Name: 147699-19-2|tert-Butyl 4-(2-((methylsulfonyl)oxy)ethyl)piperidine-1-carboxylate|97%
Brand: Ambeed
SKU: A320069
Rating: 99 (26 reviews)

1
[ 612501-52-7 ]
[ 147699-19-2 ]
6-[2-(1-tert-butoxycarbonyl)piperidin-4-yl]ethoxy}-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In N,N-dimethyl acetamide; at 60℃; for 16h;	Reference Example 5; 6-[2-(1-tert-Butoxycarbonyl) piperidin-4-yl] ethoxy}-4-(3-chloro-2-fluoroanilino)-7- methoxyquinazoline; 4- (3-Chloro-2-fluoroanilino)-6-hydroxy-7-methoxyquinazoline (Reference Example 2,500 mg, 1.56 mmol) was dissolved in DMA (25 ml). Potassium carbonate (864 mg, 6.26 mmol) and tert-butyl 4- [2- (methanesulfonyloxy) ethyl] piperidine-l-carboxylate (prepared as described in Example 20 in US 5252586; 504 mg, 1.64 mmol) were added, and the mixture was stirred at 60C for 16 hours. The solvent was evaporated, and the residue was partitioned between water (100 ml) and DCM (100 ml). The aqueous layer was extracted with DCM (3x 100 ml) and the extractions combined with the DCM layer. The combined DCM fractions were filtered through a silicone-treated filter paper, and evaporated, giving the product as a brown foam (830 mg, 100%) ; 1H NMR : 1. 00-1. 18 (m, 2H), 1.38 (s, 9H), 1.65-1. 80 (m, 5H), 2.65-2. 75 (m, 2H), 3.92 (s, 3H), 3.93 (m, 2H), 4.15 (t, 2H), 7.18 (s, 1H), 7.26 (dd, 1H), 7.46 (dd, 1H), 7.51 (dd, 1H), 7.77 (s, 1H), 8.36 (s, 1H), 9.54 (s, 1H); Mass Spectrum: 531.6, 533. 6.

Reference： [1]Patent: WO2003/82831,2003,A1 .Location in patent: Page/Page column 163-164

2
4-(7-hydroxy-4-methyl-quinazolin-2-ylamino)benzenesulfonamide [ No CAS ]
[ 147699-19-2 ]
tert-butyl 4-(2-(4-methyl-2-(4-sulfamoyl-phenylamino)-quinazolin-7-yloxy)ethyl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; lithium hexamethyldisilazane; In N,N-dimethyl-formamide; at 170℃; for 0.166667h;Microwave irradiation;	Step 6. Preparation of 4-(4-methyl-7-(2-(piperidin-4-yl)ethoxy)quinazolin-2-ylamino)benzene sulfonamideTo 4-(7-hydroxy-4-methylquinazolin-2-ylamino)benzenesulfonamide (leq) in DMF was added potassium carbonate (1.1 eq) and KHMDS (1.2eq) and tert-butyl 4-(2-(methylsulfonyloxy)ethyl)piperidine-l-carboxylate (1.5eq). The reaction mixture was microwaved at 1700C for lOmin. Formation of tert-butyl 4-(2-(4-methyl-2-(4- sulfamoylphenylamino)quinazolin-7-yloxy)ethyl)piperidine-l-carboxylate was confirmed by 1HNMR and LC/MS. The crude reaction mixture of tert-butyl 4-(2-(4-methyl-2-(4-sulfamoylphenylamino) quinazolin-7-yloxy) ethyl) piperidine-1-carboxylate was purified using prep HPLC and the purified fractions of the product was concentrated. To it was added a few drops of 30% TFA/ DCM and the mixture was stirred for 30 min. The deprotection went to completion yielding 4- (4-methyl-7-(2-(piperidin-4-yl)ethoxy)quinazolin-2-ylamino)benzene sulfonamide that was confirmed by LC/MS. ES/MS m/z 442(MH+).

Reference： [1]Patent: WO2007/117607,2007,A2 .Location in patent: Page/Page column 346

3
[ 122-97-4 ]
[ 147699-19-2 ]
C₂₁H₃₃NO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; at 0 - 100℃; for 20h;	Sodium hydride (541 mg, 60% in oil) was added to a DMF (80 ml) solution containing the resulting compound (2.0 g) and phenylpropanol (1.3 g) at 0C, followed by heating at 100C for 20 hours. The reaction solution was cooled, water was added thereto, followed by extraction with EtOAc. This was washed with an aqueous 1 M hydrochloric acid solution, an aqueous saturated sodium hydrogencarbonate solution and saturated brine in that order, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: chloroform:methanol = 20:1 (v/v)) to obtain a yellow oil (1.96 g).

Reference： [1]Patent: EP1849773,2007,A1 .Location in patent: Page/Page column 29

4
1-[3-(trifluoromethyl)phenyl]piperazine hydrochloride [ No CAS ]
[ 147699-19-2 ]
[ 1000030-01-2 ]

Yield	Reaction Conditions	Operation in experiment
71%	With potassium carbonate; In acetonitrile;Heating / reflux;	A mixture of 1 g (3.25 mmol) of 4-(2-methanesulfonyloxyethyl)-piperidine-1- carboxylic acid terf-butyl ester, 0.87 g (3.25 mmol) of 1-(3-trifluoromethyl- phenyl)piperazine hydrochloride, 0.95 g (6.9 mmol) of potassium carbonate and 20 ml_ of acetonithle is refluxed overnight. <n="101"/>After concentration of solvent, the residue is taken off with ethyl acetate and water. Organic phase is separated, washed with a 0.5N aqueous solution of hydrochloric acid, dried over magnesium sulfate, filtered and partially concentrated. The solid is filtered, washed with diethyl ether and dried under reduced pressure to give 1.1 g (71%) of A- {2[4-(3-trifluoromethyl-phenyl)piperazin-1-yl]-ethyl}piperidine-1-carboxylic acid fe/t-butyl ester, hydrochloride as a white solid.Melting point 188C1H NMR : 13.1 (broad s, 1 H) ; 7.4 (t, 1 H, J = 7.5) ; 7.25 (d, 1 H, J = 7.5) ; 7.2 to 7.0 (ms, 2H) ; 4.1 (m, 2H) ; 3.9 to 3.5 (ms, 6H) ; 3.15 to 2.8 (ms, 4H) ; 2.7 (m, 2H) ; 1.95 (m, 2H) ; 1.8 to 1.5 (ms, 3H) ; 1.45 (s, 9H) ; 1.3 (m, 2H)

Reference： [1]Patent: WO2007/148208,2007,A2 .Location in patent: Page/Page column 99-100

5
[ 79099-07-3 ]
[ 147699-19-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172
[2]Patent: US2012/71461,2012,A1
[3]European Journal of Medicinal Chemistry,2016,vol. 123,p. 332 - 353
[4]Patent: CN107793408,2018,A

6
[ 135716-08-4 ]
[ 147699-19-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172
[2]Patent: US2012/71461,2012,A1
[3]Patent: CN107793408,2018,A

7
[ 135716-09-5 ]
[ 147699-19-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172
[2]Patent: US2012/71461,2012,A1
[3]Patent: CN107793408,2018,A

8
[ 147699-19-2 ]
[ 146093-46-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4805 - 4811

9
[ 147699-19-2 ]
[ 70042-98-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172

10
[ 147699-19-2 ]
4-(2-aminoethyl)-1-{(2R)-2-((1R)-3, 3-difluorocyclopentyl)-2-hydroxy-2-phenylacetyl}piperidine [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172

11
[ 147699-19-2 ]
[ 663170-84-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172

12
[ 147699-19-2 ]
(R)-2-((R)-3,3-Difluoro-cyclopentyl)-2-hydroxy-2-phenyl-N-(2-piperidin-4-yl-ethyl)-acetamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172

13
[ 147699-19-2 ]
4-{2-[(R)-2-((R)-3,3-Difluoro-cyclopentyl)-2-hydroxy-2-phenyl-acetylamino]-ethyl}-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 2167 - 2172

14
potassium cyanide [ No CAS ]
[ 147699-19-2 ]
[ 161975-20-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; In ethanol; for 5h;Heating / reflux;	crude 4-(2-METHANESULFONYLOXYETHYL) PIPERIDINE-1-CARBOXYLIC acid TERT- butyl ester which was dissolved in absolute ethanol (200 mL). Potassium cyanide (5.1 g, 78.5 MMOL) and potassium iodide (0.5 g) was added and the mixture was heated at reflux with vigorous stirring for 5 h. The reaction mixture was allowed to cool to ambient temperature, filtered and the solvent was evaporated. The oily residue was dissolved in ethyl acetate (100 mL) and the organic solution was washed with water (2 x 10 mL) and brine. The organic so- lution was dried (MGS04) and the solvent was evaporated to give 9.5 g of 4- (2- cyanoethyl) PIPERIDINE-1-CARBOXYLIC ACID TERT-BUTYL ester.

Reference： [1]Patent: WO2004/54973,2004,A2 .Location in patent: Page 28

15
[ 20662-53-7 ]
[ 147699-19-2 ]
1-[1-[2-[1-tert-butoxycarbonylpiperidin-4-yl]ethyl]piperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; potassium iodide; In DMF (N,N-dimethyl-formamide); at 80℃; for 10h;	To a solution of 240 mg of piperidine-4-ethanol in 3 ml of chloroform, 446 mg of DIBOC (di-tert-butyldicarbonate) was added and stirred for 3 hours at room temperature. The reaction liquid was diluted with chloroform, and the chloroform layer was washed successively with saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue so obtained was purified on silica gel chromatography (chloroform / methanol = 30 / 1) to provide 456 mg of 1-(tert-butoxycarbonyl)piperidine-4-ethanol, which was then dissolved in 2 ml of chloroform. To the solution 205 µl of methanesulfonyl chloride and 1 ml of triethylamine, followed by 10 hours' stirring at room temperature. Saturated sodium hydrogencarbonate was added to the reaction liquid, which was then extracted with chloroform three times. This solution was dried over anhydrous sodium sulfate and concentrated. To the residue, 20 ml of dimetylformamide, 499 mg of 1-(piperidin-4-yl)-1,3-dihydro- 2H-benzimidazol-2-one, 477 mg of potassium carbonate and 38 mg of potassium iodide were added, followed by 10 hours' stirring at 80C. After cooling the reaction liquid, chloroform and saturated aqueous sodium hydrogencarbonate solution were added thereto, and the resulting mixture was shaken to separate the organic layer. The organic layer was dried over anhydrous sodium sulfate and removed of the solvent. The resulting residue purified on silica gel chromatography, to provide 275 mg of 1-[1-[2-[1-tert-butoxycarbonylpiperidin-4-yl]ethyl]piperidin-4-yl]-1,3-dihydro-2H- benzimidazol-2-one. To this compound, 10 ml of 10% hydrogen chloride / methanol was added, followed by 6 hours' stirring at room temperature. The reaction liquid was concentrated, to which methanol was added and distilled under reduced pressure to remove excess of hydrogen chloride and to provide the title compound.

Reference： [1]Patent: EP1386920,2004,A1 .Location in patent: Page 44-45

16
[ 151-50-8 ]
[ 147699-19-2 ]
[ 161975-20-8 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium iodide; In ethanol; for 5h;Heating / reflux;	The mixture was filtered and the solvent was evaporated to give 13 g of crude 4-(2-methanesulfonyloxyethyl)piperidine-1-carboxylic acid tert-butyl ester which was dissolved in absolute ethanol (200 mL). Potassium cyanide (5.1 g, 78.5 mmol) and potassium iodide (0.5 g) was added and the mixture was heated at reflux with vigorous stirring for 5 h. The reaction mixture was allowed to cool to ambient temperature, filtered and the solvent was evaporated. The oily residue was dissolved in ethyl acetate (100 mL) and the organic solution was washed with water (2×10 mL) and brine. The organic solution was dried (MgSO4) and the solvent was evaporated to give 9.5 g of 4-(2-cyanoethyl)piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CDCl3) δ 1.05-1.17 (m, 2H), 1.45 (s, 9H), 1.55-1.72 (m, 5H), 2.38 (t, 2H), 2.64-2.75 (m, 2H), 4.04-4.17 (m, 2H).

Reference： [1]Patent: US2005/107434,2005,A1 .Location in patent: Page/Page column 13-14

17
[ 895126-45-1 ]
[ 147699-19-2 ]
4-[2-(furo[3,2-c]pyridin-2-ylmethoxy)ethyl]piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium tert-butylate; In tetrahydrofuran; for 6h;Heating / reflux;	Example 13; 4-[2-(Furo[3,2-c]pyridin-2-ylmethoxy)ethyl]piperidine-l-carboxylic acid tert- butyl ester; t-BuOK (45 mg, 401 μmol) and 4-(2-methanesulfonyloxyethyl)piperidine-l -carboxylic acid tert-butyl ester (134 mg, 436 μmol) were added to a stirred solution of furo[3,2-c]pyridin-2- ylmethanol (Preparation 4, 50 mg, 336 μmol) in anhydrous THF (5 mL). The reaction was heated under reflux for 6 h, before being cooled to 200C and quenched with saturated aqueous NH4Cl. The mixture was extracted twice with EtOAc, then the combined organic extracts were washed with brine, dried (MgSO4), filtered, and concentrated. The residue was purified by column chromatography (EtOAc-MeOH, 1:0 to 50:1) to furnish the title compound

Reference： [1]Patent: WO2006/67532,2006,A1 .Location in patent: Page/Page column 28

18
[ 407623-08-9 ]
[ 147699-19-2 ]
[ 407623-61-4 ]

Yield	Reaction Conditions	Operation in experiment
	In hydrochloric acid dioxane; ethyl acetate; N,N-dimethyl-formamide;	Step 1 Synthesis of 4-(4-chlorobenzoyl)-1-[2-(4-piperidinyl)ethyl]-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on: 150 mg (0.50 mmol) of 4-(4-chlorobenzoyl)-1,3,4,5-tetrahydrobenzo[e][1,4]diazepin-2-on was dissolved in 10 ml of DMF. 24 mg (0.60 mmol) of sodium hydride was added to the obtained solution. After stirring at room temperature for 30 minutes, 184 mg (0.60 mmol) of t-butyl 4-(2-((methylsulfonyl)oxy)ethyl)-1-piperidinecarboxylate was added to the obtained mixture, and they were stirred at 70 C. overnight. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the obtained crude product was dissolved in 10 ml of 4 N dioxane hydrochloride, and the obtained solution was stirred overnight. After the treatment with ethyl acetate as the extracting solvent by an ordinary method, the title compound was obtained. Yield: 179 mg (0.043 mmol) (86%) MS (ESI, m/z) 412 (MH+) H-NMR (CDCl3) δ 1.08-73 (7H, m), 2.55 (2H, br), 3.06 (2H, br), 3.82-4.15 (4H, m), 4.30-4.78 (2H, br), 7.25-7.65 (9H, m)

Reference： [1]Patent: US2003/186969,2003,A1

19
[ 78818-15-2 ]
[ 147699-19-2 ]
[ 239072-94-7 ]

Yield	Reaction Conditions	Operation in experiment
		Reference Example 20 4-Benzyloxycarbonyl-1-[2-(1-tert-butoxycarbonyl-4-piperidyl)ethyl]-2-piperazinone According to a similar method described in Reference Example 2, oil of the title compound was obtained from 4-benzyloxycarbonyl-2-piperazinone and 1-tert-butoxy-carbonyl-4-(2-methanesulfonyloxyethyl)piperidine. 1H-NMR (CDCl3) delta: 1.00-1.25 (2H, m), 1.45 (9H, s), 1.30-1.58 (3H, m), 1.58-1.70 (2H, m), 2.56-2.78 (2H, m), 3.33 (2H, t, J=5.2 Hz), 3.38-3.50 (2H, m), 3.71 (2H, t, J=5.3 Hz), 3.97-4.20 (2H, m), 4.14 (2H, s), 5.15 (2H, s), 7.26 (5H, s). IR (KBr): 1694, 1657, 1426, 1236, 1163 cm-1.

Reference： [1]Patent: US6403595,2002,B1

20
1-(4-methoxycarbonylmethyloxyphenyl)piperazine trifluoroacetate [ No CAS ]
[ 147699-19-2 ]
[ 198626-66-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In methanol;	EXAMPLE 3 4-[2-(1-tert-Butyloxycarbonylpiperidin-4-yl)ethyl]-1-(4-methoxycarbonylmethyloxyphenyl)piperazine A solution of 4.8 g (0.01 mol) of 1-(4-methoxycarbonylmethyloxyphenyl)piperazine trifluoroacetate, 3.0 g (0.01 mol) of 1-[(1-tert-butyloxycarbonyl)piperidin-4-yl]-2-methanesulphonyloxyethane and 3.9 g=5.2 ml (0.03 mol) of N-ethyldiisopropylamine in 100 ml of methanol is heated at reflux temperature for 24 hours. The methanol is then distilled off in vacuo. The residue which remains is purified by chromatography on a silica gel column, methylene chloride which contains 3% methanol being used as eluent. Yield: 2.1 g (46.6% of theory), Melting point: 197-199 C. Mass spectrum: M+ =461