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Chemical Structure| 214834-18-1 Chemical Structure| 214834-18-1

Structure of 214834-18-1

Chemical Structure| 214834-18-1

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Product Details of [ 214834-18-1 ]

CAS No. :214834-18-1
Formula : C11H20N2O2S
M.W : 244.35
SMILES Code : C(C)(C)(C)OC(=O)N1CCC(CC1)C(N)=S
MDL No. :MFCD02180954
InChI Key :SCGQNJHAAYUQOO-UHFFFAOYSA-N
Pubchem ID :2735648

Safety of [ 214834-18-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Application In Synthesis of [ 214834-18-1 ]

* 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 [ 214834-18-1 ]

[ 214834-18-1 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 91419-48-6 ]
  • [ 214834-18-1 ]
YieldReaction ConditionsOperation in experiment
92% With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; To a solution of ferf-butyl-4-carbamoylpiperidine-1-carboxylate (2.65 g, 11.62 mmol) in a DME/DCM 2: 1 mixture (78 ml_), Lawesson reagent (2.35 g, 5.81 mmol, 0.5 eq) was added and the mixture was stirred at r.t. overnight. The solvent was removed and the residue was taken up with ethyl acetate and washed with saturated aqueous K2CO3. The organic layer was separated, dried over Na2S04 and concentrated to dryness. The residue was triturated with diethyl ether and dried to give 2.65 g (92%) of the title compound as a white solid.HPLC: Rt: 5.06 min1H NMR (401 MHz, DMSO-d6) δ ppm 9.39 (br. s., 1 H), 9.09 (br. s., 1 H), 4.00 (d, J = 12.6 Hz, 2 H), 2.77 - 2.61 (m, 3 H), 1.71 - 1.51 (m, 4 H), 1.39 (br. s., 9 H)
92% With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; tert-Butyl-4-carbamothioylpiperidine-1-carboxylate, cmpd. of formula 8 [R1=1-tert-butoxycarbonyl-piperidin-4-yl] To a solution of tert-butyl-4-carbamoylpiperidine-1-carboxylate (2.65 g, 11.62 mmol) in a DME/DCM 2:1 mixture (78 mL), Lawesson reagent (2.35 g, 5.81 mmol, 0.5 eq) was added and the mixture was stirred at r.t. overnight. The solvent was removed and the residue was taken up with ethyl acetate and washed with saturated aqueous K2CO3. The organic layer was separated, dried over Na2SO4 and concentrated to dryness. The residue was triturated with diethyl ether and dried to give 2.65 g (92%) of the title compound as a white solid. HPLC: Rt: 5.06 min 1H NMR (401 MHz, DMSO-d6) δ ppm 9.39 (br. s., 1H), 9.09 (br. s., 1H), 4.00 (d, J=12.6 Hz, 2H), 2.77-2.61 (m, 3 H), 1.71-1.51 (m, 4H), 1.39 (br. s., 9H)
82% With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; for 1.33333h; Example 2: 4-Thiocarbamoyl-piperidine-l-carboxylic acid tert-butyl ester(Thioamide)[0030] To a suspension of 4-Carbamoyl-piperidine-l-carboxylic acid tert-butyl ester (288 g, 1.26 mol) in dimethoxyethane (2000 mL) and methylene chloride (800 mL) in a 5-lite of three-neck flask was added Lawesson's Reagent (255 g, 0.63 mol). The mixture was stirred at room temperature for 80 min. TLC check there was no starting material left. The solvents were removed under vacuum. The residue was dissolved in ethyl acetate (1500 mL), and washed with half saturated potassium carbonate water solution (500 mL each, two times), 50%> of brine (500 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to dry. The obtained solid was dissolved in ethyl acetate (1000 mL) and filtered at hot to remove insoluble white stuff. To the solution was added heptane (300 mL). After removing most of ethyl acetate, the solid formed was filtrated, washed with hexane-ether (1 : 1), and dried to give 252 g (82%>) of product. TLC: dichloromethane -methanol 90: 10, Rf (product) = 0.37, UV and iodine positive; Rf (starting material) = 0.28, iodine positive.
82% With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; for 1.33333h; To a suspension of 4-Carbamoyl-piperidine-1-carboxylic acid tert-butyl ester (288 g, 1.26 mol) in dimethoxyethane (2000 mL) and methylene chloride (800 mL) in a 5-lite of three-neck flask was added Lawesson's Reagent (255 g, 0.63 mol). The mixture was stirred at room temperature for 80 min. TLC check there was no starting material left. The solvents were removed under vacuum. The residue was dissolved in ethyl acetate (1500 mL), and washed with half saturated potassium carbonate water solution (500 mL each, two times), 50% of brine (500 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated to dry. The obtained solid was dissolved in ethyl acetate (1000 mL) and filtered at hot to remove insoluble white stuff. To the solution was added heptane (300 mL). After removing most of ethyl acetate, the solid formed was filtrated, washed with hexane-ether (1:1), and dried to give 252 g (82%) of product.TLC: dichloromethane-methanol 90:10, Rf (product)=0.37, UV and iodine positive; Rf (starting material)=0.28, iodine positive.
82.2% With Lawessons reagent; In tetrahydrofuran; at 20℃; for 12h; Dissolve N-Boc-4-piperidinecarboxamide 2 (1.00g, 4.38mmol) in 20mLTetrahydrofuran solution, then add Lawesson's reagent (LR) (1.06g, 2.63mmol),Mechanically stirred at room temperature for 12 hours, TLC monitored until the reaction was complete, and the solutionAdd 20mL ethyl acetate to redissolve, 15mL*2 10% citric acid wash the organic layer, 15mL*2 saturated sodium carbonate wash the organic layer, 15mL water wash the organic layer,The organic layer was dried with anhydrous magnesium sulfate, filtered and desolvated to obtain 0.88 g of white solid.The yield was 82.2%,
78% With Lawessons reagent; In tetrahydrofuran; at 20℃; for 22h;Reflux; To a stirred solution of tert-butyl 4-carbamoylpiperidine-1-carboxylate (1.3 g, 5.7 mmol) in THF (16 mL,), Lawssen's reagent 2.53 g, 6.27 mmol) was added. The reaction mixture was refluxed for 6 h and then stirred at rt for 16 h. The completion of the reaction was monitored by TLC. The reaction mixture was diluted with ethyl acetate and was washed with 10% citric acid, 10% sodium bicarbonate, water and brine, dried over anhydrous Na2SO4 and concentrated under vacuum to afford the title compound. Yield: 78% (1.09 g, colorless oil). 1H NMR (400 MHz, DMSO-d6): δ 9.41 (s, 1H), 9.11 (s, 1H), 4.03-3.97 (m, 1H), 2.66-2.61 (m, 2H), 1.64-1.52 (m, 4H), 1.40 (s, 9H), 1.38-1.34 (m, 2H). LCMS: (Method A) 245.2 (M+H), Rt. 3.38 min, 93.5% (Max).
72% With Lawessons reagent; In 1,2-dimethoxyethane (DME); chloroform; at 20℃; 4-CARBAMOYL-PIPERIDINE-L-CARBOXYLIC acid TERT-BUTYL ester (2) (45.4 g, 0.199 mol), Lawesson's reagent (40.2 g, 0.099 mol, 0.5 equiv), 1,2-dimethoxyethane (DME) (500 mL) and chloroform (200 mL) were combined and stirred at room temperature. The course of the reaction was followed by tlc analysis (30% ethyl ACETATE/HEXANE) and on completion the reaction mixture was evaporated to dryness (glassy solid). The solid was dissolved in ethyl acetate and washed with half saturated potassium carbonate solution, dried (MGSO4), filtered and concentrated to yield the title compound as a colourless solid. The crude product was crystallised from ethyl acetate and hexane to give the title compound (3) (35 g, 0.14 mol, 72%).
62.5% With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; Lawson's reagent (12.75 g, 0.032 mol) was added a solution of compound 1(14.4 g, 0.063 mol) in dichloromethane (40 mL) and ethylene glycol dimethyl ether (100 ml). The reaction was stirred at room temperature for 8 h, and monitored by TLC, then concentrated. The residue was diluted with CH2Cl2 (100 mL), washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel flash column chromatography (CH2Cl2/MeOH = 100:1) to afford compound 2 (9 g, 62.5 % yield) as a white solid. 1H NMR (400MHz, CDCl3) δ 7.55(s, 1H), 6.99(s, 1H), 4.23(s, 2H), 3.73(q, J = 7.0 Hz, 2H), 2.74-2.65(m, 1H), 1.90(dt, J =13.4 Hz, 2.6 Hz, 2H), 1.72(qd, J = 12.6 Hz, 4.4 Hz, 2H), 1.46(s, 9H).
55% With Lawessons reagent; In toluene; at 20℃; for 1h;Inert atmosphere; To a suspension of compound8(2.2 g, 9.7 mmol) in toluene (100 mL) in a reaction flask was added Lawesson’s reagent (1.9 g, 4.8 mmol). After the reaction mixture was stirred at room temperature for 1 h, the solvents were removed under vacuum. The residue was dissolved in EtOAc and washed with aqueous 1N NaOH solution (2 x 100 mL), 50% of brine (100 mL). The organic phase was dried over anhydrous Na2SO4, filtered, concentrated and purified by silica gel column chromatography using 30% acetone in hexanes as an eluent to afford compound9(1.3 g, 55%)1H-NMR (CDCl3,300 MHz) δ 7.44 (1H, s, NH2), 6.86 (1H, s, NH2), 4.24 (2H, d,J= 11.7 Hz, CH2), 2.78-2.63 (3H, m, CH+CH2), 1.93 (2H, d,J= 14.7 Hz, CH2), 1.73 (2H, dt,J= 15.0 Hz, 6.0 Hz, CH2), 1.46 (9H, s, C(CH3)3).
40.2% With Lawessons reagent; In 1,4-dioxane; at 70℃; for 4h; Dissolve compound 2 (10.2 g, 42.6 mmol) and Lawson's reagent (10.7 g, 26.4 mmol) in 1,4-dioxane (150 mL), heat at 70±5C and stir for 4 h. After the reaction was detected by TLC, the reaction system was cooled to room temperature. Adjust pH=9 with saturated aqueous NaHCO3 solution, extract with DCM (3X100 mL), combine the organic phases, dry with anhydrous sodium sulfate, filter, and concentrate the organic phase to obtain crude product, which is purified by silica gel column to obtain 4.1 g of white solid, with a yield of 40.2 %.
With Lawessons reagent; In 1,4-dioxane; at 60℃; for 2h; The amide (20 g, 76.3 mmol) was dissolved in 1,4-dioxane with heating and the clear solution placed in a 60 0C oil bath. Lawesson's Reagent was added (15.43 g, 38.15 mmol) and the solution stirred for 2 hours. The solution was cooled to RT, poured into 8:1 water : saturated NaHCO3, followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc : hexanes (1:4)) to give the titled compound.
With Lawessons reagent; In 1,4-dioxane; dichloromethane; at 20 - 50℃; for 4h; under room temperature, nitrogen protection, (27.36g, 0 . 12mol, 1eq), laurance reagent (24.26g, 0 . 06mol, 0 . 5eq), mixed, added into the 1,4-dioxane 250 ml, the mixing tabs 50 C, 4h. Quality monitoring, after the reaction is complete. The reaction system can be obtained direct turns on lathe does target product 51. 86g crude product (containing laurance reagent decay product), purity 50%. The crude product of viscosity is very high bombycinous oily liquid.
1 g With Lawessons reagent; In 1,2-dimethoxyethane; dichloromethane; at 20℃; for 16h; To a stirred solution of tert-butyl 4-carbamoylpiperidine-1 -carboxylate (1 .0 g, 4.38 mmol) in a mixture of dimethoxyethane (16 mL) and dichloromethane (8 mL) was added 2,4-bis(4-methoxyphenyl)-,3,2,4-dithiadiphosphetane-2,4-disulfide (885 mg, 2.1 9 mmol). The mixture was stirred at 20 C for 16 h,then concentrated in vacuo. The residue dissolved in ethyl acetate and washed with saturated aqueous potassium carbonate (10 mL x 2). The organic layer was separated, dried over sodium sulfate and concentrated in vacuo to give tert-butyl 4-carbamothioylpiperidine-1 -carboxylate (1 .0 g) as a yellow solid. This was used directly without further purification. 1H NMR (400 MHz, DMSO-d6) O 9.45 (br. s., 1 H), 9.17 (br. s., 1H), 4.14-3.98 (m, 2H), 3.91 -3.79 (m, 1H), 2.80-2.66 (m, 2H), 1.74-1.55 (m, 4H), 1.46 (s, 9H).

  • 2
  • [ 214834-18-1 ]
  • [ 814-75-5 ]
  • [ 1004527-71-2 ]
YieldReaction ConditionsOperation in experiment
13% With ethanol; at 200℃; for 0.0166667h;Microwave irradiation; -Bromobutan-2-one (124 mg, 0.8 mmol) and tert-butyl 4- carbamothioylpiperidine-1-carboxylate (200 mg, 0.8 mmol) in ethanol (1 iuL) were heated to 2000C for 1 minute under microwave irradiation. The black residue was purified by chromatography (DCM/MeOH/NH4OH 85/15/0.1) to yield 4,5- dimethyl-2- (piperidin-4-yl) thiazole as a brown solid (32 rag, 13%) : 1H NMR (400 MHz, DMSCHd6) δ 1.76-1.88 (m, 2H), 2.08-2.14 (m, 2H), 2.21 (s, 3H), 2.30 (s, 3H), 2.97-3.05 (m, 2H), 3.18- 3.24 (m, IH) , 3.30-3.35 (m, 2H); m/z (APCI pos) 197.1 (100%) [M+H] .
  • 3
  • [ 214834-18-1 ]
  • [ 70-23-5 ]
  • [ 365413-31-6 ]
YieldReaction ConditionsOperation in experiment
96.5% In methanol; for 4h;Reflux; Compound 3 (4.1 g, 16.8 mmol) and ethyl bromopyruvate (3.94 g, 20.2 mmol) were dissolved in anhydrous methanol (100 ml). The reaction system was heated under reflux and stirred for 4 h, until the reaction was detected by TLC. The reaction solution was concentrated and purified by a silica gel column to obtain 5.5 g of product 4 as a yellow powdery solid with a yield of 96.5%. Can be used directly in the next step.
82% 4-THIOCARBAMOYL-PIPERIDINE-L-CARBOXYLIC acid tert-butyl ester (3) (25 g, 102 mmol) was dissolved in anhydrous N, L9-DIMETHYLFORMAMIDE (DMF) (125 mL) and cooled to 0C in an ice-bath. A solution of ethyl bromopyruvate (22.2 g, 14.3 mL, 114 mmol, 1.1 equiv) in anhydrous DMF (125 mL) was added dropwise with stirring. The reaction mixture was allowed to warm slowly to room temperature and stirred overnight. Triethylamine (25 mL) was added dropwise with stirring at the rate of 1 mL/g of thioamide used. The DMF was removed in vacuo keeping the temperature below 60C. The resulting residue was partitioned between ethyl acetate (75 mL) and brine (100 mL). Sufficient water was added to ensure complete dissolution of the precipitated salts in the aqueous phase. The aqueous phase was extracted twice with ethyl acetate and the combined organic extracts washed successively with brine (x2), water (x2) and brine (x2). The organic phase was simultaneously dried with MGS04 and decolourised with finely divided charcoal. The mixture was filtered through Celite and concentrated in vacuo to give a yellow oil. Trituration with hexane yielded a yellow solid. This was diluted with an excess of hexane and cooled overnight to allow complete crystallisation of product. The product was collected by filtration, washed with hexane and dried in vacuo at room temperature. Recrystallisation from IPA/water gave the title compound (4) (28.33 g, 83 mmol, 82%).
74.2% To a suspension of tert-butyl 4-carbamothioylpiperidine- 1 -carboxylate (1.50 g, 6.14 mmol) in ethanol (6 mL) at 0 C was added dropwise a solution of ethyl 3-bromo- 2-oxopropanoate (0.788 mL, 6.26 mmol) in ethanol (6 mL). The ice bath was then removed and the reaction mixture was stirred at ambient temperature overnight. Triethylamine (1.5 mL, 10.76 mmol) was then added and the mixture was concentrated to near dryness and the concentrate was diluted with ethyl acetate, washed with brine, dried (MgS04) and evaporated to dryness. The residue was purified by flash chromatography using hexanes-ethyl acetate as eluent to give ethyl 2-(l-(tert-butoxycarbonyl)piperidin-4- yl)thiazole-4-carboxylate (1.55 g, 74.2%) as a nearly colorless oil that crystallized on standing to give a white solid. LC (Method A): 2.115 min. 1H NMR (DMSO-d6, 400 MHz) δ ppm: 8.42 (s, 1H), 7.20 (br s, 2H), 4.29 (q, J= 7.0 Hz, 2H), 4.00 (m, 1H), 3.24 (m, 1H), 2.88 (br s, 1H), 2.03 (m, 2H), 1.54 (m, 2H), 1.29 (t, J= 7.2 Hz, 3H).
71% With triethylamine; In DMF (N,N-dimethyl-formamide); at 5℃; tert-Butyl 4-(AMINOCARBOTHIOYL) TETRAHYDROPYRIDINE-1 (2H)-CARBOXYLATE (May- bridge) (85 mmol ; 20. 8 g) is dissolved in 250 ml of DIMETHYLFORMAMIDE and placed at 5C. Ethyl bromopyruvate (1 EQ. ; 85 MMOL ; 16. 6 g) dissolved in 50 ml of dimethylformamide is added dropwise. The reaction medium is stirred overnight and excess triethylamine is then added dropwise. The reaction medium is evapo- rated and the residual brown oil is taken up in ethyl acetate and washed with water (twice) and then with saturated sodium chloride solution (twice). The organic phase is dried over sodium sulfate and evaporated to dryness. The crude product is chromatographed on silica, eluting with DICHLOROMETHANE to DICHLOROMETHANE/3% methanol, to give 20. 5 g of the expected product in the form of oily crystals. TLC : 1/1 ethyl acetate/hexane : Rf = 0. 55 Yield = 71 %.
71% With triethylamine; In DMF (N,N-dimethyl-formamide); at 5℃; Tert-butyl-4-(aminocarbothioyl)tetrahydropyridine-1(2H)-carboxylate (Maybridge) (85 mmol; 20.8 g) is dissolved in 250 ml of dimethylformamide and placed at 5 C. Ethyl bromopyruvate (1 eq.; 85 mmol; 16. 6 g) dissolved in 50 ml of dimethylformamide is added dropwise. The reaction medium is stirred overnight and excess triethylamine is then added dropwise. The reaction medium is evaporated and the residual brown oil is taken up in ethyl acetate and washed with water (twice) and then with saturated sodium chloride solution (twice). The organic phase is dried over sodium sulfate and evaporated to dryness. The crude product is chromatographed on silica, eluting with dichloromethane to dichloromethane/3% methanol, to give 20.5 g of the expected product in the form of oily crystals. TLC: 1/1 ethyl acetate/hexane: Rf = 0.55 Yield = 71 %.
In ethanol; at 80℃; for 4h; (2-methyl-4,5,6,7-tetrahydro-2H-indazol-3-yl)amide 2-Piperidin-4yl-thiazole-4-carboxylic acid ethyl ester dihydrobromide salts A solution of tert-butyl-4-(aminocarbothioyl)tetrahydropyridine-1(2H)-carboxylate (2.0 g, 8.2 mmol) and ethyl bromopyruvate (1.6 g, 8.2 mmol) in 30 mL of EtOH was stirred at 80 C. for 4h. Afterwards, the mixture cooled to room temperature and then charged with 48% HBr (1.0 mL, 14 mmol. The reaction mixture was allowed to stir an additional 1 h, and then concentrated to an oily solid. Trituration with diethyl ether afforded 3.0 g (91%) of a tan solid. 1H NMR (400 Liz, DMSO-d6) δ 9.02 (br s, 1 H), 8.77 (br s, 1 H), 8.46 (s, 1 H), 7.01 (br s, 1 H),4.29 (q, J=7.1 Hz,2 H), 3.44-3.33 (m, 3 H), 3.-2 (q, J=11.7 Hz 2 H), 2.19 (d, J=13.2 Hz, 2 H), 1.97-1.88 (m, 2 H), 1.29 (t, J=7.0 Hz, 3 H). MS calculated for C11H16N2O2S+H: 241, observed: 241.
Step A: Preparation of 1 , 1 -dimethylethyl 4-[4-(ethoxycarbonyl)-2-thiazolyl]- 1 - piperidinecarboxylate; To a suspension of 1,1 -dimethylethyl 4-(aminothioxomethyl)-l-tetrahydropyridine- carboxylate (30 g, 123 mmol) in ethanol (180 mL) cooled to 0 C in an ice bath, was added dropwise a solution of ethyl bromopyruvate (15.7 mL, 125 mmol) in ethanol (180 mL). The ice bath was removed, and the mixture was stirred at ambient temperature overnight. Triethylamine (30 mL) was added, and the mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give 31 g of a brown oil, which solidified on standing. A portion of this crude product (8.1 g) was heated with ether (200 mL), and the ether was then decanted. This was repeated a second time, and the combined ether solutions <n="53"/>were evaporated under reduced pressure to give 7.6 g of the title compound as a yellow solid.1H NMR (CDCl3) δ 1.40 (t, 3H), 1.46 (s, 9H), 1.7 (m, 2H), 2.1 (m, 2H), 2.85 (m, 2H), 3.25 (m, IH), 4.2 (m, 2H), 4.42 (q, 2H), 8.08 (s, IH).
In ethanol; at 0 - 20℃; To a suspension of 1,1-dimethylethyl 4-(aminothioxomethyl)-l-tetrahydropyridine- carboxylate (30 g, 123 mmol) in ethanol (180 mL), cooled to 0 C in an ice bath, was added dropwise a solution of ethyl bromopyruvate (15.7 mL, 125 mmol) in ethanol (180 mL). The <n="71"/>ice bath was removed, and the mixture was stirred at ambient temperature overnight. Triethylamine (30 mL) was added, and the mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give 31 g of a brown oil, which solidified on standing. A portion of this crude product (8.1 g) was heated with 200 mL of ether, and the ether was then decanted. This was repeated a second time, and the combined ether solutions were evaporated under reduced pressure to give 7.6 g of the title compound as a yellow solid. 1H NMR (CDCl3) 6 1.40 (t, 3H), 1.46 (s, 9H), 1.7 (m, 2H), 2.1 (m, 2H), 2.85 (m, 2H), 3.25 (m, IH), 4.2 (m, 2H), 4.42 (q, 2H), 8.08 (s, IH).
Synthesis of 4-(4-Carboxy-thiazol-2-yl)-piperidine-l-carboxylic acid tert-butyl ester (Intermediate 1-3.2)R9 m u R11 I-3.2Step 1: Synthesis of 4-(4-Ethoxycarbonyl-thiazol-2-yl)-piperidine-l-carboxylic acid tert- butyl ester (Rl l)A solution of R9 (1.0 g, 4.09 mmol) in dimethylformamide (DMF) (5 ml) is cooled to 0C under nitrogen. To this mixture is added R10 (0.63 ml, 4.50 mmol) as a DMF solution (5 ml, drop wise addition). Upon complete addition, the reaction is allowed to gradually warm to ambient temperature and stirred over night. After this time the reaction is treated with triethylamine (1 ml, drop wise) and stirred for 10 minutes. The reaction is then poured into water and the product is extracted into EtO Ac (3x). The combined organics are dried (MgS04), filtered and concentrated. The remaining residue is purified via column chromatography (25g silica gel, 5-50% EtO Ac/heptane) to afford Rl l. (1.0 g)
EXAMPLE 1. Preparation of 2- [ 1 - [(2, 5-dimethylphenyl) acetyl] -4-piperidinyl] -N-methyl-N- [( 1R)- 1 - phenylpropyl]-4-thiazolecarboxamide (Compound 58). Step A: Preparation of 1,1-dimethylethyl 4-[4-(ethoxycarbonyl)-2-thiazolyl]-l- piperidinecarboxylate. To a suspension of 1,1-dimethylethyl 4-(aminothioxomethyl)-1-tetrahydropyridine- carboxylate (30 g, 123 mmol) in ethanol (180 mL), cooled to 0 C in an ice bath, was added dropwise a solution of ethyl bromopyruvate (15.7 mL, 125 mmol) in ethanol (180 mL). The ice bath was removed, and the mixture was stirred at ambient temperature overnight. Triethylamine (30 mL) was added, and the mixture was concentrated under reduced pressure, diluted with ethyl acetate, washed with brine, dried over magnesium sulfate and concentrated under reduced pressure to give 31 g of a brown oil, which solidified on standing. A portion of this crude product (8.1 g) was heated with 200 mL of ether, and the ether was then decanted. This was repeated a second time, and the combined ether solutions were evaporated under reduced pressure to give 7.6 g of the title compound as a yellow solid. 1H NMR (CDCl3): 1.40 (t, 3H), 1.46 (s, 9H), 1.7 (m, 2H), 2.1 (m, 2H), 2.85 (m, 2H), 3.25 (m, 1H), 4.2 (m, 2H), 4.42 (q, 2H), 8.08 (s, 1H).

  • 5
  • [ 214834-18-1 ]
  • [ 20099-90-5 ]
  • [ 860344-62-3 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 20 - 80℃; for 2.08333h; 4-Thiocarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (2.47 mmol) and 4- (2- Bromo-acetyl)-benzoic acid (2.47 mmol) were mixed in THF (12 mL). After stirring at room temperature for 5 minutes the mixture was heated to 80 C for 2 hours. The volume was reduced to 5 mL and diethylether (5 mL) was added. The mixture was then cooled to-20 C and filtered. The solid was washed with a small amount of diethylether and dried. m/z = 289.1 in MS ES+, which was characterized by hplc and MS and used in the next step without any further purification.
  • 6
  • [ 214834-18-1 ]
  • [ 62423-73-8 ]
  • [ 860344-60-1 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 20 - 80℃; for 2.08333h; 4-Methyl-piperazine-1-carbothioic acid amide (2.47 mmol) and 3- (2-Bromo-acetyl)- benzoic acid (2.47 mmo () were mixed in THF (12 mL). After stirring at room temperature for 5 minutes the mixture was heated to 80 C for 2 hours. The mixture was then cooled to room temperature and filtered. The solid was washed with a small amount of diethylether and dried. m/z = 304.1 in MS ES+, which was characterized by hpic and MS and used in the next step without any further purification.
  • 7
  • [ 214834-18-1 ]
  • [ 20656-61-5 ]
  • [ 867066-22-6 ]
YieldReaction ConditionsOperation in experiment
In toluene; at 80 - 90℃; for 2.75h; A mixture of tertiary butyl 4-(aminocarbothioyl)tetrahydropyridne-1(2H)carboxylate 25.1 (1 g) and methyl chloro(formyl)acetate (1.3 g) in toluene (20 mL) was heated in an 80-90 C. oil bath for 1.75 hours. Another spatula full of the chloro(formyl)acetate was added and the heating continued another hour. The reaction was cooled and partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The organics were washed with water and brine. Drying and evaporation of the solvent gave an oily residue that was purified by flash chromatography eluting with 30% ethyl acetate hexane to give the thiazole 25.2 as a yellow oil (0.6 g). A solution of 25.2 (0.55 g) in methylene chloride (3 mL) was treated with trifluoroacetic acid (1 mL). After three hours, another portion of trifluoroacetic acid (1 mL) was added and stirring continued for three hours. The solvent was evaporated and the residue partitioned between water and ether. The aqueous phase was made basic with 1 N sodium hydroxide and extracted with chloroform. The chloroform solution was dried and the solvent evaporated to give 25.3 as a dark gum (0.187 g). A solution of the gum in methylene chloride (5 mL) and diisopropylethylamine (0.3 mL) was cooled in ice-water and treated with 4-biphenylsulphonyl chloride (0.21 g) in methylene chloride (2 mL). The cooling was removed and the reaction stirred one hour. A crystal of 4-dimethylaminopyridine was added and stirring was continued overnight. The solvent was evaporated and the residue partitioned between water and ethyl acetate. The organics were washed with 1 N hydrochloric acid, aqueous saturated sodium bicarbonate, and brine. The solvent was dried and evaporated to give a tan solid. The solid was purified by flash chromatography eluting with 60-80% ethyl acetate-hexane to give 25.3 as a tan powder (91 mg) with the expected m/e of 443 (M+H+). A mixture of methyl 2-[1-(1,1'-biphenyl-4-ylsulfonyl)piperidin-4-yl]-1,3-thiazole-5-carboxylate 25.3 (9 mg), 50% hydroxylamine in water (0.05 mL), and dioxane (1 mL) were cooled in ice-water. To the reaction was added 1N sodium hydroxide (0.053 mL) followed by removal of the cooling bath. After stirring overnight, the reaction was neutralized with 1 N hydrochloric acid (0.053 mL) and the solvent evaporated. The residue was purified by preparative hplc to give Example 25 as a floculant white solid (3.5 mg). 1H NMR (DMSO) δ: 2.75 (m, 2H), 2.15 (m, 2H), 2.5 (m, 2H), 3.1 (m, 1H), 3.75 (m, 2H), 7.45-7.55 (m, 3H), 7.72-7.96 (m, 6H), 8.08 (s, 1H), 11.3 (s, 1H); m/e=444 (M+H+).
  • 8
  • [ 214834-18-1 ]
  • [ 864958-50-9 ]
  • [ 864958-53-2 ]
YieldReaction ConditionsOperation in experiment
89% In ethanol; for 2h;Heating / reflux; Example 7; 2- (4-Piperidine)-4- [3- (3-bromophenyl)-5-methylisoxazolyl] thiazole Hydrobromide; A mixture of 3- (3-bromophenyl)-5-methyl-4- (bromoacetyl) isoxazole (1.50 g, 4.18 mmol) of Example 3 and 4-thiocarbamoyl-piperidine-1-carboxylic acid-tert-butyl ester (1.3 equiv) in EtOH (14.0 mL) was heated to reflux. After 2 h, the reaction mixture was cooled to room temperature and poured into Et2O. The product precipitated out and was filtered and dried in vacuo to give the title compound (1.48 g, 89%) as an off-white solid (HBr salt). LCMS only : 404, 406 (M+H).
  • 9
  • [ 214834-18-1 ]
  • C8H9BrF3NO2 [ No CAS ]
  • [ 767263-46-7 ]
YieldReaction ConditionsOperation in experiment
1-(Trifluoroacetyl)hexahydro-4H-azepin-4-one (may be prepared as described in Description 3) (L00g, 4.78mmol) was dissolved in acetic acid (10ml) and the mixture EPO <DP n="32"/>heated at 60 0C. Bromine (0.25ml, 4.78mmol) in acetic acid (10ml) was then added dropwise at such a rate that the solution decolourised between drops. The mixture was left stirring at 60 0C for 30 minutes. The acetic acid was evaporated and azeotroped with toluene. The mixture was re-dissolved in ethanol, treated with 1 ,1-dimethylethyl A- (aminocarbonothioyO-i-piperidinecarboxylate (2.34g, 9.57mmol) and heated at reflux for 4 hours and then overnight. The mixture was diluted with methanol and passed down an ion exchange cartridge (SCX), washed with methanol and then a 2M ammonia in methanol solution. The basic fractions were then combined and evaporated to afford the crude product which was purified using column chromatography eluting with a mixture of 2M ammonia in methanol and dichloromethane (10%) to afford the product (D27); MS (ES+) m/e 334 [M+H]+.
  • 10
  • [ 908094-01-9 ]
  • [ 214834-18-1 ]
  • [ 20772-12-7 ]
  • [ 301220-64-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogen bromide; In ethanol; hexane; Step B 4-(5-Benzyl-thiazol-2-yl)-1-t-butyloxycarbonyl-piperidine To a solution of 65 mg of 1-bromo-3-phenyl-2-propanone (from reacting the acid chloride with diazomethane followed by hydrogen bromide) in 4 ml EtOH was added 74 mg of 1-boc-isonipecot-thioamide (from Step A). The reaction was stirred for 2 hours at 80 C. The solvent was then evaporated under reduced pressure. The residue was purified by flash chromatography with 10% EtOAc in hexane to give 37 mg of the title compound.
  • 11
  • phosphorous pentasulfide [ No CAS ]
  • [ 91419-48-6 ]
  • [ 214834-18-1 ]
YieldReaction ConditionsOperation in experiment
In 1,4-dioxane; hexane; Step A 1-t-Butyloxycarbonyl-isonipecot-thioamide To a solution of 500 mg of 1-Boc-isonipecotamide in 5 ml of 1,4-dioxane was added 243 mg of phosphorous pentasulfide. The reaction was stirred at 100 C. for 1 hour. The solvent was then evaporated under reduced pressure. The residue was purified by flash chromatography with 30% EtOAc in hexane to give 74 mg of the title compound.
  • 12
  • [ 214834-18-1 ]
  • [ 403-29-2 ]
  • [ 887625-38-9 ]
  • [ 887625-34-5 ]
YieldReaction ConditionsOperation in experiment
α-Bromo-4-fluoroacetophenone (2.0 g, 9.0 mmol) was dissolved in ethanol (20 mL) , N-tert- butoxycarbonylpiperidine-4-thioamide (2.0 g, 8.2 mmol) was added thereto, and the mixture was refluxed 1 hour. The reaction mixture was cooled to room temperature and concentrated. Saturated sodium bicarbonate (50 mL) was EPO <DP n="136"/>added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over MgSO4 and the solvent was evaporated. The residue was dissolved in N,N-diraethylformamide (15 mL) , di-tert- butyldicarbonate (1.4 g, 6.1 mmol) and triethylamine (0.7 g, β.l mmol) were added thereto, and the mixture was stirred at 50 C for 2 hours. The reaction mixture was cooled to room temperature, water (150 mL) was added thereto, and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over MgSO4 and the solvent was evaporated. The residue was purified by silica gel column chromatography (ethyl acetate :n-hexane = 1:3) to give the title compound (1.7 g, 4.7 mmol, yield 53%).
  • 13
  • [ 214834-18-1 ]
  • [ 70-11-1 ]
  • [ 926891-48-7 ]
YieldReaction ConditionsOperation in experiment
96% In methanol; at 70℃; for 22h; Example 1 Isopropyl-4-(4-phenyl-thiazol-2-yl)-piperidine Step 1: 4-(4-Phenyl-thiazol-2-yl)-piperidine hydrobromide (Intermediate 1) A mixture of 1 g (4.1 mmol) 4-thiocarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (commercially available) and 0.816 g (4.1 mmol) 2-bromo-1-phenyl-ethanone (commercially available) in 10 ml methanol was stirred at 70 C. for 22 h. After evaporation to dryness the residue was suspended in diethyl ether and filtered. The residue washed with diethyl ether and dried under vacuum to yield 1.279 g (96%) of the title compound in white crystalline form. (m/e): 245.2 (MH+(-HBr); 100%).
  • 14
  • [ 214834-18-1 ]
  • [ 70-23-5 ]
  • [ 721963-02-6 ]
YieldReaction ConditionsOperation in experiment
74% Step 1: 2-Piperidin-4-yl-thiazole-4-carboxylic acid ethyl ester A mixture of 10 g (41 mmol) 4-thiocarbamoyl-piperidine-1-carboxylic acid tert-butyl ester (commercially available) and 7.98 g (41 mmol) ethyl bromopyruvate (commercially available) in 120 ml ethanol was stirred at 70 C. for 90 min. The mixture was evaporated to dryness, Na2CO3 aq. was added and the residue was extracted with ethyl acetate. The organic phases were washed with NaCl aq., dried with MgSO4 and evaporated to dryness. The residue was purified on silica eluding with DCM/MeOH/25% NH3 in water 100/20/1 to yield after evaporation of the product fractions 7.28 g (74%) of the title compound as light brown solid.
  • 15
  • [ 214834-18-1 ]
  • [ 875639-57-9 ]
  • [ 1046793-76-3 ]
YieldReaction ConditionsOperation in experiment
100% 4-[4-(5-Bromo-lH-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-piperidine-l- carboxylic acid tert-butyl ester (XXIII-f); (XXI-a) (XXIII-f)To a solution of (XXI-a) (1.71 g, 5.38 mmol) in THF (20 mL) was added 1- Boc-4-aminothiocarbonyl piperidine (1.31 g, 5.36 mmol) and the solution was allowed to stir at RT for 3 h. The reaction mixture was then poured onto saturated aqueous NaHCO3 (50 mL) and extracted with AcOEt (2 x 50 mL).The combined organic extracts were then evaporated to afford (XXIII-f) (2.58 g, 5.41 mmol, 100%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.64-1.84 (m, 4H), 2.07-2.17 (m, 2H), 2.81-2.94 (m, 2H), 3.13-3.24 (m,IH), 7.17 (s, IH), 7.74 (d, J = 2.4 Hz, 1 H), 8.32 (d, J = 2.1 Hz, IH), 8.48 (d, J= 2.1 Hz, IH), 8.97 (br s, IH).
100% 4-[4-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (71) To a solution of 70 (1.71 g, 5.38 mmol) in THF (20 mL) was added 1-Boc-4-aminothiocarbonyl piperidine (1.31 g, 5.36 mmol) and the solution was allowed to stir at r.t. for 3 h. The reaction mixture was then poured onto saturated aqueous NaHCO3 (50 mL) and extracted with AcOEt (2 x 50 mL). The combined organic portions were then evaporated to afford 71 (2.58 g, 5.41 mmol, 100%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.64-1.84 (m, 4H), 2.07-2.17 (m, 2H), 2.81-2.94 (m, 2H), 3.13-3.24 (m, 1H), 7.17 (s, 1H), 7.74 (d, J = 2.4 Hz, 1 H), 8.32 (d, J = 2.1 Hz, 1H), 8.48 (d, J = 2.1 Hz, 1H), 8.97 (br s, 1H).
100% In tetrahydrofuran; at 20℃; for 3h; 4-[4-(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-thiazol-2-yl]-piperidine-1-carboxylic acid tert-butyl ester (71) To a solution of 70 (1.71 g, 5.38 mmol) in THF (20 mL) was added 1-Boc-4-aminothiocarbonyl piperidine (1.31 g, 5.36 mmol) and the solution was allowed to stir at r.t. for 3 h. The reaction mixture was then poured onto saturated aqueous NaHCO3 (50 mL) and extracted with AcOEt (2*50 mL). The combined organic portions were then evaporated to afford 71 (2.58 g, 5.41 mmol, 100%) as a white powder. 1H NMR (400 MHz, CDCl3) δ 1.43 (s, 9H), 1.64-1.84 (m, 4H), 2.07-2.17 (m, 2H), 2.81-2.94 (m, 2H), 3.13-3.24 (m, 1H), 7.17 (s, 1H), 7.74 (d, J=2.4 Hz, 1H), 8.32 (d, J=2.1 Hz, 1H), 8.48 (d, J=2.1 Hz, 1H), 8.97 (br s, 1H).
  • 16
  • [ 214834-18-1 ]
  • [ 717915-17-8 ]
  • [ 1070176-35-0 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; ethanol; at 20℃; The bromoketone (See Example 20 Step 2, 0.67 g, 2.2 mmol) was dissolved in 1 : 1 ethyl alcohol/THF (22 mL), the thioamide (See Example 1 Step 9, 0.52 g, 2.2 mmol)) added, and the mixture stirred at room temperature overnight. The solution was diluted with aqueous NaOH (IN, 300 mL), followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc: hexanes (1 :9)) to afford the titled compound.
  • 17
  • [ 214834-18-1 ]
  • [ 14386-64-2 ]
  • C27H40N2O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
The bromoketone (1.3 g, 4.0 mmol) was dissolved in 1:1 ethyl alcohol/THF (20 mL), the thioamide (SeeExample 1 Step 9 (0.97 g, 4.0 mmol) added, and the mixture stirred at room temperature overnight. The volatiles were removed in. vac. and the residue dissolved in DMF (6 mL). Et3N (0.48 g, 4.8 mmol) and di-Λ»rr-butyl dicarbonate (0.26 g, 1.2 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with water, followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc : hexanes (1 :9)) to afford the titled compound.
  • 18
  • [ 214834-18-1 ]
  • [ 131805-94-2 ]
  • C21H22F6N2O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; ethanol; at 20℃; The bromoketone (0.25 g, 0.75 mmol) was dissolved in 1 :4 ethyl alcohol/THF (20 mL), the thioamide (SeeExample 1 Step 9 (0.20 g, 0.82 mmol) added, and the mixture stirred at room temperature overnight. The mixture was diluted with 4: t water / saturated NaHCO3 followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc : hexanes (1:4)) to afford the titled compound.
  • 19
  • [ 214834-18-1 ]
  • [ 937047-12-6 ]
  • [ 937047-66-0 ]
YieldReaction ConditionsOperation in experiment
96% In ethanol; at 20 - 78℃; To a mixture of 1-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-2-chloroethanone (500 mg, 2.37 mmol) in EtOH (12.5 mL) was added ferf-butyl 4-aminocarbothioyl)tetrahydropyridine-1 (2 H)-carboxylate (580 mg, 2.37 mmol). The mixture was stirred at 78 9C for 4.5 h, then allowed to cool to rt and stir overnight. The mixture was partitioned between saturated, aqueous NaHCO3 (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc (50 mL). The combined organic layers were washed with brine, dried (Na2SO4), and concentrated to dryness to provide 914 mg (96%) <n="120"/>of the desired product, which contained trace impurities. ES-MS m/z 400.94 [M+H]+, HPLC RT (min) 3.12.
  • 20
  • [ 214834-18-1 ]
  • C10H4Br2F6O2 [ No CAS ]
  • C21H21BrF6N2O3S [ No CAS ]
YieldReaction ConditionsOperation in experiment
The ketone (See Example 15 Step 2, 0.16 g, 0.46 mmol) was dissolved at RT in diethyl ether (2.3 mL), and aluminum chloride (3.0 mg, 0.02 mmol) added. Bromine (80 mg, 0.50 mmol) was added dropwise to the solution and the mixture stirred at RT for 10 minutes. The mixture was diluted with a solution of concentrated HCl /ice water (1:10, 40 mL), followed by aqueous/EtOAc work-up. The resulting material was dissolved in 1:1 ethyl alcohol/THF (2.3 mL), the thioamide (See Example 1 Step 9 (0. H g, 0.46 mmol) added, and the mixture stirred at 45 0C for 3 hours. The volatiles were removed in. vac. and the residue dissolved DMF (3.0 mL). Et3N (0.46 g, 4.6 mmol) and i-ert-butyl dicarbonate (100 mg, 0.46 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with 4:1 water/ saturated NaHCO3, followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether : hexanes (3:7)) to afford the titled compound.
  • 21
  • [ 214834-18-1 ]
  • [ 1124140-87-9 ]
  • [ 1124141-11-2 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; ethanol; at 20℃; for 1h; The bromoketone (See Example 17 Step 2, (0.50 g, 0.1.38 mmol) was dissolved in 1: 1 ethyl alcohol/THF (7.0 mL), the thioamide (See Example 1 Step 9, 0.34 g, 1.4 mmol) added, and the mixture stirred at room temperature for 1 hour. The solution was diluted with aqueous NaOH (IN, 150 mL), followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3:7)) to afford the titled compound.
  • 22
  • [ 214834-18-1 ]
  • [ 1124142-20-6 ]
  • [ 1124142-45-5 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; ethanol; at 20℃; The bromoketone (See Example 18 Step 3, 0.13 g, 0.39 mmol) was dissolved in 1:1 ethyl alcohol/THF (4.0 mL), the thioamide (See Example 1 Step 13, 0.094 g, 0.39 mmol) added, and the solution stirred at room temperature overnight. The mixture was diluted with aqueous NaOH (IN5 40 mL), followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3:17)) to afford the titled compound.
  • 23
  • [ 214834-18-1 ]
  • [ 1124143-07-2 ]
  • [ 1124143-24-3 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 19 Step 3, (0.078 g, 0.23 mmol) was dissolved in 1 :1 ethyl alcohol/THF (1.1 mL), the thioamide (See Example 1 Step 9, 0.056 g, 0.23 mmol) added, and the mixture stirred at room temperature overnight. The volatiles were removed in. vac. and the residue dissolved in DMF (1.0 mL). Et3N (0.23 g, 2.3 mmol) and di-tert-butyl dicarbonate (50 mg, 0.23 mmol) were added and the solution stirred at RT for 1 hour. The solution was diluted with aqueous NaOH (IN, 40 mL), followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3:17)6) to afford the titled compound .
  • 24
  • [ 214834-18-1 ]
  • [ 1124144-10-0 ]
  • [ 1124144-28-0 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; ethanol; at 20℃; The bromoketone (See Example 21 Step 4, 0.074 g, 0.18 mmol) was dissolved in 1:1 ethyl alcohoI/THF (1.0 mL), the thioamide (See Example 1 Step 9, 0.044 g, 0.18 mmol)) added and the mixture stirred at room temperature overnight. The solution was diluted with aqueous NaOH (IN, 40 mL) followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3:7)) to afford the titled compound.
  • 25
  • [ 214834-18-1 ]
  • [ 1005515-07-0 ]
  • [ 1124145-06-7 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 22 Step 4, 0.19 g, 51 mmol) was dissolved in 1 : 1 ethyl alcohol/THF (1.3 mL), the thioamide (See Example 1 Step 9, 0.12 g, 0.51 mmol)) added and the solution stirred overnight. The volatiles were removed in. vac. and the residue dissolved DMF (2.5 mL). Et3N (0.15 g, 1.5 mmol) and di-ffer/-butyl dicarbonate (110 mg, 0.51 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with 4: 1 water / saturated NaHCO3 followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc : hexanes (3:7)) to afford the titled compound.
  • 26
  • [ 214834-18-1 ]
  • [ 1124145-36-3 ]
  • [ 1124145-48-7 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; ethanol; at 20℃; The bromoketone (See Example 23 Step 1, (0.043 g, 0.13 mmol) was dissolved in 1 :1 ethyl alcohol/THF (1.5 mL), the thioamide (See Example 1 Step 9, 0.036 g, 0.15 mmol) and NaHCO3 (12 mg, 0.15 mmol) added and the solution stirred at RT overnight. The mixture was poured into 4:1 water / saturated NaHCO3 (40 mL) followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc : hexanes (1 :9)) to afford the titled compound.
  • 27
  • [ 214834-18-1 ]
  • [ 1124146-33-3 ]
  • [ 1124146-46-8 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 24 Step 4, (0.073 g, 0.20 mmol) was dissolved in 1:1 ethyl alcohol/THF (1.0 mL), the thioamide (See Example 1 Step 9, 0.050 g, 0.20 mmol) added and the solution stirred at RT overnight. Et3N (0.20 g, 2.0 mmol) and di-tert-butyl dicarbonate (0.044 g, 0.20 mmol) were added and the solution stirred for 1 hour. The mixture was diluted with 4:1 water / saturated NaHCO3 followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3 :7)) to afford the titled compound.
  • 28
  • [ 214834-18-1 ]
  • [ 1124146-93-5 ]
  • C25H38N4O2S [ No CAS ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 25 Step 4, 0.025 g, 0.080 mmol) was dissolved in 1:1 ethyl alcohol/THF (1.0 mL), the thioamide (See Example 1 Step 9, 0.020 g, 0.080 mmol) added and the solution stirred at RT overnight. The solvent was removed in vac. and the residue dissolved in DMF (1.0 mL). Et3N (0.024 g, 0.24 mmol) and di-tert-butyl dicarbonate (0.018 g, 0.080 mmol) were added and the solution stirred at RT for 1 hour. The mixture was poured into saturated NaHCO3 (50 mL) followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (3:7)) to afford the titled compound.
  • 29
  • [ 214834-18-1 ]
  • [ 1124147-60-9 ]
  • [ 1124147-72-3 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 26 Step 4, 0.24 g, 0.74 mmol) was dissolved in 1 : 1 ethyl alcohol/THF (3.7 mL), the thioamide (See Example 1 Step 9, 0.18 g, 0.74 mmol) added and the solution stirred at RT overnight. The solvent was removed in vac. and the residue dissolved in DMF (3.7 mL). Et3N (0.75 g, 7.4 mmol) and di~ter/-butyl dicarbonate (0.16 g, 0.74 mmol) were added and the solution stirred for 1 hour. The mixture was diluted with saturated NaHCC>3 (100 mL) followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (1:7)) to afford the titled compound.
  • 30
  • [ 214834-18-1 ]
  • [ 1124148-31-7 ]
  • [ 1124148-49-7 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 27 Step 4, 0.20 g, 0.51 mmol) was dissolved in 1: 1 ethyl alcohol/THF (2.6 mL), the thioamide (See Example 1 Step 9, 0.13 g, 0.51 mmol)) added and the solution stirred at RT overnight. The solvent was removed in vac. and the residue dissolved in DMF (2.6 mL). Et3N (0.52 g, 5.1 mmol) and di-ter/-butyl dicarbonate (0.11 g, 0.51 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with 4:1 water / saturated NaHCO3 (100 mL) followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (1 :4)) to afford the titled compound.
  • 31
  • [ 214834-18-1 ]
  • [ 1124136-01-1 ]
  • C24H31F3N2O2S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
The bromoketone (SeeExampIe 1 Step 8, (2.41 g, 5.4 mmol) was dissolved in 1:1 EtOH /THF (34 mL), the thioamide (SeeExampIe 1 Step 9 (1.66 g, 6.8 mmol) added, and the mixture stirred overnight at room temperature. The volatiles were removed in vac and the residue dissolved DMF (13.5 mL). Et3N (6.87 g, 68 mmol) and di-Λ?r*-butyl dicarbonate (888 mg, 4.07 mmol) were added and the solution stirred for 1 hour. The mixture was poured into 4:1 water / saturated NaHCO3 followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether : hexanes (1 :4)) to afford the titled compound.
  • 32
  • [ 214834-18-1 ]
  • [ 1124149-52-5 ]
  • [ 1124149-65-0 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 29 Step 6, 0.050 g, 0.15 mmol) was dissolved in 1: 1 ethyl alcohol/THF (0.75 mL), the thioamide (See Example 1 Step 9, 0.037 g, 0.15 mmol)) added and the solution stirred at RT overnight. The solvent was removed in vac. and the residue dissolved in DMF (0.75 mL). Et3N (0.15 g, 1.5 mmol) and di-tert-buty dicarbonate (0.033 g, 0.15 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with 4:1 water / saturated NaHCO3, followed by aqueous/EtOAc work-up and silica gel chromatography (EtOAc: hexanes (1:9)) to afford the titled compound.
  • 33
  • [ 214834-18-1 ]
  • [ 1124149-98-9 ]
  • [ 1124150-06-6 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 30 Step 5, 0.28 g, 0.91 mmol) was dissolved in 1 : 1 ethyl alcohol/THF (5.0 mL), the thioamide (See Example 1 Step 9, 0.22 g, 0.91 mmol)) added and the solution stirred at RT overnight. The solvent was removed in vac. and the residue dissolved in DMF (4.5 mL). Et3N (0.91 g, 9.1 mmol) and di-tert-butyl dicarbonate (0.20 g, 0.91 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with saturated NaHCO3 (100 mL), followed by <n="86"/>aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (1 :4)) to afford the titled compound.
  • 34
  • [ 214834-18-1 ]
  • [ 132392-28-0 ]
  • [ 1124150-29-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In tetrahydrofuran; ethanol; at 20℃; for 2.5h; A vessel was charged with 2-bromo-l -(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)ethan-l-one (0.70 g, 2.3 mmol), thioamide (See Example 1 Step 9, 0.83 g, 3.4 mmol), and NaHCO3 (0.21 g, 2.5 mmol), the materials dissolved in 1:1 ethyl alcohol/THP (15 mL). The resulting solution was stirred at RT for 2.5 hours, diluted with water(50 mL), followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether: hexanes (1:4)) to afford the titled compound.
  • 35
  • [ 214834-18-1 ]
  • [ 1124153-36-1 ]
  • [ 1124153-40-7 ]
YieldReaction ConditionsOperation in experiment
The bromoketone (See Example 40 Step 6, 0.064 g, 0.17 mmol) was dissolved in 1:1 ethyl alcohoI/THF (1.7 mL), the thioamide (See Example 1 Step 9, 0.041 g, 0.17 mmol) added, and the mixture stirred at RT overnight. The volatiles were removed in. vac. and the residue dissolved DMF (1.0 mL). Et3N (0.17 g, 1.7 mmol) and -tert-butyl dicarbonate (36 mg, 0.17 mmol) were added and the solution stirred at RT for 1 hour. The mixture was diluted with 4: 1 water / saturated NaHCO3 followed by aqueous/EtOAc work-up and silica gel chromatography (diethyl ether : hexanes (1 :7)) to afford the titled compound.
 

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