[ CAS No. 15898-47-2 ] {[proInfo.proName]}

Name: 15898-47-2|(Cyanomethyl)triphenylphosphonium bromide|95%
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SKU: A336705
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Quality Control of [ 15898-47-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 15898-47-2 ]

SDS Specification

Alternatived Products of [ 15898-47-2 ]

Product Details of [ 15898-47-2 ]

CAS No. :	15898-47-2	MDL No. :	MFCD00031671
Formula :	C₂₀H₁₇BrNP	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	QBGFELJINDMTMH-UHFFFAOYSA-M
M.W :	382.23	Pubchem ID :	11811037
Synonyms :

Calculated chemistry of [ 15898-47-2 ]

Physicochemical Properties

Num. heavy atoms :	23
Num. arom. heavy atoms :	18
Fraction Csp3 :	0.05
Num. rotatable bonds :	4
Num. H-bond acceptors :	1.0
Num. H-bond donors :	0.0
Molar Refractivity :	104.5
TPSA :	37.38 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.81 cm/s

Lipophilicity

Log Po/w (iLOGP) :	-1.34
Log Po/w (XLOGP3) :	5.38
Log Po/w (WLOGP) :	0.51
Log Po/w (MLOGP) :	4.81
Log Po/w (SILICOS-IT) :	4.6
Consensus Log Po/w :	2.79

Druglikeness

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

Water Solubility

Log S (ESOL) :	-5.91
Solubility :	0.000466 mg/ml ; 0.00000122 mol/l
Class :	Moderately soluble
Log S (Ali) :	-5.92
Solubility :	0.000461 mg/ml ; 0.00000121 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-8.02
Solubility :	0.00000362 mg/ml ; 0.0000000095 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	4.43

Safety of [ 15898-47-2 ]

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

Application In Synthesis of [ 15898-47-2 ]

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

Upstream synthesis route of [ 15898-47-2 ]
Downstream synthetic route of [ 15898-47-2 ]

[ 15898-47-2 ] Synthesis Path-Upstream 1~4

1
[ 15898-47-2 ]
[ 16640-68-9 ]

Reference： [1] Journal of the American Chemical Society, 2007, vol. 129, # 7, p. 1987 - 1995
[2] Journal of Organic Chemistry, 2014, vol. 79, # 3, p. 1386 - 1398
[3] Chemische Berichte, 1961, vol. 94, p. 578 - 584
[4] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1978, p. 786 - 793
[5] Organic Letters, 2011, vol. 13, # 10, p. 2586 - 2589
[6] Angewandte Chemie - International Edition, 2018, vol. 57, # 22, p. 6597 - 6600[7] Angew. Chem., 2018, vol. 130, p. 6707 - 6710,4

2
[ 872-53-7 ]
[ 15898-47-2 ]
[ 591769-05-0 ]

Yield	Reaction Conditions	Operation in experiment
26.2%	Stage #1: With n-butyllithium In tetrahydrofuran; hexane at 0℃; for 0.5 h; Inert atmosphere Stage #2: at 0 - 20℃; for 1 h; Inert atmosphere	Under nitrogen, a suspension of (cyanomethyl)triphenylphosphanium bromide (12 g, 31.49 mmol) in anhydrous THF (100 mL) was cooled to 0° C., a solution of 2.5 M n-BuLi in n-hexane (13 mL, 34.64 mmol) was added dropwise. The mixture was stirred at 0° C. for another 30 minutes, then cyclopentane-carbaldehyde (3.1 g, 31.49 mmol) was added, and the mixture was warmed to the room temperature and stirred for further 1 hour. The reaction was quenched with saturated aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate (100 mL×3). The organic layers were combined, washed with water (60 mL×3) and saturated brine (60 mL) in sequence, dried over anhydrous sodium sulfate. The mixture was filtrated, the filtrate was concentrated in vacuum, the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=10:1) to give colorless oil 3-b (1.0 g, yield: 26.2percent). LC-MS (ESI): m/z=122 [M+H]⁺.

Reference： [1] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0122; 0125; 0126

3
[ 398489-26-4 ]
[ 15898-47-2 ]
[ 1153949-11-1 ]

Yield	Reaction Conditions	Operation in experiment
37%	With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 1 h; Inert atmosphere	Under nitrogen, a suspension of (cyanomethyl)triphenylphosphanium bromide (13.4 g, 35.09 mmol) in anhydrous THF (100 mL) was cooled to 0° C., a solution of 2.5 M n-BuLi in n-hexane (15.5 mL, 38.59 mmol) was added dropwise. The mixture tert-butyl-3-oxoazetidine-1-carboxylate (6.0 g, 35.09 mmol) was added, and the mixture was warmed to room temperature and stirred for further 1 hour. The reaction was quenched with saturated aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate (150 mL×3). The organic layers were combined, washed with water (100 mL×3) and saturated brine (100 mL) in sequence, dried over anhydrous sodium sulfate. The resultant mixture was filtrated, the filtrate was concentrated in vacuum, and the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=5:1) to give a white solid 5-c (2.5 g, yield: 37percent). LC-MS (ESI): m/z=217 [M+Na]⁺.

Reference： [1] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0134; 0135

4
[ 6704-31-0 ]
[ 15898-47-2 ]
[ 1123787-67-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	at 20℃; for 16 h;	At room temperature, (cyanomethyl)triphenylphosphanium bromide (10.0 g, 33.2 mmol) and 3-oxetanone (1.2 g, 16.7 mmol) were dissolved in dichloromethane (100 mL), the mixture was stirred for 16 hours, then concentrated under reduced pressure. The residue was added into a component solvent (50 mL) of petroleum ether and ethyl acetate (10:1), and there was white solid precipitated. After filtration, the filtrate was concentrated under reduced pressure, the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=5:1) to give compound 20-b (1.0 g, yield: 63percent). (0205) ¹H-NMR (400 MHz, CDCl₃) δ: 5.39 (m, 2H), 5.30 (m, 2H), 5.25 (m, 1H) ppm

Reference： [1] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0203; 0204; 0205

[ 15898-47-2 ] Synthesis Path-Downstream 1~52

1
[ 15898-47-2 ]
[ 16640-68-9 ]

Reference： [1]Journal of the American Chemical Society,2007,vol. 129,p. 1987 - 1995
[2]Journal of Organic Chemistry,2014,vol. 79,p. 1386 - 1398
[3]Chemistry - A European Journal,2019,vol. 25,p. 2793 - 2802
[4]Chemische Berichte,1961,vol. 94,p. 578 - 584
[5]Journal of the Chemical Society. Perkin transactions II,1978,p. 786 - 793
[6]Organic Letters,2011,vol. 13,p. 2586 - 2589
[7]Angewandte Chemie - International Edition,2018,vol. 57,p. 6597 - 6600
Angew. Chem.,2018,vol. 130,p. 6707 - 6710,4

2
[ 603-35-0 ]
[ 590-17-0 ]
[ 15898-47-2 ]

Yield	Reaction Conditions	Operation in experiment
46%	In diethyl ether; for 17h;Heating / reflux;	[0343] To a solution of PPh3 (1.57 g, 5.99 mmol) in Et2O (30 mL) was added BrCH2CN (0.42 mL, 6.0 mmol). The reaction was stirred at reflux for 17 hours. The solvent was removed under reduced pressure, the residue was suction filtered from a small portion of ice-cold Et2O, and washed with a small amount of cold Et2O, giving the phosphonium salt as a white powder (1.05 g, 2.74 mmol, 46%). 1H NMR (CDCl3) delta 6.39 (d, 2H, J=15.3 Hz), 7.69-7.76 (m, 6H), 7.82-7.87 (m, 3H), 7.96-8.03 (m, 6H). [0344] Preparation of 3-(2H-pyrazol-3-yl)-acrylonitrile: [0345] To a suspension of the phosphonium salt (900 mg, 2.35 mmol) in THF (10 mL) under nitrogen was added NaH (60% in mineral oil, 99 mg, 2.5 mmol) in one portion. The suspension stirred at room temperature for 10 minutes, then pyrazole-3-carboxaldehyde (211 mg, 2.20 mmol) was added as a solid in one portion. The reaction was heated to reflux for 30 minutes, then cooled to room temperature and saturated aqueous NH4Cl (10 mL) was added. The mixture was extracted with CH2Cl2 (25 mL×3) and the combined organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica (EtOAc/hexane, 1:1) gave the alkene (white solid) as an approximately 1.5:1 mixture of the E:Z isomers (232 mg, 1.95 mmol, 89%). [0346] Data for E-isomer: 1H NMR (CDCl3) delta 5.92 (d, 1H, J=16.5 Hz), 6.54 (d, 1H, J=2.4 Hz), 7.43 (d, 1H, J=16.8 Hz), 7.60 (d, 1H, J=2.4 Hz). [0347] Data for Z-isomer: 1H NMR (CDCl3) delta 5.46 (d, 1H, J=12.0 Hz), 6.98 (d, 1H, J=2.4 Hz), 7.24 (d, 1H, J=12.3 Hz), 7.66 (d, 1H, J=2.4 Hz). [0348] Preparation of 3-(2H-pyrazol-3-yl)-propylamine: [0349] The alpha,beta-unsaturated nitrile (mixture of isomers, 250 mg, 2.10 mmol) was hydrogenated (45 psi) over Raney-nickel in MeOH saturated with NH3 (15 mL) for 15.5 hours. The mixture was suction filtered through Celite and washed with MeOH. The filtrate was concentrated under reduced pressure giving a brown oil. Purification by flash column chromatography on silica (CH2Cl2/MeOH/NH4OH, 5.6:1:0.07) gave the saturated primary amine as a yellow oil (197 mg, 1.57 mmol, 75%). 1H NMR (CDCl3) delta 1.82 (quint, 2H, J=7.1 Hz), 2.76 (apparent q, 4H, J=6.8 Hz), 4.46 (br. s, 3H), 6.07 (d, 1H, J=2.1 Hz), 7.47 (d, 1H, J=1.8 Hz). [0350] Preparation of [3-(2H-pyrazol-3-yl)-propyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine: [0351] A solution of the primary amine (190 mg, 1.52 mmol) and 8-oxo-5,6,7,8-tetrahydroquinoline (270 mg, 1.83 mmol) in MeOH (4 mL) was stirred at room temperature for 6 hours. NaBH4 (75 mg, 2.0 mmol) was added and the reaction was stirred for an additional 15 minutes, then the solvent was evaporated under reduced pressure. The residue was taken up into CH2Cl2 (20 mL) and was washed with saturated aqueous NaHCO3 (5 mL) and brine (5 mL). The organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica (CH2Cl2/MeOH/NH4OH, 19:1:0.1, then MeOH) gave the secondary amine as a yellow oil (100 mg, 0.39 mmol, 26%). 1H NMR (CDCl3) delta 1.67-1.87 (m, 12H), 1.90-2.03 (m, 3H), 2.11-2.23 (m, 1H), 2.67-2.89 (m, 6H), 3.84 (dd, 1H, J=7.7, 5.3 Hz), 6.03 (d, 1H, J=1.8 Hz), 7.09 (dd, 1H, J=7.7, 4.7 Hz), 7.39 (d, 1H, J=7.6 Hz), 7.41 (d, 1H, J=1.8 Hz), 8.42 (d, 1H, J=3.9 Hz). [0352] Preparation of 2-[[3-(2H-pyrazol-3-yl)-propyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic Acid Tert-Butyl Ester: [0353] A solution of the amine (100 mg, 0.39 mmol),tert-butyl 2-chloromethyl-benzimidazole-1-carboxylate (107 mg, 0.40 mmol), DIPEA (0.10 mL, 0.57 mmol) and KI (approx. 10 mg) in CH3CN (2.5 mL) was heated to 60 C. under nitrogen for 18.5 hours. Once cooled to room temperature, saturated aqueous NaHCO3 (10 mL) was added and the mixture was extracted with CH2Cl2 (15 mL×3). The combined organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Three attempts at purification by flash column chromatography on silica, the first eluted with CH2Cl2/MeOH/NH4OH, 19:1:0.1, the second eluted with CH2Cl2/MeOH/NH4OH, 49:1:0.25, gradually increased to 19:1:0.1, and the third eluted with CH2Cl2/MeOH/NH4OH, 49:1:0.25, gave the tertiary amine as a white foam (70.6 mg, 0.15 mmol, 37%1). 1H NMR (CDCl3) delta 1.64 (s, 9H), 1.64-1.80 (m, 2H), 1.90-2.12 (m, 3H), 2.19-2.33 (m, 1H), 2.41-2.51 (m, 1H), 2.60-2.86 (m, 4H), 3.06-3.15 (m, 1H), 3.23-3.37 (m, 1H), 4.04 (dd, 1H, J=10.4, 6.8 Hz), 4.19 (d, 1H, J=15.0 Hz), 4.53 (d, 1H, J=15.0 Hz), 6.00 (d, 1H, J=1.5 Hz), 6.72 (dd, 1H, J=7.5, 4.8 Hz), 6.89 (d, 1H, J=7.5 Hz), 7.14-7.29 (m, 2H), 7.45 (d, 1H, J=1.5 Hz), 7.63 (dd, 1H, J=7.9, 1.5 Hz), 7.73 (dd, 1H, J=7.9, 1.5 Hz), 8.35 (d, 1H, J=3.6 Hz). [0354] Preparation of COMPOUND 35: [0355] To a solution of the tertiary amine (30.8 mg, 0.063 mmol) in glacial HOAc (1.0 mL) was added a saturated solution of HBr in HOAc (0.5 mL). The mixture was stirred at room temperature for 1 hour, then was...
	In diethyl ether; at 20℃; for 24h;	To a solution of triphenylphosphine (32.8 g, 125.1 mmol) in Et2O (50 mL) was added 2-bromoacetonitrile (12.0 g, 100 mmol) at RT. The reaction mixture was stirred at RT for 24 hours. The precipitate was filtered from the solution. The solid was washed with Et2O (3 x 20 mL) and dried under vacuum to afford the title compound: LCMS [M - Br ]+: 302.

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 1339 - 1341
[2]Journal of Organic Chemistry,2014,vol. 79,p. 1386 - 1398
[3]Journal of the American Chemical Society,2007,vol. 129,p. 1987 - 1995
[4]European Journal of Organic Chemistry,2019,vol. 2019,p. 7870 - 7873
[5]Chemistry - A European Journal,2019,vol. 25,p. 2793 - 2802
[6]Patent: US2003/220341,2003,A1 .Location in patent: Page/Page column 33-34
[7]Chemische Berichte,1961,vol. 94,p. 578 - 584
[8]Organic Letters,2011,vol. 13,p. 2586 - 2589
[9]Organic Letters,2011,vol. 13,p. 3730 - 3733
[10]Angewandte Chemie - International Edition,2018,vol. 57,p. 6597 - 6600
Angew. Chem.,2018,vol. 130,p. 6707 - 6710,4
[11]Patent: WO2019/18186,2019,A1 .Location in patent: Page/Page column 47

3
[ 5271-67-0 ]
[ 15898-47-2 ]
[ 5068-04-2 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 1125 - 1127

4
[ 25054-53-9 ]
[ 15898-47-2 ]
[ 123796-93-0 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 1125 - 1127

5
[ 42926-52-3 ]
[ 15898-47-2 ]
[ 123825-39-8 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 1125 - 1127

6
[ 102-92-1 ]
[ 15898-47-2 ]
[ 123796-92-9 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 1125 - 1127

7
[ 2094-72-6 ]
[ 15898-47-2 ]
[ 123796-91-8 ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1988,vol. 27,p. 1125 - 1127

8
[ 15898-47-2 ]
[ 6006-24-2 ]
[ 100946-55-2 ]

Reference： [1]Journal of the American Chemical Society,1986,vol. 108,p. 2013 - 2019

9
[ 15898-47-2 ]
[ 100-52-7 ]
[ 4360-47-8 ]
Sodium; 3-(diphenyl-phosphinoyl)-propionate [ No CAS ]

Reference： [1]Tetrahedron Letters,1987,vol. 28,p. 1165 - 1168

10
[ 15898-47-2 ]
[ 75-07-0 ]
[ 1190-76-7 ]
[ 4786-20-3 ]

Reference： [1]Journal of the Chemical Society. Chemical communications,1989,p. 568 - 569
[2]Journal of the Chemical Society. Chemical communications,1989,p. 568 - 569
[3]Journal of the Chemical Society. Chemical communications,1989,p. 568 - 569

11
[ 6399-81-1 ]
[ 107-14-2 ]
[ 15898-47-2 ]

Reference： [1]Phosphorus and Sulfur and the Related Elements,1987,vol. 29,p. 111 - 114

12
[ 107-14-2 ]
[ 603-35-0 ]
[ 15898-47-2 ]

Reference： [1]Phosphorus and Sulfur and the Related Elements,1987,vol. 29,p. 111 - 114
[2]Journal of Organic Chemistry,1966,vol. 31,p. 3885 - 3890

13
[ 15898-47-2 ]
[ 407-25-0 ]
[ 81850-43-3 ]
[ 96102-02-2 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 5558 - 5562

14
[ 15898-47-2 ]
[ 3839-48-3 ]
[ 58299-12-0 ]

Reference： [1]Journal of Chemical Research, Miniprint,1998,p. 2363 - 2380

Yield	Reaction Conditions	Operation in experiment
		Preparation of (cyanomethyl)triphenylphosphonium Bromide: To a solution of PPh3 (1.57 g, 5.99 mmol) in Et2O (30 mL) was added BrCH2CN (0.42 mL, 6.0 mmol). The reaction was stirred at reflux for 17 hours. The solvent was removed under reduced pressure, the residue was suction filtered from a small portion of ice-cold Et2O, and washed with a small amount of cold Et2O, giving the phosphonium salt as a white powder (1.05 g, 2.74 mmol, 46%). 1H NMR (CDCl3) delta 6.39 (d, 2H, J=15.3 Hz), 7.69-7.76 (m, 6H), 7.82-7.87 (in, 3H), 7.96-8.03 (m, 6H).

17
[ 104-53-0 ]
[ 15898-47-2 ]
[ 5320-30-9 ]
[ 82125-05-1 ]

Reference： [1]Tetrahedron,2000,vol. 56,p. 7893 - 7902

18
[ 6318-51-0 ]
[ 15898-47-2 ]
[ 405551-69-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1959 - 1961

19
[ 444622-08-6 ]
[ 15898-47-2 ]
3-{2-isopropyl-3-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-3<i>H</i>-imidazol-4-yl}-acrylonitrile [ No CAS ]
3-{2-isopropyl-3-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-3<i>H</i>-imidazol-4-yl}-acrylonitrile [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 695 - 700

20
[ 15898-47-2 ]
[ 103-72-0 ]
[ 102-01-2 ]
2-anilino-5-cyano-4-methyl-N-phenyl-thiophene-3-carboxamide [ No CAS ]

Reference： [1]Phosphorus, Sulfur and Silicon and the Related Elements,2007,vol. 182,p. 551 - 562

21
(5-formyl-10,20-diphenylporphyrinato)nickel(II) [ No CAS ]
[ 15898-47-2 ]
(5-cyanoethenyl-10,20-diphenylporphyrinato)nickel(II) [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2007,p. 3833 - 3848

22
[ 15898-47-2 ]
[ 3920-50-1 ]
E-3-(2H-pyrazol-3-yl)-acrylonitrile [ No CAS ]
Z-3-(2H-pyrazol-3-yl)-acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[0343] To a solution of PPh3 (1.57 g, 5.99 mmol) in Et2O (30 mL) was added BrCH2CN (0.42 mL, 6.0 mmol). The reaction was stirred at reflux for 17 hours. The solvent was removed under reduced pressure, the residue was suction filtered from a small portion of ice-cold Et2O, and washed with a small amount of cold Et2O, giving the phosphonium salt as a white powder (1.05 g, 2.74 mmol, 46%). 1H NMR (CDCl3) delta 6.39 (d, 2H, J=15.3 Hz), 7.69-7.76 (m, 6H), 7.82-7.87 (m, 3H), 7.96-8.03 (m, 6H). [0344] Preparation of 3-(2H-pyrazol-3-yl)-acrylonitrile: [0345] To a suspension of the phosphonium salt (900 mg, 2.35 mmol) in THF (10 mL) under nitrogen was added NaH (60% in mineral oil, 99 mg, 2.5 mmol) in one portion. The suspension stirred at room temperature for 10 minutes, then pyrazole-3-carboxaldehyde (211 mg, 2.20 mmol) was added as a solid in one portion. The reaction was heated to reflux for 30 minutes, then cooled to room temperature and saturated aqueous NH4Cl (10 mL) was added. The mixture was extracted with CH2Cl2 (25 mL×3) and the combined organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica (EtOAc/hexane, 1:1) gave the alkene (white solid) as an approximately 1.5:1 mixture of the E:Z isomers (232 mg, 1.95 mmol, 89%). [0346] Data for E-isomer: 1H NMR (CDCl3) delta 5.92 (d, 1H, J=16.5 Hz), 6.54 (d, 1H, J=2.4 Hz), 7.43 (d, 1H, J=16.8 Hz), 7.60 (d, 1H, J=2.4 Hz). [0347] Data for Z-isomer: 1H NMR (CDCl3) delta 5.46 (d, 1H, J=12.0 Hz), 6.98 (d, 1H, J=2.4 Hz), 7.24 (d, 1H, J=12.3 Hz), 7.66 (d, 1H, J=2.4 Hz). [0348] Preparation of 3-(2H-pyrazol-3-yl)-propylamine: [0349] The alpha,beta-unsaturated nitrile (mixture of isomers, 250 mg, 2.10 mmol) was hydrogenated (45 psi) over Raney-nickel in MeOH saturated with NH3 (15 mL) for 15.5 hours. The mixture was suction filtered through Celite and washed with MeOH. The filtrate was concentrated under reduced pressure giving a brown oil. Purification by flash column chromatography on silica (CH2Cl2/MeOH/NH4OH, 5.6:1:0.07) gave the saturated primary amine as a yellow oil (197 mg, 1.57 mmol, 75%). 1H NMR (CDCl3) delta 1.82 (quint, 2H, J=7.1 Hz), 2.76 (apparent q, 4H, J=6.8 Hz), 4.46 (br. s, 3H), 6.07 (d, 1H, J=2.1 Hz), 7.47 (d, 1H, J=1.8 Hz). [0350] Preparation of [3-(2H-pyrazol-3-yl)-propyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine: [0351] A solution of the primary amine (190 mg, 1.52 mmol) and 8-oxo-5,6,7,8-tetrahydroquinoline (270 mg, 1.83 mmol) in MeOH (4 mL) was stirred at room temperature for 6 hours. NaBH4 (75 mg, 2.0 mmol) was added and the reaction was stirred for an additional 15 minutes, then the solvent was evaporated under reduced pressure. The residue was taken up into CH2Cl2 (20 mL) and was washed with saturated aqueous NaHCO3 (5 mL) and brine (5 mL). The organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica (CH2Cl2/MeOH/NH4OH, 19:1:0.1, then MeOH) gave the secondary amine as a yellow oil (100 mg, 0.39 mmol, 26%). 1H NMR (CDCl3) delta 1.67-1.87 (m, 12H), 1.90-2.03 (m, 3H), 2.11-2.23 (m, 1H), 2.67-2.89 (m, 6H), 3.84 (dd, 1H, J=7.7, 5.3 Hz), 6.03 (d, 1H, J=1.8 Hz), 7.09 (dd, 1H, J=7.7, 4.7 Hz), 7.39 (d, 1H, J=7.6 Hz), 7.41 (d, 1H, J=1.8 Hz), 8.42 (d, 1H, J=3.9 Hz). [0352] Preparation of 2-[[3-(2H-pyrazol-3-yl)-propyl]-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzimidazole-1-carboxylic Acid Tert-Butyl Ester: [0353] A solution of the amine (100 mg, 0.39 mmol),tert-butyl 2-chloromethyl-benzimidazole-1-carboxylate (107 mg, 0.40 mmol), DIPEA (0.10 mL, 0.57 mmol) and KI (approx. 10 mg) in CH3CN (2.5 mL) was heated to 60 C. under nitrogen for 18.5 hours. Once cooled to room temperature, saturated aqueous NaHCO3 (10 mL) was added and the mixture was extracted with CH2Cl2 (15 mL×3). The combined organic solution was dried (MgSO4), filtered and concentrated under reduced pressure. Three attempts at purification by flash column chromatography on silica, the first eluted with CH2Cl2/MeOH/NH4OH, 19:1:0.1, the second eluted with CH2Cl2/MeOH/NH4OH, 49:1:0.25, gradually increased to 19:1:0.1, and the third eluted with CH2Cl2/MeOH/NH4OH, 49:1:0.25, gave the tertiary amine as a white foam (70.6 mg, 0.15 mmol, 37%1). 1H NMR (CDCl3) delta 1.64 (s, 9H), 1.64-1.80 (m, 2H), 1.90-2.12 (m, 3H), 2.19-2.33 (m, 1H), 2.41-2.51 (m, 1H), 2.60-2.86 (m, 4H), 3.06-3.15 (m, 1H), 3.23-3.37 (m, 1H), 4.04 (dd, 1H, J=10.4, 6.8 Hz), 4.19 (d, 1H, J=15.0 Hz), 4.53 (d, 1H, J=15.0 Hz), 6.00 (d, 1H, J=1.5 Hz), 6.72 (dd, 1H, J=7.5, 4.8 Hz), 6.89 (d, 1H, J=7.5 Hz), 7.14-7.29 (m, 2H), 7.45 (d, 1H, J=1.5 Hz), 7.63 (dd, 1H, J=7.9, 1.5 Hz), 7.73 (dd, 1H, J=7.9, 1.5 Hz), 8.35 (d, 1H, J=3.6 Hz). [0354] Preparation of COMPOUND 35: [0355] To a solution of the tertiary amine (30.8 mg, 0.063 mmol) in glacial HOAc (1.0 mL) was added a saturated solution of HBr in HOAc (0.5 mL). The mixture was stirred at room temperature for 1 hour, then was...

Reference： [1]Patent: US2003/220341,2003,A1 .Location in patent: Page/Page column 33-34

23
[ 1092486-13-9 ]
[ 15898-47-2 ]
[ 1092486-88-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 6218 - 6221

24
[ 15898-47-2 ]
[ 123-11-5 ]
[ 30115-95-8 ]
[ 14482-11-2 ]

Reference： [1]Tetrahedron,2010,vol. 66,p. 4032 - 4039

25
[ 15898-47-2 ]
[ 1296203-18-3 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 2586 - 2589

26
[ 15898-47-2 ]
[ 57597-64-5 ]
[ 1312992-77-0 ]

Reference： [1]Organic Letters,2011,vol. 13,p. 3730 - 3733

27
[ 15898-47-2 ]
[ 137736-06-2 ]
[ 1380429-63-9 ]

Yield	Reaction Conditions	Operation in experiment
91%	With sodium hydroxide; In dichloromethane; water; at 0 - 20℃; for 4h;	D62: 3-(4-(4-fluorophenoxy)pTo a solution of <strong>[15898-47-2](cyanomethyl)triphenylphosphonium bromide</strong> ( 10.61 g, 27.8 mmol) and NaOH ( 1.387 g, 34.7 mmol) in water (30 mL) and DCM ( 15 mL) was added 4-(4- fluorophenoxy)benzaldehyde (5 g, 23.13 mmol) at 0 C. The mixture was stirred at room temperature for 4 h. DCM (50 mL) and water (50 mL) was added to the mixture, the organic phase was washed with water (50 mL), brine (50 mL), dried over anhydrous sodium sulfate and concentrated. Purification via flash chromatography afforded the title compound (5.1 g, 21.09 mmol, 91 % yield) as white solid. LCMS: rt = 1.60 min, [M+H+] = 240

Reference： [1]Patent: WO2012/76435,2012,A1 .Location in patent: Page/Page column 45

28
[ 15898-47-2 ]
[ 77771-02-9 ]
[ 1380429-23-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sodium hydroxide; In dichloromethane; water; at 0 - 20℃; for 2h;	D13: (£)-3-(3-Bromo-4-fluorophenTo a mixture of (cyanomethyl)triphenylphosphonium bromide (70.6 g, 185 mmol) and sodium hydroxide (7.39 g, 185 mmol) in DCM (100 mL) and water (300.00 mL) at 0C was added <strong>[77771-02-9]3-bromo-4-fluorobenzaldehyde</strong> (25.0 g, 123 mmol). It was allowed to warm to room temperature and stirred for 2 h. The organic layer was separated, and the water layer was extracted with DCM twice. The combined organic phases were dried over Na2S04 and concentrated to give a crude product, which was washed with diethyl ether. The residue was purified to give the title compound as a white solid (35 g, 88 % yield). LCMS: rt =1.50 min, [M+H+] =226

Reference： [1]Patent: WO2012/76435,2012,A1 .Location in patent: Page/Page column 30-31

29
[ 441354-26-3 ]
[ 15898-47-2 ]
[ 1380429-67-3 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hydroxide; In dichloromethane; water; at 0 - 20℃; for 4h;	D66: 3-(4-(3-(trifluoromethyTo a solution of <strong>[15898-47-2](cyanomethyl)triphenylphosphonium bromide</strong> (8.61 g, 22.54 mmol) and NaOH (1.127 g, 28.2 mmol) in water (24 mL) and DCM (12 mL) was added 4-(3-(trifluoromethyl)phenoxy)benzaldehyde (5 g, 18.78 mmol) at 0 C. The mixture was stirred at room temperature for 4 h. DCM (50 mL) and water (50 mL) was added to the mixture, the organic phase was washed with water (50 mL), brine (50 mL), dried over anhydrous sodium sulfate and concentrated. Purification via flash chromatography afforded the title compound (5.07 g, 17.26 mmol, 92 % yield) as pale yellow oil (slowly solidify to white solid). LCMS: rt = 1.67 min,[M+H+] = 290

Reference： [1]Patent: WO2012/76435,2012,A1 .Location in patent: Page/Page column 46

30
[ 1278587-62-4 ]
[ 15898-47-2 ]
[ 1384518-87-9 ]

Yield	Reaction Conditions	Operation in experiment
60%		In an oven dried round bottom flask, the <strong>[15898-47-2]triphenyl(cyanomethyl)phosphonium bromide</strong> (840 mg, 2.2 mmol) in dry benzene (1 mL) is transfered under nitrogen atmosphere. The reaction flask is cooled to 0 omicronC, the Potassium tert-butoxide (246 mg, 2.2 mmol) was added at a time and the contents were stirred for one h. After the mixture becomes light yellow color, the ethyl 2-(chloromethyl)-2-hydroxy-2H-chromene-3-carboxylate 2a (268 mg, 1 mmol) in benzene (1 mL) was added slowly at the same temperature. The contents were slowly brought to room temperature (6 h), after completion of the reaction (TLC), the reaction mixture was quenched with aqueous NH4Cl solution, and extracted with ether (3 X 10 mL). The organic layer was dried over Na2SO4, solvent removed under reduced pressure and crude product was purified by column chromatography (hexane/ethyl acetate 9:1) to give 3d (150 mg, 60% yield) as colorless solid.

Reference： [1]Tetrahedron,2012,vol. 68,p. 6289 - 6297

31
5-(but-1’-en-4’-yl)dihydrofuran-2(3H)-ol [ No CAS ]
[ 15898-47-2 ]
[ 1415260-57-9 ]
[ 1415260-58-0 ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of <strong>[15898-47-2](cyanomethyl)triphenyl-phosphonium bromide</strong> (2.23 g, 5.83 mmol) in CH2Cl2 was added a 1 M aqueous solution of NaOH (10 mL). The mixture was shaken at 20 C for 1 min. The layers were separated. The organic layer was kept and the aqueous layer was extracted with CH2Cl2 (2 × 15 mL). Combined organic solutions were washed with brine (20 mL), dried (MgSO4) and the solvent was removed under reduced pressure. The resulting colorless solid (1.56 g) was suspended in toluene (25 mL) in an atmosphere of nitrogen (5.0-quality, purged through a tube filled with CaCl2) and treated with neat 5-(but-1?-en-4?-yl)dihydrofuran-2(3H)-ol (491 mg, 3.45 mmol). The reaction mixture was stirred for 4 h at 60 C and cooled to 20 C. The precipitate that was formed during cooling to 20 C was filtered off by suction and washed with toluene (10 mL). Combined filtrates and washings were concentrated under reduced pressure. The residue was purified by chromatography [SiO2, petroleum ether/Et2O = 1:2 (v/v)]. Yield: 514 mg [3.11 mmol, 90%, (E):(Z) = 81:19], colorless oil, Rf 0.45 [SiO2, petroleum ether/Et2O = 1:2 (v/v)].

Reference： [1]Tetrahedron,2012,vol. 68,p. 10378 - 10390

32
[ 15898-47-2 ]
5-(but-1’-en-4’-yl)dihydrofuran-2(3H)-ol [ No CAS ]
[ 1415260-59-1 ]
[ 1415260-60-4 ]

Yield	Reaction Conditions	Operation in experiment
78%; 3%		To a solution of (methoxycarbonyl-methyl)triphenylphosphonium bromide (6.90 g, 16.60 mmol) in CH2Cl2 (100 mL) was added a 1 M aqueous solution of NaOH (10 mL). The mixture was shaken at 20 C for 1 min. The layers were separated. The organic layer was kept and the aqueous layer was extracted with CH2Cl2 (2 × 40 mL). Combined organic solutions were washed with brine (40 mL), dried (MgSO4) and the solvent was removed under reduced pressure. The resulting colorless solid (5.14 g) was suspended in toluene (25 mL) in an atmosphere of nitrogen (5.0-quality, purged through a tube filled with CaCl2) and treated with neat 5-(but-1?-en-4?-yl)dihydrofuran-2(3H)-ol (1.09 g, 7.68 mmol). The reaction mixture was stirred for 4 h at 60 C and cooled to 20 C. The precipitate that was formed during cooling to 20 C was filtered off by suction and washed with toluene (30 mL). Combined filtrate and washings were concentrated under reduced pressure. The residue was purified by chromatography [SiO2, petroleum ether/Et2O = 1:1 (v/v)].

Reference： [1]Tetrahedron,2012,vol. 68,p. 10378 - 10390

33
[ 467452-00-2 ]
[ 15898-47-2 ]
[ 1421282-63-4 ]