[ CAS No. 2840-26-8 ] {[proInfo.proName]}

Name: 2840-26-8|3-Amino-4-methoxybenzoic acid|95%
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SKU: A143141
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Quality Control of [ 2840-26-8 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 2840-26-8 ]

CAS No. :	2840-26-8	MDL No. :	MFCD00002521
Formula :	C₈H₉NO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	FDGAEAYZQQCBRN-UHFFFAOYSA-N
M.W :	167.16	Pubchem ID :	17823
Synonyms :

Calculated chemistry of [ 2840-26-8 ]

Physicochemical Properties

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	44.3
TPSA :	72.55 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.78 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.81
Log Po/w (XLOGP3) :	0.76
Log Po/w (WLOGP) :	0.98
Log Po/w (MLOGP) :	-0.37
Log Po/w (SILICOS-IT) :	0.5
Consensus Log Po/w :	0.54

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.56

Water Solubility

Log S (ESOL) :	-1.59
Solubility :	4.27 mg/ml ; 0.0255 mol/l
Class :	Very soluble
Log S (Ali) :	-1.86
Solubility :	2.29 mg/ml ; 0.0137 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.53
Solubility :	4.91 mg/ml ; 0.0294 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.19

Safety of [ 2840-26-8 ]

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

Application In Synthesis of [ 2840-26-8 ]

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

Upstream synthesis route of [ 2840-26-8 ]
Downstream synthetic route of [ 2840-26-8 ]

[ 2840-26-8 ] Synthesis Path-Upstream 1~9

1
[ 110-53-2 ]
[ 89-41-8 ]
[ 2840-26-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate In ethanol; hydrogen; ethyl acetate; N,N-dimethyl-formamide	PREPARATIVE EXAMPLE 52 4Methoxy-3-nitrobenzoic acid (5 g, 25.4 mmol), DMF (30 ml), potassium carbonate (5.53 g, 40 mmol) and pentyl bromide (4 ml, 32.3 mmol) were mixed, and this solution was stirred at 100° C. for 1.5 hours. The reaction mixture was filtered to remove the inorganic salt, and DMF was evaporated under reduced pressure. Ethyl acetate (100 ml) was added to the obtained residue. The mixture was washed 3 times with saturated brine (30 ml) and dried over anhydrous magnesium sulfate. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. Ethanol (150 ml) and 10percent palladium-carbon catalyst (0.5 g) were added to the obtained residue, and the mixture was stirred at room temperature for 5.5 hours in a stream of hydrogen. The palladium-carbon catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=3/1) to give 3-amino -4-methoxybenzoic acid (5.98 g, 99percent in 2 steps) as colorless crystals. ¹ H-NMR (CDCl₃)δ: 7.48(1 H, dd, J=8.3, 1.9 Hz), 7.38(1 H, d, J=2.1 Hz), 6.79(1 H, d, J=8.3 Hz), 4.26(2 H, t, J=6.7 Hz), 4.09(3 H, s), 3.86(2 H, bs), 1.78-1.66(2 H, m), 1.47-1.29(4 H, m), 0.93(3 H, t, J=7.1 Hz). FABMS (m/z): 238[M⁺ H⁺ (60), 237(100).

Reference： [1] Patent: US6017919, 2000, A,

2
[ 89-41-8 ]
[ 2840-26-8 ]

Reference： [1] Tetrahedron Letters, 1984, vol. 25, # 32, p. 3415 - 3418
[2] Synlett, 2000, # 7, p. 993 - 994
[3] Justus Liebigs Annalen der Chemie, 1859, vol. 109, p. 29
[4] Chemische Berichte, 1897, vol. 30, p. 1477
[5] Justus Liebigs Annalen der Chemie, 1854, vol. 92, p. 327
[6] Chemische Berichte, 1897, vol. 30, p. 1477
[7] Chemische Berichte, 1925, vol. 58, p. 1784
[8] Journal of the Chemical Society, 1917, vol. 111, p. 232

3
[ 24812-90-6 ]
[ 2840-26-8 ]

Reference： [1] Chemische Berichte, 1897, vol. 30, p. 1477

4
[ 40757-20-8 ]
[ 2840-26-8 ]

Reference： [1] Chemische Berichte, 1897, vol. 30, p. 1477

5
[ 99-58-1 ]
[ 2840-26-8 ]

Reference： [1] Gazzetta Chimica Italiana, 1884, vol. 14, p. 235

6
[ 954815-08-8 ]
[ 2840-26-8 ]

Reference： [1] Gazzetta Chimica Italiana, 1884, vol. 14, p. 235

7
[ 2840-26-8 ]
[ 113928-90-8 ]

Reference： [1] Patent: WO2008/114022, 2008, A1, . Location in patent: Page/Page column 55

8
[ 24424-99-5 ]
[ 2840-26-8 ]
[ 306937-12-2 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium hydroxide In tetrahydrofuran at 20℃; for 12.5 h; Cooling with ice	3-Amino-p-anisic acid (1) (20.0 g,119 mmol)was suspended in asolution of NaOH (1 mol/L, 180 mL) and THF (150 mL). The mixturewas cooled in an ice bath. A solution of di-tert-butyl dicarbonate(Boc)2O (104.4 g, 479 mmol) in THF (70 mL) was then addeddropwise over a period of 30 min under stirring. The ice-bath wasremoved after dropping and the mixture was stirred for another12 h at room temperature. Thereafter, the THF was removed invacuo, and the remaining aqueous solution was diluted with water.The resulting mixture was extracted three times with AcOEt(70mL 3). The aqueous layer was acidified with concentrated HClto neutralize PH to 4e5 and extracted with AcOEt (80 mL 3). Thecombined organic layers were washed with water, and dried overNa2SO4. Then filtration and concentration in vacuo gave (2) (20.78 g,65percent) as off-white solid, which was used for the next step withoutfurther purification.
65%	With sodium hydroxide In tetrahydrofuran at 20℃; for 5 h; Cooling with ice	20 g of 3-amino-4-methoxybenzoic acid (Compound 1) was dissolved in 180 ml of sodium hydroxide solution, 150 ml of tetrahydrofuran was added thereto, and a solution of BOC anhydride (104,4 g) in tetrahydrofuran (70 ml) was added dropwise to the ice bath The ice bath was removed and stirred at room temperature for 5 hours. After the completion of the stirring, the product was extracted with 80 ml of ethyl acetate, and the organic phase was combined and washed with saturated sodium chloride, and the mixture was washed with anhydrous sulfuric acid Sodium dry.Rotate the liquid to give 20.78 g of an off-white solid 3 - ((tert-butoxycarbonyl) amino) -4-methoxybenzoic acid (Compound 2) in 65percent yield;
50%	Stage #1: With sodium hydroxide In water at 50℃; Stage #2: With hydrogenchloride In water	1) 1.0 g (6 mmol) 3-amino-4-methoxybenzoic acid is dissolved in 10 ml 4N NaOH aqueous solution, 2.5 ml (11 mmol) tert-butyric anhydride is slowly dropped into the solution. The mixture is heated up to 50° C. until the reaction finishes and the resulted alkaline solution is quickly acidified to pH=2 using 1 N hydrochloric acid and extracted three times using chloroform. The chloroform extract is pooled and desiccated with anhydrate sodium sulfate, subsequently condensed to dryness to obtain 0.8 g off- white solid, yield: 50percent.

Reference： [1] European Journal of Organic Chemistry, 2001, # 2, p. 311 - 322
[2] European Journal of Medicinal Chemistry, 2015, vol. 103, p. 80 - 90
[3] Patent: CN104817489, 2017, B, . Location in patent: Paragraph 0037-0040
[4] Patent: US2011/178108, 2011, A1, . Location in patent: Page/Page column 17

9
[ 2840-26-8 ]
[ 102774-86-7 ]
[ 256935-69-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2001, vol. 44, # 25, p. 4416 - 4430

[ 2840-26-8 ] Synthesis Path-Downstream 1~88

1
[ 89-41-8 ]
[ 2840-26-8 ]

Reference： [1]Tetrahedron Letters,1984,vol. 25,p. 3415 - 3418
[2]Synlett,2000,p. 993 - 994
[3]Justus Liebigs Annalen der Chemie,1859,vol. 109,p. 29
[4]Chemische Berichte,1897,vol. 30,p. 1477
[5]Chemische Berichte,1925,vol. 58,p. 1784
[6]Journal of the Chemical Society,1917,vol. 111,p. 232

2
[ 108-31-6 ]
[ 2840-26-8 ]
[ 66832-25-5 ]

Reference： [1]Chemical and pharmaceutical bulletin,1981,vol. 29,p. 1130 - 1135
[2]Synthetic Communications,2008,vol. 38,p. 303 - 308

3
[ 573-54-6 ]
[ 2840-26-8 ]
2'-Methoxy-2-nitrodiphenylamin-5',6-dicarbonsaeure [ No CAS ]

Reference： [1]Zeitschrift fur Naturforschung - Teil A Physik, Physikalische Chemie, Kosmophysik,1981,vol. 36,p. 1037 - 1046

4
[ 2840-26-8 ]
[ 120623-41-8 ]

Reference： [1]Journal of the Chemical Society. Perkin transactions I,1989,p. 851 - 855

5
[ 4774-14-5 ]
[ 2840-26-8 ]
[ 1000068-59-6 ]

Yield	Reaction Conditions	Operation in experiment
	With 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 135℃; for 3h;	A mixture of 2,6-dichloropyrazine (200 mg, 1.35 mmol), 3-amino 4-methoxy benzoic acid (251 mg, 1.5 mmol), Pd2(dba)3 (10 mg), Xantphos (20 mg) and NaOtBu (288 mg, 3 mmol) was suspended in dioxane (10 ml) and stirred under nitrogen atl35C in a sealed tube for 3h. The resulting suspension was partitioned between ethyl acetate and water. The aqueous phase was neutralised with a few drops of cone, hydrochloric acid to produce a precipitate. Back extraction of the mixture with ethyl acetate followed by drying and concentration of the organic phase gave the title product a brown solid, used without further purification.

Reference： [1]Patent: WO2007/147874,2007,A1 .Location in patent: Page/Page column 120

6
[ 2840-26-8 ]
[ 137-07-5 ]
2-(4-methoxy-3-aminophenyl)benzothiazole [ No CAS ]

Reference： [1]Magnetic Resonance in Chemistry,2006,vol. 44,p. 102 - 105

7
[ 2407-11-6 ]
[ 2840-26-8 ]
C₁₅H₁₁N₃O₅S [ No CAS ]

Reference： [1]Magnetic Resonance in Chemistry,2006,vol. 44,p. 102 - 105

8
[ 67-56-1 ]
[ 2840-26-8 ]
[ 24812-90-6 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sulfuric acid; for 24h;Reflux;	Step 1: Preparation of methyl 3-amino-4-methoxybenzoate (69) A mixture of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (2.00 g, 11.96 mmol) and sulfuric acid (1.275 ml, 23.93 mmol) in MeOH (25 ml) was heated to reflux for 24 hours. After cooling to room temperature the solvent was removed under vacuum and the residue was partitioned between aq. NaHCO3 sat. sol. and ethyl acetate. The organic layer was dried over Na2SO4 and evaporated to dryness affording methyl 3-amino-4-methoxybenzoate as an off-white powder (2.00 g, 11.04 mmol, 92% yield, MS/ESI+ 182.1 [MH]+).
90%		3-Amino-4-methoxy benzoic acid (40 g, 0.239 mol) was dissolved in methanol, H2SO4 (38.14 ml, 0.717 mol) was added dropwise thereto and refluxed for 12 hours. The resulting mixture was cooled to room temperature and concentrated under a reduced pressure to remove methanol, neutralized with NaHCO3, extracted with ethyl acetate, and the extract was concentrated under a reduced pressure. The resulting residue was purified by recrystallization from ethyl acetate/hexane to obtain the title compound (39 g, 0.215 mol) in a yield of 90 %. 1H NMR (CDCl3): delta 7.87-7.78 (2H, m), 7.22 (1H, d), 3.93 (3H, s), 3.82 (3H, s) MW: 181
0.509 g	With sulfuric acid; In water; for 48h;Reflux;	A mixture of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (0.500 g, 2.99 mmol) and a catalytic amount of aqueous conc. sulfuric acid in MeOH (30 ml) was heated to reflux for 48 hours. The solvent was removed, and the crude was portioned between EtOAc and NaHCO3 5%. The organic phase was dried over Na2SO4 and the solvent was removed affording methyl 3-amino-4-methoxybenzoate (0.509 g, 2.81 mmol, 94% yield, MS/ESI+ 181.9 [MH]+). This product was used without purification.

0.509 g

With sulfuric acid; for 48h;Reflux;

A mixture of [2840-26-8]3-amino-4-methoxybenzoic acid (0.500 g, 2.99 mmol) and a catalytic amount of aqueous cone, sulfuric acid in MeOH (30 ml) was heated to reflux for 48h. The solvent was removed and the crude was portioned between EtOAc and NaHC03 5%. The organic phase was dried over Na2S04 and the solvent was removed affording methyl 3-amino-4-methoxybenzoate (0.509 g, 2.81 mmol, 94% yield, MS/ESI+ 181.9 [MH] +). This product was used without purification.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5686 - 5689
[2]Patent: US2014/155391,2014,A1 .Location in patent: Paragraph 0416; 0417
[3]Patent: WO2004/65370,2004,A1 .Location in patent: Page 18
[4]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 1891 - 1894
[5]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 6724 - 6731
[6]Patent: US2013/79313,2013,A1 .Location in patent: Paragraph 0740
[7]Patent: WO2013/45280,2013,A1 .Location in patent: Page/Page column 146
[8]Journal of Medicinal Chemistry,2016,vol. 59,p. 2423 - 2435

9
[ 2840-26-8 ]
[ 864348-34-5 ]

Reference： [1]Organic Letters,2005,vol. 7,p. 3673 - 3676

10
[ 2840-26-8 ]
5-tert-butyl-9-methoxy-4-phenyl-4,5-dihydro-1,5-diaza-phenalen-6-one [ No CAS ]

Reference： [1]Organic Letters,2005,vol. 7,p. 3673 - 3676

11
[ 2840-26-8 ]
[ 685824-74-2 ]

Reference： [1]Organic Letters,2005,vol. 7,p. 3673 - 3676
[2]Patent: US2014/94487,2014,A1

12
[ 2840-26-8 ]
N-benzyl-4-methoxy-3-(4-methyl-piperazin-1-yl)-benzamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

13
[ 2840-26-8 ]
4-[4-methoxy-3-(4-methyl-piperazin-1-yl)-benzoylamino]-benzoic acid methyl ester [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

14
[ 2840-26-8 ]
4-methoxy-3-(4-methyl-piperazin-1-yl)-N-[2-(4-nitro-phenyl)-ethyl]-benzamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

15
[ 2840-26-8 ]
N-[5-(4-chloro-phenyl)-thiazol-2-yl]-4-methoxy-3-(4-methyl-piperazin-1-yl)-benzamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

16
[ 2840-26-8 ]
3-(4-methyl-1-piperazinyl)-4-methoxybenzoic acid [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

17
[ 2840-26-8 ]
N-{4-[4-(3,5-dioxo-4-aza-tricyclo[5.2.1.0^2,6]dec-8-en-4-yl)-benzyl]-phenyl}-4-methoxy-3-(4-methyl-piperazin-1-yl)-benzamide [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2004,vol. 39,p. 305 - 321

18
[ 2840-26-8 ]
3-(4-amino-3,5-dicyanopyrazol-1-yl)-4-methoxy-benzoic acid cyanomethyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research,2004,p. 115 - 117

19
[ 2840-26-8 ]
N-(3,5-dichloro-4-pyridinyl)-8-methoxyquinoline-5-carboxamide [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 1613 - 1615

20
[ 2840-26-8 ]
8-methoxy-quinoline-4-carboxylic acid chloride hydrochloride [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2002,vol. 12,p. 1613 - 1615

21
[ 2840-26-8 ]
2-methoxy-5-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-oxazol-2-yl]-phenylamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4416 - 4430

22
[ 2840-26-8 ]
[ 256935-71-4 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4416 - 4430

23
[ 2840-26-8 ]
[ 256935-70-3 ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 4416 - 4430

24
[ 2840-26-8 ]
[ 167993-22-8 ]

Reference： [1]European Journal of Organic Chemistry,2001,p. 311 - 322

25
[ 2840-26-8 ]
[ 330807-52-8 ]

Reference： [1]European Journal of Organic Chemistry,2001,p. 311 - 322

26
[ 2840-26-8 ]
Boc-(L)-Pro-AB(4-OCH₃)-OBn [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2001,p. 311 - 322

27
[ 2840-26-8 ]
3-(N'-Dicyanomethylene-hydrazino)-4-methoxy-benzoic acid cyanomethyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1995,p. 924 - 937

28
[ 2840-26-8 ]
4-Amino-5-cyano-2-(5-ethoxycarbonylmethoxycarbonyl-2-methoxy-phenyl)-2H-pyrazole-3-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Chemical Research, Miniprint,1995,p. 924 - 937

29
[ 2840-26-8 ]
4-Methoxyphenazin-1,6-dicarbonsaeure [ No CAS ]

Reference： [1]Zeitschrift fur Naturforschung - Teil A Physik, Physikalische Chemie, Kosmophysik,1981,vol. 36,p. 1037 - 1046

30
[ 2840-26-8 ]
[ 73113-72-1 ]

Reference： [1]Zeitschrift fur Naturforschung - Teil A Physik, Physikalische Chemie, Kosmophysik,1981,vol. 36,p. 1037 - 1046

31
[ 2840-26-8 ]
[ 66832-26-6 ]

Reference： [1]Chemical and pharmaceutical bulletin,1981,vol. 29,p. 1130 - 1135

32
[ 2840-26-8 ]
[ 66832-27-7 ]

Reference： [1]Chemical and pharmaceutical bulletin,1981,vol. 29,p. 1130 - 1135

33
[ 2840-26-8 ]
[ 67745-31-7 ]

Reference： [1]Roczniki Chemii,1931,vol. 11,p. 203,214
Chemisches Zentralblatt,1931,vol. 102,p. 2868

34
[ 99-58-1 ]
[ 2840-26-8 ]

Reference： [1]Gazzetta Chimica Italiana,1884,vol. 14,p. 235

35
[ 954815-08-8 ]
[ 2840-26-8 ]

Reference： [1]Gazzetta Chimica Italiana,1884,vol. 14,p. 235

36
[ 2840-26-8 ]
2-hydroxy-4-methoxy-naphtho[1,2,3-de]quinolin-7-one [ No CAS ]

Reference： [1]Chemische Berichte,1925,vol. 58,p. 1784

37
[ 64-17-5 ]
[ 2840-26-8 ]
[ 16357-44-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With sulfuric acid; at 0℃; for 12h;Inert atmosphere; Reflux;	6.3.1 3-Amino-4-methoxyl-benzoic acid ethyl ester (2) 3-Amino-4-methoxyl benzoic acid (6.01 g, 36 mmol) was dissolved in 100 mL dehydrated ethanol. Under 0 C, 2 mL concentrated H2SO4 was dropped slowly to the above solution, and then the solution was heated to reflux for 12 h. After the reaction was completed, ethanol was removed by reduced pressure distillation. Under 0 C, 100 mL water was added, and the solution was adjusted to pH 6-7 with sodium bicarbonate. Then the aqueous was extracted with ethyl acetate (50 mL * 2). The organic phase was combined, and was washed by water (30 mL * 2), saturated sodium chloride (30 mL). The organic layer was dried over Na2SO4, filtered, and distilled under vacuum to give the crude product. The crude product was purified by chromatography (petroleum ether/ethyl acetate = 1:1), giving a white solid (6.87 g). The total yield was 98%, mp 55-57 C. EI-MS (m/z): 195.1 ([M]+). 1H NMR (400 MHz, CDCl3): delta = 1.39 (t, J = 6.0 Hz, 3H), 3.92 (s, 3H), 4.34 (q, J = 6.0 Hz, 14.00 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H), 7.42 (s, 1H), 7.50 (d, J = 8.0 Hz, 1H).

Reference： [1]Bioorganic and Medicinal Chemistry,2013,vol. 21,p. 2527 - 2534
[2]Patent: EP1180514,2002,A1 .Location in patent: Example 46

38
[ 2840-26-8 ]
[ 29754-04-9 ]
ethyl (RS)-3-(3-amino-4-methoxy-benzoylamino)-3-phenyl-propionate [ No CAS ]

Reference： [1]Patent: US6344562,2002,B1 .Location in patent: Page column 64-65

39
[ 2840-26-8 ]
[ 1134-36-7 ]
[ 599201-51-1 ]

Yield	Reaction Conditions	Operation in experiment
	With PPA; at 200℃; for 4h;	3-Amino-4-methoxybenzoic acid (3. 0MMOL) and 2-amino-4-phenylphenol (3. 0MMOL) were mixed in polyphosphoric acid (SML) and the mixture was heated to 200C for 4 h. The reaction mixture was slowly poured into ice water (100ML) and the resulting mixture basified with solid sodium hydroxide. At pH5-6 the precipitate was filtered, washed with water and dried under vacuum. MS (APCI-) M/Z 317.

Reference： [1]Patent: WO2004/67480,2004,A2 .Location in patent: Page 12

40
[ 3998-28-5 ]
[ 2840-26-8 ]
[ 612035-46-8 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile;	b 3-[3-(2,4-Dichlorobenzoyl)ureido]-4-methoxybenzoic Acid 20 g (120 mmol) of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> were made to react with 36 g (168 mmol) of 2,4-dichlorobenzoyl isocyanate from step a in 400 ml of acetonitrile and left to react therewith at reflux for 2 hours. After the mixture has cooled down to room temperature, the precipitate is filtered off with suction, washed twice with in each case 20 ml of acetonitrile, sucked dry and dried under high vacuum. 44 g (96%) of the desired product are obtained. m.p.: 290 C.

Reference： [1]Patent: JP2005/522481,2005,A .Location in patent: Page/Page column 16; 19
[2]Patent: US2003/216370,2003,A1

41
[ 438249-85-5 ]
[ 2840-26-8 ]
[ 438249-20-8 ]

Yield	Reaction Conditions	Operation in experiment
33%		EXAMPLE 184 4-(5-Carboxy-2-methoxyanilino)-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine The title compound was prepared from 4-chloro-2-(2-pyrazinyl)-6-trifluoromethylpyrimidine (40 mg, 0.154 mmol) and 5-carboxy-2-methoxyaniline (38 mg, 0.231 mmol), similar to Example 180 and was isolated as an off white solid (20 mg, 33%). 1H NMR (CDCl3): 9.99 (brs, 1H), 9.660 (d, J=1.5 Hz, 1H), 8.86 (m, 3H), 7.80 (d, 2H), 7.2 (m, 2 H), 3.94 (s, 3H).

Reference： [1]Patent: US2003/69239,2003,A1

42
[ 112-71-0 ]
[ 2840-26-8 ]
[ 170082-19-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In methanol; water; ethyl acetate; N,N-dimethyl-formamide;	EXAMPLE 3 Synthesis of Tetradecyl 3-Amino-4-methoxybenzoate 16.7 g (0.1 mol) of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> was added to 50 ml of N,N-dimethylformamide. Then 13.8 g (0.1 mol) of potassium carbonate was added to the solution obtained above, and the resulting mixture was stirred in the temperature range of from 20 to 30 C. for 30 min. 30.5 g (0.11 mol) of tetradecyl bromide was poured into the solution thus obtained, and the resulting solution was heated to 80 C., and allowed to react at the temperature for 1 hour. After completing the reaction, 50 ml of ethyl acetate, and 50 ml of water were added to the reaction mixture, and the organic layer obtained was separated, concentrated, diluted with 100 ml of methanol, and then cooled to precipitate crystals. The crystals were separated by filtration, and then dried to obtain 33.1 g (yield 91%) of the desired product. Purity 98% or higher. Melting point 54.0-56.0 C. A result of the elemental analysis of this sample was as follows:

Reference： [1]Patent: US5908955,1999,A

43
[ 110-53-2 ]
[ 2840-26-8 ]
pentyl 4-methoxy-3-pentylaminobenzoate [ No CAS ]
[ 194360-47-9 ]

Yield	Reaction Conditions	Operation in experiment
67%	With potassium carbonate; In N,N-dimethyl-formamide;	PREPARATIVE EXAMPLE 53 3-Amino-4-methoxybenzoic acid (1.53 g, 6.45 mmol), DMF (15 ml), potassium carbonate (2.07 g, 15 mmol) and pentyl bromide (1.86 ml, 15 mmol) were mixed, and the solution was stirred at 100 C. for 10.5 hours. The reaction mixture was filtered to remove the inorganic salt, and DMF was evaporated under reduced pressure. The obtained residue was purified by column chromatography on silica gel (hexane/ethyl acetate=10/1) to give pentyl 4-methoxy-3-pentylaminobenzoate (1.32 g, 67%) and pentyl 3-dimethylamino-4-methoybenzoate (334 mg, 14%) as colorless oils. pentyl 4-methoxy-3-pentylaminobenzoate 1 H-NMR (CDCl3)delta: 7.41(1 H, dd, J=8.1, 2.1 Hz), 7.24(1 H, d, J=2.1 Hz), 6.75(1 H, d, J=8.1 Hz), 4.27(2 H, t, J=6.6 Hz), 4.20(1 H, bs), 3.90(3 H, s), 3.17(2 H, t, J=7.2 Hz), 1.82-1.62(4 H, m), 1.5-1.3(8 H, m), 0.93(3 H, t, J=7.2 Hz). FABMS (m/z): 308[M+ H+ ] (50), 307(100), 250(50). pentyl 3-dimethylamino-4-methoxybenzoate 1 H-NMR (CDCl3)delta: 7.67(1 H, dd, J=8.5, 2.1 Hz), 7.66(1 H, d, J=2.0 Hz), 6.84(1 H, d, J=8.5 Hz), 4.28(2 H, t, J=6.7 Hz), 3.89(3 H, s), 3.08(4 H, t, J=7.7 Hz), 1.80-1.70(2 H, m), 1.5-1.18(16 H, m), 0.93(3 H, t, J=7.1 Hz), 0.86(3 H, t, J=7.0 Hz). FABMS (m/z): 378[M+ H+ ] (100), 320(100), 264(40).

Reference： [1]Patent: US6017919,2000,A

44
[ 2840-26-8 ]
[ 29754-04-9 ]
ethyl rac-3-(3-amino-4-methoxy-benzoylamino)-3-phenyl-propionate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The ethyl (RS)-3-(3-amino-4-methoxy-benzoylamino)-3-phenyl-propionate can be prepared according to the method given in Example 5 from <strong>[2840-26-8]3-amino-4-methoxy-benzoic acid</strong> and ethyl (RS)-3-amino-3-phenyl-propionate hydrochloride; m.p. 116-118 C., MS: 343 (M+H)+.

Reference： [1]Patent: US6100282,2000,A

45
[ 110-53-2 ]
[ 89-41-8 ]
[ 2840-26-8 ]

Yield	Reaction Conditions	Operation in experiment
99%	With potassium carbonate;palladium-carbon catalyst; In ethanol; hydrogen; ethyl acetate; N,N-dimethyl-formamide;	PREPARATIVE EXAMPLE 52 4Methoxy-3-nitrobenzoic acid (5 g, 25.4 mmol), DMF (30 ml), potassium carbonate (5.53 g, 40 mmol) and pentyl bromide (4 ml, 32.3 mmol) were mixed, and this solution was stirred at 100 C. for 1.5 hours. The reaction mixture was filtered to remove the inorganic salt, and DMF was evaporated under reduced pressure. Ethyl acetate (100 ml) was added to the obtained residue. The mixture was washed 3 times with saturated brine (30 ml) and dried over anhydrous magnesium sulfate. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. Ethanol (150 ml) and 10% palladium-carbon catalyst (0.5 g) were added to the obtained residue, and the mixture was stirred at room temperature for 5.5 hours in a stream of hydrogen. The palladium-carbon catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by column chromatography (hexane/ethyl acetate=3/1) to give 3-amino -4-methoxybenzoic acid (5.98 g, 99% in 2 steps) as colorless crystals. 1 H-NMR (CDCl3)delta: 7.48(1 H, dd, J=8.3, 1.9 Hz), 7.38(1 H, d, J=2.1 Hz), 6.79(1 H, d, J=8.3 Hz), 4.26(2 H, t, J=6.7 Hz), 4.09(3 H, s), 3.86(2 H, bs), 1.78-1.66(2 H, m), 1.47-1.29(4 H, m), 0.93(3 H, t, J=7.1 Hz). FABMS (m/z): 238[M+ H+ (60), 237(100).

Reference： [1]Patent: US6017919,2000,A

46
[ 2840-26-8 ]
2-(3-Amino-4-methoxyphenyl)-5,6,7,8-tetrahydro-4H-thiazolo [5,4-b]azepine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
13.0%		EXAMPLE 108 2-(3-Amino-4-methoxyphenyl)-5,6,7,8-tetrahydro-4H-thiazolo [5,4-b]azepine dihydrochloride By the method of Example 18, the title compound was obtained by reacting <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> and phosphorus pentasulfide, purifying and neutralizing with hydrogen chloride. Yield 13.0%. m.p. 194-197 (recrystallized from methanol). IR(KBr)cm-1: 3318, 1603, 1591, 1536, 1485, 1371, 1352, 1289, 1245, 1165, 1035. NMR(d6 -DMSO)delta: 1.63(2H,m), 1.81(2H,m), 2.90(2H,t), 3.08(2H,t), 3.94(3H,s), 6.05(2H,br.s), 7.27(1H,d,J=8.67 Hz), 7.81(1H,dd), 7.88(1H,d,J=2.12 Hz). Elemental analysis for C14 H19 N3 SCl2 O. Calculated: C, 48.28; H, 5.50; N, 12.06; S, 9.21; Cl, 20.36. Found: C, 47.80; H, 5.57; N, 11.82; S, 9.23; Cl, 20.17.

Reference： [1]Patent: US4956360,1990,A

47
[ 54-96-6 ]
[ 74-93-1 ]
[ 2840-26-8 ]
[ 87346-53-0 ]
2-(3-Methylthio-4-methoxyphenyl)-1H-imidazo-[4,5-c]pyridine dihydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; triethylamine; In pyridine; methanol; ethylene glycol; toluene;	EXAMPLE 34 2-(3-Methylthio-4-methoxyphenyl)-1H-imidazo-[4,5-c]pyridine dihydrochloride 3-Methylthio-4-methoxybenzoic acid (obtained by diazotization of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong>, followed by treatment with methylmercaptan) was suspended in dry toluene and thionyl chloride (1.1 eq) was added slowly to it. The mixture was refluxed for 3.5 hours. T.l.c. indicated reaction to be complete. The solvent was removed in vacuo to leave a dark brown residue. The acid chloride obtained above was suspended in the minimum quantity of dry ether and added portionwise to a suspension of 3,4-diaminopyridine (1 eq) in dry pyridine and triethylamine. The resulting mixture was refluxed for 5 hours. T.l.c. indicated the reaction to be complete. The cooled reaction mixture was filtered through hyflo and the filtrate evaporated in vacuo. The residue was triturated with ether and then dissolved in methanol. The solid that separated was filtered off and the methanol filtrate was evaporated under reduced pressure to give a viscous oil. NMR indicated this to consist mainly of the intermediate amide. This oil was dissolved in ethylene glycol and the solution obtained heated at 200 for 4 hours. T.l.c. indicated reaction to be complete. The cooled reaction mixture was poured into water. A white solid precipitated and was filtered and dried. The solid was triturated into ethyl acetate/ether to give a solid which was converted to the title dihydrochloride, m.p. 275-277 C.

Reference： [1]Patent: US4603139,1986,A

48
[ 40056-43-7 ]
[ 2840-26-8 ]
N-(5-carboxy-2-methoxyphenyl)-3,5-di-t-butyl-4-hydroxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,2-dimethoxyethane;	EXAMPLE 6 Preparation of N-(5-Carboxy- 2-methoxyphenyl)-3,5-di-t-butyl-4-hydroxybenzamide A solution of 5.06g (0.02 mole) of 3,5-di-t-butyl-4-hydroxybenzoyl chloride in 100 ml of 1,2-dimethoxyethane was mixed with a solution of 6.69g (0.04 mole) of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> in 125 ml of 1,2-dimethoxyethane, and the mixture was stirred at 25 C. for about 16 hours. The reaction mixture was heated gently for 30 minutes and then allowed to cool before being filtered to remove the hydrochloride salt of the excess starting amine. The filtrate was concentrated under vacuum and then diluted with water. The resulting precipitate was collected and was then recrystallized three times from a mixture of ethanol and water to give 1.9g of white solid N-(5-carboxy-2-methoxyphenyl)-3,5-di-t-butyl-4-hydroxybenzamide, m.p. 259-261 C. Analysis: Calculated for C23 H29 NO5: %C, 69.2; %H, 7.3; %N, 3.5; Found: %C, 69.3; %H, 7.3; %H, 3.6.

Reference： [1]Patent: US5049572,1991,A

49
[ 2840-26-8 ]
2,4-diamino-3'-carboxy-6'-methoxydiphenylamine dihydrochloride dihydrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		1.7 2,4-diamino-3'-carboxy-6'-methoxydiphenylamine dihydrochloride dihydrate Starting from <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong>, the 2,4-dinitro-3'-carboxy-6'-methoxydiphenylamine sodium salt was obtained in the form of orange-colored crystals melting above 250 C. by the method described in 1.4. The 2,4-diamino-3'-carboxy-6'-methoxydiphenylamine dihydrochloride dihydrate in the form of gray crystals melting at 249 C. (with decomposition) was obtained therefrom by hydrogenation.

Reference： [1]Patent: US4698066,1987,A

Yield	Reaction Conditions	Operation in experiment
		2,4- and 2,5-dichloraniline, ... 4-chloro-3-aminobenzoic acid-2'4'5'-trichloranilide, 4-chloro-3-aminobenzoic acid-2'-methyl-3'-chloroanilide, 4-carbethoxy-3-aminobenzoic acid-2'5'-dichloranilide, 4-chloro-3-aminobenzoic acid, 4-methoxy-3-aminobenzoic acid, 4-methyl-3-aminobenzoic acid,
		A process according to claim 1 wherein the diazotizable amine is selected from the group consisting of 2,4- and 2,5-dichloraniline, ... 4-chloro-3-aminobenzoic acid-2'4'5'-trichloranilide, 4-chloro-3-aminobenzoic acid-2'-methyl-3'-chloroanilide, 4-carbethoxy-3-aminobenzoic acid-2'5'-dichloranilide, 4-chloro-3-aminobenzoic acid, 4-methoxy-3-aminobenzoic acid, 4-methyl-3-aminobenzoic acid, 3,3'-dichlorobenzidine, 2,5,2'5'-tetrachlorobenzidine, ...

51
[ 582-33-2 ]
[ 2840-26-8 ]
3-(3-Amino-4-methoxy-benzoylamino)-benzoic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 148 3-(3-Amino-4-methoxy-benzoylamino)-benzoic acid ethyl ester The title compound has been made using the procedure of Example 1, but using <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> and ethyl 3-aminobenzoate as starting materials, which are commercially available from Aldrich; m.p. 144-146 C.

Reference： [1]Patent: US6268387,2001,B1

52
aqueous potassium carbonate [ No CAS ]
[ 2840-26-8 ]
[ 24812-90-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sulfuric acid; In methanol;	Step A 3-Amino-4-methoxybenzoic acid methyl ester Concentrated H2SO4 (9 mL) was added in portions to a stirred solution of <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (20.06 g, 110.4 mmol) in methanol (280 mL). The mixture was heated to reflux overnight then cooled to room temperature, and the solvent was removed in vacuo. The residue was shaken with 10% aqueous potassium carbonate then extracted with ethyl acetate three times. The combined extracts were washed with saturated sodium bicarbonate, dried (MgSO4), filtered, and stripped of solvent under reduced pressure. The residual solid was triturated with hexane and filtered to yield the product (10.82 g); m.p. 75-77 C. Calculated for C9H11NO3: C, 59.66; H, 6.12; N, 7.73. Found: C, 59.93; H, 6.22; N, 7.54.

Reference： [1]Patent: US6268387,2001,B1

53
[ 2840-26-8 ]
[ 117738-82-6 ]

Yield	Reaction Conditions	Operation in experiment
	In (CD3)2CO;	Synthesis of 3-cyano-4-methoxybenzoic acid (used in the synthesis of Compound 20) 3-Cyano-4-methoxybenzoic acid was prepared from <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (supplied by Aldrich) using the methodology used in the synthesis of 3-cyano-4-chlorobenzoic acid. Nuclear magnetic resonance spectrum (NMR) was as follows: 'H (ppm from TMS in (CD3)2CO, integral, number of peaks): 4.05, 3H, s; 7.3, 1H, d; 8.25, 2H, m.

Reference： [1]Patent: EP279698,1990,A3

54
[ 2840-26-8 ]
[ 129694-52-6 ]
[ 931424-04-3 ]

Reference： [1]Journal of Heterocyclic Chemistry,2007,vol. 44,p. 13 - 19

55
4-(4-Piperidinyl)benzonitrile [ No CAS ]
[ 2840-26-8 ]
[ 1027354-86-4 ]

Yield	Reaction Conditions	Operation in experiment
83%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; for 72h;	Intermediate K; 4-[ 1 -(3-amino-4-methoxy-benzoyl)-4-piperidyl]benzonitrile; A stirred mixture of 4-(4'-cyanophenyl)piperidine (3 g, 16 mmol); 3-amino-4- methoxybenzoic acid (2.675 g, 16 mmol, 1 eq) and DIPEA (4.2 ml, 24 mmol, 1.5 eq) in DCM (100 mL) was blanketed with nitrogen and treated with N-(3-Dimethylaminopropyl)- N'-ethylcarbodiimide hydrochloride (EDAC) (3.4 g, 17.6 mmol, 1.1 eq). The reaction mixture was stirred for three days. Addition of water to the reaction mixture resulted in an emulsion and a colourless precipitate. The solid was isolated by filtration and washed with EtOAc (2 x 75 mL portions) to give a colourless solid (2.5 g). The ethyl acetate washings were combined, washed with water, dried (MgSO4) and evaporated to give a further 2 g; the solids thus prepared were identical and combined to give the title compound as (4.5 g, 83%), 1H NMR (300.073 MHz, dmso, 30 deg. C) delta 1.48 - 1.67 (2H, m), 1.71 - 1.87 (2H, m), 2.80 - 3.08 (3H, m), 3.78 (3H, s), 3.88 - 4.63 (2H, m), 4.84 (2H, s), 6.56 - 6.64 (IH, m), 6.67 - 6.73 (IH, m), 6.80 (IH, dJ = 8.1 Hz), 7.49 (2H, dJ = 8.1 Hz), 7.76 (2H, dJ = 9.4 Hz), m/z 336 (M+H)+.
83%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; for 72h;	Intermediate C4-[l-(3-amino-4-methoxy-benzoyl)-4-piperidyl]benzonitrileA stirred mixture of 4-(4'-cyanophenyl)piperidine (3 g, 16 mmol); 3-amino-4- methoxybenzoic acid (2.675 g, 16 mmol, 1 eq) and DIPEA (4.2 ml, 24 mmol, 1.5 eq) in DCM (100 mL) was blanketed with nitrogen and treated with N-(3-Dimethylaminopropyl)- N'-ethylcarbodiimide hydrochloride (EDAC) (3.4 g, 17.6 mmol, 1.1 eq). The reaction mixture was stirred for three days. Addition of water to the reaction mixture resulted in an emulsion and a colourless precipitate. The solid was isolated by filtration and washed with EtOAc (2 x 75 mL portions) to give a colourless solid (2.5 g). The ethyl acetate washings were combined, washed with water, dried (MgSO4) and evaporated to give a further 2 g; the solids thus prepared were identical and combined to give the title compound as (4.5 g,83%), 1H NMR (300.073 MHz, d6-DMSO, 300C) delta 1.48 - 1.67 (2H, m), 1.71 - 1.87 (2H, m), 2.80 - 3.08 (3H, m), 3.78 (3H, s), 3.88 - 4.63 (2H, m), 4.84 (2H, s), 6.56 - 6.64 (IH, m), 6.67 - 6.73 (IH, m), 6.80 (IH, dJ = 8.1 Hz), 7.49 (2H, dJ = 8.1 Hz), 7.76 (2H, dJ = 9.4 Hz), m/z 336 (M+H)+.
83%	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; for 72h;	Intermediate B 4-[l-(3-amino-4-methoxy-benzoyl)-4-piperidyl]benzonitrile <n="146"/>A stirred mixture of 4-(4'-cyanophenyl)piperidine (3 g, 16 mmol); 3-amino-4- methoxybenzoic acid (2.675 g, 16 mmol, 1 eq) and DIPEA (4.2 ml, 24 mmol, 1.5 eq) in DCM (100 mL) was blanketed with nitrogen and treated with N-(3-Dimethylaminopropyl)- N'-ethylcarbodiimide hydrochloride (EDAC) (3.4 g, 17.6 mmol, 1.1 eq). The reaction mixture was stirred for three days. Addition of water to the reaction mixture resulted in an emulsion and a colourless precipitate. The solid was isolated by filtration and washed with EtOAc (2 x 75 mL portions) to give a colourless solid (2.5 g). The ethyl acetate washings were combined, washed with water, dried (MgSO4) and evaporated to give a further 2 g; the solids thus prepared were identical and combined to give the title compound as (4.5 g,83%), 1H NMR (300.073 MHz, DMSO-(I6, 30C) delta 1.48 - 1.67 (2H, m), 1.71 - 1.87 (2H, m), 2.80 - 3.08 (3H, m), 3.78 (3H, s), 3.88 - 4.63 (2H, m), 4.84 (2H, s), 6.56 - 6.64 (IH, m), 6.67 - 6.73 (IH, m), 6.80 (IH, dJ = 8.1 Hz), 7.49 (2H, dJ = 8.1 Hz), 7.76 (2H, dJ = 9.4 Hz), m/z 336 (M+H)+.

83%

With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; for 72h;

Intermediate G; o 4-[l-(3-amino-4-methoxy-benzoyl)-4-piperidyl]benzonitrile; A stirred mixture of 4-(4'-cyanophenyl)piperidine (3 g, 16 mmol), 3-amino-4- methoxybenzoic acid (2.675 g, 16 mmol, 1 eq) and DIPEA (4.2 ml, 24 mmol, 1.5 eq) in DCM (100 mL) was blanketed with nitrogen and treated with N-(3-Dimethylaminopropyl)- 5 N'-ethylcarbodiimide hydrochloride (EDAC) (3.4 g, 17.6 mmol, 1.1 eq). The reaction mixture was stirred for three days. Addition of water to the reaction mixture resulted in an emulsion. Evaporation of most of the DCM resulted in the formation of a solid precipitate. The solid was isolated by filtration and washed with EtOAc (2 x 75 mL portions) to give a colourless solid (2.5 g). The ethyl acetate washings were combined and added to the o aqueous filtrate; the phases were separated and the organic phase washed with water, dried (MgSO4) and evaporated to give a further 2 g of colourless solid. The solids thus prepared were identical and combined to give the title compound as (4.5 g, 83%), 1H NMR (300.073 MHz, dmso, 30C) delta 1.48 - 1.67 (2H, m), 1.71 - 1.87 (2H, m), 2.80 - 3.08 (3H, m), 3.78 (3H, s), 3.88 - 4.63 (2H, m), 4.84 (2H, s), 6.56 - 6.64 (IH, m), 6.67 - 6.73 (IH, " 5 m), 6.80 (IH, dJ = 8.1 Hz), 7.49 (2H, dJ = 8.1 Hz), 7.76 (2H, dJ = 9.4 Hz), m/z 336 (M+H)+.

Reference： [1]Patent: WO2008/59214,2008,A1 .Location in patent: Page/Page column 147
[2]Patent: WO2008/75064,2008,A1 .Location in patent: Page/Page column 214
[3]Patent: WO2008/75070,2008,A1 .Location in patent: Page/Page column 144-145
[4]Patent: WO2008/75077,2008,A1 .Location in patent: Page/Page column 42

56
[ 2840-26-8 ]
[ 113928-90-8 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium aluminium tetrahydride; In tetrahydrofuran; at 20 - 50℃; for 4.0h;	Synthesis 9 (3-Amino-4-methoxy-phenyl)-methanol (ABD526); Method B: 3-Amino-4-methoxy-benzoic acid (5 g) was dissolved in THF (100 mL) and added dropwise to a suspension of LiAIH4 (5 g) in THF (200 mL). The mixture was stirred at room temperature for 2 hours followed by 500C for 2 hours. Further THF (100 mL) and water (100 mL) were added and the mixture was allowed to settle and the liquid decanted from the top level, leaving behind a thick residue. The liquid was evaporated until all the THF was removed and residue was extracted with ethyl acetate, washed repeatedly, dried (Na2SO4), and evaporated to give a white powder which was recrystallised from ethyl acetate / petrol to give the title compound. 13C NMR (CDCI3): delta 55.3, 63.0, 110.2, 112.9, 115.0, 134.5, 136.9 and 145.5.

Reference： [1]Patent: WO2008/114022,2008,A1 .Location in patent: Page/Page column 55

57
[ 2840-26-8 ]
[ 407-25-0 ]
[ 915094-38-1 ]

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 3094 - 3103

58
[ 1214265-79-8 ]
[ 2840-26-8 ]
[ 1214266-00-8 ]

Yield	Reaction Conditions	Operation in experiment
66%	hydrogenchloride; In water; isopropyl alcohol; at 95℃;	Preparation 22: (R)-3-(7-Cyano-6-ethyl-5-isopropyl-5,6-dihydroimidazo[l,5- f]pteridin-3 -ylamino)-4-methoxybenzoic acid; [0139] (R)-3-Chloro-6-ethyl-5-isopropyl-5,6-dihydroimidazo[l,5-f]pteridine-7- carbonitrile (1.51 g, 5.0 mmo) and <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (1.25 g, 7.5 mmol) were combined in iso-propanol (50 mL) and a catalytic cone. HCl was added. The resulting suspension was stirred overnight at 95C, then cooled to room temperature and filtered to give the title compound which can be used without further purification, yield 1.42g, 66%. MS ES [M+H] found 434.

Reference： [1]Patent: WO2010/25073,2010,A1 .Location in patent: Page/Page column 32

59
[ 75-15-0 ]
[ 2840-26-8 ]
[ 114380-04-0 ]

Yield	Reaction Conditions	Operation in experiment
94%		EXAMPLE 8 3-Isothiocyanato-4-methoxybenzoic acid Carbon disulfide (0.26 mL, 4.4 mmol) was added to a mixture comprising <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (0.25 g, 1.5 mmol), tetrahydrofuran (1.0 mL), water (1.0 mL) and triethylamine (0.51 mL, 3.6 mmol), followed by stirring at room temperature for 6 hours. To the obtained reaction mixture, a tetrahydrofuran (1.0 mL) solution of iodine (0.41 g, 1.6 mmol) was dropwise added over a period of 5 minutes at 0C, followed by stirring at 0C for further 2.5 hours. Thereafter, 1 M hydrochloric acid (1.5 mL) and sodium sulfite (38 mg, 0.30 mmol) were added and mixed. Then, ethyl acetate (6 mL) was added, and the organic layer was separated and concentrated under reduced pressure to dryness. To the obtained residue, ethyl acetate (6 mL), water (2 mL), sodium hydrogencarbonate (6 mg, 0.07 mmol) and sodium sulfite (9 mg, 0.07 mmol) were added. the organic layer was separated and concentrated under reduced pressure to dryness to obtain 3-isothiocyanato-4-methoxybenzoic acid as a colorless solid (0.29 g, yield: 94%, HPLC purity: 99%, HPLC retention time: 3.5 min). LC-MS ES- 208 (retention time: 21.6 min, condition 3).

Reference： [1]Patent: EP2248800,2010,A1 .Location in patent: Page/Page column 10
[2]Journal of Medicinal Chemistry,2019,vol. 62,p. 1817 - 1836

60
[ 1187344-30-4 ]
[ 2840-26-8 ]
[ 1273072-95-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In 1,4-dioxane; butan-1-ol; at 80℃; for 18h;	Intermediate lb3-(5-Flouro-4-(2-(methylsulfonamido)phenylamino)pyrimidin-2-ylamino)-4-macidA mixture of Intermediate la (100 mg, 0.30 mmol), <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (53 mg 0.33 mmol), 4M HC1 in dioxane (0.1 mL) and n-butanol (2 mL) was heated at 80C for 18 hrs. The precipitate was collected by filtration and washed with n-butanol (2 x 10 mL) and diethyl ether (2 x 10 mL) to afford 3-(5-Fluoro-4-(2-(methylsulfonamido)phenylamino)pyrimidin-2-ylamino acid as a white solid. LCMS method C, (ES+) 447, RT = 1.76 min.
	With hydrogenchloride; In 1,4-dioxane; butan-1-ol; at 80℃; for 18h;	A mixture of Intermediate 1a (100 mg, 0.30 mmol), <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (53 mg, 0.33 mmol), 4M HCl in dioxane (0.1 mL) and n-butanol (2 mL) was heated at 80 C. for 18 hrs. The precipitate was collected by filtration and washed with n-butanol (2×10 mL) and diethyl ether (2×10 mL) to afford 3-(5-Fluoro-4-(2-(methylsulfonamido)phenylamino)pyrimidin-2-ylamino)-4-methoxybenzoic acid as a white solid. LCMS method C, (ES+) 447, RT=1.76 min.

Reference： [1]Patent: WO2011/29807,2011,A1 .Location in patent: Page/Page column 36
[2]Patent: US2012/172385,2012,A1 .Location in patent: Page/Page column 13

61
[ 2840-26-8 ]
[ 1131312-73-6 ]

Reference： [1]Patent: US2011/178108,2011,A1
[2]Patent: EP2351731,2011,A1

62
[ 2840-26-8 ]
[ 1131312-67-8 ]

Reference： [1]Patent: US2011/178108,2011,A1
[2]Patent: EP2351731,2011,A1

63
[ 2840-26-8 ]
[ 1131312-77-0 ]

Reference： [1]Patent: US2011/178108,2011,A1
[2]Patent: EP2351731,2011,A1

64
[ 2840-26-8 ]
[ 1131313-20-6 ]

Reference： [1]Patent: US2011/178108,2011,A1

65
[ 24424-99-5 ]
[ 2840-26-8 ]
[ 1131314-64-1 ]

Reference： [1]Patent: US2011/178108,2011,A1

66
[ 2840-26-8 ]
[ 79-03-8 ]
[ 712286-88-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	With triethylamine; In dichloromethane; at 0 - 20℃;	4.2.1.1 4-Methoxy-3-propionamidobenzoic acid (1-M1) A total of 2.5 mL (30 mmol) of propionyl chloride was added dropwise to a solution of 5.0 g (30 mmol) of 1 and 4.3 mL (30 mmol) of TEA in dichloromethane at 0 C. The mixture was then stirred at room temperature until the starting material was completely disappeared. The solvent was evaporated in vacuo to produce a sticky residue that was extracted with dichloromethane and 0.5 N HCl (25 mL). The organic phase was concentrated, and the residue was purified by column chromatography (silica gel) eluted with petroleum ether and ethyl acetate (v:v = 2:1) to yield the desired compound as a white solid (yield: 76%). Mp: 372-373 C. 1H NMR (400 MHz, DMSO-d6) delta (ppm): 12.59 (1H, br s, COOH), 9.12 (1H, s, NH), 8.56 (1H, s, PhH), 7.68 (1H, d, J = 8.8 Hz, PhH), 7.11 (1H, d, J = 8.8 Hz, PhH), 3.89 (3H, s, OCH3), 2.42 (2H, q, J = 7.6 Hz, CH2), 1.07 (3H, t, J = 7.6 Hz, CH3). ESI-MS (m/z): 224 (M + H)+.
67%		Example 1 Synthesis of N-(3',4',5'-trimethoxyphenyl) 3-propionamido-4-methoxybenzamide (261) 0.6 g <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (1.0 g, 6 mmol) is dissolved in dry THF (tetrahydrofuran) in a 25 ml flask, triethylamine (1.2 ml, 12 mmol) is subsequently added to obtain transparent yellow solution. The mixture is stirred under nitrogen protection, propionyl chloride (0.78 ml, 9 mmol) is added into the flask in an ice-water bath. After finishing addition of propionyl chloride the mixture is naturally raised to room temperature. The reacted mixture is filtered, the filtrate is evaporated to dryness and separated using a silica column to obtain 3-propionamido-4-methoxybenzoic acid 1.3 g (yield: 67%).100 mg of the aforementioned product is mixed with 53 mg (mmol) HOBT and 0.03 ml (mmol) DIC, dissolved into dry DMF in a flask in ice-water bath. The mixture is stirred for 30 min under N2 protection, 72 mg 3,4,5-trimethoxyaniline (mmol) is subsequently added, then the mixture is naturally raised to room temperature and stirred overnight. The reacted mixture is evaporated to dryness and the residue is dissolved into ethyl acetate and subsequently filtered, the filtrate is evaporated to dryness and separated using a preparatory thin layer silica plate to obtain 40 mg compound 261 (yield: 30%).1H NMR (CDCl3, delta) 1.3 (t, 3H, CH3), 2.5 (q, 2H, CH2), 3.82 (s, 3H, 4'-OCH3), 3.9 (s, 6H, 3',5'-OCH3), 3.95 (s, 3H, 4-OCH3), 6.98 (s, 2H, 2',6'-H), 7.0 (d, 1H, 5-H), 7.8 (dd, 1H, 6-H), 7.9 (br, 2H, NH), 8.9 (d, 1H, 2-H)
67%	With triethylamine; In tetrahydrofuran; at 20℃;Inert atmosphere; Cooling with ice;	Example 1 Synthesis of N-(3',4',5'-trimethoxyphenyl) 3-propionamido-4-methoxybenzamide (261) 0.6g <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> (1.0g, 6mmol) is dissolved in dry THF (tetrahydrofuran) in a 25ml flask, triethylamine (1.2my, 12mmol) is subsequently added to obtain transparent yellow solution. The mixture is stirred under nitrogen protection, propionyl chloride (0.78ml, 9mmol) is added into the flask in an ice-water bath. After fmishing addition of propionyl chloride the mixture is naturally raised to room temperature. The reacted mixture is filtered, the filtrate is evaporated to dryness and separated using a silica column to obtain 3-propionamido-4-methoxybenzoic acid 1.3g (yield: 67%).

at 0℃; for 0.5h;Alkaline conditions;

Propionyl chloride (1.1 eq) was added to a solution of [2840-26-8]3-amino-4-methoxybenzoic acid (1.0 eq) in dichloromethane or DMF at 0 C under basic conditions.For example, after stirring for 30 minutes under the catalysis of triethylamine or pyridine (1.5-2.0 eq),The reaction solution was allowed to warm to room temperature and the reaction was stirred.The reaction was stopped until TLC monitored the disappearance of [2840-26-8]3-amino-4-methoxybenzoic acid.After the reaction solution was diluted with a certain amount of ethyl acetate,Wash with saturated sodium bicarbonate solution and brine,Dry over anhydrous sodium sulfate,Filtered, concentrated,3-Propylamido-4-methoxybenzoic acid was obtained.

Reference： [1]European Journal of Medicinal Chemistry,2012,vol. 55,p. 117 - 124
[2]Patent: US2011/178108,2011,A1 .Location in patent: Page/Page column 14
[3]Patent: EP2351731,2011,A1 .Location in patent: Page/Page column 17
[4]Molecules,2013,vol. 18,p. 3630 - 3640
[5]Patent: CN109503518,2019,A .Location in patent: Paragraph 0366; 0369; 0370; 0371; 0372

67
[ 2840-26-8 ]
[ 1538-75-6 ]
[ 1030576-13-6 ]

Yield	Reaction Conditions	Operation in experiment
50%		Example 28: Synthesis of N-(3',4',5'-trimethoxyphenyl) 3-amino-4-methoxybenzamide (262). 1) 1.0g (6mmol) <strong>[2840-26-8]3-amino-4-methoxybenzoic acid</strong> is dissolved in 10ml 4N NaOH aqueous solution, 2.5ml (11mmol) tert-butyric anhydride is slowly dropped into the solution. The mixture is heated up to 50C until the reaction finishes and the resulted alkaline solution is quickly acidified to pH=2 using 1 N hydrochloric acid and extracted three times using chloroform. The chloroform extract is pooled and desiccated with anhydrate sodium sulfate, subsequently condensed to dryness to obtain 0.8g off-white solid, yield: 50%.

Reference： [1]Patent: EP2351731,2011,A1 .Location in patent: Page/Page column 21

68
[ 2840-26-8 ]
[ 1538-75-6 ]
C₂₂H₂₈N₂O₆ [ No CAS ]

Reference： [1]Patent: EP2351731,2011,A1

69
[ 2840-26-8 ]
C₁₆H₁₄Cl₂N₂O₃ [ No CAS ]