[ CAS No. 51628-12-7 ] {[proInfo.proName]}

Name: 51628-12-7|2-(4-Iodophenyl)acetonitrile|98%
Brand: Ambeed
SKU: A146276
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2D 3D

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Quality Control of [ 51628-12-7 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 51628-12-7 ]

SDS Specification

Alternatived Products of [ 51628-12-7 ]

Product Details of [ 51628-12-7 ]

CAS No. :	51628-12-7	MDL No. :	MFCD00060306
Formula :	C₈H₆IN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PNXWQTYSBFGIFD-UHFFFAOYSA-N
M.W :	243.04	Pubchem ID :	142866
Synonyms :

Calculated chemistry of [ 51628-12-7 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.12
Num. rotatable bonds :	1
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	48.68
TPSA :	23.79 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.39 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.87
Log Po/w (XLOGP3) :	1.96
Log Po/w (WLOGP) :	2.36
Log Po/w (MLOGP) :	2.67
Log Po/w (SILICOS-IT) :	3.1
Consensus Log Po/w :	2.39

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.96
Solubility :	0.267 mg/ml ; 0.0011 mol/l
Class :	Soluble
Log S (Ali) :	-2.08
Solubility :	2.0 mg/ml ; 0.00823 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.84
Solubility :	0.0348 mg/ml ; 0.000143 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.64

Safety of [ 51628-12-7 ]

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

Application In Synthesis of [ 51628-12-7 ]

* 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 [ 51628-12-7 ]
Downstream synthetic route of [ 51628-12-7 ]

[ 51628-12-7 ] Synthesis Path-Upstream 1~12

1
[ 16532-79-9 ]
[ 51628-12-7 ]

Reference： [1] Journal of the American Chemical Society, 2002, vol. 124, # 50, p. 14844 - 14845
[2] Journal of the American Chemical Society, 2015, vol. 137, # 26, p. 8328 - 8331

2
[ 624-31-7 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
68.9%	With N-Bromosuccinimide In tetrachloromethane; water; dimethyl sulfoxide	Referential Example 3 Synthesis of 4-iodophenylacetonitrile A mixture of 4.36 g (20.0 mmol) of p-iodotoluene (purchased from Tokyo Kasei), 3.92 g (22.0 mmol) of N-bromosuccinimide (purchased from Tokyo Kasei) and 60 ml of carbon tetrachloride (purchased from Wako Junyaku Kogyo) was refluxed under irradiation by an incandescent lamp for 4 hours to give 2.67 g (yield: 45.0percent) of 4-iodobenzyl bromide (as a white crystalline). Subsequently, to a solution of 0.49 g (10.0 mmol) of sodium cyanide (purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) heated at 50° C. was added 1.48 g (5.0 mmol) of the above 4-iodobenzyl bromide, the mixture was stirred at ambient temperature for 3 hours, the resultant reaction mass was dissolved in water and extracted with hexane, and hexane was removed to give 0.84 g (yield: 68.9percent) of 4-iodophenylacetonitrile as a white crystalline.
68.9%	With N-Bromosuccinimide In tetrachloromethane; water; dimethyl sulfoxide	Referential Example 9 Synthesis of 4-iodophenylacetonitrile A mixture of 4.36 g (20.0 mmol) of p-iodotoluene (purchased from Tokyo Kasei), 3.9 g (22 mmol) of N-bromosuccinimide (purchased from Tokyo Kasei) and 60 ml of carbon tetrachloride (purchased from Wako Junyaku Kogyo) was refluxed under the irradiation by means of an incandescent lamp for 4 hours to give 2.67 g (yield: 45.0percent) of 4-iodobenzyl bromide (as a white crystalline). Subsequently, to 0.49 g (10 mmol) of sodium cyanide (purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) solution heated at 50° C. was added 1.48 g (5.00 mmol) of the above 4-iodobenzyl bromide, the mixture was stirred at ambient temperature for 3 hours, the resultant reaction mass was dissolved in water and extracted with hexane, and hexane was removed to give 0.84 g (yield: 68.9percent) of 4-iodophenylacetonitrile as a white crystalline.

Reference： [1] Patent: US5574062, 1996, A,
[2] Patent: US5574062, 1996, A,
[3] Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126

3
[ 624-31-7 ]
[ 16004-15-2 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
45%	With N-Bromosuccinimide In tetrachloromethane; water; dimethyl sulfoxide	Referential Example 4 [Preparation of 4-Iodophenylacetonitrile] A mixture of p-iodotoluene (4.36 g, 20 mmol, purchased from Tokyo Kasei) and N-bromosuccinimide (3.92 g, 22 mmol, purchased from Tokyo Kasei) in 60 ml of carbontetrachloride (purchased from Wako Junyaku Kogyo) was refluxed for 4 hours under irradiation by means of an incandescent lamp to give 2.67 g (yield: 45.0percent) of 4-iodobenzyl bromide as a white crystalline. To a hot solution (50° C.) of sodium cyanide 0.49 g, 10.0 mmom, purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) was added the above 4-iodobenzyl bromide (1.48 g, 5.0 mmol) and the mixture was stirred for three hours at ambient temperature. To the resultant reaction mass was added water and extracted with hexane. The solvent was removed to give 0.84 g (yield: 69percent) of 4-iodophenylacetonitrile as a white crystalline.

Reference： [1] Patent: US5589506, 1996, A,
[2] Patent: US5589506, 1996, A,

4
[ 16004-15-2 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	for 1 h; Reflux	General procedure: To 8 mmol of the correspondingly substituted bromomethylbenzene in 40 ml of ethanol was added 2 ml of 6 M potassium cyanide solution. The reaction mixture was refluxed for 1 h. On cooling, the mixture was concentrated by rotary evaporation under vacuum to remove the ethanol. The residue was washed with deionized water and recrystallized from ethanol/water to give the product.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 15, p. 3341 - 3345
[2] European Journal of Medicinal Chemistry, 2013, vol. 65, p. 1 - 11
[3] Patent: WO2003/99276, 2003, A1, . Location in patent: Page 366-367

5
[ 5122-99-6 ]
[ 6011-14-9 ]
[ 51628-12-7 ]

Reference： [1] Angewandte Chemie - International Edition, 2014, vol. 53, # 39, p. 10510 - 10514[2] Angew. Chem., 2014, vol. 126, # 39, p. 10678 - 10682,5

6
[ 16004-15-2 ]
[ 151-50-8 ]
[ 51628-12-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 5, p. 1336 - 1343
[2] Chemische Berichte, 1878, vol. 11, p. 56

7
[ 773837-37-9 ]
[ 16004-15-2 ]
[ 51628-12-7 ]

Reference： [1] Journal of Organic Chemistry, 2017, vol. 82, # 2, p. 1114 - 1126

8
[ 54589-53-6 ]
[ 75-86-5 ]
[ 51628-12-7 ]

Reference： [1] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1957, p. 976,978; engl. Ausg. S. 1000, 1002

9
[ 555-21-5 ]
[ 51628-12-7 ]

Reference： [1] Roczniki Chemii, 1968, vol. 42, p. 1619 - 1629

10
[ 51628-12-7 ]
[ 1798-06-7 ]

Reference： [1] Chemische Berichte, 1878, vol. 11, p. 56

11
[ 75-91-2 ]
[ 51628-12-7 ]
[ 120363-13-5 ]

Reference： [1] RSC Advances, 2016, vol. 6, # 104, p. 102023 - 102027

12
[ 51628-12-7 ]
[ 630384-36-0 ]

Reference： [1] Patent: WO2013/25733, 2013, A1,

[ 51628-12-7 ] Synthesis Path-Downstream 1~87

1
[ 98-03-3 ]
[ 51628-12-7 ]
2-[4-iodo-phenyl]-3c(?)-[2]thienyl]-acrylonitrile [ No CAS ]

Reference： [1]Journal of the Chemical Society,1952,p. 4590,4593

2
[ 83322-23-0 ]
[ 51628-12-7 ]
3c(?)-(5-benzyl-[2]thienyl)-2-(4-iodo-phenyl)-acrylonitrile [ No CAS ]

Reference： [1]Journal of the Chemical Society,1952,p. 4590,4593

3
[ 7570-45-8 ]
[ 51628-12-7 ]
3c(?)-(9-ethyl-carbazol-3-yl)-2-(4-iodo-phenyl)-acrylonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,1951,vol. 16,p. 1327,1330

4
[ 51628-12-7 ]
[ 1798-06-7 ]

Reference： [1]Chemische Berichte,1878,vol. 11,p. 56

5
[ 51628-12-7 ]
[ 73918-57-7 ]

Yield	Reaction Conditions	Operation in experiment
	With borane; In tetrahydrofuran; for 1h;Heating / reflux;	Example 94 Synthesis of N-{2-[4-(3-(3-pyridyl)-4-methoxyphenyl)aminophenyl]ethyl}-(R)-2-hydroxy-2-(8-hydroxy-2(1H)-quinolinon-5-yl)ethylamine (94) Compound 94: Formula (XI) where R11 is 3-pyridyl a.Synthesis of 4-iodophenethylamine <strong>[51628-12-7]4-Iodophenylacetonitrile</strong> (4.80 g, 19.7 mmol) was dissolved in tetrahydrofuran (25 ML) under nitrogen, and 1.0 M borane in tetrahydrofuran (29.6 ML, 29.6 mmol) was added via syringe.The reaction was heated at reflux for 1 hour, then cooled in ice and the excess borane was quenched by the addition of methanol (100 ML).When hydrogen evolution ceased, the solvents were removed under reduced pressure.The residue was dissolved in tetrahydrofuran (25 ML) and 4N HCl in dioxane (6.0 ML, 24 mmol) was added, followed by ether (75 ML).The hydrochloride salt of 4-iodophenethylamine was collected on a Buchner funnel, washed with ether (250 ML) and dried under reduced pressure.To generate the free base, the solid was partitioned between dichloromethane (200 ML) and 1N NaOH (100 ML).The aqueous layer was extracted with dichloromethane (2100 ML).The combined organic layers were dried (Na2SO4) and concentrated to give 4-iodophenethylamine (4.52 g) as a colorless oil.

Reference： [1]Journal of Organic Chemistry,1958,vol. 23,p. 1979,1980
[2]Patent: US2003/229058,2003,A1 .Location in patent: Page 57
[3]Journal of Medicinal Chemistry,2009,vol. 52,p. 4613 - 4622

6
[ 16004-15-2 ]
[ 151-50-8 ]
[ 51628-12-7 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1336 - 1343
[2]Chemische Berichte,1878,vol. 11,p. 56

7
[ 555-21-5 ]
[ 51628-12-7 ]

Reference： [1]Roczniki Chemii,1968,vol. 42,p. 1619 - 1629

8
[ 51628-12-7 ]
[ 107-14-2 ]
[ 21455-95-8 ]

Reference： [1]Roczniki Chemii,1968,vol. 42,p. 1619 - 1629

9
[ 542-18-7 ]
[ 51628-12-7 ]
[ 76633-63-1 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

10
[ 51628-12-7 ]
[ 14275-61-7 ]
[ 117417-09-1 ]

Reference： [1]Tetrahedron Letters,1988,vol. 29,p. 2783 - 2786

11
[ 1003-29-8 ]
[ 51628-12-7 ]
2-(4-iodo-phenyl)-3-(1H-pyrrol-2-yl)-acrylonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 993 - 997

12
[ 51628-12-7 ]
2-(4-iodo-phenyl)-4-oxo-2-(2-oxo-ethyl)-butyronitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1336 - 1343
[2]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3273 - 3276

13
[ 51628-12-7 ]
[ 258500-82-2 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1336 - 1343
[2]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3273 - 3276

14
[ 51628-12-7 ]
[ 473735-58-9 ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1336 - 1343
[2]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3273 - 3276

15
[ 51628-12-7 ]
4-(4-iodophenyl)-1-methylpiperidine-4-carboxylic acid ethyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2005,vol. 48,p. 1336 - 1343
[2]Bioorganic and Medicinal Chemistry Letters,1999,vol. 9,p. 3273 - 3276

16
[ 51628-12-7 ]
[ 1026545-15-2 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

17
[ 51628-12-7 ]
[ 1026264-35-6 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

18
[ 51628-12-7 ]
{1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

19
[ 51628-12-7 ]
{2-hydroxy-1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethyl}-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

20
[ 51628-12-7 ]
C₁₆H₂₂IN₃O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

21
[ 51628-12-7 ]
C₁₆H₂₂IN₃O₅ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

22
[ 51628-12-7 ]
Phosphoric acid mono-[4-((S)-2-acetylamino-2-{(S)-1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl] ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

23
[ 51628-12-7 ]
Phosphoric acid mono-[4-((S)-2-acetylamino-2-{(S)-2-hydroxy-1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl] ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

24
[ 51628-12-7 ]
Phosphoric acid 4-((S)-2-acetylamino-2-{(S)-1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl ester dibenzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

25
[ 51628-12-7 ]
Phosphoric acid 4-((S)-2-acetylamino-2-{(S)-2-hydroxy-1-[3-(4-iodo-benzyl)-[1,2,4]oxadiazol-5-yl]-ethylcarbamoyl}-ethyl)-phenyl ester dibenzyl ester [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 4088 - 4098

26
[ 51628-12-7 ]
[ 76633-64-2 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

27
[ 51628-12-7 ]
[ 76619-01-7 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

28
[ 51628-12-7 ]
[ 76619-04-0 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

29
[ 51628-12-7 ]
[ 76619-02-8 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

30
[ 51628-12-7 ]
[ 76619-03-9 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

31
[ 51628-12-7 ]
[ 76618-79-6 ]

Reference： [1]Liebigs Annalen der Chemie,1980,p. 1637 - 1650

32
potassium cyanide [ No CAS ]
[ 16004-15-2 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
56%	In ethanol; for 1h;Reflux;	General procedure: To 8 mmol of the correspondingly substituted bromomethylbenzene in 40 ml of ethanol was added 2 ml of 6 M potassium cyanide solution. The reaction mixture was refluxed for 1 h. On cooling, the mixture was concentrated by rotary evaporation under vacuum to remove the ethanol. The residue was washed with deionized water and recrystallized from ethanol/water to give the product.
	In ethanol; for 24h;Heating / reflux;	Part A. To 4-iodobenzylbromide (25 g, 84 mmol) in boiling EtOH (100 mL) was added potassium cyanide (8.2 g, 126 mmol) through the condenser. The reaction was heated 24h, then <Desc/Clms Page number 367>cooled and EtOH removed. The aqueous layer was extracted with EtOAc and dried(Na2SO4) to afford crude 4- iodobenzylnitrile. The 4-iodobenzylnitrile was first treated with HC1 gas in MeOH to afford conversion to the ester. The mixture was concentrated in vacuo and treated with MeOH (4.7 mL) and chlorotrimethylsilane (10.7 mL) at50 C for 4h. The reaction was cooled and quenched withH20 (3.5 mL). Dichloromethane (150 mL) was added followed byNa2CO3 (8.9 g) and the mixture was stirred at room temperature forlh. The organics were separated and dried(Na2SO4), filtered, and concentrated to afford 21 g crude (4-iodo-phenyl) -acetic acid methyl ester. 1H NMR(CDC13) a 7.66 (d,J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 3.69 (s, 3H), 3.56 (s, 2H) ppm.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 3341 - 3345
[2]European Journal of Medicinal Chemistry,2013,vol. 65,p. 1 - 11
[3]Patent: WO2003/99276,2003,A1 .Location in patent: Page 366-367

33
[ 51628-12-7 ]
[ 925-90-6 ]
[ 630385-11-4 ]

Yield	Reaction Conditions	Operation in experiment
60%		Part A. <strong>[51628-12-7]4-Iodophenylacetonitrile</strong> (0.90 g, 3.70 mmol) was stirred in Et20 (7 mL) at rt underN2, Ti (O-iPr) 4 (1.20 ml, 1.1 eq) was added followed by dropwise addition of EtMgBr (2.0 M inEt2O, 2.5 mL, 2.0 eq) at rt. The reaction mixture was stirred at rt for 0.5 h.BF3*Et2O (0.94 ml, 2.0 eq) was added dropwise within 2 mins. The mixture was stirred at rt for 20 min. LC/MS showed one peak corresponding to the desired product. 1NNaOH (ca. 3 mL) <Desc/Clms Page number 427>was added. It was extracted with Et20 (2 x), washed with H2O, dried overMgSO4, filtered, and concentrated to dryness to give1- (4-iodo-benzyl)-cyclopropylamine (0.60 g, yield:60%). LC/MS (ESI+) 274.2 (M+H), tR=1. 61 min(10-90%CH3CN inH20 in a 4-min run).

Reference： [1]Patent: WO2003/99276,2003,A1 .Location in patent: Page 426-427

34
[ 51628-12-7 ]
[ 25015-63-8 ]
[ 138500-86-4 ]

Yield	Reaction Conditions	Operation in experiment
96.2%	With triethylamine;(1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; In acetonitrile; for 3h;Heating / reflux;	EXAMPLE 26 Preparation of 2-{4-[4-(1-Methyl-2-[(methylethyl)sulfonyl]amino}ethoxy)phenyl]phenyl}ethanenitrile. Preparation of 4-(cyanomethyl-phenylboronic acid, pinacol ester. Using the method of Murata, M., et al., Y. J. Org. Chem, 62 6458-6459 (1997), 4-iodophenylacetonitrile (23.9 g, 0.100 mol), Et3N (42 ML, 0.30 mol), acetonitrile (400 ML) and Pd(dppf)2Cl2 catalyst ([1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with CH2Cl2) were combined in a 1 L flask and the resulting solution was evacuated and purged with nitrogen three times.The pinacolborane (22 ML, 0.15 mol) was added and the mixture was heated at reflux for 3 h. 1H NMR analysis of an aliquot indicated complete consumption of starting 4-iodophenylacetonitrile.The mixture was cooled to room temperature, concentrated to an oil and taken up in CH2Cl2.This solution was extracted with 0.1 N HCl (3*100 ML) and the organic phase was separated, concentrated and re-dissolved in methyl tert-butyl ether (MTBE).The MTBE solution was passed through a filter packed with silica gel (300 g).The eluant was concentrated to a dark red oil.This oil was extracted with hexanes (500 ML) and the soluble fraction was decanted away from a black oil (5 g). MTBE (5 ML) was added to this oil to give a suspension that was filtered through Celite.This filtrated was combined with the hexanes fraction and the solution was concentrated to an oil.Finally, the oil was re-dissolved in di-isopropyl ether (150 ML) and was diluted with hexanes (400 ML).This mixture was allowed to stand for 2 h, and then filtered to remove a dark precipitate.The resulting amber filtrate was concentrated to an oil, re-dissolved in hexanes (400 ML) and concentrated to 75 ML without added heat.This treatment resulted in the precipitation of the desired intermediate title compound as a golden waxy solid that was air-dried to afford 23.0 g (96.2%): 1H NMR (CDCl3, 300 MHz): delta7.8 (d, 2H); 7.35 (d, 2H); 3.8 (s, 2 H) 1.15 (s, 12H).

Reference： [1]Patent: US2003/225266,2003,A1 .Location in patent: Page 23

35
[ 51628-12-7 ]
[ 118753-70-1 ]
[ 473736-90-2 ]

Yield	Reaction Conditions	Operation in experiment
	With NaNH2; In dimethyl sulfoxide;	To a solution of <strong>[51628-12-7]4-iodophenylacetonitrile</strong> (6.88 g, 28.3 mmol, 1 eq.) and bis-(2-chloro-ethyl)-carbamic acid tert-butyl ester (7.2 g, 30 mmol, 1.05 eq.) in DMSO (100 mL) under argon (Ar) was added NaNH2 (2.46 g, 60 mmol, 2 eq.) in portions over 15 min. The reaction was stirred at room temperature for 0.5 h, then poured onto ice (200 g), diluted with EtOAc (250 mL) and stirred for 1 h. The organic layer was separated and the aqueous layer was washed repeatedly with EtOAc until colorless. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to afford an orange oil which was purified by flash column chromatography by eluding with 7-12% EtOAc/hexanes to yield 4-cyano-4-(4-iodo-phenyl)-piperidine-1-carboxylic acid tert-butyl ester as a pale orange oil/solid (8.28 g, 18.96 mmol, 67%). 1H NMR (300 MHz, CDCl3): delta 7.82 (dd, 2H), 7.26 (dd, 2H), 4.38 (br. s, 2H), 4.28 (br. t, 2H), 2.15 (m, 2H), 2.0 (td, 2H), 1.59 (s, 9H).

Reference： [1]Patent: US2003/13720,2003,A1

36
4-bromo-2-bromomethyl-thiophene [ No CAS ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
37.0%		Thus obtained 5.12 g of 2-bromomethyl-4-bromothiophene was reacted with sodium cyanide according to the same procedure as in the synthesis of 4-iodophenylacetonitrile of example 5 to give 1.50 g (yield: 37.0%) of 4-bromothiophen-2-ylacetonitrile as a white crystal, removing by-product of alpha,alpha-bis[(4-bromothiophen-2-yl)methyl]-4-bromothiopheneaetonitrile by means of recrystalization.
37.0%		Thus obtained 5.12 g of 2-bromomethyl-4-bromothiophene was reacted with sodium cyanide according to the same procedure as in the synthesis of 4-iodophenylacetonitrile of example 5 to give 1.50 g (yield: 37.0%)of 4-bromothiophen-2-ylacetonitrile as a white crystal, removing by-product of alpha,alpha-bis[(4-bromothiophen-2-yl)methyl]-4-bromothiopheneaetonitrile by means of recrystalization.

Reference： [1]Patent: US5589506,1996,A
[2]Patent: US5589506,1996,A

37
[ 51628-12-7 ]
[ 4460-86-0 ]
α-cyano-4-iodo-2',4',5'-trimethoxystilbene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74.4%		EXAMPLE 10 alpha-cyano-4-iodo-2',4',5'-trimethoxystilbene was obtained in the same method as in Referential Example 1 except that 392 mg (2.0 mmol) of 2,4,5-trimethoxybenzaldehyde (purchased from Lancaster) and 486 mg (2.0 mmol) of <strong>[51628-12-7]4-iodophenylacetonitrile</strong> instead of 4-bromophenylacetonitrile were used. <strong>[51628-12-7]4-iodophenylacetonitrile</strong> was obtained in the same method described in Referential Example 3. And 566 mg (yield: 74.4%) of the compound as a yellow crystalline represented by the following formula was obtained in the same method as in Example 1 except that 421 mg (1.0 mmol) of the above alpha-cyano-4-iodo-2',4',5'-trimethoxystilbene was used instead of alpha-cyano-4-bromo-2',4',5'-trimethoxystilbene: STR133 melting point of the obtained compound was 273-276 C.

Reference： [1]Patent: US5574062,1996,A

38
[ 624-31-7 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
68.9%	With N-Bromosuccinimide; In tetrachloromethane; water; dimethyl sulfoxide;	Referential Example 3 Synthesis of 4-iodophenylacetonitrile A mixture of 4.36 g (20.0 mmol) of p-iodotoluene (purchased from Tokyo Kasei), 3.92 g (22.0 mmol) of N-bromosuccinimide (purchased from Tokyo Kasei) and 60 ml of carbon tetrachloride (purchased from Wako Junyaku Kogyo) was refluxed under irradiation by an incandescent lamp for 4 hours to give 2.67 g (yield: 45.0%) of 4-iodobenzyl bromide (as a white crystalline). Subsequently, to a solution of 0.49 g (10.0 mmol) of sodium cyanide (purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) heated at 50 C. was added 1.48 g (5.0 mmol) of the above 4-iodobenzyl bromide, the mixture was stirred at ambient temperature for 3 hours, the resultant reaction mass was dissolved in water and extracted with hexane, and hexane was removed to give 0.84 g (yield: 68.9%) of 4-iodophenylacetonitrile as a white crystalline.
68.9%	With N-Bromosuccinimide; In tetrachloromethane; water; dimethyl sulfoxide;	Referential Example 9 Synthesis of 4-iodophenylacetonitrile A mixture of 4.36 g (20.0 mmol) of p-iodotoluene (purchased from Tokyo Kasei), 3.9 g (22 mmol) of N-bromosuccinimide (purchased from Tokyo Kasei) and 60 ml of carbon tetrachloride (purchased from Wako Junyaku Kogyo) was refluxed under the irradiation by means of an incandescent lamp for 4 hours to give 2.67 g (yield: 45.0%) of 4-iodobenzyl bromide (as a white crystalline). Subsequently, to 0.49 g (10 mmol) of sodium cyanide (purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) solution heated at 50 C. was added 1.48 g (5.00 mmol) of the above 4-iodobenzyl bromide, the mixture was stirred at ambient temperature for 3 hours, the resultant reaction mass was dissolved in water and extracted with hexane, and hexane was removed to give 0.84 g (yield: 68.9%) of 4-iodophenylacetonitrile as a white crystalline.

Reference： [1]Patent: US5574062,1996,A
[2]Patent: US5574062,1996,A
[3]Journal of Organic Chemistry,2017,vol. 82,p. 1114 - 1126

39
[ 624-31-7 ]
[ 16004-15-2 ]
[ 51628-12-7 ]

Yield	Reaction Conditions	Operation in experiment
45.0%	In tetrachloromethane; water; dimethyl sulfoxide;	[synthesis of 4-Iodophenylacetonitrile] A mixture of p-iodotoluene (4.36 g, 20 mmol, purchased from Toko Kasei) and N-bromoeuccinimide (3.92 g, 2 mmol, purchased from Tokyo Kasei) in 60 ml of carbontetrachloride (purchased from Wako Junyaku Kogyo) was refluxed for 4 hours under irradiation by means of an incandescent lamp to give 2.67 g (yield: 45.0%) of 4-iodobenzyl bromide as a white crystalline. To a hot solution (50 C.) of sodium cyanide 0.49 g, 10.0 mmom, purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) was added the above 4-iodobenzyl bromide (1.48 g, 5.0 mmol) and the mixture was stirred for three hours at ambient temperature. To the resultant reaction mass was added water and extracted with hexane. The solvent was removed to give 0.84 g (yield: 68.9%) of 4-iodophenylacetonitrile as a white crystalline.
45.0%	With N-Bromosuccinimide; In tetrachloromethane; water; dimethyl sulfoxide;	Referential Example 4 [Preparation of 4-Iodophenylacetonitrile] A mixture of p-iodotoluene (4.36 g, 20 mmol, purchased from Tokyo Kasei) and N-bromosuccinimide (3.92 g, 22 mmol, purchased from Tokyo Kasei) in 60 ml of carbontetrachloride (purchased from Wako Junyaku Kogyo) was refluxed for 4 hours under irradiation by means of an incandescent lamp to give 2.67 g (yield: 45.0%) of 4-iodobenzyl bromide as a white crystalline. To a hot solution (50 C.) of sodium cyanide 0.49 g, 10.0 mmom, purchased from Kokusan Kagaku) in 10 ml of dimethyl sulfoxide (purchased from Aldrich) was added the above 4-iodobenzyl bromide (1.48 g, 5.0 mmol) and the mixture was stirred for three hours at ambient temperature. To the resultant reaction mass was added water and extracted with hexane. The solvent was removed to give 0.84 g (yield: 69%) of 4-iodophenylacetonitrile as a white crystalline.

Reference： [1]Patent: US5589506,1996,A
[2]Patent: US5589506,1996,A

40
[ 51628-12-7 ]
[ 1196879-28-3 ]

Reference： [1]Synlett,2009,p. 2338 - 2340

41
[ 51628-12-7 ]
[ 27373-99-5 ]
[ 1187627-98-0 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; copper(l) iodide; N,N`-dimethylethylenediamine; In water; toluene; at 100℃; for 21h;Inert atmosphere;	B. Coupling of (1R,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide with 4-(cyanomethyl)phenyl iodide. A 250 mL 3-neck flask was fitted with a condenser and a nitrogen inlet was charged with 10.00 g (0.0546 mol) of (lR,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide, 0.522 g (0.0027 mol) copper (I) iodide, 13.26 g (0.0546 mol) of 4-(cyanomethyl)phenyl iodide, 23.18 g (0.109 mol) of potassium phosphate. The system was purged with nitrogen and a magnetic stir bar was added. After the addition of 170 mL of toluene, 3.42g (0.190 mol) of water and 0.964 g (0.0109 mol) of N,N'-dimethylethylene diamine, the mixture was heated to 1000C and stirred for 21 h under nitrogen. The crude reaction mixture was filtered through 50 g of silica gel (wet with 1: 1 ethyl acetate / methylene chloride), and the bed was rinsed three times with 1:1 ethyl acetate / methylene chloride (150 + 75 + 75 mL). Concentration of the mixture in vacuo provided N-[4- (cyanomethyl)phenyl]-(lR,2S,5R)-2-isopropyl-5-methylcyclohexanecarboxamide as a thick oil oil which was further purified by flash chromatography on silica gel eluting with mixtures of ethyl acetate and hexanes. The product has the following properties with the structure confirmed by obtaining an X-ray crystal structure of a sample crystallized from hexane/ethyl acetate. 1H NMR (500 MHz, CDCl3): delta 0.82 (d, 3H), 0.89 (d, 3H), 0.93 (d, 3H), 0.95-1.06 (m, 2H), 1.35 (m,lH), 1.38 (m, IH), 1.63 (t, IH), 1.71-1.83 (m, 3H), 1.91 (d, IH), 2.20 (td, IH), 3.72 (s, 2H), 7.23 (d, 2H), 7.51 (br s, IH), 7.56 (d, 2H).13C NMR (125 MHz, CDCl3): delta 16.54, 21.64, 22.55, 23.33, 24.10, 29.09, 32.52, 34.71, 39.63, 44.76, 50.90, 118.24, 120.68, 125.48, 128.74, 138.22, 174.86. MS (Ionspray): m/e 299 (MH+, 100%) Mp: 146.0-149.50C [Ct]27 5D -42.9 (0.0103 g/mL, CHCl3)

Reference： [1]Patent: WO2010/19730,2010,A1 .Location in patent: Page/Page column 31-32

42
[ 51628-12-7 ]
[ 925-90-6 ]
[ 1219497-52-5 ]

Yield	Reaction Conditions	Operation in experiment
		A solution of the nitrile (50.0 g, 206 mmol) in toluene (500 mL) was cooled to -25 0C, then Ti(O1Pr)4 (60.3 mL, 206 mmol) was added. A commercial (Aldrich) solution of EtMgBr (3.0 M, 137 mL, 411 mmol) was then added dropwise at a rate which maintained the internal temperature between -20 and -25 0C (over approximately 60 minutes). The mixture was stirred for 60 minutes at this temperature, then the BF3OEt2 (52.1 mL, 411 mmol) was added dropwise maintaining a constant internal temperature (over approximately 30 minutes). After stirring the resulting solution for 60 minutes, the mixture was poured into 750 mL 3 N HCl(aq) and stirred rapidly for 30 minutes while warming to room temperature. The mixture was then transferred to a separatory funnel, and allowed to settle for 30 minutes. The thick yellow oil which separated on the bottom was carefully removed, then dissolved in CH2Cl2 (1 L), dried (Na2SO4) and concentrated in vacuo to provide 24 g of the amine salt (RE2a) of sufficient purity (approximately 80%) to be used directly.

Reference： [1]Patent: WO2010/34110,2010,A1 .Location in patent: Page/Page column 27; 34-35; 51-52; 60

43
[ 51628-12-7 ]
C₃₈H₅₀N₃O₈Pol [ No CAS ]
C₄₆H₅₅N₄O₈Pol [ No CAS ]

Reference： [1]Chemistry - A European Journal,2010,vol. 16,p. 2692 - 2695

44
[ 51628-12-7 ]
[ 51608-60-7 ]
[ 1354637-94-7 ]
(2RS,3RS)-3-(4-methylbenzenesulfonyl)amino-2-(4-iodophenyl)-3-phenylpropionitrile [ No CAS ]

Reference： [1]Advanced Synthesis and Catalysis,2011,vol. 353,p. 3385 - 3390

45
[ 51628-12-7 ]
tetramethylammonium trifluoromethanethiolate [ No CAS ]
[ 70124-90-2 ]

Reference： [1]Journal of the American Chemical Society,2012,vol. 134,p. 183 - 185

46
[ 201230-82-2 ]
[ 51628-12-7 ]
[ 100-44-7 ]
[ 170688-50-3 ]

Reference： [1]Chemistry - An Asian Journal,2012,vol. 7,p. 40 - 44

47
[ 51628-12-7 ]
[ 111-44-4 ]
[ 1257107-36-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dimethyl sulfoxide; ethyl acetate; Petroleum ether;	Preparation 10 4-(4-Iodophenyl)-tetrahydropyrane-4-carbonitrile. To a solution of (4-iodophenyl)-acetonitrile (2.43 g, 10.0 mmol) in DMSO (50 ml) was added sodium hydride (60% in oil, 1.2 g, 30 mmol) at room temperature. After stirring for 30 min., bis-2-chloroethyl ether (1.57 g, 11 mmol) was added. After stirring for a further 1 hr. at room temperature, the solution was poured into brine/water (1:1) and extracted twice with diethyl ether. The combined organic phases were dried over magnesium sulphate and concentrated in vacuo. The residue was purified by chromatography (15% ethyl acetate in petroleum ether), giving the title compound as a solid.

Reference： [1]Patent: US2012/101039,2012,A1

48
[ 51628-12-7 ]
(R)-4-(4-[3-(1-naphthalen-1-yl-ethylamino)-prop-1-ynyl]-phenyl)-tetrahydropyrane-4-carbonitrile [ No CAS ]

Reference： [1]Patent: US2012/101039,2012,A1

49
[ 51628-12-7 ]
(R)-4-(4-[3-(1-naphthalen-1-yl-ethylamino)-propyl]-phenyl)-tetrahydropyrane-4-carbonitrile [ No CAS ]

Reference： [1]Patent: US2012/101039,2012,A1

50
[ 51628-12-7 ]
[ 1401660-92-1 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

51
[ 51628-12-7 ]
[ 1401660-93-2 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

52
[ 51628-12-7 ]
[ 1401660-94-3 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

53
[ 51628-12-7 ]
[ 1401660-95-4 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

54
[ 51628-12-7 ]
[ 1401660-88-5 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

55
[ 51628-12-7 ]
[ 1401660-89-6 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

56
[ 51628-12-7 ]
[ 1401660-90-9 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143
[2]European Journal of Inorganic Chemistry,2016,vol. 2016,p. 545 - 553

57
[ 51628-12-7 ]
[ 1401660-91-0 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143
[2]European Journal of Inorganic Chemistry,2016,vol. 2016,p. 545 - 553
[3]ChemBioChem,2019,vol. 20,p. 2255 - 2261

58
[ 51628-12-7 ]
[ 17754-90-4 ]
[ 1401660-96-5 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143

59
[ 673-22-3 ]
[ 51628-12-7 ]
[ 1401660-97-6 ]

Reference： [1]Chemical Communications,2012,vol. 48,p. 10141 - 10143
[2]European Journal of Inorganic Chemistry,2016,vol. 2016,p. 545 - 553
[3]ChemBioChem,2019,vol. 20,p. 2255 - 2261

60
[ 51628-12-7 ]
[ 60656-87-3 ]
[ 1774-47-6 ]
(1R,2S)-2-(benzyloxymethyl)-1-(4-iodophenyl)cyclopropanecarbonitrile [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2013,vol. 78,p. 780 - 785

61
[ 51628-12-7 ]
[ 124276-89-7 ]

Reference： [1]Patent: WO2013/25733,2013,A1

62
[ 51628-12-7 ]
[ 630384-36-0 ]

Reference： [1]Patent: WO2013/25733,2013,A1

63
[ 51628-12-7 ]
[ 1423702-76-4 ]

Reference： [1]Patent: WO2013/25733,2013,A1

64
[ 51628-12-7 ]
[ 1423702-79-7 ]

Reference： [1]Patent: WO2013/25733,2013,A1

65
[ 51628-12-7 ]
[ 107-04-0 ]
1-(4-iodophenyl)cyclopropanecarbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With N-benzyl-N,N,N-triethylammonium chloride; sodium hydroxide; at 60℃;	A solution of NaOH (50%, 8 ml) was added dropwise to a mixture of compound LII-1 (2 g, 8.23 mmol), l-bromo-2-chloroethane (2.37 g, 16.5 mmol) and benzyl- triethylammonium chloride (0.094 g, 0.41 mmol) at room temperature. The reaction mixture was stirred and heated to 60 C overnight. Reaction was monitored by TLC. The reaction mixture was quenched with water and extracted with CH2CI2. The organic layer was washed two times with dilute hydrochloric acid, dried over Na2S04 and concentrated. The residue was purified by column chromatography (PE: EA = 50: 1-20: 1) to give compound LII-2 (1.35 g, yield: 61%).

Reference： [1]Patent: WO2013/25733,2013,A1 .Location in patent: Paragraph 0607

66
[ 51628-12-7 ]
[ 1427086-37-0 ]

Reference： [1]Patent: WO2013/36869,2013,A2

67
[ 51628-12-7 ]
[ 1427087-08-8 ]

Reference： [1]Patent: WO2013/36869,2013,A2

68
[ 51628-12-7 ]
[ 1427087-09-9 ]

Reference： [1]Patent: WO2013/36869,2013,A2

69
[ 51628-12-7 ]
[ 1427085-62-8 ]

Reference： [1]Patent: WO2013/36869,2013,A2

70
[ 51628-12-7 ]
[ 1427087-10-2 ]

Reference： [1]Patent: WO2013/36869,2013,A2

71
[ 51628-12-7 ]
1-(4-(3-[¹⁸F]fluoropropyl)phenethyl)guanidine formic acid salt [ No CAS ]

Reference： [1]Patent: WO2013/36869,2013,A2

72
[ 51628-12-7 ]
[ 107-19-7 ]
[ 1427086-38-1 ]

Yield	Reaction Conditions	Operation in experiment
64.3%	With copper(l) iodide; diethylamine; triphenylphosphine; palladium dichloride; at 20℃; for 48h;	(4-Iodophenyl)acetonitrile (1.00 g, 4.12 mmol), PPh3 (11.0mg, 0.041 mmol) and propargyl alcohol (243 muL, 4.12 mmol) were dissolved in N,N-diethylamine (14.0 mL) then treated with 8.0mg Cul (0.041 mmol; 1.0 mol %) and 11.0mg PdCl2 (0.041 mmol; 1.0 mol %) at ambient temperature. After 48 h, all volatiles were removed in vacuo and the residue purified by chromatography on silica using a hexanes/EtOAc gradient from 0-100% EtOAc over 18 mm to afford the title compound as an orange solid (0.453 g, 2.65 mmol; 64.3%).

Reference： [1]Patent: WO2013/36869,2013,A2 .Location in patent: Page/Page column 243; 244

73
[ 51628-12-7 ]
[ 1443159-54-3 ]
[ 1443159-65-6 ]