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Chemical Structure| 127294-75-1 Chemical Structure| 127294-75-1

Structure of 127294-75-1

Chemical Structure| 127294-75-1

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Product Details of [ 127294-75-1 ]

CAS No. :127294-75-1
Formula : C5H13ClN2
M.W : 136.62
SMILES Code : NC1CNCCC1.[H]Cl

Safety of [ 127294-75-1 ]

Application In Synthesis of [ 127294-75-1 ]

* 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.

  • Downstream synthetic route of [ 127294-75-1 ]

[ 127294-75-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 93107-30-3 ]
  • [ 127294-75-1 ]
  • [ 138060-06-7 ]
  • 2
  • [ 94695-52-0 ]
  • [ 127294-75-1 ]
  • [ 127294-60-4 ]
  • 3
  • [ 127294-75-1 ]
  • [ 118829-17-7 ]
  • [ 138060-04-5 ]
  • 4
  • [ 578-57-4 ]
  • [ 127294-75-1 ]
  • 3-(2-methoxyphenylamino)piperidine [ No CAS ]
  • 1-(2-methoxyphenyl)-3-(2-methoxyphenylamino)piperidine [ No CAS ]
  • 1-(2-methoxy-phenyl)-piperidin-3-ylamine [ No CAS ]
  • 5
  • [ 623-00-7 ]
  • [ 127294-75-1 ]
  • 3-[(4-cyanophenyl)amino]piperidine [ No CAS ]
  • 6
  • [ 23095-31-0 ]
  • [ 127294-75-1 ]
  • [ 956468-14-7 ]
YieldReaction ConditionsOperation in experiment
61% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h; A solution of 3-aminopipehdine dihydrochloride (268 mg, 1.55 mmol), 3,4-bis(methyl)oxybenzenesulfonyl chloride (752 mg, 3.17 mmol) and DIEA (1.13 ml_, 6.51 mmol) in 25 ml. DCM was stirred at room temperature for 2 h. The reaction was washed with 1 N HCI followed by saturated bicarbonate solution. The organics were separated, dried over Na2SO4, filtered and concentrated in vacuo. The desired product was afforded as white solids (470 mg, 61 % yield). LCMS (M+H = 486.9, M-H = 485.2). 1H NMR (DMSO-d6, 400MHz) delta: 7.66 (1 H, d), 7.36 (1 H, dd), 7.31 (1 H, d), 7.17 (1 H, dd), 7.1 1 (2 H, m), 7.02 (1 H, <n="82"/>d), 3.83 (6 H, s), 3.79 (3 H, s), 3.30 (2 H, m), 3.00 (1 H, m), 2.24 (1 H, m), 2.03 (1 H, m), 1.62 (1 H, m), 1.46 (1 H, m), 1.31 (1 H, m), 1.01 (1 h, M).
  • 7
  • [ 769158-11-4 ]
  • [ 127294-75-1 ]
  • 2-((2-(3-aminopiperidin-1-yl)-8-chloro-4-oxoquinazolin-3(4H)-yl)methyl)benzonitrile [ No CAS ]
  • 8
  • [ 607-69-2 ]
  • [ 127294-75-1 ]
  • [ 22115-41-9 ]
  • 2-((2-(3-aminopiperidin-1-yl)-4-oxoquinazolin-3(4H)-yl)methyl)benzonitrile [ No CAS ]
  • 9
  • [ 769158-09-0 ]
  • [ 127294-75-1 ]
  • 2-((2-(3-aminopiperidin-1-yl)-8-methoxy-4-oxoquinazolin-3(4H)-yl)methyl)benzonitrile [ No CAS ]
  • 10
  • [ 389062-89-9 ]
  • [ 127294-75-1 ]
  • [ 485820-18-6 ]
YieldReaction ConditionsOperation in experiment
43% With triethylamine; In isopropyl alcohol; at 130℃;Microwaves; [2- (8-CHLORO-1, 3-DIMETHYL-2, 6-DIOXO-1,] 2,3, 6-tetrahydropurin-7-ylmethyl) benzonitrile [(1A)] (100 mg, 0.30 [MMOL)] and 3-aminopiperidine [DIHYDROCHLORIDE] (262 mg, 1.52 [MMOL)] were dissolved in 20 mi of 2-propanol and triethylamine (0.127 [MI,] 0.91 [MMOL)] and subjected to microwaves (method F, [130C,] [300W)] for ten hours. The solvents were evaporated and the crude product was purified by preparative HPLC, (method [A1,] Rt = 6.78 min. ) to give the title compound as oily crystals. Yield : 66 mg (43%). 'H-NMR [(MEOD,] 300 MHz) [8] : 1.73 (m, 3H), 2.10 (m, [1H),] 3.02 (m, [1H),] 3.20 (m, 2H), 3.27 (s, 3H), 3.52 (m, 4H), 3.65 (m, 1H), 5.59 (s, 2H), 7.22 (d, 1H), 7.47 (m, [1 H),] 7.61 (m, [1H),] 7.78 (d, [1 H).] HPLC-MS (Method B): m/z = 394 (M+1), Rt = 1.55 min.
  • 11
  • [ 346597-03-3 ]
  • [ 127294-75-1 ]
  • [ 485820-41-5 ]
YieldReaction ConditionsOperation in experiment
7% With triethylamine; In isopropyl alcohol; at 130℃; for 10h; [7- (2-BROMOBENZYL)-8-CHLORO-1, 3-DIMETHYL-3,] 7-dihydropurine-2,6-dione [(10A)] (100 mg, 0.26 [MMOL)] and <strong>[127294-75-1]3-aminopiperidine dihydrochloride</strong> (226 mg, 1.31 [MMOL)] were dissolved in 2-propanol (20 [ML),] triethylamine (0.109 [MI,] 0.78 [MMOL)] and DMF (5 ml) and subjected to microwaves (method F, [130C,] [300W)] for ten hours. The solvents were evaporated and the crude product was purified by preparative HPLC, (method [A1,] Rt = 7.52 min.) to give the title compound as a brown oil. Yield : 10 mg (7%). HPLC-MS (Method B): m/z = 447 (M+), Rt = 2.05 min.
  • 12
  • [ 127294-75-1 ]
  • [ 105627-79-0 ]
  • [ 842135-73-3 ]
YieldReaction ConditionsOperation in experiment
86% With triethylamine; In dichloromethane; at 0℃; To a solution of <strong>[127294-75-1]3-aminopiperidine dihydrochloride</strong> (50 mg, 0.29 mmol) and triethylamine (0.14 ml, 1 mmol) in dichloromethane (5 ml) was added in small portions isoquinolin-5-ylsulphonyl chloride hydrochloride (64 mg, 0.28 mmol) with stirring and ice-cooling. Water (10 ml) was added to the reaction mixture after stirring overnight. The organic layer was separated and washed twice with water, dried (MGSO4) and concentrated in vacuo. The crude product was purified by flash silica column eluting with 10% methanol in dichloromethane to afford the target compound as a white solid (71 mg, 0.24 mmol, 86%). Characterising Data: (CL4HL7N302S) : MS (ESI) m/z 292.2 [(M+H) +], 1H NMR (CD30D, 250 MHz) 8 1.13-1. 23 (M, 1H), 1.47-1. 65 (M, 1H), 1.75-1. 89 (m, 2H), 2.41-2. 49 (m, 1H), 2.64- 2.86 (M, 2H), 3.59-3. 78 (m, 2H), 7.88 (t, J= 8 Hz, 1H), 8.46 (d, J= 8 Hz, 1H), 8.47 (DD, J= 5 Hz AND J= 2 Hz, 1H), 8. 62 (D, J= 8 Hz, 1H), 8.64 (d, J= 8 Hz, 1H), 9.42 (s, 1H).
  • 13
  • [ 668271-93-0 ]
  • [ 127294-75-1 ]
  • [ 668271-78-1 ]
  • 14
  • [ 4424-20-8 ]
  • [ 32315-10-9 ]
  • [ 127294-75-1 ]
  • [ 7087-68-5 ]
  • [ 535960-93-1 ]
YieldReaction ConditionsOperation in experiment
0.165 g (66%) With sodium hydrogencarbonate; EXAMPLE 17 N-Piperidin-3-yl-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxamide To a solution of 2,3,4,5-tetrahydro-1H-3-benzazepine (0.122 g, 0.825 mmol) and Hunig's base (0.17 mL, 0.128 g, 0.99 mmol) was added triphosgene (0.135 g, 0.454 mmol) at 0 C. The mixture was stirred at 0 C. for 1 hour and then at room temperature for 2 h. The mixture was again cooled to 0 C. and another portion of Hunig's base (0.78 mL, 0.576 g, 4.46 mmol) and <strong>[127294-75-1]3-aminopiperidine dihydrochloride</strong> (0.0.25 g, 1.44 mmol) were added and the mixture was stirred at room temperature for 16 h. Sodium bicarbonate solution was added and the mixture was extracted twice with CH2Cl2. The combined organic layers was dried over MgSO4 and filtered. The filtrate was concentrated in vacuo to dryness and the residue was subjected to column chromatography (CH2Cl2:MeOH:NH4Cl, 90:10:1) to give 0.165 g (66%) of colorless solid as the desired product: mp 214-216 C.; IR (diffuse reflectance) 3105, 3059, 3030, 3017, 2999, 2988, 2978, 2941, 2910, 2901, 2841, 1635, 1592, 1511, 1470, 1451, 1420, 1387, 1378, 1303, 1254, 1223, 947, 905, 740 cm-1; 1H NMR (400 MHz, DMSO-d6) delta7.15-7.10 (m, 4H), 3.63 (m, 1H), 3.34-3.31 (m, 5H), 3.20-3.10 (m, 1H), 2.92-2.77 (m, 6H), 2.05-1.97 (m, 1H), 1.76-1.72 (m, 1H), 1.56-1.46 (m, 2H); 13C NMR (100 MHz, DMSO-d6) delta163.4, 140.8, 129.1, 126.1, 48.9, 48.4, 47.3, 46.2, 36.4, 28.0, 22.4; MS (EI) m/z 273 (MH+); HRMS (FAB) calcd for C16H23N3O+H 274.1919, found 274.1923; Anal. calcd. for Cl16H23N3O+HCl: C, 62.02; H, 7.81; N, 13.56. Found: C, 61.80; H, 7.75; N, 13.44.
  • 15
  • [ 335428-58-5 ]
  • [ 127294-75-1 ]
  • 8-(3-aminopiperidinyl)-1-cyclopropyl-9-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 4 8-(3-aminopiperidinyl)-1-cyclopropyl-9-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid A series of procedures similar to Example 2 above is used using Ethyl-8-chloro-1-cyclopropyl-9-methoxy-4-oxo-4H-quinolizine-3-carboxylate (Precursor B) and 3-S-aminopiperidine dihydrochloride (Precursor E) as the starting materials.
  • 16
  • [ 436799-88-1 ]
  • [ 127294-75-1 ]
  • [ 1098598-01-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In acetonitrile; Example 2 8-(3-aminopiperidinyl)-1-ethyl-9-methoxy-4-oxo-4H-quinolizine-3-carboxylic acid, ethyl ester Ethyl-8-chloro-1-ethyl-9-methoxy-4-oxo-4H-quinolizine-3-carboxylate (Precursor A) (0.05 g) is dissolved in acetonitrile (3 ml) and triethylamine (0.3 ml). To this solution is added 3-S-aminopiperidine dihydrochloride (Precursor E) (0.055 g) and the mixture is stirred at 40 C. for five days. The reaction mixture is evaporated and the desired product obtained by recrystallization in isopropyl alcohol.
  • 17
  • [ 127294-75-1 ]
  • [ 190654-77-4 ]
  • [ 190654-14-9 ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; Analogously to Example 1, 6-(3-chloro-phenyl-amino)-9-ethyl-2-(3-formylamino-piperidin-1-yl)-9H-purine is obtained from 308 mg (1.0 mmol) of 2-chloro-6-(3-chloro-phenyl-amino)-9-ethyl-9H-purine [described in Stage 1.2], 190 mg (1.1 mmol of <strong>[127294-75-1]3-amino-piperidine dihydrochloride</strong> and 0.314 ml (2.1 mmol) of 1,8-diazabicyclo[5.4.0]undec-7-ene(1.5-5) (= DBU) in 7.5 ml of dimethylformamide in a glass pressure reactor after 40 h at 150 C and purification by means of column chromatography (MPLC); m.p. 184.3C; FAB-MS: (M+H)+ = 400; HPLC: tret (grad20/2) = 12.56 minutes. Example 49
  • 18
  • [ 127294-75-1 ]
  • [ 66548-88-7 ]
  • 1-(6-(4-trifluoromethylphenyl)-pyridazin-3-yl)-piperidin-3-ylamine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
25% Example 38 (General procedure A) 1-[6-(4-Trifluoromethylphenyl)pyridazin-3-yl]piperidin-3-ylamine, hydrochloride: 3-Chloro-6-(4-trifluoromethylphenyl)pyridazine (0.2 g, 0.77 mmol), 3-aminopiperidine dihy- drochloride (0.27 g, 1 .54 mmol) and potassium carbonate (0.53 g, 3.87 mmol) were mixed in acetone (4 ml_) in a 20 ml_ microwave vessel. The reaction mixture was heated in a micro- wave oven for 2 h at 1200C. The reaction mixture was filtered and the precipitate was washed with MeOH. The combined organic phases were evaporated. The crude oil was purified on a silicagel column (0.04-0.063 mesh) using dichloromethane/MeOH (9:1 ) as eluent. This afforded 110 mg of a oil that was dissolved in MeOH and acidified with concentrated HCI (5 ml_). The mixture was evaporated and the residue was dissolved in MeOH (1 ml_) and ether (100 ml_) was added with stirring. The mixture was evaporated to give 76 mg (25 %) of the title compound as a yellow solid. Mp = 97-1350C.1H NMR (400 MHz, CD3OD) delta 1 .74 (m, 2H) 1 .93 (m, 1 H) 2.16 (m, 1 H) 3.35 (m, 3H) 3.44 (m, 1 H) 4.14 (Cj1Cl1 1 H) 4.45 (d,d, 1 H) 4.97 (s, 3H) 7.39 (d, 1 H) 7.75 (d, 2H) 7.78 (s, 2H) 7.95 (s, 1 H) 8.13 (d, 2H).HPLC-MS (Method G): M+1 = 323; tr= 1 .1 17 min.
  • 19
  • [ 389062-89-9 ]
  • [ 127294-75-1 ]
  • [ 76-05-1 ]
  • [ 485820-18-6 ]
YieldReaction ConditionsOperation in experiment
43% 2-(8-Chloro-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydropurin-7-ylmethyl)benzonitrile (1A) (100 mg, 0.30 mmol) and <strong>[127294-75-1]3-aminopiperidine dihydrochloride</strong> (262 mg, 1.52 mmol) were dissolved in 20 ml of 2-propanol and triethylamine (0.127 ml, 0.91 mmol) and subjected to microwaves (method F, 130 C., 300W) for ten hours. The solvents were evaporated and the crude product was purified by preparative HPLC, (method A1, Rt=6.78 min.) to give the title compound as oily crystals.
  • 20
  • [ 346597-03-3 ]
  • [ 127294-75-1 ]
  • [ 76-05-1 ]
  • [ 485820-41-5 ]
YieldReaction ConditionsOperation in experiment
7% 7-(2-Bromobenzyl)-8-chloro-1,3-dimethyl-3,7-dihydropurine-2,6-dione (10A) (100 mg, 0.26 mmol) and <strong>[127294-75-1]3-aminopiperidine dihydrochloride</strong> (226 mg, 1.31 mmol) were dissolved in 2-propanol (20 ml), triethylamine (0.109 ml, 0.78 mmol) and DMF (5 ml) and subjected to microwaves (method F, 130 C., 300W) for ten hours. The solvents were evaporated and the crude product was purified by preparative HPLC, (method A1, Rt=7.52 min.) to give the title compound as a brown oil.
  • 21
  • [ 24424-99-5 ]
  • [ 1215167-26-2 ]
  • [ 127294-75-1 ]
  • [ 1215205-23-4 ]
YieldReaction ConditionsOperation in experiment
81% Preparation Example 1-70-1{1-[6-Propyl-4-(3-trifluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-thieno[2,3-d]pyrimidin-2-yl]-piperidin-3-yl}-carbamic acid tert-butyl ester 40 mg (0.1 mmol) of the compound obtained from Preparation Example 1-1-3 and 35 mg (0.2 mmol) of 3-aminopiperidine; 2 hydrochloride were dissolved in 2 mL of butanol, heated to 150 C. in a microwave reactor and stirred for 1 hour. The reaction solution was cooled to room temperature, distilled in vacuo and dissolved in 5 mL of methanol. To the solution was added 109 mg (0.5 mmol) of di-tert-butyl dicarbonate, and stirred for 16 hours. A solvent was removed by distillation in vacuo. The residue was purified by column chromatography using a mixed solution of methanol and dichloromethane in the ratio of 3:97 to obtain the title compound 46 mg (81%).1H NMR (400 MHz, CDCl3); delta 6.79 (1H, s), 5.19 (2H, m), 4.484.25 (4H, m), 4.204.10 (2H, m), 3.63 (1H, m), 3.45 (1H, m), 3.30 (1H, m), 2.77 (2H, t), 1.91 (1H, m), 1.821.53 (5H, m), 1.45 (9H, s), 1.00 (3H, t)
  • 22
  • [ 462-08-8 ]
  • [ 127294-75-1 ]
  • 23
  • [ 17026-42-5 ]
  • [ 127294-75-1 ]
  • [ 1352756-66-1 ]
  • (S)-3-aminopiperidine dibenzoyl (D)-tartrate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Sodium hydroxide (10.3 g of a 46-48% solution, 4.74 g a./., 1 18.5 mmol) was added by drops to an ice-water bath cooled suspension of rac-3- aminopiperidine dihydrochloride (rac-4, 10. Og, 57.8 mmol) in methanol (145 ml). Once the addition was complete the solution was stirred at room temperature for one hour and then filtered (through porosity No.3 filter paper: 4.90g sodium chloride collected, 71 % of theory) and the solid was washed with methanol (2 ml). Dibenzoyl-(D)-tartaric acid (22.16 g, 61 .84 mmol) was then added to the solution which was subsequently heated to 60 C (very gentle reflux) for 2 hours. The resultant suspension was cooled to 20 C over 1 -2 hours and then stirred at this temperature for 20 hours. The solid was collected by filtration and sequentially washed with a mixture of methanol/water (19 ml/1 ml), then methanol (20 ml) and dried in vacuo to provide the title compound as a white solid (19.9 g, 75%) with 13.2% de.
  • 24
  • [ 17026-42-5 ]
  • [ 127294-75-1 ]
  • [ 1352756-66-1 ]
YieldReaction ConditionsOperation in experiment
41% Sodium hydroxide (44.3 g of a 10-12% solution, 4.74 g a.i., 1 18.5 mmol) was added in drops to an ice-water bath cooled suspension of rac-3- aminopiperidine dihydrochloride (10. Og, 57.8 mmol) in methanol (70 ml). Once the addition was complete the solution was stirred at room temperature for one hour, filtered through porosity No.3 filter paper (4.90g sodium chloride collected, 71 % Th.), and the solid was washed with methanol (10 ml). Dibenzoyl-(D)-tartaric acid (22.16 g, 61 .84 mmol) was then added to the solution which was subsequently heated to 60 C (very gentle reflux) for 2 hours. The resultant suspension was cooled to 20-25 C over 1 -2 hours and then stirred at 20-25C for 8 hours. The reaction mixture was then cooled further to -10 to -5 C and stirred at this temperature for 8 hours. The solid was collected by filtration and washed with a methanol (10 mL) and dried in vacuo to provide the title compound as a white solid (10.8 g, 41 %) with 93% de.
  • 25
  • [ 1352756-67-2 ]
  • [ 127294-75-1 ]
  • 26
  • [ 1353094-64-0 ]
  • [ 127294-75-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In water; acetic acid; for 18h;Reflux;Product distribution / selectivity; Preparation of rac-3-aminopiperidine dihydrochloride (rac- 4) Acetic anhydride (65.1 g, 638 mmol) was added dropwise over 10 minutes to a solution of 3-aminopyridine (50.0 g, 531 mmol) in acetic acid (150 ml) cooled to 10 C. An exotherm of 15 C was observed. Once the addition was complete the solution was stirred at room temperature for 2 hours and then added to a glass liner along with 10% palladium/carbon (2.5 g). After securing in a pressure vessel, the solution was charged with nitrogen to a pressure of 10 bar, stirred until equilibrated, and then vented. This nitrogen charge/stir/vent cycle was repeated two times. The vessel was then charged with hydrogen to a pressure of 1 -2 bar and vented, without stirring. This hydrogen charge/vent cycle was repeated two times. The vessel was then charged to 10 bar, heated to 80 C and stirred, with the pressure being maintained between 16-20 bar. After 10 hours hydrogen consumption ceased. The contents were cooled to room temperature and the vessel was charged with nitrogen to a pressure of 10 bar, stirred for 20 minutes, and then vented. This nitrogen charge/stir/vent cycle was repeated one more time and the contents were then filtered through Celite and washed with acetic acid (12.5 ml). The filtrate was completely concentrated in vacuo to a bulk weight of 150 g. Hydrochloric acid (125 ml, 35% solution) was added to the solution in acetic acid and heated at reflux for 12 hours. The solution was cooled to room temperature and concentrated in vacuo. Isopropyl alcohol (150 ml) was charged to the residue which was subsequently concentrated in vacuo. This Isopropyl alcohol charge/concentration process was repeated a further two times with the same quantity of solvent to provide the title compound as a white solid (80.5 g, 87%).
  • 27
  • [ 4138-26-5 ]
  • [ 127294-75-1 ]
YieldReaction ConditionsOperation in experiment
96.5% In a 2 L reaction flask, 146 g of 1-fluoronaphthalene (1 mol) was added to a mixed solution of 925 mL of ethanol and 75 mL of water, and 105.4 g (1.2 mol) of borofluoride and 136 g (1.2 mol) of 30percent Hour, then add 3-formamido-piperidine 128.2g (1mol), the reaction was carried out at room temperature for 8 hours.The solvent was evaporated to dryness and the residue was dispersed with 500 mL of ethyl acetate. 150 mL of concentrated hydrochloric acid was added and the mixture was stirred for 0.5 h, filtered and dried to give 167.0 g of racemic 3-aminopiperidine dihydrochloride in 96.5percent yield.
  • 28
  • [ 4816-81-3 ]
  • [ 127294-75-1 ]
  • (R)-3-aminopiperidine di(S)-2-(4-methylphenyl)sulfonylamino-propionate [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% A solution of 400 mg (10 mmol) sodium hydroxide in 5.0 g water were added dropwise to a solution of 865 mg (5 mmol) <strong>[127294-75-1]rac-APIP dihydrochloride</strong> in 5.0 g water and the mixture was stirred for 10 min. 2428 mg (10 mmol) Ts-L-Ala were added and the mixture was heated at 80C until a clear solutions was obtained. The solution was cooled slowly to r.t. and the suspension was stirred for 3 h. The formed solid was collected by filtration, washed with mother liquor, water, isobutanol, TBME and pentane (1 ml each) and dried to afford (R)-APIP-2 Ts-L-Ala-H20. Yield: 1435 mg, 95% (based on the amount of enantiomer used). Enantiomeric ratio S/R =2.06 : 97.94; S-factor (efficiency of optical resolution) = 0.91 . The obtained acid addition salt was purified by recrystallization from 13.0 g water. Yield: 1087 mg, 72% (based on the amount of enantiomer used). Enantiomeric ratio S/R =0.0 :100.0. Melting point: 152C. Specific rotation [a]D20=-3.8 (c=0.5, MeOH).
  • 29
  • [ 59724-70-8 ]
  • [ 127294-75-1 ]
  • (R)-3-aminopiperidine di(S)-2-(4-chlorophenyl)sulfonylamino-propionate [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% 80 mg (2mmol) sodium hydroxide in 1.0 g water were added dropwise to a solution of 173 mg (1 mmol) <strong>[127294-75-1]rac-APIP dihydrochloride</strong> in 1 .0 g water and the mixture was stirred for 10 min. 527 mg (2mmol) pCI-Ps-L-Ala was added and the mixture was heated at 40C for 30 min. The solution was cooled slowly to r.t. and the suspension was stirred for 2 h. The formed solid was collected by filtration, washed with mother liquor, water (2 x 0.5 ml), acetone (1 ml), and pentane (2 ml ) and dried to afford (R)-APIP-2 pCI-Ps-L- Ala-H20. Yield: 273 mg, 85% (based on the amount of enantiomer used). Enantiomeric ratio S/R =4.41 : 95.59; S-factor (efficiency of optical resolution) = 0.77. A pure acid addition salt was independently prepared from 5 mmol (R)-APIP FontWeight="Bold" FontSize="10" 2 HCI, 10 mmol NaOH and 10 mmol pCI-Ps-L-Ala in 10 g water which had an optical purity of 100 % and shows the following physical data: Enantiomeric ratio S/R =0.0 :100.0. Melting point: 139C. Specific rotation [a]D20=-0.3 (c=1 .0, MeOH).
  • 30
  • [ 127294-75-1 ]
  • [ 29268-18-6 ]
  • (R)-3-aminopiperidine di(S)-2-phenylsulfonylamino-propionate [ No CAS ]
YieldReaction ConditionsOperation in experiment
42% 400 mg (10 mmol) sodium hydroxide in 5.0 g water and 300 mg (5 mmol) acetic acid were added dropwise to a solution of 865 mg (5 mmol) <strong>[127294-75-1]rac-APIP dihydrochloride</strong> in 5.0 g water and the mixture was stirred for 10 min.1 146 mg (5 mmol) of Ps-L-Ala were added and the mixture was heated at 80C until a clear solutions was obtained. The solution was cooled slowly to r.t. and the suspension was stirred for 3 h. The formed solid was collected by filtration, washed with mother liquor, water, isobutanol, TBME and pentane (1 ml each) and dried to afford (R)-APIP-2 Ps-L-Ala-hbO as white solid. Yield: 1069 mg, 74% (based on the amount of enantiomer used). Enantiomeric ratio S/R = 3.71 : 96.29. The obtained acid addition salt was purified by recrystallization from 6.0 g of water. Yield: 605 mg, 42% (based on the amount of enantiomer used). Enantiomeric ratio S/R =0.03 : 99.97. Melting point: 180.6C. Specific rotation [a]D20=-4.4 (c=0.5, MeOH).
  • 31
  • [ 93850-62-5 ]
  • [ 127294-75-1 ]
  • (S)-3-aminopiperidine di(S)-2-(3-phenylureido)-propionate [ No CAS ]
YieldReaction ConditionsOperation in experiment
504 mg 400 mg (10 mmol) sodium hydroxide in 5.0 g water were added dropwise to a solution of 865 mg (5 mmol) <strong>[127294-75-1]rac-APIP dihydrochloride</strong> in 5.0 g water and the mixture was stirred for 10 min. 2082 mg (10 mmol) of PC-L-Ala were added and the mixture was heated at 80C until a clear solution- was obtained. The solution was cooled slowly to r.t. and the suspension was stirred for 3 h. The formed solid was collected by filtration, washed with mother liquor, water, isobutanol, TBME and pentane (1 ml each) and dried to afford (S)-APIP-2 PC-L-Ala-2 H20 as white solid. Yield: 1220 mg, 88% (based on the amount of enantiomer used). Enantiomeric ratio S/R = 98.88 : 1 .12. S-factor (efficiency of optical resolution) = 0.86. 1000 mg of the obtained acid addition salt was purified by recrystallization from 6.0 g of water. Yield: 504 mg. Enantiomeric ratio S/R = 99.93 : 0.07. Melting point: 135.2C. Specific rotation [a]D20= +3.4 (c=0.5, MeOH).
  • 32
  • piperidine-3-carboxylic acid hydrazide dihydrochloride [ No CAS ]
  • [ 127294-75-1 ]
YieldReaction ConditionsOperation in experiment
84% With acetic acid; isopentyl nitrite; In water; at -15℃; for 2.16667h;Reflux; To 5.40 g of racemic nipecotic acid hydrazide dihydrochloride (25 mmol) in 10 g water and 2.5 g acetic acid were added dropwise 3.5 g isopentyl nitrite (30 mmol) at -15 C. The clear solution was warmed to 0 C during a period of 2 h and poured at once into 50 ml of boiling water. Boiling was continued for additional 10 min. The solution was cooled to r.t, cone, hydrochloride acid (2 ml) was added and the solution was concentrated to a viscous mass, which was dissolved in 10 ml of hot methanol. On cooling the clear solution to r.t. a thick crystalline mass developed. Acetone (20 ml) was added and the crystals were isolated via filtration. After drying for 12 h at 50 C, 3.71 g of racemic 3-aminopiperidine dihydrochloride (21 mmol, corresponds to 84 % yield) with a water content of 0.68 % were obtained.
  • 33
  • [ 71962-74-8 ]
  • [ 127294-75-1 ]
  • 34
  • [ 689758-90-5 ]
  • [ 127294-75-1 ]
YieldReaction ConditionsOperation in experiment
77% With hydrogenchloride; isopentyl nitrite; In water; at 0℃; for 2.16667h;Reflux; To 36 g (250 mmol) of racemic nipecotic acid hydrazide in 125 ml water were added 45 ml (500 mmol) of cone, hydrochloric acid under cooling (ice/ salt). 25.1 g isopentyl nitrite (300 mmol) was added during 30 min at 0 C and stirred at the same temperature for additional 30 min. HPLC shows complete conversion to the desired azide with no starting material left. The mixture was poured drop wise during 10 min onto 500 ml of hot (80 C) water. Boiling was continued for additional 60 min. The solution was cooled to room temperature, cone, hydrochloric acid (40 ml) was added and the solution was concentrated to a viscous mass. Water (100 ml) was added, and the solution was concentrated again. Isopropyl alcohol (100 ml) was added, and the solution was concentrated again. The residue was dissolved in hot methanol (50 ml). To the cooled methanol solution was added acetone (100 g) dropwise under vigorous stirring. The precipitated 3-aminopiperidine dihydrochloride was isolated (40 g of wet product) and dried via azeotropic distillation under reduced pressure with two portions (50 ml each) of isopropanol. Hot methanol was added and the suspension was stirred over night at r.t. The suspension was diluted with 70 g acetone and the solid material was isolated via filtration. 33.2 g (192 mmol, corresponds to 77 % yield) of 3- aminopiperidine dihydrochloride was obtained as a white powder. Chemical purity (HPLC) is 98.7 % with a water content (determined by Karl Fischer titration) of 0.046 %.
  • 35
  • [ 1622856-04-5 ]
  • [ 127294-75-1 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; sodium nitrite; In water; at -10℃; for 1h;Reflux; 18 g of racemic nipecotic acid hydrazide monohydrochloride (100 mmol) were dissolved in 36 g water and 21 g of 37% hydrochloric acid (210 mmol) and cooled to -10 C. To the solution were added 7.6 g of NaN02 (1 10 mmol) in small portions in such a way that the temperature is kept < -5C. Stirring was continued for 30 min at a temperature of -5 to 0C. The cold solution was then poured in small portions into 20 g of boiling water. The reaction mixture was stirred under reflux for additional 30 min and then cooled - to r.t. to give a solution of racemic APIP dihydrochloride in water.
 

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