[ CAS No. 54012-73-6 ] {[proInfo.proName]}

Name: 54012-73-6|Piperidin-3-amine|95%
Brand: Ambeed
SKU: A221133
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Quality Control of [ 54012-73-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 54012-73-6 ]

SDS Specification

Alternatived Products of [ 54012-73-6 ]

Product Details of [ 54012-73-6 ]

CAS No. :	54012-73-6	MDL No. :	MFCD04972497
Formula :	C₅H₁₂N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	PEUGKEHLRUVPAN-UHFFFAOYSA-N
M.W :	100.16	Pubchem ID :	148119
Synonyms :

Calculated chemistry of [ 54012-73-6 ]

Physicochemical Properties

Num. heavy atoms :	7
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	33.46
TPSA :	38.05 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.33 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.42
Log Po/w (XLOGP3) :	-0.59
Log Po/w (WLOGP) :	-0.68
Log Po/w (MLOGP) :	-0.16
Log Po/w (SILICOS-IT) :	0.5
Consensus Log Po/w :	0.1

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.09
Solubility :	81.5 mg/ml ; 0.814 mol/l
Class :	Very soluble
Log S (Ali) :	0.26
Solubility :	183.0 mg/ml ; 1.83 mol/l
Class :	Highly soluble
Log S (SILICOS-IT) :	-0.65
Solubility :	22.4 mg/ml ; 0.223 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.43

Safety of [ 54012-73-6 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405	UN#:	3259
Hazard Statements:	H302-H314	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 54012-73-6 ]

* 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 [ 54012-73-6 ]
Downstream synthetic route of [ 54012-73-6 ]

[ 54012-73-6 ] Synthesis Path-Upstream 1~1

1
[ 54012-73-6 ]
[ 24424-99-5 ]
[ 144243-24-3 ]
[ 184637-48-7 ]

Yield	Reaction Conditions	Operation in experiment
91.5%	With sodium hydroxide In ethanol at 10 - 15℃; for 1 h;	90 g of ethanol and 10.0 g (0.1 mols) of 3-aminopiperidine were fed into a 200-ml 4-neck flask equipped with a stirrer, a pH sensor and two strapped dropping funnels, and stirred at 10 to 15°C. 21.8 g (0.1 mols) of di-tertiary butyl dicarbonate was fed into it via one dropping funnel, and 17.6 g (0.11 mols) of aqueous solution of 25 percent sodium hydroxide was thereinto via the other dropping funnel. With stirring at 10 to 15°C, di-tertiary butyl dicarbonate was dropwise added to the reaction system over a period of about 1 hour. During this, the aqueous solution of 25 percent sodium hydroxide was dropwise added thereto so as to make the reaction system have a pH of from 11.8 to 12.2. The reaction mixtures were analyzed for its composition, and it comprised 6 percent of the starting 3-aminopiperidine, 91.5 percent of the product, 3-amino-1-tertiary butoxycarbonylpiperidine, and 1.1 percent of 3-tertiary butoxycarbonylaminopiperidine.

Reference： [1] Patent: EP1460061, 2004, A1, . Location in patent: Page 6-7

[ 54012-73-6 ] Synthesis Path-Downstream 1~88

1
[ 462-08-8 ]
[ 54012-73-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;pyrographite; In acetic acid; at 50℃; under 75007.5 Torr;Industry scale;	10.00 kg (106.25 mol) of 3-aminopyridine, 500 g of industrial grade activated charcoal and 65 litres of acetic acid are placed in the hydrogenation reactor. 50 g of Nishimura catalyst (a commercially obtainable mixed rhodium/platinum catalyst) are added, suspended in 2.5 litres of acetic acid, and the mixture is rinsed with 2.5 litres of acetic acid. It is hydrogenated at 50 C. and 100 bar excess hydrogen pressure until the hydrogen uptake has stopped and then hydrogenated for a further 30 minutes at 50 C. The catalyst and the activated charcoal are filtered off and washed with 10 litres of acetic acid.
	With hydrogen;Rh/Al2O3; In methanol; at 80℃; under 11251.1 - 15001.5 Torr; for 17h;Product distribution / selectivity;	A Parr pressure vessel is charged with 3-aminopyridine (100 g), 5 wt% rhodium on alumina (10 g) and methanol (1 litre). The vessel is charged with nitrogen to a pressure of 10 bar, stirred for 15 minutes and vented. This process is repeated three times. The vessel is then charged with hydrogen to a pressure of 10 bar and subsequently vented without the mixture being stirred. This process is repeated three times. The vessel is then charged with hydrogen to a pressure of 15 bar, and heated to 80 0C and stirred. Once the temperature is <n="6"/>' attained, the hydrogen pressure is increased to 20 bar. After 17 hours, the vessel is cooled to room temperature and the hydrogen is vented. The vessel is then charged with nitrogen to a pressure of 10 bar and the mixture stirred for 10 minutes and then vented. This process is repeated three times. The contents of the vessel are filtered through a pad of celite and washed with fresh methanol (300 ml). Analysis of an aliquot (0.1 ml) reveals the conversion to be >98% as determined by proton NMR comparing the integrals associated with 3-aminopyridine and 3- aminopiperidine. The hydrogenation is undertaken 3 times. Each batch is diluted to 3.6L with methanol and heated to 40 0C in a jacketed vessel with overhead stirring. Dibenzoyl- D-tartaric acid (371.7g:leq) is then added via a solids addition funnel and the vessel is heated to 60 0C with vigorous stirring for lhr, during which time crystallization occurred. The temperature is then reduced to 20 0C over 2 hours and the reaction stirred for a further 16 hours. The crystals are then filtered, washed with methanol (300ml) and dried to give a 40-44% yield with 88-91 % diastereomeric excess (%de). These batches of material are then combined (59Og) and slurried in methanol (4L) at 50 0C for 16 hours, cooled to 22 0C over 1 hour and stirred for a further 1 hour. The solid is then filtered, washed with methanol (5 x 100ml) and dried to give 543.5g of white solid, 92.1% yield and 96.4 %de. This solid is reslurried in methanol (3.75L) at 60 C for 2 hours, cooled to 22 0C and stirred for 16 hours. The solid is then filtered, washed with methanol (5 x 100ml) and dried to give 511.83g of white solid, 94.2% yield and 98.1 %de.495g of this material is then slurried in 3L of methyl t-butyl ether (MTBE) and HCI (3eq) in MTBE (IL) is added slowly over 2 hours with stirring. This material is then heated to 50 0C for 1 hour, cooled to 5 0C and stirred over night. The solid is then filtered, washed with MTBE and dried to give 179.5g of white solid, 96% yield. This material, the hydrochloride salt of (i?)-3-aminopiperidine, is analysed by chiral HPLC and determined to be of >99% chemical purity and >98%ee.
	Rh/C; In methanol; at 80℃; under 15001.5 Torr; for 17h;Product distribution / selectivity;	A glass liner is charged with 3-aminopyridine (500 mg, 5.31 mmol), 5% Rh/C (Engelhard type 44966, 56% water content)) (113 mg) and methanol (5 ml). The liner is secured in an Argonaut Endeavor multi-well pressure reactor. The reactor is charged is charged with nitrogen to a pressure of 10 bar, stirred for 15 minutes and vented. This process is repeated three times. The reactor is then charged with hydrogen to a pressure of 10 bar and subsequently vented without the mixture being stirred. This process is repeated two times. The reactor is then charged with hydrogen to a pressure of 20 bar, heated to 80 C <n="7"/>and stirred at 1000 rpm. The pressure of hydrogen is maintained at 20 bar for 17 hours. The reactor is vented and the reaction mixture analysed without concentration. Analysis of an aliquot (0.1 ml) reveals the conversion to be 94% as determined by proton NMR comparing the integrals associated with 3-aminopyridine and 3-aminopirhoeridine.

Reference： [1]Chemische Berichte,1937,vol. 70,p. 635,637
[2]Patent: WO2006/48427,2006,A1 .Location in patent: Page/Page column 6-7
[3]Patent: US2007/27168,2007,A1 .Location in patent: Page/Page column 3
[4]Patent: WO2007/75630,2007,A1 .Location in patent: Page/Page column 4-5
[5]Patent: WO2007/75630,2007,A1 .Location in patent: Page/Page column 5-6

2
[ 54012-73-6 ]
[ 72810-57-2 ]
[ 77281-90-4 ]

Reference： [1]European Journal of Medicinal Chemistry,1981,vol. 16,p. 65 - 68

3
[ 462-08-8 ]
[ 54012-73-6 ]
[ 694-05-3 ]

Reference： [1]Heterocycles,1993,vol. 36,p. 2383 - 2396

4
[ 42538-31-8 ]
[ 54012-73-6 ]

Yield	Reaction Conditions	Operation in experiment
63%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 15.25h;Inert atmosphere; Reflux;	Lithium aluminum hydride (21.0 g, 553 mmol) dissolved in THF (500 mL)was stirred for 15 min at 0 C under Ar. Compound 2 (28.0 g, 186 mmol) was added and the solution wasstirred for 15 min at 0 C, and then refluxed for 15 h. Then, water (21 mL), 15% sodium hydroxidesolution (21 mL), and water (63 mL) were added sequentially. After vacuum filtration, the solvent wasremoved in vacuo. The crude product was purified by distillation at 75 C in vacuo (20 Torr) to give(S)-piperidin-3-amine (3: 11.8 g, yield 63%)

Reference： [1]Heterocycles,2017,vol. 94,p. 964 - 978
[2]Journal of the Chemical Society, Dalton Transactions,1987,p. 1127 - 1132
[3]Chemistry Letters,1981,p. 1691 - 1694

5
[ 369-25-5 ]
[ 54012-73-6 ]
[ 334618-09-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 2131 - 2150

6
[ 54012-73-6 ]
trifluoro-methanesulfonic acid 1-(4-methoxy-benzyl)-6-methyl-2-oxo-3-(1-trifluoromethanesulfonyloxy-1<i>H</i>-benzoimidazol-2-yl)-1,2-dihydro-quinolin-4-yl ester [ No CAS ]
trifluoro-methanesulfonic acid 2-[1-(4-methoxy-benzyl)-6-methyl-2-oxo-4-(piperidin-3-ylamino)-1,2-dihydro-quinolin-3-yl]-benzoimidazol-1-yl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3121 - 3124

7
[ 54012-73-6 ]
1-[(4-methoxyphenyl)methyl]-2-oxo-3-{1-[(trifluoromethyl)sulfonyl]benzimidazol-2-yl}-6-chloro-4-hydroquinolyl(trifluoromethyl)sulfonate [ No CAS ]
trifluoro-methanesulfonic acid 2-[6-chloro-1-(4-methoxy-benzyl)-2-oxo-4-(piperidin-3-ylamino)-1,2-dihydro-quinolin-3-yl]-benzoimidazol-1-yl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3121 - 3124

8
[ 54012-73-6 ]
[ 1755-15-3 ]
5,5-dimethyl-2-[1-(piperidin-3-ylamino)-ethylidene]-cyclohexane-1,3-dione [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 5653 - 5663

9
[ 54012-73-6 ]
[ 323183-73-9 ]
1-{(S)-2-[(R)-2-(3-Amino-piperidine-1-carbonyl)-pyrrolidine-1-carbonyl]-pyrrolidin-1-yl}-3,3,3-triphenyl-propan-1-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 5653 - 5663

10
[ 54012-73-6 ]
[ 108-86-1 ]
1-phenyl-3-(N-phenylamino)piperidine [ No CAS ]
[ 63921-21-1 ]
3-(phenylamino)piperidine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 2030 - 2039

11
[ 54012-73-6 ]
[ 591-50-4 ]
1-phenyl-3-(N-phenylamino)piperidine [ No CAS ]
[ 63921-21-1 ]
3-(phenylamino)piperidine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 2030 - 2039

12
[ 54012-73-6 ]
[ 108-90-7 ]
1-phenyl-3-(N-phenylamino)piperidine [ No CAS ]
[ 63921-21-1 ]
3-(phenylamino)piperidine [ No CAS ]

Reference： [1]Journal of Organic Chemistry,2007,vol. 72,p. 2030 - 2039

13
[ 54012-73-6 ]
[ 109286-40-0 ]
1,3-dimethyl-7-benzyl-8-(3-amino-piperidin-1-yl)-xanthine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 6450 - 6453

14
[ 54012-73-6 ]
3-(1H-benzimidazol-2-yl)-6-chloro-4-(piperidin-3-ylamino)quinolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3121 - 3124

15
[ 54012-73-6 ]
3-(1H-benzimidazol-2-yl)-6-methyl-4-(piperidin-3-ylamino)quinolin-2(1H)-one [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3121 - 3124

16
[ 54012-73-6 ]
(R)-1-[(S)-1-(3,3,3-Triphenyl-propionyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carboxylic acid piperidin-3-ylamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 5653 - 5663

17
[ 16682-12-5 ]
[ 54012-73-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 4158 - 4181

18
[ 54012-73-6 ]
NBI 58702 [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 4417 - 4423

19
[ 54012-73-6 ]
3-(3-{2-[4-(3-<i>o</i>-tolyl-ureido)-phenyl]-acetylamino}-piperidin-1-yl)-propionic acid [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry,2001,vol. 9,p. 2195 - 2202

20
[ 54012-73-6 ]
[ 24424-99-5 ]
[ 144243-24-3 ]
[ 184637-48-7 ]

Yield	Reaction Conditions	Operation in experiment
91.5%; 1.1%	With sodium hydroxide; In ethanol; at 10 - 15℃; for 1h;pH 11.8 - 12.2;	90 g of ethanol and 10.0 g (0.1 mols) of <strong>[54012-73-6]3-aminopiperidine</strong> were fed into a 200-ml 4-neck flask equipped with a stirrer, a pH sensor and two strapped dropping funnels, and stirred at 10 to 15C. 21.8 g (0.1 mols) of di-tertiary butyl dicarbonate was fed into it via one dropping funnel, and 17.6 g (0.11 mols) of aqueous solution of 25 % sodium hydroxide was thereinto via the other dropping funnel. With stirring at 10 to 15C, di-tertiary butyl dicarbonate was dropwise added to the reaction system over a period of about 1 hour. During this, the aqueous solution of 25 % sodium hydroxide was dropwise added thereto so as to make the reaction system have a pH of from 11.8 to 12.2. The reaction mixtures were analyzed for its composition, and it comprised 6 % of the starting <strong>[54012-73-6]3-aminopiperidine</strong>, 91.5 % of the product, 3-amino-1-tertiary butoxycarbonylpiperidine, and 1.1 % of 3-tertiary butoxycarbonylaminopiperidine.

Reference： [1]Patent: EP1460061,2004,A1 .Location in patent: Page 6-7

21
[ 54012-73-6 ]
[ 85-44-9 ]
[ 62813-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid; for 1h;Heating / reflux; Industry scale;	15.74 kg (106.25 mol) phthalic anhydride are placed in the reactor and combined with the filtrate from the hydrogenation. The mixture is rinsed with 7.5 litres of acetic acid, and then the reaction mixture is refluxed, while about 30% of the acetic acid used are distilled off within one hour. The reaction solution is cooled to 90 C

Reference： [1]Patent: WO2006/48427,2006,A1 .Location in patent: Page/Page column 6-8
[2]Patent: US2007/27168,2007,A1 .Location in patent: Page/Page column 3

22
[ 54012-73-6 ]
[ 105627-79-0 ]
1-(5-isoquinolinesulfonyl)-3-aminopiperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane;	EXAMPLE 1 In 50 ml of ice water was dissolved 5.3 g of 5-isoquinolinesulfonyl chloride hydrochloride, and the pH of the solution was adjusted to 6 with a saturated aqueous sodium hydrogencarbonate solution, followed by extraction with 100 ml of dichloromethane. The dichloromethane layer was added dropwise to a 50 ml of dichloromethane solution containing 6.0 g of <strong>[54012-73-6]3-aminopiperidine</strong> over 20 minutes while cooling with ice. The mixture was stirred at a temperature of 15 C. to 20 C. for 2 hours, washed with water, and dried with anhydrous magnesium sulfate. Then, the dichloromethane was removed under reduced pressure to obtain an oily residue. The thus obtained oily residue was subjected to purification by silica gel column chromatography (Wacogel C-200, 200 g; solvent: chloroform) to obtain 5.32 g of 1-(5-iso-quinolinesulfonyl)-<strong>[54012-73-6]3-aminopiperidine</strong> [Compound (63)] in a yield of 91%. Compound (63) was analyzed to give the following data. IR absorption spectrum (cm-1): 2950, 1340, 1160. NMR spectrum (CD3 OD-DCl): 0.8-2.0(4H), 2.1-3.2 (3H), 3.3-3.8(2H), 7.4-7.9(1H), 8.0-8.7(4H), 9.3(1H).
91%	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane;	Example 1 In 50 ml of ice water was dissolved 5.3 g of 5-isoquinolinesulfonyl chloride hydrochloride, and the pH of the solution was adjusted to 6 with a saturated aqueous sodium hydrogencarbonate solution, followed by extraction with 100 ml of dichloromethane. The dichloromethane layer was added dropwise to a 50 ml of dichloromethane solution containing 6.0 g of <strong>[54012-73-6]3-aminopiperidine</strong> over 20 minutes while cooling with ice. The mixture was stirred at a temperature of 15 C to 20 C for 2 hours, washed with water, and dried with anhydrous magnesium sulfate. Then, the dichloromethane was removed under reduced pressure to obtain an oily residue. The thus obtained oily residue was subjected to purification by silica gel column chromatography (Wacogel C-200, 200 g; solvent: chloroform) to obtain 5.32 g of 1-(5-iso-quinolinesulfonyl)-<strong>[54012-73-6]3-aminopiperidine</strong> [Compound (63)] in a yield of 91 %. Compound (63) was analyzed to give the following data. IR absorption spectrum (cmmin1): 2950, 1340, 1160. NMR spectrum (CD3OD-DCl): 0.8-2.0(4H), 2.1-3.2 (3H), 3.3-3.8(2H), 7.4-7.9(1H), 8.0-8.7(4H), 9.3(1H).

Reference： [1]Patent: US4798897,1989,A
[2]Patent: EP287696,1988,A1

23
[ 54012-73-6 ]
[ 85-44-9 ]
[ 62813-08-5 ]
[ 62813-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride;	EXAMPLE 27 A mixture of 10 g. of <strong>[54012-73-6]3-aminopiperidine</strong> and 29.6 g. of phthalic anhydride is heated at 150 C. for 30 minutes. This mixture which contains 1-(2-carboxybenzoyl)-3-phthalimidopiperidine is heated at reflux with 500 ml. of 6N hydrochloric acid for two hours. The aqueous phase is extracted with ether and then concentrated in vacuo. The residue is extracted with dilute aqueous sodium hydroxide solution and methylene chloride. The organic phase is dried and concentrated in vacuo to give 3-phthalimidopiperidine.

Reference： [1]Patent: US4005208,1977,A

24
[ 54012-73-6 ]
1-chloro-5-isoquinolinesulfonyl chloride hydrochloride [ No CAS ]
1-(1-chloro-5-isoquinolinesulfonyl)-3-aminopiperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; dichloromethane;	Example 2 In 30 ml of ice water was dissolved 3.0 g of 1-chloro-5-isoquinolinesulfonyl chloride hydrochloride, and the pH of the solution was adjusted to 6 with a saturated aqueous sodium hydrogencarbonate solution, followed by extraction with 50 ml of dichloromethane. The dichloromethane layer was added dropwise to a 50 ml of dichloromethane solution containing 3.0 g of <strong>[54012-73-6]3-aminopiperidine</strong> over 20 minutes while cooling with ice. The mixture was stirred at a temperature of 15 C to 20 C for 2 hours, washed with water, and dried with anhydrous magnesium sulfate. Then, the dichloromethane was removed under reduced pressure to obtain an oily residue. The thus obtained oily residue was subjected to purification by silica gel column chromatography (Wacogel C-200, 200 g; solvent: chloroform) to obtain 2.73 g of 1-(1-chloro-5-isoquinolinesulfonyl)-<strong>[54012-73-6]3-aminopiperidine</strong> [Compound (96)] in a yield of 84 %. Compound (96) was analyzed to give the following data. IR absorption spectrum (cmmin1): 2950, 1340, 1160. NMR spectrum (CD3OD-DCl): 0.8-2.0(4H), 2.1-3.2(3H), 3.3-3.8(2H), 7.4-7.9(1H), 8.0-8.7(4H).

Reference： [1]Patent: EP287696,1988,A1

25
[ 54012-73-6 ]
[ 17026-42-5 ]
[ 1352756-66-1 ]
(S)-3-aminopiperidine dibenzoyl (D)-tartrate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40 - 44%	In methanol; at 20 - 60℃; for 19h;	A Parr pressure vessel is charged with 3-aminopyridine (100 g), 5 wt% rhodium on alumina (10 g) and methanol (1 litre). The vessel is charged with nitrogen to a pressure of 10 bar, stirred for 15 minutes and vented. This process is repeated three times. The vessel is then charged with hydrogen to a pressure of 10 bar and subsequently vented without the mixture being stirred. This process is repeated three times. The vessel is then charged with hydrogen to a pressure of 15 bar, and heated to 80 0C and stirred. Once the temperature is <n="6"/>' attained, the hydrogen pressure is increased to 20 bar. After 17 hours, the vessel is cooled to room temperature and the hydrogen is vented. The vessel is then charged with nitrogen to a pressure of 10 bar and the mixture stirred for 10 minutes and then vented. This process is repeated three times. The contents of the vessel are filtered through a pad of celite and washed with fresh methanol (300 ml). Analysis of an aliquot (0.1 ml) reveals the conversion to be >98% as determined by proton NMR comparing the integrals associated with 3-aminopyridine and 3- aminopiperidine. The hydrogenation is undertaken 3 times. Each batch is diluted to 3.6L with methanol and heated to 40 0C in a jacketed vessel with overhead stirring. Dibenzoyl- D-tartaric acid (371.7g:leq) is then added via a solids addition funnel and the vessel is heated to 60 0C with vigorous stirring for lhr, during which time crystallization occurred. The temperature is then reduced to 20 0C over 2 hours and the reaction stirred for a further 16 hours. The crystals are then filtered, washed with methanol (300ml) and dried to give a 40-44% yield with 88-91 % diastereomeric excess (%de). These batches of material are then combined (59Og) and slurried in methanol (4L) at 50 0C for 16 hours, cooled to 22 0C over 1 hour and stirred for a further 1 hour. The solid is then filtered, washed with methanol (5 x 100ml) and dried to give 543.5g of white solid, 92.1% yield and 96.4 %de. This solid is reslurried in methanol (3.75L) at 60 C for 2 hours, cooled to 22 0C and stirred for 16 hours. The solid is then filtered, washed with methanol (5 x 100ml) and dried to give 511.83g of white solid, 94.2% yield and 98.1 %de.495g of this material is then slurried in 3L of methyl t-butyl ether (MTBE) and HCI (3eq) in MTBE (IL) is added slowly over 2 hours with stirring. This material is then heated to 50 0C for 1 hour, cooled to 5 0C and stirred over night. The solid is then filtered, washed with MTBE and dried to give 179.5g of white solid, 96% yield. This material, the hydrochloride salt of (i?)-<strong>[54012-73-6]3-aminopiperidine</strong>, is analysed by chiral HPLC and determined to be of >99% chemical purity and >98%ee.
28%	In water; at 35 - 55℃;	Add <strong>[54012-73-6]3-aminopiperidine</strong> 50g (0.5mol) to a 500ml reaction vialAnd 350g (19.44mol) of water, after stirring at room temperature,179 g (0.50 mol) of the resolving agent D-dibenzoyltartaric acid was added in portions.After the addition is completed, the temperature is controlled at 35 to 55 degrees Celsius.Stir the reaction for 1-2 hours and slowly cool to room temperature.Stirring for 5 to 8 hours, after crystallization is completed,Filtration gave 89.4 g of the wet product of the compound shown, and the ee value was 76.3%.The obtained wet product was added to 625.8 g (34.77 mol) of water and stirred well.The temperature is controlled at 35 to 55 C for 1 to 2 hours.Then slowly cool to room temperature 20 ~ 30 C, stirring and crystallization for 5 ~ 8 hours,After the crystallization is completed, the wet product of the compound shown in the figure 4 is obtained by filtration.The compound 4 was dried to 64.7 g (0.14 mol), the ee value was 89.6%, and the yield was 28%.

Reference： [1]Patent: WO2007/75630,2007,A1 .Location in patent: Page/Page column 4-5
[2]Patent: CN108689914,2018,A .Location in patent: Paragraph 0088-0090; 0094-0096

26
[ 54012-73-6 ]
acetylmandelic acid [ No CAS ]
C₅H₁₂N₂*C₁₀H₁₀O₄ [ No CAS ]
C₅H₁₂N₂*C₁₀H₁₀O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20℃; for 24h;	Racemic <strong>[54012-73-6]3-aminopiperidine</strong> is screened against 20 potential resolving agents to determine if any produce suitable diastereomeric salt crystals. Initially, 0.2 g of racemate is dissolved in 2ml MeOH, 1 mole eq of the resolving agent is added and any crystals obtained are isolated after stirring at room temperature for 24 hours. Where crystals do not form, the solvent is removed and replaced with a mixture of ethanol, isopropanol and ethyl acetate in an attempt to produce crystals of diastereomeric salts. The salts and liquors are recovered, cracked to liberate 3-aminopirhoeridine free base and the enantiomeric excess (ee) of the <strong>[54012-73-6]3-aminopiperidine</strong> from Crystals and in the mother liquors (ML) is determined as well as the Yield of Crystals. Results are shown in the Table below.The data in the table above indicate that dibenzoyltartric acid, di(ortho-tolyl)tartaric acid, and iV-acetylphenylalanine are surprisingly suitable for use as resolving agents.

Reference： [1]Patent: WO2007/75630,2007,A1 .Location in patent: Page/Page column 4

27
[ 54012-73-6 ]
copper(II) bis(tetrafluoroborate) [ No CAS ]
Cu((RS)-3-aminopiperidine)2(BF₄)2 [ No CAS ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548

28
[ 54012-73-6 ]
copper(II) perchlorate [ No CAS ]
Cu(3-aminopiperidine)2(ClO₄)2 [ No CAS ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548

29
[ 54012-73-6 ]
copper(II) perchlorate [ No CAS ]
Cu((RS)-3-aminopiperidine)2(ClO₄)2 [ No CAS ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548
[2]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548

30
[ 54012-73-6 ]
copper(II) bromide monohydrate [ No CAS ]
CuBr((RS)-3-aminopiperidine)Br * H₂O [ No CAS ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548

31
[ 54012-73-6 ]
copper(II) nitrate monohydrate [ No CAS ]
Cu((RS)-3-aminopiperidine)2(NO₃)2 [ No CAS ]

Reference： [1]Journal of the Chemical Society, Dalton Transactions,1988,p. 1543 - 1548

32
[ 54012-73-6 ]
[ 100-52-7 ]
N-(phenylmethylene)piperidine-3-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 20℃; for 3h;	16a) 1-[2-(4-fluorophenyl)ethvnpiperidine-3-amine. (Compound Xl: R3 = 4-F, R4 = H, R6+R7 = -CH2-CH2-CH2-, Y = CH, W = N, n = 0, p = 1 , m = 2). Benzaldehyde (21.2 g; 0.2 mol) was added, dropwise, to a solution of <strong>[54012-73-6]3-aminopiperidine</strong> (20 g; 0.2 mol) in toluene (80 ml). The solution thus obtained was stirred at room temperature, After 3 h the solvent was removed by evaporation at reduced pressure and the residue was taken up twice with toluene. 29 g N-(phenylmethylene)piperidine-3-amine was thus obtained, and was used in the subsequent reactions without further purification.An aliquot of this product (1.88 g, 10 mmol) was used, according to the procedure described in Example 7d), together with 1-(2- bromoethyl)-4-fluorobenzene (Example 7c) (2.0 g; 10 mmol).1.5 g of 1-[2-(4-fluorophenyl)ethyl]piperidine-3-amine was thus obtained.1H-NMR (delta ppm, CDCI3): 1.00-2.20 (m, 8 H), 2.40-2.90 (m, 7 H), 6.80- 7.20 (m, 4 H)

Reference： [1]Patent: WO2008/61688,2008,A1 .Location in patent: Page/Page column 45-46
[2]ChemMedChem,2018,vol. 13,p. 1597 - 1607

33
[ 54012-73-6 ]
[ 127294-73-9 ]
[ 54012-73-6 ]

Reference： [1]Advanced Synthesis and Catalysis,2008,vol. 350,p. 807 - 812

34
[ 54012-73-6 ]
[ 2164-34-3 ]
[ 1106939-09-6 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 153℃; for 2h;Microwave irradiation;	EXAMPLE 82: l-(2,3-Dihydrobenzo[l,4]dioxin-2-ylmethyl)piperidin-3-ol. A mixture of 2-bromomethyl-2,3-dihydrobenzo[ 1 ,4]dioxine (2.26 g, 9.88 mmol), piperidin-3-ol (1.0 g, 9.88 mmol) and K2CO3 (6.8 g, 49.43 mmol) in DMF (30 ml) was heated under microwaves at 153 C for 120 min to give the crude title compound after the usual work-up. The product was purified by column chromatography (DCM/MeOH, 98:2). 1H NMR (DMSO-d6): delta 1.04 (m, IH), 1.38 (m, IH), 1.41 (m, IH), 1.59 (m, IH), 1.60-2.10 (m, 3H), 2.40-2.90 (m, 3H), 3.45 (br. s, IH), 3.93 (m, IH), 4.29 (m, 2H), 4.61 (m, IH), 6.82 (m, 4H).

Reference： [1]Patent: WO2009/13390,2009,A1 .Location in patent: Page/Page column 70

35
[ 54012-73-6 ]
[ 1082604-63-4 ]
[ 1082604-72-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 5294 - 5298

36
[ 54012-73-6 ]
[ 128666-84-2 ]
[ 1166854-96-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3019 - 3022

37
[ 54012-73-6 ]
[ 108-77-0 ]
C₈H₁₁Cl₂N₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 945 - 949

38
[ 54012-73-6 ]
[ 1214284-59-9 ]
C₃₆H₅₂N₆O₆ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 1388 - 1394

39
[ 54012-73-6 ]
[ 1493-27-2 ]
[ 1247828-69-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 3138 - 3141

40
[ 54012-73-6 ]
[ 1318802-89-9 ]
C₃₀H₄₀N₆O₅ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4203 - 4205

41
[ 57120-54-4 ]
[ 54012-73-6 ]
[ 1258779-36-0 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 6277 - 6285

42
[ 54012-73-6 ]
[ 127294-73-9 ]

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 221 - 224

43
[ 54012-73-6 ]
[ 54012-73-6 ]

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 221 - 224

44
[ 54012-73-6 ]
[ 13505-32-3 ]
C₅H₁₂N₂*2C₁₆H₁₇NO₄S [ No CAS ]
C₅H₁₂N₂*2C₁₆H₁₇NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
4.4 g	In ethanol; at 20 - 60℃;	A typical experimental procedure involving the preparation of (S)-1/2(S)-2 salt is as follows (Table 1, entry 11): to a 300 mL flask, free diamine (RS)-1 (3.0 g, 30.0 mmol) and ethanol (90 g) were added. The solution was stirred, and then (S)-2 (9.6 g, 30.0 mmol) was added at room temperature, and heated up to approximately 60 C to give a clear solution. The mixture was gradually cooled to 37 C, kept for 2 h at 36-38 C (corresponding to the crystallization temperature), and then gradually cooled again to 20 C. After aging the suspension at the same temperature for 2 h, the crystals were filtered off and washed twice with ethanol (8 mL in total) to yield wet salt crystals, which were dried at 60 C for 3 h to afford the crude (S)-1/2(S)-2 salt (6.0 g, 8.12 mmol, yield 27%, 89% de, E 48%).The crude salt was recrystallized from ethanol. To a 500 mL flask, (S)-1/2(S)-2 salt (5.0 g, 6.77 mmol) and ethanol (230 g) were added. The suspension was stirred, then heated up to approximately 72 C to give a clear solution. The solution was then gradually cooled, seeded (2 mg) at 71 C, kept for 2 h at 62-64 C (corresponding to the crystallization temperature), and then cooled again to 20 C. After leaving the suspension at this temperature overnight, the crystals were filtered off and washed twice with ethanol (8 mL in total) to give wet salt crystals, which were dried at 60 C for 3 h to afford pure (S)-1/2(S)-2 salt (4.4 g, yield 88%, 96% de). Analytical data for the recrystallized salt are as follows. (S)-1/2(S)-2: (c 0.01, MeOH/H2O = 1/1); 96% de; Mp 193.0-195.0 C; IR (KBr) cm-1: 3449, 3211, 3185, 1655, 1551, 1524, 1390, 1323, 1162; 1H NMR (CD3OD, 500 MHz): delta 7.55-7.53 (4H, m), 7.22 (4H, d, J = 8.0 Hz), 7.18-7.12 (10H, m), 3.82 (2H, dd, J = 7.5, 5.0 Hz), 3.36 (1H, dd, J = 12.0, 4.0 Hz), 3.30-3.26 (1H, m), 3.15 (1H, dt, J = 13.0, 4.0 Hz), 3.01 (2H, dd, J = 13.5, 5.0 Hz), 2.86-2.81 (1H, m), 2.84 (2H, dd, J = 13.5, 7.5 Hz), 2.81 (1H, dd, J = 12.0, 10.0 Hz), 2.09-2.03 (1H, m), 1.94 (1H, dquit, J = 15.0, 4.0 Hz), 1.70 (1H, dtt, J = 15.0, 11.0, 4.0 Hz), 1.55 (1H, dtd, J = 13.0, 11.0, 4.0 Hz); Anal. Calcd for C37H46N4O8S2 (FW 738.91): C, 60.14; H, 6.27; N, 7.58. Found C, 60.14; H, 6.13; N, 7.63.

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 221 - 224

45
[ 54012-73-6 ]
[ 13505-32-3 ]
C₅H₁₂N₂*2C₁₆H₁₇NO₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 20 - 60℃;	To a 50 mL flask, free diamine (RS)-1 (3.0 g, 30.0 mmol) and methanol (18 g) were added. The solution was stirred, and (S)-2 (9.6 g, 30.0 mmol) was added at room temperature, and then heated up to approximately 60 C to give a clear solution. The mixture was gradually cooled to 35 C, kept for 2 h at 34-36 C (corresponding to the crystallization temperature), and then gradually cooled again to 20 C. After aging the suspension at this temperature for 2 h, crystals were filtered off and washed twice with methanol (6 mL in total) to yield wet salt crystals, which were dried at 60 C for 3 h to afford the crude (R)-1/2(S)-2/H2O salt (5.0 g, 6.61 mmol, yield 22%, 91% de, E 40%).The crude salt can be recrystallized from methanol or 92% ethanol to afford pure (R)-1/2(S)-2/H2O salt. The test results are follows; from methanol: yield 83%, >99% de; from 92% ethanol: yield 83%, >99% de. Analytical data for the recrystallized salt are as follows. (R)-1/2(S)-2/H2O: (c 0.01, MeOH/H2O = 1/1); >99% de; Mp 175.5-177.0 C; IR (KBr) cm-1: 3384, 3228, 1656, 1569, 1411, 1386, 1306, 1160; 1H NMR (CD3OD, 500 MHz): delta 7.55-7.53 (4H, m), 7.22 (4H, d, J = 8.0 Hz), 7.17-7.11 (10H, m), 3.82 (2H, dd, J = 7.5, 5.0 Hz), 3.35 (1H, dd, J = 12.5, 4.0 Hz), 3.28-3.24 (1H, m), 3.15 (1H, dt, J = 12.5, 4.0 Hz), 3.01 (2H, dd, J = 13.5, 5.0 Hz), 2.87-2.80 (1H, m), 2.84 (2H, dd, J = 13.5, 7.5 Hz), 2.80 (1H, dd, J = 12.5, 9.5 Hz), 2.08-2.03 (1H, m), 1.97-1.90 (1H, m), 1.70 (1H, dtt, J = 14.5, 11.0, 4.0 Hz), 1.55 (1H, dtd, J = 14.0, 11.0, 4.0 Hz); Water content (KF): calcd for 1.0 equiv: 2.38%. found: 2.38%. Anal. Calcd for C37H48N4O9S2 (FW 756.93): C, 58.71; H, 6.39; N, 7.40. Found C, 58.77; H, 6.29; N, 7.39.

Reference： [1]Tetrahedron Asymmetry,2012,vol. 23,p. 221 - 224

46
[ 54012-73-6 ]
[ 1042985-59-0 ]
[ 1042982-37-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4645 - 4649

47
[ 54012-73-6 ]
(S)-2-(3-(4-chlorophenyl)ureido)-propionic acid [ No CAS ]
(S)-3-aminopiperidine di(S)-2-(3-(4-chlorophenyl)ureido)-propionate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In ethanol; water; at 22 - 70℃; for 2h;	A mixture of 350 mg (3,5 mmol) <strong>[54012-73-6]rac-APIP</strong> and 1723 mg (7 mmol (S)-2-(3-(4- chlorophenyl)ureido)-propionic acid in 7000 mg of aqueous ethanol (50%(v/v)) was homogenized at 70C and cooled down to 40C thereby obtaining a precipitation. The suspension was stirred at this temperature for 1 h and then at r.t. for another 1 h. The solid was collected by filtration, washed with mother liquor, isopropanol, TBME and pentane, (1 ml each) and dried to afford (S)-APIP-2 L-p-Chlor-PC-Ala-2 H20. Yield: 1025 mg, 93% (based on the amount of enantiomer used). Enantiomeric ratio S/R =90.04 : 9.96. The obtained acid addition salt was purified by stirring in 5.0 g of aqueous ethanol (50%(v/v)) at 70C, then at r.t. Yield: 858 mg, 78% (based on the amount of enantiomer used). Enantiomeric ratio S/R = 99. 7: 0.3. Melting point: 138. Specific rotation [a]D20= +3.2 (c=0.5, MeOH)

Reference： [1]Patent: WO2014/128139,2014,A1 .Location in patent: Page/Page column 38

48
[ 54012-73-6 ]
N-[5-chloro-2-(4-chlorophenoxy)phenyl]-N-{2-[2,3-dihydro-1H-inden-2-yl(methyl)amino]-2-oxoethyl}glycine [ No CAS ]
C₃₁H₃₄Cl₂N₄O₃ [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 4336 - 4340

49
[ 54012-73-6 ]
7-(4-methoxybenzyl)-6-oxo-5-(1-((trifluoromethyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)-6,7-dihydrothieno[2,3-b]pyridin-4-yl trifluoromethanesulfonate [ No CAS ]
C₂₈H₂₆F₃N₅O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 2h;	General procedure: To a solution of the bis-triflate (0.3 mmol) prepared above in acetonitrile (5 mL), the corresponding amine (0.8 mmol) dissolved in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, and then evaporated under reduced pressure. The yellow oil obtained was used for the next step without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4882 - 4892

50
[ 54012-73-6 ]
2-chloro-7-(4-methoxybenzyl)-6-oxo-5-(1-((trifluoromethyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)-6,7-dihydrothieno[2,3-b]pyridin-4-yl trifluoromethanesulfonate [ No CAS ]
C₂₈H₂₅ClF₃N₅O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 2h;	General procedure: To a solution of the bis-triflate (0.3 mmol) prepared above in acetonitrile (5 mL), the corresponding amine (0.8 mmol) dissolved in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, and then evaporated under reduced pressure. The yellow oil obtained was used for the next step without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4882 - 4892

51
[ 54012-73-6 ]
2-bromo-7-(4-methoxybenzyl)-6-oxo-5-(1-((trifluoromethyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)-6,7-dihydrothieno[2,3-b]pyridin-4-yl trifluoromethanesulfonate [ No CAS ]
C₂₈H₂₅BrF₃N₅O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 2h;	General procedure: To a solution of the bis-triflate (0.3 mmol) prepared above in acetonitrile (5 mL), the corresponding amine (0.8 mmol) dissolved in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, and then evaporated under reduced pressure. The yellow oil obtained was used for the next step without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4882 - 4892

52
[ 54012-73-6 ]
7-(4-methoxybenzyl)-2-methyl-6-oxo-5-(1-((trifluoromethyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)-6,7-dihydrothieno[2,3-b]pyridin-4-yl trifluoromethanesulfonate [ No CAS ]
C₂₉H₂₈F₃N₅O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 2h;	General procedure: To a solution of the bis-triflate (0.3 mmol) prepared above in acetonitrile (5 mL), the corresponding amine (0.8 mmol) dissolved in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, and then evaporated under reduced pressure. The yellow oil obtained was used for the next step without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4882 - 4892

53
[ 54012-73-6 ]
4-(4-methoxybenzyl)-5-oxo-6-(1-((trifluoromethyl)sulfonyl)-1H-benzo[d]imidazol-2-yl)-4,5-dihydrothieno[3,2-b]pyridin-7-yl trifluoromethanesulfonate [ No CAS ]
C₂₈H₂₆F₃N₅O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃; for 2h;	General procedure: To a solution of the bis-triflate (0.3 mmol) prepared above in acetonitrile (5 mL), the corresponding amine (0.8 mmol) dissolved in acetonitrile (3 mL) was added dropwise. The reaction mixture was stirred at room temperature for 2 h, and then evaporated under reduced pressure. The yellow oil obtained was used for the next step without further purification.

Reference： [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 4882 - 4892

54
[ 54012-73-6 ]
[ 38267-96-8 ]
N-3-piperidinyl-6-(1,3-thiazol-5-yl)-4-quinazolinamine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 3548 - 3571

55
[ 54012-73-6 ]
[ 38267-96-8 ]
C₁₃H₁₅BrN₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 3548 - 3571

56
[ 54012-73-6 ]
5-(1-(piperidin-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2015,vol. 6,p. 1317 - 1330

57
[ 54012-73-6 ]
3-azidopiperidine [ No CAS ]

Reference： [1]ACS Chemical Neuroscience,2015,vol. 6,p. 1317 - 1330

58
[ 54012-73-6 ]
C₁₂H₈ClN₃O [ No CAS ]
C₁₇H₁₉N₅O [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2016,vol. 26,p. 1803 - 1808

59
[ 54012-73-6 ]
N-benzenesulphonyl-L-aspartic acid [ No CAS ]
C₁₀H₁₁NO₆S*C₅H₁₂N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In methanol; water;	Using 5.0 mmol of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,The results of optical resolution with various optical resolving agents are shown in Table 1.In Comparative Examples 2 to 5, 7, 8, 12 and 14,It can not be optically split,A racemate was obtained.In Comparative Examples 1, 6, 9, 10, 15,Although optical resolution was possible,The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> is 84% e. E.Or less,The optical purity was low.In Comparative Examples 11 and 13, salt of <strong>[54012-73-6]3-aminopiperidine</strong> could not be obtained.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Page/Page column 0044; 0045

60
[ 54012-73-6 ]
[ 105441-57-4 ]
C₁₄H₁₃NO₄S*C₅H₁₂N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
30%	In methanol;	Using 5.0 mmol of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,The results of optical resolution with various optical resolving agents are shown in Table 1.In Comparative Examples 2 to 5, 7, 8, 12 and 14,It can not be optically split,A racemate was obtained.In Comparative Examples 1, 6, 9, 10, 15,Although optical resolution was possible,The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> is 84% e. E.Or less,The optical purity was low.In Comparative Examples 11 and 13, salt of <strong>[54012-73-6]3-aminopiperidine</strong> could not be obtained.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0044; 0045

61
[ 54012-73-6 ]
[ 99076-56-9 ]
C₁₀H₁₃NO₄S*C₅H₁₂N₂ [ No CAS ]
C₁₀H₁₃NO₄S*C₅H₁₂N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	Using 5.0 mmol of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,The results of optical resolution with various optical resolving agents are shown in Table 1.In Comparative Examples 2 to 5, 7, 8, 12 and 14,It can not be optically split,A racemate was obtained.In Comparative Examples 1, 6, 9, 10, 15,Although optical resolution was possible,The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> is 84% e. E.Or less,The optical purity was low.In Comparative Examples 11 and 13, salt of <strong>[54012-73-6]3-aminopiperidine</strong> could not be obtained.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0044; 0045

62
[ 54012-73-6 ]
[ 143816-10-8 ]
(R)-3-aminopiperidine N-p-toluyl-L-glutamic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	In methanol; water; at 60℃;	In a sample bottle with stopper of capacity 10 ml,0.50 g (5.0 mmol) of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,1.33 g (5.0 mmol) of N-p-toluyl-L-glutamic acid,2.78 g of methanol,And 0.48 g of water, and the mixture was heated to 60 C. for dissolution,10 mg of N-p-toluyl-L-glutamate of (R) -<strong>[54012-73-6]3-aminopiperidine</strong> was added.After cooling to 10 C.,After filtering the precipitated crystals,And dried to obtain 0.84 g of a salt.The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> contained in the salt was 94.0% e. E. (R form).When a portion of this salt was collected and <strong>[54012-73-6]3-aminopiperidine</strong> was determined, the content was 27.3%This salt,It was confirmed to be a 1: 1 salt of <strong>[54012-73-6]3-aminopiperidine</strong> and Np-toluyl-L-glutamic acid. Yield 46%.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0033; 0034

63
[ 54012-73-6 ]
[ 143816-10-8 ]
(R)-3-aminopiperidine N-p-toluyl-L-glutamic acid salt [ No CAS ]
(S)-3-aminopiperidine N-p-toluyl-L-glutamic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; at 60℃;	0.50 g (5.0 mmol) of racemic <strong>[54012-73-6]3-aminopiperidine</strong>, 0.50 g1.33 g (5.0 mmol) of N-p-toluyl-L-glutamic acid,After charging 17.5 g of methanol, it was dissolved by warming to 60 C.,10 mg of N-p-toluyl-L-glutamate of (R) -<strong>[54012-73-6]3-aminopiperidine</strong> was added.After cooling to 27 C.,After filtering the precipitated crystals,And dried to obtain 0.94 g of a salt.The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> contained in the salt was 76.8% e. E. (R form). Yield 51%.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0040

64
[ 54012-73-6 ]
N-p-toluyl-D-glutamic acid [ No CAS ]
(S)-3-aminopiperidine N-p-toluyl-D-glutamic acid salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	In methanol; water; at 60℃;	In a sample bottle with stopper with a volume of 20 ml,1.00 g (10.0 mmol) of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,2.65 g (10.0 mmol) of N-p-toluyl-D-glutamic acid,5.55 g of methanol,And 0.97 g of water, and the mixture was heated to 60 C. for dissolution,10 mg of N-p-toluyl-D-glutamate of (S) -<strong>[54012-73-6]3-aminopiperidine</strong> was added.After cooling to 10 C.,After filtering the precipitated crystals,And dried to obtain 1.57 g of a salt.The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> contained in the salt was 95.5% e. E. (S form).A portion of this salt was collected to quantify <strong>[54012-73-6]3-aminopiperidine</strong>,The content rate is 27.5%This salt,It was confirmed to be a 1: 1 salt of <strong>[54012-73-6]3-aminopiperidine</strong> and Np-toluyl-D-glutamic acid.Yield 43%.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0037; 0038

65
[ 54012-73-6 ]
[ 20531-36-6 ]
C₁₁H₁₃NO₆S*C₅H₁₂N₂ [ No CAS ]
C₁₁H₁₃NO₆S*C₅H₁₂N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol; water;	Using 5.0 mmol of racemic <strong>[54012-73-6]3-aminopiperidine</strong>,The results of optical resolution with various optical resolving agents are shown in Table 1.In Comparative Examples 2 to 5, 7, 8, 12 and 14,It can not be optically split,A racemate was obtained.In Comparative Examples 1, 6, 9, 10, 15,Although optical resolution was possible,The optical purity of <strong>[54012-73-6]3-aminopiperidine</strong> is 84% e. E.Or less,The optical purity was low.In Comparative Examples 11 and 13, salt of <strong>[54012-73-6]3-aminopiperidine</strong> could not be obtained.

Reference： [1]Patent: JP5838590,2016,B2 .Location in patent: Paragraph 0044; 0045

66
[ 54012-73-6 ]
[ 1744-91-8 ]
3-nitro-N-(piperidin-3-yl)acridin-9-amine [ No CAS ]

Reference： [1]New Journal of Chemistry,2017,vol. 41,p. 4087 - 4095

67
[ 54012-73-6 ]
(R)-(+)-4-(2-chlorophenyl)-5,5-dimethyl-2-hydroxy-1,3,2-dioxaphosphorinane 2-oxide [ No CAS ]
(+)-4-(2-chlorophenyl)-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (R)-(+)-3-aminopiperidine [ No CAS ]
(+)-4-(2-chlorophenyl)-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane (S)-(-)-3-aminopiperidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.85 g; 5.8 g	In ethanol; water; for 2h;Reflux;	the 7.06g of (+)- 4-(2- chlorophenyl)-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane was dissolved into 60ml of 95% ethanol water, stirred, then added 2.12g of Racemic <strong>[54012-73-6]3-aminopiperidine</strong> was added, heated to reflux for 2h. the reaction was cooled down for crystallization, then precipitation of white solid , which was filtrated to obtain (+)-4-(2-chlorophenyl)-2-hydroxy-5,5- dimethyl-2- oxo-1,3,2-dioxaphosphorinane * (R)-(+)-<strong>[54012-73-6]3-aminopiperidine</strong> double salt 3.85g. then subjected to Mother liquor spin dry to obtain (+)- 4-(2-chlorophenyl)-2-hydroxy-5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinane * (S)-(-)-<strong>[54012-73-6]3-aminopiperidine</strong> double salt 5.8g

Reference： [1]Patent: CN104876856,2017,B .Location in patent: Paragraph 0037; 0038

68
[ 54012-73-6 ]
3-(R)-aminopiperidine dihydrochloride [ No CAS ]

Reference： [1]Patent: CN104876856,2017,B

69
[ 54012-73-6 ]
3-(R)-aminopiperidine dihydrochloride [ No CAS ]
(S)-(-)-3-aminopiperidine dihydrochloride [ No CAS ]

Reference： [1]Patent: CN104876856,2017,B

70
[ 54012-73-6 ]
[ 117-08-8 ]
C₁₃H₁₀Cl₄N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88.6%	With triethylamine; In toluene; for 48h;Reflux;	Step a will tetrachloro phthalic anhydride (142g) and 3 - amino piperidine (50.1g) mixing, adding 400 ml toluene and triethylamine (59.8g), refluxing separating water for 48 hours, evaporate the solvent. Residue by adding water and ethyl acetate, then adding triethylamine (about 60g), stirring to dissolve, extracted with ethyl acetate, to obtain the compound of formula b (163g, yield 88.6%).

Reference： [1]Patent: CN103450201,2017,B .Location in patent: Paragraph 0029; 0030

71
[ 54012-73-6 ]
[ 4808-48-4 ]
C₂₁H₂₀N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90.6%	In dichloromethane; at 20℃; for 3h;Reflux;	The steps will be a 2, 3 - diphenyl maleic anhydride (125g) and 3 - amino piperidine (50.1g) mixing, adding 1L dichloromethane, stirring at room temperature for 1 hour, the solvent is removed. Residue by adding acetic anhydride and sodium acetate mixture, heating to reflux 2 hours, after the reaction is complete, cooling, adding water and ethyl acetate extraction, to obtain the compound of formula d (150.5g, yield 90.6%).

Reference： [1]Patent: CN103450201,2017,B .Location in patent: Paragraph 0036-0037

72
[ 54012-73-6 ]
[ 110-13-4 ]
C₁₁H₁₈N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.1%	In toluene; for 6h;Inert atmosphere; Reflux;	The steps will be a 3 - amino piperidine (50.1g), 2, 5 - hexanedione (110 ml), toluene 200 ml mixing, nitrogen protection, stirring, heating reflux water diversion to the reaction is complete (about 6 hours). Cooling, ether treatment reaction solution, concentrated, compound of formula f results in the type 82.8g (yield 93.1%)

Reference： [1]Patent: CN103450201,2017,B .Location in patent: Paragraph 0044-0046

73
[ 54012-73-6 ]
[ 13528-93-3 ]
C₁₃H₂₆N₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.4%	With triethylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere;	The steps will be a 3 - amino piperidine (50.1g), 2, 5 - hexanedione (110 ml), toluene 200 ml mixing, nitrogen protection, stirring, heating reflux water diversion to the reaction is complete (about 6 hours). Cooling, ether treatment reaction solution, concentrated, compound of formula f results in the type 82.8g (yield 93.1%)

Reference： [1]Patent: CN103450201,2017,B .Location in patent: Paragraph 0048-0050

74
[ 54012-73-6 ]
[ 21240-34-6 ]
C₂₀H₂₀N₂O₂ [ No CAS ]