[ CAS No. 1664-57-9 ] {[proInfo.proName]}

Name: 1664-57-9|3-(3-Nitrophenyl)propionic acid|98%
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Quality Control of [ 1664-57-9 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1664-57-9 ]

CAS No. :	1664-57-9	MDL No. :	MFCD01310835
Formula :	C₉H₉NO₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZOANOABZUNJOJT-UHFFFAOYSA-N
M.W :	195.17	Pubchem ID :	2760224
Synonyms :

Calculated chemistry of [ 1664-57-9 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	4
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	51.62
TPSA :	83.12 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.18 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.14
Log Po/w (XLOGP3) :	1.84
Log Po/w (WLOGP) :	1.61
Log Po/w (MLOGP) :	0.89
Log Po/w (SILICOS-IT) :	-0.25
Consensus Log Po/w :	1.05

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.26
Solubility :	1.07 mg/ml ; 0.00547 mol/l
Class :	Soluble
Log S (Ali) :	-3.21
Solubility :	0.121 mg/ml ; 0.000622 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-1.97
Solubility :	2.12 mg/ml ; 0.0108 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.67

Safety of [ 1664-57-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1664-57-9 ]

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

Upstream synthesis route of [ 1664-57-9 ]
Downstream synthetic route of [ 1664-57-9 ]

[ 1664-57-9 ] Synthesis Path-Upstream 1~14

1
[ 1664-57-9 ]
[ 58161-35-6 ]

Reference： [1] Patent: CN103370324, 2016, B,

2
[ 2033-24-1 ]
[ 99-61-6 ]
[ 1664-57-9 ]

Yield	Reaction Conditions	Operation in experiment
72%	With formic acid; triethylamine In N,N-dimethyl-formamideLarge scale	General procedure: NEt3 (56.6 g, 0.56 mol) was added dropwise to stirred formicacid (64.4 g, 1.4 mol) at 5 8C. To the resulting reagent were addedDMF (150 ml), Meldrum’s acid (57.6 g, 0.4 mol) and aldehyde 2a–c(60.4 g, 0.4 mol). The reaction mixture was heated at reflux for 4 h.The solvent was evaporated under vacuum.The residue was triturated with water (1000 ml) and acidifiedwith conc. aq HCl to pH = 2. The formed product was filtered off,dried on air, and crystallized from EtOAc (3a) or CCl4 (3b,c) toobtain the pure material.

Reference： [1] Journal of Fluorine Chemistry, 2015, vol. 171, p. 174 - 176
[2] Archiv der Pharmazie, 2011, vol. 344, # 12, p. 840 - 842

3
[ 555-68-0 ]
[ 1664-57-9 ]

Reference： [1] Journal of Medicinal Chemistry, 1995, vol. 38, # 4, p. 636 - 646

4
[ 555-68-0 ]
[ 1664-57-9 ]

Reference： [1] Journal of Medicinal Chemistry, 1989, vol. 32, # 9, p. 2104 - 2110

5
[ 7116-33-8 ]
[ 1664-57-9 ]

Yield	Reaction Conditions	Operation in experiment
18%	Stage #1: With water; sodium hydroxide In ethanolReflux Stage #2: With hydrogenchloride In water	To a solution of Intermediate 79 (48.76 g, 0.23 mol) in ethanol (50 mL) was added sodium hydroxide 2N (400 mL). The mixture was refluxed overnight. The crude reaction was cooled and the aqueous phase was treated with hydrochloric acid and extracted with ether. The solvent was removed under reduced pressure obtaining an oil, which was purified by column chromatography with silica gel, eluding with methylene chloride/methanol (98:2). The title compound was obtained as a solid (8.13 g, 18percent).

Reference： [1] Patent: EP2096105, 2009, A1, . Location in patent: Page/Page column 31

6
[ 13331-27-6 ]
[ 79-10-7 ]
[ 1664-57-9 ]

Reference： [1] Synlett, 2011, # 17, p. 2517 - 2520

7
[ 1772-65-2 ]
[ 1664-57-9 ]
[ 1504-76-3 ]

Reference： [1] Journal of the American Chemical Society, 1992, vol. 114, # 26, p. 10110 - 10112

8
[ 501-52-0 ]
[ 16642-79-8 ]
[ 1664-57-9 ]
[ 2001-32-3 ]

Reference： [1] Journal of Organic Chemistry, 1998, vol. 63, # 4, p. 952 - 958

9
[ 619-23-8 ]
[ 1664-57-9 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 1674

10
[ 54405-44-6 ]
[ 1664-57-9 ]

Reference： [1] Chemische Berichte, 1882, vol. 15, p. 846
[2] Chemische Berichte, 1882, vol. 15, p. 846

11
[ 7151-20-4 ]
[ 1664-57-9 ]

Reference： [1] Journal of the Chemical Society, 1929, p. 1674
[2] Journal of the Chemical Society, 1929, p. 1674

12
[ 501-52-0 ]
[ 16642-79-8 ]
[ 1664-57-9 ]
[ 2001-32-3 ]

Reference： [1] Journal of Organic Chemistry, 1998, vol. 63, # 4, p. 952 - 958

13
[ 1664-57-9 ]
[ 1664-54-6 ]

Reference： [1] Chemische Berichte, 1882, vol. 15, p. 846
[2] Patent: US2003/225125, 2003, A1, . Location in patent: Page 9

14
[ 1664-57-9 ]
[ 83304-13-6 ]

Yield	Reaction Conditions	Operation in experiment
59%	Stage #1: With sodium azide; sulfuric acid In chloroform at 50℃; for 4 h; Stage #2: With potassium carbonate In chloroform	To a solution of Intermediate 80 (7.75 g, 39.71 mmol) in sulphuric acid (19 mL) was added chloroform (10 mL). The mixture was stirred at 50°C and sodium azide (3.8 g, 58.45 mmol) was slowly added (addition time: 2 hours). The reaction was stirred at 50°C for 2 hours. The crude was poured into potassium carbonate (40 g) to neutralize the reaction, then water was added (30 mL) and the crude was extracted with ethyl acetate. The crude was purified by column chromatography with silica gel, eluding with methylene chloride/methanol (from 98:2 to 9:1) to give the title compound as an oil (3.92 g, 59percent).

Reference： [1] Patent: EP2096105, 2009, A1, . Location in patent: Page/Page column 31

[ 1664-57-9 ] Synthesis Path-Downstream 1~86

1
[ 1664-57-9 ]
[ 1664-54-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;10% palladium on activated carbon; In ethyl acetate; at 20℃;	A solution of 3-nitro dihydrocinnamic acid (500 mg) in ethyl acetate was treated with 10% Pd/C (500 mg). The resulting suspension was flushed with hydrogen and allowed to stir overnight at room temperature The reaction mixture was purged with argon and then filtered through celite. The filtrate was concentrated and the residue was recrystallized from toluene and ethyl acetate. 1H NMR (DMSO) 6.95 t (1H), 6.4 m (3 H), 2.7 t (2H), 2.45 t (2H)

Reference： [1]Chemische Berichte,1882,vol. 15,p. 846
[2]Patent: US2003/225125,2003,A1 .Location in patent: Page 9

2
[ 54405-44-6 ]
[ 1664-57-9 ]

Reference： [1]Chemische Berichte,1882,vol. 15,p. 846
[2]Chemische Berichte,1882,vol. 15,p. 846

3
[ 7151-20-4 ]
[ 1664-57-9 ]

Reference： [1]Journal of the Chemical Society,1929,p. 1674
[2]Journal of the Chemical Society,1929,p. 1674

4
[ 555-68-0 ]
[ 1664-57-9 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

5
[ 1664-57-9 ]
[ 19008-62-9 ]

Reference： [1]Recueil des Travaux Chimiques des Pays-Bas,1992,vol. 111,p. 22 - 28

6
[ 1664-57-9 ]
[ 63307-44-8 ]

Yield	Reaction Conditions	Operation in experiment
97%		Step A: 3-(3-Nitrophenyl)propan-1-ol 3-(3-Nitrophenyl)propanoic acid (3.0 g, 15 mmol) was dissolved in dry tetrahydrofuran (7.6 mL) in a flame-dried flask and cooled in an ice bath. A solution of borane in tetrahydrofuran (20 mL, 20 mmol, 1.0 M) was added dropwise over a period of 30 minutes. The reaction mixture was stirred for an additional 2 hours at rt, then quenched slowly with ice water, and followed by an addition of ether (40 mL). The ether layer was washed with water and saturated aqueous solution of NaHCO3 successively, dried, and concentrated to give the desired product as a yellow gel (2.7 g, 97%).
		(95-1) Synthesis of 3-(3-nitrophenyl)-1-propanol (compound 95-1) [Show Image] 3-(3-Nitrophenyl)propionic acid (1.00 g) was dissolved in tetrahydrofuran (20 ml), and a tetrahydrofuran-borane tetrahydrofuran solution (1 mol/l, 7.25 ml) was added dropwise to the mixture under ice-cooling. The mixture was stirred under ice-cooling for 30 min, and further at room temperature for 2.5 hr. Water was added to the reaction mixture, and 1 mol/l aqueous hydrochloric acid solution was added. The mixture was extracted with ethyl acetate, washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography to give the object product (220 mg) as a yellow oil. 1H-NMR(CDCl3) delta (ppm): 1.31(1H, t, J=5.0Hz), 1.90-1.97(2H, m), 2.85(2H, t, J=7.8Hz), 3.71(2H, q, J=6.1Hz), 7.46(1H, t, J=7.8Hz), 7.55(1H, d, J=7.5Hz), 8.05-8.08(2H, m).

Reference： [1]Patent: US2010/190804,2010,A1 .Location in patent: Page/Page column 73
[2]Journal of Medicinal Chemistry,1995,vol. 38,p. 636 - 646
[3]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110
[4]Patent: EP2168944,2010,A1 .Location in patent: Page/Page column 182

7
[ 1772-65-2 ]
[ 1664-57-9 ]
[ 1504-76-3 ]

Reference： [1]Journal of the American Chemical Society,1992,vol. 114,p. 10110 - 10112

8
[ 555-68-0 ]
[ 1664-57-9 ]

Reference： [1]Journal of Medicinal Chemistry,1995,vol. 38,p. 636 - 646

9
[ 501-52-0 ]
[ 16642-79-8 ]
[ 1664-57-9 ]
[ 2001-32-3 ]

Reference： [1]Journal of Organic Chemistry,1998,vol. 63,p. 952 - 958

10
[ 1664-57-9 ]
(2-amino-3-[1,2,4]triazol-1-yl-propyl)-phosphonic acid diethyl ester [ No CAS ]
{2-[3-(3-nitro-phenyl)-propionylamino]-3-[1,2,4]triazol-1-yl-propyl}-phosphonic acid diethyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2053 - 2058

12
[ 7647-01-0 ]
[ 1664-57-9 ]
tin [ No CAS ]
[ 1664-54-6 ]

Reference： [1]Chemische Berichte,1882,vol. 15,p. 846

13
[ 1664-57-9 ]
[ 100-46-9 ]
3-(3-amino-phenyl)-<i>N</i>-benzyl-propionamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 6531 - 6535

14
[ 1664-57-9 ]
[ 39515-51-0 ]
3-[3-(3-phenoxy-benzylamino)-phenyl]-propionic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1584 - 1589

15
[ 1664-57-9 ]
[ 3218-36-8 ]
3-{3-[(biphenyl-4-ylmethyl)-amino]-phenyl}-propionic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1584 - 1589

16
[ 1664-57-9 ]
{2-[3-(3-nitro-phenyl)-propionylamino]-3-[1,2,4]triazol-1-yl-propyl}-phosphonic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 2053 - 2058

17
[ 1664-57-9 ]
[ 1823-16-1 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

18
[ 1664-57-9 ]
[ 121269-70-3 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

19
[ 1664-57-9 ]
[ 121269-68-9 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

20
[ 1664-57-9 ]
[ 121269-69-0 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

21
[ 1664-57-9 ]
[ 121269-67-8 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

22
[ 1664-57-9 ]
[ 121269-63-4 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

23
[ 1664-57-9 ]
[ 121269-64-5 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

24
[ 1664-57-9 ]
[ 121269-74-7 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

25
[ 1664-57-9 ]
[ 121269-75-8 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

26
[ 1664-57-9 ]
[ 121269-78-1 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

27
[ 1664-57-9 ]
[ 121269-76-9 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

28
[ 1664-57-9 ]
[ 121269-66-7 ]

Reference： [1]Journal of Medicinal Chemistry,1989,vol. 32,p. 2104 - 2110

29
[ 619-23-8 ]
[ 1664-57-9 ]

Reference： [1]Journal of the Chemical Society,1929,p. 1674

30
[ 1664-57-9 ]
[ 600723-80-6 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; In toluene; at 110℃; for 1h;	3-Nitrophenyl-propionic acid (992 mg, 5.08 mmol) was suspended in toluene (10 mL). Thionyl chloride (1.82 mL, 25.0 mmol) was added dropwise and the resulting mixture was stirred at HO0C for 1 h. The reaction mixture was concentrated and the residue was dissolved in dry dichloromethane (15 mL). To this solution was added 4- <n="113"/>aminobenzonitrile (590mg, 5.2 mmol) and Hunig's base (1.85 niL, 10.0 mmol). The reaction mixture was stirred for 4h then diluted with ethyl acetate (150 rnL) and quenched with NH4Cl (150 rnL satd. aq.) The organic fraction was isolated and washed with brine (50 mL), dried with MgSO4 and concentrated. The residue was purified by flash chromatography using an ethyl acetate/hexane gradient to provide 1.273 g of JV-(4-cyano- phenyl)-3-(3-nitro-phenyl)-propionamide (85% yield). This intermediate (103 mg, 0.35 mmol) was dissolved in methanol (5 mL) under an atmosphere of argon, and sodium borohydride (26.3 mg, 0.7 mmol) and Pd/C (20 mg) were added. The resulting mixture was stirred at room temperature for 1 h, filtered through celite, and concentrated. The residue was suspended in NH4Cl (20 mL, saturated aqueous), and this mixture was extracted with ethyl acetate (2x20 mL). The combined organic fractions were washed with brine (20 mL), dried and concentrated to provide 3-(3-amino-phenyl)-JV-(4-cyano-phenyl)- propionamide (80 mg, 87% yield) which was used without further purification. This intermediate was converted to the title compound as described in example 20. MS, electrospray, 405 (M+H).

Reference： [1]Patent: WO2008/86047,2008,A1 .Location in patent: Page/Page column 111-112

31
[ 1664-57-9 ]
[ 83304-13-6 ]

Yield	Reaction Conditions	Operation in experiment
59%		To a solution of Intermediate 80 (7.75 g, 39.71 mmol) in sulphuric acid (19 mL) was added chloroform (10 mL). The mixture was stirred at 50C and sodium azide (3.8 g, 58.45 mmol) was slowly added (addition time: 2 hours). The reaction was stirred at 50C for 2 hours. The crude was poured into potassium carbonate (40 g) to neutralize the reaction, then water was added (30 mL) and the crude was extracted with ethyl acetate. The crude was purified by column chromatography with silica gel, eluding with methylene chloride/methanol (from 98:2 to 9:1) to give the title compound as an oil (3.92 g, 59%).

Reference： [1]Patent: EP2096105,2009,A1 .Location in patent: Page/Page column 31

32
[ 7116-33-8 ]
[ 1664-57-9 ]

Yield	Reaction Conditions	Operation in experiment
18%		To a solution of Intermediate 79 (48.76 g, 0.23 mol) in ethanol (50 mL) was added sodium hydroxide 2N (400 mL). The mixture was refluxed overnight. The crude reaction was cooled and the aqueous phase was treated with hydrochloric acid and extracted with ether. The solvent was removed under reduced pressure obtaining an oil, which was purified by column chromatography with silica gel, eluding with methylene chloride/methanol (98:2). The title compound was obtained as a solid (8.13 g, 18%).

Reference： [1]Patent: EP2096105,2009,A1 .Location in patent: Page/Page column 31

33
[ 109-01-3 ]
[ 1664-57-9 ]
[ 618446-02-9 ]

Yield	Reaction Conditions	Operation in experiment
45%		Synthesis of 22; To a solution of 21 (3.0 g, 15 mmol) and DIPEA (7.9 g, 62 mmol) in DMF (50 mL) was added HBTU (7.0 g, 18 mmol). The reaction mixture was stirred for 30 min and a solution of amine (2.7 g, 15 mmol) in DMF (10 mL) was added. After stirring at room temperature for 7 days, the reaction mixture was diluted in ethyl acetate (500 mL) and washed with satd. aq. NH4CI (250 mL), water (3 x 200 mL), and 5 wt % LiCI (200 mL).The organic layer was dried over sodium sulfate, filtered and concentrated to obtain 22 (1.9 g, 45%) as a brown oil: 1H NMR (500 MHz, DMSO-c/6) delta 8.13-8.12 (m, 1 H),8.06-8.04 (m, 1 H)1 7.73-7.72 (m, 1 H)1 7.59-7.55 (m, 1 H), 3.44-3.43 (m, 4H), 2.97-2.94 (m, 2H), 2.73-2.69 (m, 2H), 2.30-2.28 (m, 4H), 2.21 (s, 3H).

Reference： [1]Patent: WO2007/18941,2007,A2 .Location in patent: Page/Page column 92

34
[ 13331-27-6 ]
[ 79-10-7 ]
[ 1664-57-9 ]

Reference： [1]Synlett,2011,p. 2517 - 2520

35
[ 2033-24-1 ]
[ 99-61-6 ]
[ 1664-57-9 ]

Yield	Reaction Conditions	Operation in experiment
72%	With formic acid; triethylamine; In N,N-dimethyl-formamide;Large scale;	General procedure: NEt3 (56.6 g, 0.56 mol) was added dropwise to stirred formicacid (64.4 g, 1.4 mol) at 5 8C. To the resulting reagent were addedDMF (150 ml), Meldrum?s acid (57.6 g, 0.4 mol) and aldehyde 2a-c(60.4 g, 0.4 mol). The reaction mixture was heated at reflux for 4 h.The solvent was evaporated under vacuum.The residue was triturated with water (1000 ml) and acidifiedwith conc. aq HCl to pH = 2. The formed product was filtered off,dried on air, and crystallized from EtOAc (3a) or CCl4 (3b,c) toobtain the pure material.

Reference： [1]Journal of Fluorine Chemistry,2015,vol. 171,p. 174 - 176
[2]Archiv der Pharmazie,2011,vol. 344,p. 840 - 842

36
[ 64-17-5 ]
[ 1664-57-9 ]
[ 10039-64-2 ]

Reference： [1]Archiv der Pharmazie,2011,vol. 344,p. 840 - 842

37
[ 1664-57-9 ]
[ 1613694-70-4 ]
[ 1613694-75-9 ]

Reference： [1]Journal of the American Chemical Society,2014,vol. 136,p. 9308 - 9319

38
[ 1664-57-9 ]
3-(3,3,3-trifluoropropyl)aniline [ No CAS ]

Reference： [1]Journal of Fluorine Chemistry,2015,vol. 171,p. 174 - 176

39
[ 1664-57-9 ]
1-nitro-3-(3,3,3-trifluoropropyl)benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sulfur tetrafluoride; at 35℃; for 48h;	General procedure: Acid 3a-c (97.5 g, 0.5 mol) was placed in a 500-ml stainless steel autoclave which was then evacuated, cooled with liquid nitrogen and charged with SF4 (162 g, 1.5 mol). The autoclave was kept at RT for 4 days (3c) or at RT for 2 days and 2 days at 35 C (3a-b). The gaseous products were vented off, and the residue was dissolved in CH2Cl2, poured onto ice and triturated with conc. aq.NaHCO3 (200 ml). After 2 h the mixture was filtered, the organicphase was separated, dried over Na2SO4 and concentrated. The residue was subjected to vacuum distillation.

Reference： [1]Journal of Fluorine Chemistry,2015,vol. 171,p. 174 - 176
[2]Journal of Organic Chemistry,2019,vol. 84,p. 16105 - 16115

40
[ 1664-57-9 ]
[ 64-19-7 ]
[ 4080-83-5 ]

Yield	Reaction Conditions	Operation in experiment
	With iron; In ethanol; water;Heating;	Iron powder 100g is added to the ethanol-water (4:1) in solution, by adding 5 ml glacial acetic acid, until heated and stirred to bubble, then batch by adding 3-nitrobenzene ethyl propionate 100g (according to the technical personnel synthetic method of preparation), after the reaction, filtration, concentration

Reference： [1]Patent: CN103370324,2016,B .Location in patent: Paragraph 0198-0200

41
[ 1664-57-9 ]
[ 58161-35-6 ]

Reference： [1]Patent: CN103370324,2016,B

42
[ 1664-57-9 ]
5-acetamido-2,3-indan-1-ol [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

43
[ 1664-57-9 ]
N-(1-chloro-2,3-dihydro-1H-inden-5-yl)acetamide [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

44
[ 1664-57-9 ]
N-(1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden-5-yl)acetamide [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

45
[ 1664-57-9 ]
1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden-5-amine [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

46
[ 1664-57-9 ]
3-(imidazo[1,2-b]pyridazin-3-yl-ethynyl)-4-methyl-N-(1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-inden-5-yl)benzamide [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

47
[ 1664-57-9 ]
3-iodo-4-methyl-N-(1-(4-methyl piperazin-1-yl)-2,3-dihydro-1H-inden-5-yl) benzamide [ No CAS ]

Reference： [1]Patent: CN103370324,2016,B

48
[ 1664-57-9 ]
2-amino-4-(4-methylpiperazin-1-yl)benzamide [ No CAS ]
7-(4-methylpiperazin-1-yl)-2-(3-nitrophenylethyl)quinazolin-4(3H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93%		The 3-nitrophenyl propionic acid (796mg, 3mmol),HATU (1.37g, 3.6mmol), DIPEA (1.0mL, 6mmol) was stirred at room temperature for 1 hour,2-amino-4- (4-methyl-piperazin-1-yl) benzamide (703mg, 5mmol),At 50 C overnight,The reaction was quenched with water,Was added and extracted with dichloromethane,Dried over anhydrous sodium sulfate,After concentration dissolved in 20mL of ethanol,Was added after cooling to 0 10MNaOH solution (1.2mL),After stirring for 30 minutes at room temperature,PH was adjusted to neutral with concentrated hydrochloric acid,After ethanol was removed under reduced pressure,Extracted with dichloromethane,Dried over anhydrous sodium sulfate,After concentrating column chromatography to obtain a pale brown solid(1.1g, 93%).

Reference： [1]Patent: CN105503837,2016,A .Location in patent: Paragraph 0214; 0215; 0216

49
[ 1664-57-9 ]
[ 811-68-7 ]
(3-nitrophenethyl)(trifluoromethyl)sulfane [ No CAS ]

Reference： [1]RSC Advances,2017,vol. 7,p. 880 - 883

50
[ 1664-57-9 ]
Grushin’s reagent [ No CAS ]
1-nitro-3-(3,3,3-trifluoropropyl)benzene [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2017,vol. 139,p. 12430 - 12433

51
[ 1664-57-9 ]
C₂₅H₂₅BrCl₂FN₇O₄ [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

52
[ 1664-57-9 ]
[ 4252-25-9 ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

53
[ 1664-57-9 ]
3-(3-(bis(2-chloroethyl)amino)phenyl)-N-(2-((4-(N-(3-bromo-4-fluorophenyl)-N’-hydroxycarbamimidoyl)-1,2,5-oxadiazol-3-yl)amino)ethyl)propanamide [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

54
[ 1664-57-9 ]
C₁₅H₂₁Cl₂NO₂ [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

55
[ 1664-57-9 ]
C₁₅H₂₃NO₄ [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

56
[ 1664-57-9 ]
[ 10039-64-2 ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

57
[ 64-17-5 ]
[ 1664-57-9 ]
[ 7116-33-8 ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 30 - 36

58
[ 1664-57-9 ]
[ 618-40-6 ]
C₁₆H₁₇N₃O₃ [ No CAS ]

Reference： [1]Organic Letters,2019,vol. 21,p. 8501 - 8505

59
[ 67-56-1 ]
[ 1664-57-9 ]
[ 22768-05-4 ]

Yield	Reaction Conditions	Operation in experiment
	With thionyl chloride; at 60.0℃; for 2.0h;	To a solution of above product (1.0 eq) in MeOH (0.74 M) was added SOCb (2.0 eq) at RT. The resulting mixture was stirred at 60 C for 2 h. Then the mixture was cooled down to r.t, concentrated under reduced pressure. The residue was diluted withH20 (150 mL), and extracted with EtOAc (2x50 mL). The organic phase was washed with sat. aq NaHCOs (2x20 mL), dried over Na2S04, concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (eluent: petroleum ether/EtOAc 10:1) to give the title compound as a white solid.
	With hydrogenchloride; at 60.0℃; for 1.0h;	A mixture of intermediate 1 (5 g, 25.62 mmol, 1 eq) and HCl/MeOH (50 mL) was heated to 60 C, and the mixture was stirred at 60 C for 1 h. The reaction was monitored by LCMS and when omplete, the reaction mixture was concentrated in vacuo to yield intermediate 2 (5.3 g, crude) was obtained as a white solid. LCMS: m/z = 210.1 (M+H+), 1H-NMR: (400 MHz, DMSO-de) δ 8.10 (s, 1 H) 8.05 (dd, >8.13, 1.65 Hz, 1 H) 7.71 (d, >7.58 Hz, 1 H) 7.53 - 7.61 (m, 1 H) 3.57 s, 3 H) 2.94- 3.03 (m, 2 H) 2.66 - 2.75 (m, 2 H).
	With hydrogenchloride; at 60.0℃; for 1.0h;	A mixture of intermediate 1 (5 g, 25.62 mmol, 1 eq) and HCl/MeOH (50 mL) was heated to 60 C, and the mixture was stirred at 60 C for 1 h. The reaction was monitored by LCMS and when omplete, the reaction mixture was concentrated in vacuo to yield intermediate 2 (5.3 g, crude) was obtained as a white solid. LCMS: m/z = 210.1 (M+H+), 1H-NMR: (400 MHz, DMSO-de) δ 8.10 (s, 1 H) 8.05 (dd, >8.13, 1.65 Hz, 1 H) 7.71 (d, >7.58 Hz, 1 H) 7.53 - 7.61 (m, 1 H) 3.57 s, 3 H) 2.94- 3.03 (m, 2 H) 2.66 - 2.75 (m, 2 H).

Reference： [1]Patent: WO2020/139636,2020,A1 .Location in patent: Paragraph 00285-00286
[2]Patent: WO2021/257754,2021,A1 .Location in patent: Page/Page column 243
[3]Patent: WO2021/257754,2021,A1 .Location in patent: Page/Page column 243

60
[ 1664-57-9 ]
[ 35418-08-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: thionyl chloride / 2 h / 60 °C 2: palladium 10% on activated carbon; hydrogen / methanol / 16 h / 20 °C
	Multi-step reaction with 2 steps 1: hydrogenchloride / 1 h / 60 °C 2: ammonia hydrochloride; iron⁽⁰⁾ / water monomer; ethanol / 2 h / 90 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: NEXYS THERAPEUTICS - WO2020/139636, 2020, A1
[2]Current Patent Assignee: RIPKA AMY - WO2021/257754, 2021, A1

61
[ 1664-57-9 ]
[ 134306-94-8 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-(3-nitrophenyl)propanoic acid With HATU In dichloromethane at 20℃; for 0.5h; Stage #2: With ammonium chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 4h;	1 Step 1 : 3-(3-nitrophenyl)propanamide To a solution of 3-(3-nitrophenyl)propanoic acid (1.0 eq) in DCM (0.25 M) was added HATU (1.2 eq), the mixture was stirred at rt for 30 min, then NH4CI (1.5 eq) and DIEA (3.0 eq) were added. The mixture was stirred at rt for 4 h then quenched with H2O (50 mL). The aqueous was extracted with DCM (3 x 30 mL). The combined organic layer was dried over NazSCN, concentrated to give the title compound as a yellow oil, which was used directly for the next step without further purification. LC-MS {m/z): [M+l]+= 195.

Reference： [1]Current Patent Assignee: NEXYS THERAPEUTICS - WO2020/139636, 2020, A1 Location in patent: Paragraph 00289-00290

62
[ 1664-57-9 ]
β-(3-nitrophenyl)-propionitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: HATU / dichloromethane / 0.5 h / 20 °C 1.2: 4 h / 20 °C 2.1: 1,3,5-trichloro-2,4,6-triazine / N,N-dimethyl-formamide / 2 h / 20 °C