), and DIPEA (0.43 ml, 2.47 mmol) were dissolved in acetonitrile (5 ml) and stirred under microwave irradiation into a sealed vial at 100C for 60 minutes (UPLC-MS: complete conversion). Acetonitrile was evaporated and the crude residue was purified by flash chromatography (DCM/EtOAc=8/2) to obtain ethyl 2-(3-(methylcarbamoyl)phenylamino)-2-phenylacetate (475 mg, 92% yield).

Reference： [1]Patent: US2011/311459,2011,A1
[2]Patent: WO2011/160919,2011,A1 .Location in patent: Page/Page column 37

45
[ 99-05-8 ]
[ 74-89-5 ]
[ 25900-61-2 ]

Reference： [1]Bulletin of the Korean Chemical Society,2011,vol. 32,p. 4444 - 4446

46
[ 25900-61-2 ]
[ 79-04-9 ]
[ 871217-47-9 ]

Reference： [1]Bulletin of the Korean Chemical Society,2011,vol. 32,p. 4444 - 4446

47
C₁₀H₁₀ClN₃S [ No CAS ]
[ 25900-61-2 ]
[ 1421694-82-7 ]

Yield	Reaction Conditions	Operation in experiment
55 mg	With zinc(II) chloride; at 90 - 120℃;	General procedure: To a stirred solution of 3,5-dichloro-1,2,4-thiadiazole (1.0 eq) and DIPEA (3.0 eq) in cyclohexanol (3 vols ie. dilution of 300 mg in 900 mul of solvent), was added the first amine (1.0 eq) and the reaction mixture was stirred overnight at room temperature to 80 C. The reaction mixture was then split six ways into separate microwave tubes and treated with the second amine (0.25 eq ie. 1.5 eq based on 0.167 eq of intermediate chloride) and ZnCl2 (0.183 eq ie. 1.1 eq based on 0.167 eq of intermediate chloride). The reaction mixture was heated at 90-120 C overnight. The reaction mixture was allowed to cool and purified by preparative HPLC using a Waters X-Bridge reverse-phase column (C-18, 5 microns silica, 19 mm diameter, 100 mm length, flow rate of 40 ml / minute) and decreasingly polar mixtures of water (containing 0.2% ammonium carbonate) and acetonitrile as eluent. The fractions containing the desired compound were evaporated to dryness to afford the title compounds usually as solids.

Reference： [1]Tetrahedron Letters,2013,vol. 54,p. 788 - 791

48
[ 1374867-87-4 ]
[ 25900-61-2 ]
[ 76-05-1 ]
7-(2,4-dimethoxypyrimidin-5-yl)-4-((3-(methylcarbamoyl)phenyl)amino)quinoline-3-carboxamide trifluoroacetic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42.2%		Example 33 7-(2,4-dimethoxypyrimidin-5-yl)-4-((3-(methylcarbamoyl)phenyl)amino)quinoline-3- carboxamide A mixture of <strong>[25900-61-2]3-amino-N-methylbenzamide</strong> (43.6 mg, 0.290 mmol) and 4-chloro-7- (2,4-dimethoxypyrimidin-5-yl)quinoline-3-carboxamide (100 mg, 0.290 mmol) in acetic acid (5 mL) was kept stirring overnight. The reaction was purified by reverse-phase preparative HPLC (YMC 75 X 30 mm column, acetonitrile/water + 0.1 % trifluoroacetic acid) to afford 7-(2,4-dimethoxypyrimidin-5-yl)-4-((3- (methylcarbamoyl)phenyl)amino)quinoline-3-carboxamide, trifluoroacetic acid salt (70 mg, 0.122 mmol, 42.2 % yield) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) delta ppm 2.78 (d, J=4.55 Hz, 3 H) 3.98 (s, 3 H) 4.01 (s, 3 H) 7.44 - 7.49 (m, 1 H) 7.50 - 7.57 (m, 1 H) 7.78 - 7.84 (m, 3 H) 7.88 (br. s., 1 H) 8.04 (d, J=9.09 Hz, 1 H) 8.28 (d, J=1.52 Hz, 1 H) 8.40 (br. s., 1 H) 8.50 (q, J=4.21 Hz, 1 H) 8.64 (s, 1 H) 9.05 (s, 1 H) 12.09 (br. s., 1 H).

Reference： [1]Patent: WO2013/96151,2013,A1 .Location in patent: Page/Page column 101

49
[ 795310-69-9 ]
[ 32315-10-9 ]
[ 25900-61-2 ]
[ 1443247-54-8 ]