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[ CAS No. 17768-41-1 ] {[proInfo.proName]}

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Product Details of [ 17768-41-1 ]

CAS No. :17768-41-1 MDL No. :MFCD00074750
Formula : C11H19N Boiling Point : -
Linear Structure Formula :- InChI Key :XSOHXMFFSKTSIT-UHFFFAOYSA-N
M.W : 165.28 Pubchem ID :86625
Synonyms :

Calculated chemistry of [ 17768-41-1 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 51.1
TPSA : 26.02 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -5.75 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.31
Log Po/w (XLOGP3) : 2.19
Log Po/w (WLOGP) : 2.16
Log Po/w (MLOGP) : 2.74
Log Po/w (SILICOS-IT) : 2.21
Consensus Log Po/w : 2.32

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.18
Solubility : 1.1 mg/ml ; 0.00663 mol/l
Class : Soluble
Log S (Ali) : -2.37
Solubility : 0.705 mg/ml ; 0.00426 mol/l
Class : Soluble
Log S (SILICOS-IT) : -1.98
Solubility : 1.72 mg/ml ; 0.0104 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 3.59

Safety of [ 17768-41-1 ]

Signal Word:Danger Class:8
Precautionary Statements:P280-P305+P351+P338-P310 UN#:2735
Hazard Statements:H227-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 17768-41-1 ]

* 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 [ 17768-41-1 ]

[ 17768-41-1 ] Synthesis Path-Downstream   1~85

  • 2
  • [ 5511-18-2 ]
  • [ 17768-41-1 ]
YieldReaction ConditionsOperation in experiment
98% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃;Reflux; A solution of <strong>[5511-18-2]adamantane-1-carboxamide</strong> (0.500 g, 2.79 mmol, 1.0 eq.) in dryTHF (7.50 mL) was added dropwise in a solution of LiA1H4 (0.423 g, 11.16 mmol,4.0 eq.) in dry THF (5.0 mL) at 0 C. The reaction mixture was stirred overnight at reflux.The reaction mixture was cooled to 0 C and 3.0 equivalents of 1 N aqueous NaOH wasadded dropwise with vigorous stuffing. After 1 h of stirring at room temperature, themixture was filtrated over Celite and the residue was washed with CH2C12. The filtratewas dried over Na2504 and concentrated under reduced pressure to give as a yellow oil1-adamantanylmethylamine (0.450 g, 98%). MS (ESI+): mlz = 166 [M+Hf. ?H NMR(CDC13) oe (ppm): 2.35 (s, 2H), 2.01 (br s, 3H), 1.80-1.62 (m, 6H), 1.48 (d, 6H, J =2.3 Hz). ?3C NMR (CDC13) oe (ppm): 68.0, 40.0, 37.2, 33.9, 28.4. The urea was obtainedaccording general procedure A from 1-adamantanylmethylamine and 2-amino-5- nitrothiazole. Pale brown solid (0.076 g, 11%). Purity = 100%; tr = 3.17 mm; MS (ESI-):m/z = 335 [M-Hf; HRMS mlz calculated for C,5H,9N4035 [M-Hf 335.1183, found335.1195. ?H NMR (DMSO-d6) oe (ppm): 11.26 (s, 1H), 8.51 (s, 1H), 6.78 (t, 1H, J =5.8 Hz), 2.94-2.84 (m, 2H), 1.95 (s, 3H), 1.70-1.67 (m, 3H), 1.61-1.58 (m, 3H), 1.46 (d, 6H, J = 2.2 Hz). ?3C NMR (DMSO-d6) oe (ppm): 164.1, 153.4, 143.4, 140.9, 50.9, 39.1, 36.4, 33.5, 27.6.
80% Step 2: 1-Adamantylmethylamine: To a stirred and cooled (0 C) suspension of lithium aluminium hydride (846 mg, 22.29 mmol) in dry THF (10 ml) was added dropwise a solution of Step 1 intermediate (1.0 g, 5.58 mmol) in dry THF (15 ml). The reaction mixture was gently refiuxed overnight. The mixture was cooled to 10 0C and then quenched with a few drops of ethyl acetate followed by addition of a saturated solution of Na2SO4. The mixture was filtered over celite, the filtrate was dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford the product as a pale yellow semisolid (737 mg, 80%).
60% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0 - 20℃; for 16h;Heating / reflux; Powdered LiAlH4 (3 g, 80 mmol) was added to a solution of the 1 -cubanecarboxamide in THF (120 mL) at 00C with stirring. After warming to room temperature, the suspension was heated at reflux for 16 h, cooled to room temperature, and saturated aq. NaOH (ca. 20 mL) was added dropwise at 0 0C with vigorous stirring. After stirring for 1 h at room temperature, the white mixture was filtered and the residue was washed with CH2Cl2 (60 mL). The combined organic portions were dried (Na2SO
60% With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 16h;Reflux; Powdered LiAlH4 (3 g, 80 mmol) was added to a stirred solution of the carboxamide in THF (120 mL) at 0 C. After warming to ambient temperature, the suspension was heated at reflux for 16 h, cooled, and saturated aqueous sodium hydroxide (20 mL) was added dropwise at 0 C with vigorous stirring. After stirring for 1 h at ambient temperature, the mixture was filtered and the residue was washed with CH2Cl2 (60 mL). The combined organic portions were dried (MgSO4) and evaporated in vacuo to give the crude amine S8 (4.1 g, 60% over 3 steps) as a colourless oil with some solid impurities. The crude was then purified by flash chromatography on silica eluting with CH2Cl2-MeOH-NH4OH (90:9:1) to give the pure amine S8 as a colourless oil; deltaH (200 MHz; CDCl3) 2.31 (2 H, s), 1.98 (3 H, br s), 1.76-1.60 (6 H, m), 1.46-1.45 (6 H, m). The spectroscopic data matched that reported by the Aldrich Library.
59% To a solution of admantane-1 -carboxamide (2 g, 11.17 mmol) in THF (50 mL) was added BH3. Me2S (10.2 M, 3.4 mL, 34.7 mmol) under nitrogen. The mixture was heated at reflux overnight. The solution was cooled to rt. Methanol (20 mL) was added to the solution. The mixture was concentrated under vacuum to give crude product, which was purified by chromatography on silica gel to afford (i-adamantyl)methylamine (1.09 g, 59 %). 1H NMR (CDCI3, 400 MHZ): delta=1.44-1.96 (m, 15H), 2.30 (s, 2H).
With lithium aluminium tetrahydride; In tetrahydrofuran; at 20℃; for 6h;Reflux; General procedure: To a stirred solution of 13, 10k or 10m (130 mmol) in dried THF (150 mL) cooled in an ice-waterbath was added portionwise LiAlH4 (6.41 g, 169 mmol). Thereafter the reaction mixture was stirredat room temperature for 1 h and then at reflux for another 5 h, when the reaction completed asindicated by TLC analysis. On cooling to room temperature, the reaction mixture was carefullypoured into ice-water (500 mL) while stirring, and the resulting mixture was diluted with CH2Cl2(300 mL), stirred for 0.5 h and filtered off through Celite. The organic phase was separated from thefiltrate, and the aqueous phase was back-extracted with CH2Cl2 (200 mL × 2). The combined organicphases were washed with saturated brine (200 mL), dried (Na2SO4) and evaporated on a rotaryevaporator to give a residue, which was purified by column chromatography through a short silicagel column to afford 2d, 2k or 2m. These amines were used directly in the next step without furtherpurification and characterization.

  • 4
  • [ 17768-41-1 ]
  • [ 768-91-2 ]
  • 5
  • [ 17768-41-1 ]
  • [ 13200-85-6 ]
  • (S)-N-Adamantan-1-ylmethyl-2-formylamino-3-phenyl-propionamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With dicyclohexyl-carbodiimide Ambient temperature;
  • 6
  • [ 3724-19-4 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)-3-(pyridin-3-yl)propanamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dmap; dicyclohexyl-carbodiimide In tetrahydrofuran at 35℃; for 48h;
  • 7
  • [ 17768-41-1 ]
  • [ 2351-37-3 ]
  • biphenyl-4,4'-dicarboxylic acid-bis(1-adamantanemethylamide) [ No CAS ]
YieldReaction ConditionsOperation in experiment
50% With triethylamine In dichloromethane at 20℃; for 0.5h;
  • 8
  • [ 17768-41-1 ]
  • [ 207557-35-5 ]
  • (S)-1-{2-[(Adamantan-1-ylmethyl)-amino]-acetyl}-pyrrolidine-2-carbonitrile [ No CAS ]
  • 9
  • [ 2516-96-3 ]
  • [ 17768-41-1 ]
  • [ 227327-87-9 ]
YieldReaction ConditionsOperation in experiment
With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide
1.7 g Stage #1: 2-chloro-5-nitrobenzoic acid With 1,1'-carbonyldiimidazole In N,N-dimethyl-formamide for 2.5h; Stage #2: adamantylmethylamine In N,N-dimethyl-formamide for 14h; Further stages.;
With 1,1'-carbonyldiimidazole In dichloromethane; N,N-dimethyl-formamide 4.a a) a) 2-Chloro-5-nitro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide To a solution of 2-chloro-5-nitrobenzoic acid (1.22 g) in N,N-dimethylformamide (1.5 ml) was added carbonyldiimidazole (1.0 g). The resulting reaction mixture was stirred for 2.5 h and then 1-adamantanemethylamine (1.0 g) was added. After 14 h the reaction mixture was partitioned between ethyl acetate and water and the organic layer was separated, washed with water and brine and then dried over sodium sulphate (Na2SO4). The organic layer was concentrated under reduced pressure to give a residue which was purified by silica gel chromatography (eluding with 3-10% methanol in dichloromethane) to yield the subtitle compound as a yellow solid (1.7 g). MS (APCI+ve) 348/350 (M+H)+ 1H NMR (CDCl3) δ 8.53 (1H, d), 8.2 (1H, dd), 7.6 (1H, d), 6.2 (1H, bs), 3.2 (2H, d), 2.0 (3H,bs), 1.8 (12H, m)
  • 10
  • [ 17768-41-1 ]
  • [ 52853-40-4 ]
  • [ 677298-11-2 ]
YieldReaction ConditionsOperation in experiment
40% In N,N-dimethyl acetamide; 6-[(Adamantan-1-yl-methyl)-amino]-methyl}-2,4-pteridinediamine To a solution of 6-bromomethyl-2,4-pteridinediamine hydrobromide (41.6 mg, 0.124 mmol) in anhydrous N,N dimethylacetamide was added 1-aminomethyl adamantane (35.43 ul, 0.2 mmol). The reaction mixture was stirred at 50 C. overnight. The crude product was poured into saturated bicarbonate solution. The resulted precipitate was collected and purified by preparative HPLC. 12.7 mg product was obtained. Yield: 40%; 1H NMR (500 MHz, DMSO-d6): delta 1.56754-1.67101 (m, 13H), 1.96741 (s, 2H), 2.71139 (s, 2H), 4.49166 (s, 2H), 8.89918 (s, 1H); ESI-MS: m/z 340 (M++1)
  • 11
  • [ 17768-41-1 ]
  • [ 52010-97-6 ]
  • C19H25NO [ No CAS ]
YieldReaction ConditionsOperation in experiment
99% With sodium sulfate In dichloromethane at 20℃; for 3h;
  • 12
  • [ 109-04-6 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With copper(l) iodide; 2-(2-methyl-1-oxopropyl)cyclohexanone; caesium carbonate; In N,N-dimethyl-formamide; at 140℃; for 24h;Schlenk technique; General procedure: a. Palladium(0)-catalyzed reactions. A Schlenk flask was charged with Pd(dba)2 (1-8 mol %, 2.9-23 mg), phosphine ligand (1.25-9 mol %), and bromopyridine2-8 (0.5 mmol), and 5 mL of dioxane, amine 1 or 21 (0.625 mmol), and sodium tert-butoxide(0.75 mmol, 72 mg) were added. The mixture was refluxed for 12 h with stirring and cooled to room temperature, the organic phase was separated, the precipitate was washed with methylene chloride (5 mL),and the organic phase was combined with the washings and evaporated under reduced pressure. The residue was dissolved in methylene chloride (5 mL), and the solution was washed with water (3 × 5 mL), dried over 4A molecular sieves, and thoroughly evaporated under reduced pressure (1 mm). b. A Schlenk flask was charged with copper(I)iodide (10 or 20 mol %, 9.5 or 19 mg), 2-isobutyrylcyclohexanone(20 or 40 mol %, 17 or 34 mg), and bromopyridine 2-8 (0.5 mmol), and 1 mL of DMF,amine 1 or 21 (0.5 mmol), and cesium carbonate(0.75 mmol, 250 mg) were added. The mixture was heated for 24 h at 140C with stirring and cooled to room temperature, the organic phase was separated,and the residue was washed with methylene chloride(5 mL). The organic phase was combined with the washings and evaporated under reduced pressure, the residue was dissolved in methylene chloride (5 mL),and the solution was washed with water (3 × 5 mL),dried over 4A molecular sieves, and thoroughly evaporated under reduced pressure (1 mm). The spectral parameters of compounds 9, 16 [21], 22, and 29 [26]were consistent with published data
  • 13
  • [ 109-04-6 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)pyridin-2-amine [ No CAS ]
  • N-(1-adamantylmethyl)-N-(2-pyridyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
95%; 5% With bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate; DavePhos; In 1,4-dioxane; at 100℃; for 12h;Schlenk technique; General procedure: a. Palladium(0)-catalyzed reactions. A Schlenk flask was charged with Pd(dba)2 (1-8 mol %, 2.9-23 mg), phosphine ligand (1.25-9 mol %), and bromopyridine2-8 (0.5 mmol), and 5 mL of dioxane, amine 1 or 21 (0.625 mmol), and sodium tert-butoxide(0.75 mmol, 72 mg) were added. The mixture was refluxed for 12 h with stirring and cooled to room temperature, the organic phase was separated, the precipitate was washed with methylene chloride (5 mL),and the organic phase was combined with the washings and evaporated under reduced pressure. The residue was dissolved in methylene chloride (5 mL), and the solution was washed with water (3 × 5 mL), dried over 4A molecular sieves, and thoroughly evaporated under reduced pressure (1 mm). b. A Schlenk flask was charged with copper(I)iodide (10 or 20 mol %, 9.5 or 19 mg), 2-isobutyrylcyclohexanone(20 or 40 mol %, 17 or 34 mg), and bromopyridine 2-8 (0.5 mmol), and 1 mL of DMF,amine 1 or 21 (0.5 mmol), and cesium carbonate(0.75 mmol, 250 mg) were added. The mixture was heated for 24 h at 140C with stirring and cooled to room temperature, the organic phase was separated,and the residue was washed with methylene chloride(5 mL). The organic phase was combined with the washings and evaporated under reduced pressure, the residue was dissolved in methylene chloride (5 mL),and the solution was washed with water (3 × 5 mL),dried over 4A molecular sieves, and thoroughly evaporated under reduced pressure (1 mm). The spectral parameters of compounds 9, 16 [21], 22, and 29 [26]were consistent with published data
  • 14
  • [ 17768-41-1 ]
  • [ 6280-89-3 ]
  • [ 227327-85-7 ]
  • 15
  • [ 79-37-8 ]
  • [ 17768-41-1 ]
  • [ 88912-26-9 ]
  • [ 380217-24-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; dichloromethane; a 2,5-Dichloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-pyridine-4-carboxamide To a stirred suspension of <strong>[88912-26-9]2,5-dichlorpyridine-4-carboxylic acid</strong> (1.53 g, WO 96/33975) in dichloromethane (20 ml) and dimethylformamide (0.02 ml) at room temperature was added portionwise oxalyl chloride (3 ml). Once complete solution was achieved the mixture was stirred for a further 1 hour then concentrated in vacuo. The compound was redissolved in dichloromethane and added slowly to a solution of adamantylmethylamine in dichloromethane (20 ml) and diisopropylethylamine (2 ml). The mixture was partitioned between saturated aqueous sodium bicarbonate solution and dichloromethane and the organic layer dried over magnesium sulphate. Concentration in vacuo and crystallization (diethyl ether: isohexane) gave the sub-title compound as colourless crystals (1.62 g). MS (APCI+ve) 339.1038 (M+H)+ 1H NMR (DMSO-d6) delta 8.59 (1H, t); 8.58 (1H, s); 7.65 (1H, s); 2.94 (2H, d); 1.94 (3H, bs); 1.7-1.57 (6H, m); 1.51 (6H, s).
  • 16
  • [ 79-37-8 ]
  • [ 59748-90-2 ]
  • [ 17768-41-1 ]
  • [ 301672-92-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In <i>N</i>-methyl-acetamide; dichloromethane 41.a a) a) 4-Bromo-2-chloro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide To a suspension of 4-bromo-2-chlorobenzoic acid (5.00 g) in dichloromethane (25 ml) at 0° C. was added oxalyl chloride (3.7 ml) and dimethylformamide (5 drops). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour, then concentrated under reduced pressure to yield a solid. The solid was dissolved in dichloromethane (20 ml) and added dropwise to a solution of 1-adamantanemethylamine (3.36 g) and N,N-diisopropylethylamine (5.55 ml) in dichloromethane (20 ml). The resulting solution was allowed to stir at room temperature under a nitrogen atmosphere for 20 h. The reaction mixture was diluted with dichloromethane and washed with water, 10% aqueous potassium carbonate, 10% aqueous potassium hydrogen sulfate and saturated brine. The organic phase was then dried over sodium sulfate, filtered and concentrated under reduced pressure to afford the subtitle compound as a solid (4.28 g). MS (APCI+ve) 382/384 (M+H)+ 1H NMR (DMSO-d6) δ 8.39-8.34 (1H, t); 7.78 (1H, m); 7.62-7.59 (1H, m); 7.37-7.34 (1H, d), 2.94-2.92 (2H, d); 1.94 (3H, br s); 1.69-1.57 (6H, br AB); 1.52 (6H, s).
  • 17
  • [ 79-37-8 ]
  • [ 4771-47-5 ]
  • [ 17768-41-1 ]
  • [ 301672-64-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; dichloromethane; a) 3-Chloro-2-nitro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide To a suspension of <strong>[4771-47-5]3-chloro-2-nitrobenzoic acid</strong> (2.68 g) in dichloromethane (10 ml) at 0 C. was added oxalyl chloride (3 ml) and dimethylformamide (1 drop). The resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour, then concentrated under reduced pressure to yield a solid. The solid was dissolved in dichloromethane (10 ml) and cooled to 0 C. A solution of 1-adamantanemethylamine (2.19 g) and N,N-diisopropylethylamine (11 ml) in dichloromethane (10 ml) was added portion-wise and the resulting solution allowed to stir at room temperature under a nitrogen atmosphere for 2 h. The reaction mixture was poured into water and the organic phase separated and washed with 2N hydrochloric acid, 10% aqueous sodium hydroxide and saturated brine. The organic phase was then dried over sodium sulfate, filtered and concentrated under reduced pressure and the resulting solid recrystallized from iso-propanol to afford the subtitle compound as a solid (3.52 g). MS (APCI+ve) 349 (M+H)+ 1H NMR (DMSO-d6) delta 8.74 (1H, t); 7.89 (1H, m); 7.75-7.69 (2H, m); 2.91 (2H, d), 1.93 (3H, bs); 1.64 (6H, dd); 1.47 (6H, d)
  • 18
  • [ 17768-41-1 ]
  • [ 56961-30-9 ]
  • [ 530-62-1 ]
  • [ 227327-85-7 ]
YieldReaction ConditionsOperation in experiment
In dichloromethane; N,N-dimethyl-formamide; a) 2-Chloro-5-hydroxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide To a solution of <strong>[56961-30-9]2-chloro-5-hydroxybenzoic acid</strong> (3.12 g) in N,N-dimethylformamide (50 ml) was added 1,1'-carbonyldiimidazole (3.0 g). The resulting reaction mixture was stirred for 2.5 h and then 1-adamantanemethylamine (3.0 g) was added. Stirring was continued for 14 h. The reaction mixture was partitioned between ethyl acetate and water and the organic layer was separated, washed with water and brine and then dried over sodium sulphate (Na2SO4). The organic layer was concentrated under reduced pressure to give a residue which was purified by silica gel chromatography (eluding with 3-10percent methanol in dichloromethane) to yield the subtitle compound as a white solid (0.15 g). MS (APCI+ve) 319/321 (M+H)+ 1H NMR (DMSO-d6) delta 9.85(1H,s), 8.25 (1H, t), 7.24(1H, d), 6.76-6.82(2H, m), 2.90 (2H,d), 1.93(3H, s), 1.67 (3H, d), 1.57 (3H, d), 1.51 (6H, s)
  • 19
  • [ 17768-41-1 ]
  • [ 1501-98-0 ]
YieldReaction ConditionsOperation in experiment
60% With hydrogenchloride; In dichloromethane; at 0℃; Step 3: 1-Adamantylmethylamine hydrochloride: Dry HCl gas was bubbled into a solution of Step 2 intermediate (737 mg, 4.46 mmol) in dichloromethane (10 ml) at 0 0C. The solvent was removed under reduced pressure and the solid so obtained was triturated with dry diethyl ether to afford the pure product as a white solid (540 mg, . 60 %); 1H NMR (300 MHz, DMSO-J6) delta 1.50-1.69 (m, 12 H), 1.96 (brs, 3H), 2.46- 2.51 (m, 2H), 7.85 (brs, 3H).
  • 20
  • [ 17768-41-1 ]
  • [ 146949-07-7 ]
  • [ 885431-62-9 ]
YieldReaction ConditionsOperation in experiment
59% General method for synthesis of adamantylmethyl arylsulphonamide derivatives:; To a solution of arylsulphonyl chloride (0.53 mmol, 1.06 eq.) in DCM (6 mL) was added pyridine (0.2 mL)5 followed by the corresponding amine (0.50 mmol, 1 eq.). The reaction mixture was stirred at ambient temperature under nitrogen overnight. PS-PS-trisamine (4.1 mmol/g5 100 mg) was added, the mixture was kept stirring for another 2h5 filtered and concentrated in vacuo to give the crude product that was purified by flash chromatography (Ethyl acetate-hexane gradient elution) to give desired arylsulphonamide as crystalline solid or amorphous solid.N-Adamantan-l-yImethyI-4-propyl-benzenesulfonamide (XDS03080, STX1368)The compound was prepared with general method. White crystals (102 mg5 59%) were obtained, mp 148-149 C; TLC single spot at Rf. 0.50 (20% ethyl acetate/hexane); 1H NMR (270 MHz5 CDCl3) delta 0.93 (3H, t, J= 7.2 Hz, CH3), 1.42 (6H5 d, J= 2.6 Hz5 3 x CH2), 1.54-1.70 (8H5 m, 4 x CH2), 1.95 (3H5 broad S5 3 x CH)5 2.57 (2H5 d, J= 6.7 Hz5 NCH2), 2.64 (2H, t, J= 7.2 Hz, CH2), 4.60 (IH5 1, J= 6.6 Hz, NH)5 7.29 (2H, m, ArH)5 and 7.73 (2H5 m5 ArH); HRMS (FAB+) calcd. for C20H30NO2S (M+-FH) 348.1997, found 348.2007; LC/MS (APCI) m/z 348 (M++..); HPLC tr = 3.29 min (>99%) in 10% water- acetonitrile.
  • 21
  • [ 17768-41-1 ]
  • [ 102940-86-3 ]
  • 2-Chloro-3-fluoro-N-(tricyclo[3.3.1.13.7]dec-1-ylmethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1,1'-carbonyldiimidazole; In N,N-dimethyl-formamide; EXAMPLE 41 2-Chloro-3-fluoro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide A solution of <strong>[102940-86-3]2-chloro-3-fluorobenzoic acid</strong> (0.098 g) and carbonyldiimidazole (0.091 g), in N,N-dimethylformamide (3.0 ml) was stirred for 2.5 hours at room temperature. 1-Adamantanemethylamine (0.1 ml) was then added and stirring continued overnight. The reaction mixture was partitioned between ethyl acetate and 2N hydrochloric acid and the organic layer was separated, washed with 10% aqueous sodium hydroxide, water and brine and then dried over sodium sulphate (Na2SO4). The organic layer was subsequently concentrated under reduced pressure to yield the title compound as a white solid (0.138 g). Melting point: 149-151 C. MS (APCI+ve) 322/324 (M+H)+ 1H NMR (DMSO-d6) delta 8.42 (1H, t), 7.50 - 7.40 (2H, m), 7.29 - 7.24 (1H, m), 2.94 (2H, d), 1.94 (3H, s), 1.64 (6H, dd), 1.53 (6H, m)
  • 22
  • [ 17768-41-1 ]
  • [ 2252-50-8 ]
  • 2-Chloro-5-fluoro-N-(tricyclo[3.3.1.13.7]dec-1-ylmethyl)-benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 43 2-Chloro-5-fluoro-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide Prepared according to the method of Example 41 from 1-adamantanemethylamine (0.1 ml) and <strong>[2252-50-8]2-chloro-5-fluorobenzoic acid</strong> (0.098 g) to give the title compound as a white solid (0.165 g). Melting point: 176-177 C. MS (APCI+ve) 366/367 (M+H)30 1H NMR (DMSO-d6) delta 8.37 (1H, t), 7.71 - 7.65 (1H, dd), 7.28 -7.20 (2H, m), 2.92 (2H, d), 1.94 (3H, s), 1.64 (6H, dd), 1.53 (6H, d)
  • 23
  • [ 17768-41-1 ]
  • [ 56961-30-9 ]
  • [ 227327-85-7 ]
YieldReaction ConditionsOperation in experiment
EXAMPLE 51 2-Chloro-5-hydroxy-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-benzamide Prepared according to the method of Example 14 from <strong>[56961-30-9]2-chloro-5-hydroxybenzoic acid</strong> (0.3 g) and 1-adamantanemethylamine (0.31 ml) to give the title compound as a white solid (0.15 g). Melting point: 263-264° C. MS (APCI+ve) 320 (M+H)30 1H NMR (DMSO-d6) delta 9.85(1H,s), 8.25 (1H, t), 7.24(1H, d), 6.76-6.82(2H, m), 2.90 (2H,d), 1.93(3H, s), 1.67 (3H, d), 1.57 (3H, d), 1.51 (6H, s)
  • 24
  • Fmoc-PEG5000-NHS [ No CAS ]
  • [ 17768-41-1 ]
  • AD-Peg5000-NH2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
76% 266 mg OfFMOC-PEG500O-NHS (78.2 mutnol, Shearwater Polymers, Huntsville AL) were added to a glass vial equipped with a magnetic stirbar. 10 eq. of 1-adamantane-methylamine (1.5 mmol, Aldrich) dissolved in 3 mL of dichloromethane were then added and the solution stirred overnight at room temperature. The solvent was removed in vacuo and water was added to the remaining solution to dissolve the PEG product. The solution was centrifuged at 2OK rcf for 10 minutes, whereupon the adamantane-methylamine phase-separated as a denser liquid. The aqueous portion was collected and water removed in vacuo. The remaining viscous liquid was redissolved in 20% piperidine in DMF for FMOC deprotection and stirred for 30 minutes at room temperature. The solvent was removed in vacuo, washed several times with DMF, redissolved in water, and run on EPO <DP n="116"/>an anionic exchange column to remove unreacted PEG. The first fractions were collected and lyophilized to yield 222 mg of a white, fluffy powder (76% yield) of the desired product which was confirmed by MALDI-TOF analysis.
  • 25
  • [ 17768-41-1 ]
  • [ 261635-93-2 ]
  • N-(1-adamantylmethyl)-2-methyl-6-(trifluoromethyl)nicotinamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; triethylamine; trifluoroacetic acid In dichloromethane; water; acetonitrile 166 N-(1-adamantylmethyl)-2-methyl-6-(trifluoromethyl)nicotinamide EXAMPLE 166 N-(1-adamantylmethyl)-2-methyl-6-(trifluoromethyl)nicotinamide A suspension of 2-methyl-6-(trifluoromethyl)nicotinic acid (6 mmol) in dry dichloromethane (9 mL) was treated with thionyl chloride (12.4 mmol) at 0° C., stirred for one hour, and concentrated in vacuo. The concentrate was added dropwise to a cold solution of 1-adamantylmethylamine (6 mmol) and triethylamine (4.5 mL) in dichloromethane (20 mL). The mixture was stirred for 4 hours and then concentrated in vacuo. The residue was dissolved in dichloromethane, washed sequentially with saturated sodium bicarbonate, water, and brine, dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified by HPLC on a C-18 column using a solvent system increasing in gradient from 5% to 100% acetonitrile/water containing 0.01% TFA over 50 minutes to provide the desired product as the trifluoroacetate salt. MS m/e 353.1 (M+H)+; 1H NMR (DMSO-d6) δ 1.52 (br d, 6H), 1.58-1.71 (br m, 6H), 1.95 (br s, 3H), 2.58 (s, 3H), 2.98 (d, 2H), 7.78 (d, 1H), 7.95 (d, 1H), 8.44 (br t, 1H).
  • 26
  • [ 17768-41-1 ]
  • [ 10130-87-7 ]
  • [ 874568-98-6 ]
YieldReaction ConditionsOperation in experiment
97% With N-ethyl-N,N-diisopropylamine; In dichloromethane; Adamantanyl methyl) [(2- methoxyphenyl)sulfonyl]amine was prepared by treating 2-methoxybenzene sulfonyl chloride (0.41 g, 2 mmols) with Adamantanylmethyl amine (0.33 g, 2mmols) in Dichloromethane (10 ml) in presence of Diisopropylethyl amine (0.696 ml, 4 mmols). Yield: 0.65 g (97%). MH+: 336
  • 27
  • [ 17768-41-1 ]
  • [ 393-52-2 ]
  • [ 850461-25-5 ]
YieldReaction ConditionsOperation in experiment
96% With triethylamine; In acetonitrile; at 0 - 20℃; for 16h; A solution of the acyl chloride (1.0 mmol) in MeCN (10 mL) was added dropwise to a solution of the amine (1.0 mmol) and NEt3 (0.10 g, 1.0 mmol) in MeCN (10 mL) at 0 0C. After stirring for 16 h at room temperature, the reaction mixture was concentrated under reduced pressure. H2O (35 mL) was added, followed by extraction with CH2Ch (3 x 35 mL). The organic layers were washed sequentially with NaHCOj (40 mL) and H?O (40 mL), dried (Na2SO4), and concentrated in vacuo to give the crude amide, ? which was then purified by flash chromatography (80:20 v/v cyclohexane.EtOAc). Following the general procedure, the crude benzamide 1 (275 rag, 96%) was obtained as a colourless solid; m.p. 121-125 0C, Rr 0.44 (80:20 v/v hexane: EtOAc); IR (thin film) 3394, 2924, 2899, 2847, 1647 (C-O), 1537, 1450, 617, 509 cm"1; 1H NMR (300 MHz, CD3OD) delta 7.70-7.65 (1 H, overlapping dd, 6-CH), 7.55-7.47 (IH, m, 4-CH), 7.29-7.17 (2H, m, 3-CH, 5-CH), 3.10 (2H, s, CH2-NH), 1.99 (3H, s),1.80-1.67 (6H1 m), 1.61-1.60 (6H, m); 13C NMR (75.5 MHz, CD3OD) delta 167.5, 161.5 (1Jc-P = 248.7 Hz), 134.0 (CH, 3Jc-F = 8.7 Hz), 131.6 (CH, VC-F = 2.5 Hz), 125.9 (CH, <n="63"/>3J = 3.5 Hz), 125.3 (CH, 2Jc-F = 14.2 Hz), 1 17.4 (2Jc-F = 23.0 Hz), 52.7 (CH2), 41.7 (CH2), 38.4 (CH2), 35.9, 30.1 (CH); HRMS (+ESI) CaIc. for C18H22ONF [M + H]+: 288.1758, found: 288.1749; m/z (+ESI) 288 ([M + H]+, 100), 242 (12); Anal. (Ci8H22ONF): calc, C 75.23, H 7.72, N 4.87; found, C 74.91, H 7.59, N 4.85.
  • 28
  • [ 17768-41-1 ]
  • [ 1702-17-6 ]
  • [ 1031846-98-6 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; at 20℃; for 2h; M. 5-[(ADAMANTAN- 1-YLMETHYL)-CARB AMOYL]-6-CHLORO-IMIDAZO[1,2-lambda]PYRIDINE-2- CARBOXYLIC ACID ETHYL ESTER; Step 1. S.6-Dichloro-pyridine^-carboxylic acid (adamantan-1-ylmethyl)-amide; A mixture of <strong>[1702-17-6]3,6-dichloro-pyridine-2-carboxylic acid</strong> (1.92 g, 0.01 mol), 1- admantylmethylamine (1.65 g, 0.01 mol), TEA (2.02 g, 0.02 mol) and DMC (2.03 g, 0.012 mol) inDCM (20 mL) is stirred at RT for 2 h. The reaction is quenched with NaHCO3. The organic layer is separated and dried over Na2SO4. Silica gel chromatography (hexanes/EtOAc 3:1) gives the title compound.
  • 29
  • [ 479028-72-3 ]
  • [ 17768-41-1 ]
  • [ 1031827-81-2 ]
YieldReaction ConditionsOperation in experiment
With 2-chloro-1,3-dimethylimidazolinium chloride; triethylamine In ISOPROPYLAMIDE; toluene; acetonitrile at 20℃; for 16h;
  • 30
  • [ 543739-84-0 ]
  • [ 17768-41-1 ]
  • [ 1104269-71-7 ]
YieldReaction ConditionsOperation in experiment
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; benzotriazol-1-ol; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20℃; for 14.0h;Product distribution / selectivity; Step 2. 3-Trifluoromethyl-lH-pyrazole-4-carboxylic acid (adamantan-l-ylmethyl)-amide; BOP (2.6 g, 5.8 mmol) is added to a solution of 3-trifluoromethyl-lH-pyrazole-4- carboxylic acid (1.0 g, 5.55 mmol), admantan-1-yl-methylamine (959 mg, 5.8 mmol), HOBt (200 mg, 1.4 mmol) and DIEA (1.1 mL, 6.5 mmol) in DMF (25 mL) at RT. The mixture is stirred for 14 h. The mixture is poured into a sat. NH4Cl (450 mL) and filtered to afford the title compound as a white solid.
With 2-chloro-1,3-dimethylimidazolinium chloride; triethylamine; In N,N-dimethyl acetamide; toluene; acetonitrile; at 20℃; for 16.0h;Product distribution / selectivity; EXAMPLE 3; Synthesis of Additional Representative 5-Membered Heterocyclic Amides and RelatedCompounds; Additional 5-membered heterocyclic amides and related compounds are synthesized by DMC (2 eq) coupling of carboxylic acid (1.2 eq) and amine (1.0 eq):The amine (0.2 M in toluene; 0.10 mL) and acid (0.2 M in DMA; 0.12 mL) are added to a vial along with DMC 3 (0.2 M in ACN, freshly prepared; 0.2 mL) and TEA (0.3 M in toluene; 0.10 mL) are added to a vial and incubated at RT for 16 h. The reaction mixture is then extracted with 1 N NaOH (0.5 mL) and EtOAc (0.5 mL). The upper organic layer is removed and concentrated to dryness. The residue is purified via solid phase extraction chromatography eluting with 25%MeOH/EtOAc (4.0 mL) to afford the title compound.
  • 31
  • [ 17768-41-1 ]
  • [ 40704-11-8 ]
  • [ 1104275-16-2 ]
YieldReaction ConditionsOperation in experiment
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane; D. N-(ADAMANTAN- 1 -YLMETHYL)-3 -METHYL- 1 -[5-METHYL-4-(MORPHOLIN-4-YLCARBONYL) PYRIMIDIN-2-YL]-1H-PYRAZOLE-4-CARBOXAMIDE (COMPOUND 4); Step 1. 3 -Methyl- lH-pyrazole-4-carboxylic acid (adamantan- 1 -ylmethyl)-amide; <n="81"/>BOP (3.53 g, 8 mmol) is added to a solution of adamantan-1-yl-methylamine (1.32 g, 8 mmol), 3 -methyl- lH-pyrazole-4-carboxylic acid (1 g, 7 mmol) and DIEA (2.6 g, 20 mmol) in DCM (25 mL). The solution is stirred overnight and evaporated, and then partitioned between EtOAc and saturated aqueous sodium bicarbonate. The organic layer is washed with brine, dried and evaporated. The residue is triturated with DCM and air-dried to give the title compound.
  • 32
  • [ 17768-41-1 ]
  • [ 54811-38-0 ]
  • 5-iodo-2-methyl-N-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 553-[4-Methyl-3-[[(tricycIo[3.3.1.13)7]dec-l-ylmethyl)amino]carbonyl]phenyl]-2-pyridinecarboxylic acida) 5-Iodo-2-methyl-7V-(tricyclo[3.3.1.13>7]dec-l-ylmethyl)-benzamide5-Iodo-2-methyl-benzoic acid (3.0 g) was stirred in dichloromethane (40 mL) undernitrogen. Oxalyl chloride (5 mL) was added followed by JV.JV-dimethylfonnamide (1 drop).After 2 hours the volatiles were removed under vacuum and the residue was redissolved indichloromethane (40 mL). Tricyclo[3.3.1.13>7]decane-l-methanamine (2.23 mL) andtriethylamine (3.18 mL) were added and the mixture was stirred under nitrogen for 2 hours.2M aqueous hydrochloric acid was added, the layers were separated and the aqueousfraction was extracted twice with dichloromethane. The combined organics were washedwith water, brine, dried (MgSO/O, filtered and concentrated in vacua. Purification bytrituration with diethyl ether afforded the sub-title compound (4.7 g).MS: APCI(+ve) 410 (M+H4).
  • 33
  • [ 17768-41-1 ]
  • [ 164365-88-2 ]
  • C20H36N2O2 [ No CAS ]
  • 34
  • [ 17768-41-1 ]
  • [ 28479-22-3 ]
  • [ 903226-75-5 ]
YieldReaction ConditionsOperation in experiment
91% With triethylamine; In dichloromethane; at 20℃; General procedure: In a round bottom flask equipped with a stir bar, 1.2 mmol of the appropriate amine was added to 10 mL of anhydrous dichloromethane. To this solution, 1.0 mmol of the appropriate isocyanate followed by 3.6 mmol of triethylamine was added. The reaction was stirred at room temperature overnight. The solvent was removed by rotary evaporation. The resulting residue was purified by flash chromatography using a petroleum ether to ethyl acetate gradient to elute the final compound.
  • 35
  • [ 17768-41-1 ]
  • [ 1381925-20-7 ]
  • [ 1381924-99-7 ]
YieldReaction ConditionsOperation in experiment
100% With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine; In tetrahydrofuran; at 20℃; To (R)-1-(1,3-dioxo-2-pyridin-4-ylmethyl-2,3-dihydro-1H-isoindol-4-yl)-piperidine-3-carboxylic acid (0.34 g, 0.93 mmol) and TEA (0.094 g, 0.93 mmol) in THF (7 mL) were added adamantan-1-ylmethylamine (0.16 g, 0.96 mmol) and BOP (0.425 g, 0.96 mmol). The reaction mixture was stirred at room temperature overnight, then concentrated to reduced volume and passed through a thick pad of silica (5% methanol in CHCl3 eluant) to afford (R)-1-(1,3-dioxo-2-pyridin-4-ylmethyl-2,3-dihydro-1H-isoindol-4-yl)-piperidine-3-carboxylic acid (adamantan-1-ylmethyl)-amide (475 mg, 100%) as a yellow foam: LC/MS-ESI observed [M+H]+ 513.
  • 36
  • [ 773-64-8 ]
  • [ 17768-41-1 ]
  • [ 885431-00-5 ]
YieldReaction ConditionsOperation in experiment
95% With sodium hydroxide; In chloroform; water; at 0 - 20℃; for 2h; N-Adamantan-1-yl-methylamine (119, 1.88 g, 11.39 mmol) in 30 ml CHCl3 was mixed at 00C with 14 ml 2N NaOH. 2-mesitylenesulfonyl chloride (5, 2.48 g, 11.39 mmol) was added and the reaction mixture was stirred for 2 hrs to room temperature. The reaction was monitored by TLC (silica, hexane:EtOAc 8:2). The CHCl3 phase was separated, washed with NH4Cl solution (2X), dried, and evaporated to provide N-Adamantan-1- ylmethyl-mesitylene-2-sulfonamide (120, 3.77 g, 95%). 1H and 13C NMR confirmed the identity of the product.
  • 37
  • [ 6066-82-6 ]
  • [ 1189745-30-9 ]
  • [ 17768-41-1 ]
  • [ 25952-53-8 ]
  • c,t,c-[PtCl2(OH)(O2CCH2CH2CO(1-(adamantan-1-yl)methanamine(-1H)))(NH3)2] [ No CAS ]
YieldReaction ConditionsOperation in experiment
57.2% In dimethyl sulfoxide; at 20℃; for 24h; General procedure: The conjugate Pt-AD,2,was synthesized by adding 1-adamatanemethylamine (18.2 mg, 110 lmol), 1 (43.4 mg, 100 lmol) [5], N-hydroxysuccinimide (12.7mg, 110 lmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 23.0mg, 120 lmol) to anhydrous DMSO (0.6 ml) and stirring the resulting solution at room temperature for 24 h.The volume of th esolution was reduced in vacuo to produce bright yellow oil which was washed with 10 ml diethylether. After removal of the diethyl ether, 5ml of water was added which produced a light yellow precipitate. The product was collected by filtration, washed with ice cold diethyl ether and dried in vacuo.
  • 38
  • [ 17768-41-1 ]
  • [ 4755-77-5 ]
  • [ 1423035-68-0 ]
YieldReaction ConditionsOperation in experiment
72% With triethylamine; In dichloromethane; at 0 - 20℃; for 12h; General procedure: A solution of 400 mg (2.91 mmol) of ethyl chloroxoacetate in 1 mL of methylene chloride was added to a cold (0 C) solution of 500 mg (3.03 mmol) of [(adamantan-1-yl)methyl]amine and 920 mg (9.09 mmol) of triethylamine in 10 mL of methylene chloride. The reaction mixture was stirred for 12 h at room temperature, after which the product was extracted with 50 mL of ether, and the ether extract was washed with 30 mL of 1N HCl and two 50-mL portions of distilled water, dried over Na2SO4, and evaporated to dryness. The remaining solid material was dried in a vacuum. Yield 357 mg (72 %), white solid, mp 86.7 - 87.2 C. 1H NMR spectrum (DMSO-d6), delta, ppm: 8.64 s (1H, NH), 4.17 q (2H, CH2CH3, J 7.1 Hz), 4.17 q (2H, CH2NH, J 8.1 Hz), 1.85 - 1.36 m (15H, Ad), 1.21 t (3H, CH3CH2, J 7.3 Hz). Mass spectrum, m/z (Irel, %): 265 (1) [M]+, 192 (30), 135 (100) [Ad]+. Found, %: C 67.88; H 8.76; N 5.25. C15H23NO3. Calculated, %: C 67.90; H 8.74; N 5.28.
With triethylamine; In dichloromethane; at 0 - 20℃; General procedure: To a solution of adamant-2-ylamine hydrochloride (1.00 g, 5.53 mmol) and triethylamine (1.47 g, 10.6 mmol) in dichloromethane (20 mL) was added ethyl (chlorocarbonyl)formate (0.73 g, 5.32 mmol) in dichloromethane (2 mL) at 0 C. After stirring overnight at room temperature, the product was extracted with diethyl ether (50 mL), washed with an aqueous solution of 1 N HCl (30 mL) and water (50 mL * 2), and dried over MgSO4. The ether solution was evaporated to dryness and the residue was used for the next reaction without purification. An aqueous solution of 1 N NaOH (2 mL) was added dropwise to a solution of the above residue in ethanol (10 mL) and the reaction mixture was stirred for 30 min at room temperature. After the reaction was acidified to pH 2 by adding an aqueous solution of 1 N HCl, the acid product was extracted with dichloromethane (50 mL * 2). The combined organic solution was washed with water (50 mL * 2), dried over MgSO4, and evaporated to dryness. To the residue (0.19 g, 0.85 mmol) in dichloromethane (20 mL) was added 4-dimethylaminopyridine (DMAP; 0.10 g, 0.85 mmol) and benzyloxyamine hydrochloride (0.14 g, 0.85 mmol) at room temperature. After the reaction was stirred for 5 min, 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide (EDCI; 0.16 g, 0.85 mmol) was added to the reaction mixture at room temperature. After stirring overnight, the product was extracted with diethyl ether (50 mL). The organic layer was washed with an aqueous solution of 1 N HCl (30 mL * 2) and water (50 mL * 2), dried over MgSO4, and evaporated. The residue was purified by using silica gel column chromatography (hexane/ethyl acetate = 3:1) to afford compound 6 as a solid in 85% yield.
  • 39
  • [ 4470-83-1 ]
  • [ 17768-41-1 ]
  • [ 1450744-06-5 ]
  • [ 1450744-08-7 ]
  • 40
  • [ 21617-12-9 ]
  • [ 17768-41-1 ]
  • [ 1450744-18-9 ]
  • 42
  • [ 463-71-8 ]
  • [ 17768-41-1 ]
  • 1-isothiocyanatomethyl-adamantane [ No CAS ]
YieldReaction ConditionsOperation in experiment
92% With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 2h;Cooling with ice; General procedure: To a stirred solution of thiophosgene (15.18 g, 132 mmol) in dried CH2Cl2 (150 mL) cooled in anice-water bath was added dropwise a solution prepared by dissolving 2c-2k, 2m-2n or 2ha-2hi (120mmol) and DIPEA (46.53 g, 360 mmol) in dried CH2Cl2 (150 mL). The resulting mixture was stirredfor 1 h in an ice-water bath and for another 1 h at room temperature. The reaction mixture was thenpoured into ice-water (300 mL) while stirring. The organic phase was separated, and the aqueousphase was back-extracted with CH2Cl2 (200 mL × 2). The combined organic phases were washedsuccessively with 5% hydrochloric acid (100 mL × 2; for 3f and 3n, the washing with 5% hydrochloricacid is omitted) and saturated brine (300 mL), dried (Na2SO4) and evaporated on a rotary evaporatorto give a residue, which was purified by column chromatography to afford 3c-3k, 3m-3n or3ha-3hi.
In water; ethyl acetate; at 0 - 5℃; for 0.5h; Step a-Synthesis of adamantyl methyl isothiocyanate (2) (Adamantyl MITC) Adamantyl methyl amine (1) was dissolved in the mixture of ethyl acetate and water (1:1) and stirred at 0 C. to 5 C. To the reaction mixture, thiophosgene (1.25 eq) was added dropwise in a well ventilated fume hood. The reaction mixture stirred at 0 C. to 5 C. temperature for 30 minutes, and thin layer chromatography (TLC) indicated complete conversion. The reaction mixture was transferred to a separatory funnel and organic layer collected, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford a semi solid which soon solidified to afford (2) as an off-white solid.
  • 43
  • [ 14441-90-8 ]
  • [ 17768-41-1 ]
  • [ 1450606-88-8 ]
YieldReaction ConditionsOperation in experiment
34% Stage #1: 5-phenyl-3-isoxazolecarboxylic acid With benzotriazol-1-ol; O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In chloroform at 20℃; for 0.75h; Stage #2: adamantylmethylamine In chloroform at 20℃; for 24h; 3 4.1.5. General procedure for the preparation of 5-arylisoxazole-3-carboxamides (44-70) General procedure: To a solution of carboxylic acid 33-43 in dry chloroform (20 mL) were added N,N-diisopropylethylamine (DIEA) (2 equiv) and 1-hydroxybenzotriazole (HOBt) (0.5 equiv), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (1.5 equiv). The resulting mixture was stirred at room temperaturefor 45 min. The appropriate amine (1.2 equiv) was then added, and the solution was stirred at room temperature for additional 24 h. The solution was filtered and washed with 0.5 N aqueous NaOH (20 mL), with 1 N aqueous HCl (20 mL), and water (20 mL). The organic layer was dried over MgSO4 and evaporated under reduce pressure to give a brown oil. The crude material was purified by TLC using the appropriate eluent (cyclohexane/EtOAc 7:3, v/v) and recrystallized in heptane to afford the desired compounds.
  • 44
  • [ 17768-41-1 ]
  • ethyl 4-trifluoromethoxyphenylimidate hydrochloride [ No CAS ]
  • [ 1551368-26-3 ]
YieldReaction ConditionsOperation in experiment
65% With triethylamine; In ethanol; at 20℃; for 16h; General procedure: To a suspension of ethyl 4-trifluoromethoxybenzimidate hydrochloride salt (8) (1 equiv) in ethanol (0.25 M) was added the appropriate amine (0.9 equiv). Triethylamine (3 equiv) was added and the resulting reaction mixture stirred at ambient temperature for 16 h. The reaction mixture was then concentrated and the crude product purified by flash chromatography on silica.
  • 45
  • [ 17768-41-1 ]
  • [ 6280-89-3 ]
  • [ 645403-23-2 ]
YieldReaction ConditionsOperation in experiment
With (benzotriazol-1 -yloxy)tripyrrolidinophosphonium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In dichloromethane;Inert atmosphere; Benzotriazol-l -yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP, 1.1 mmol) was added to a solution of adamantan-1-ylmethylamine (1.0 mmol), 2-chloro-5- methoxybenzoic acid (1.1 mmol), and diisopropylethylamine (1.75 mmol) dissolved in dichloromethane or tetrahydrofuran (10 mL). The reaction was stirred overnight (18 h) at room temperature under a nitrogen atmosphere. The reaction was then washed with aqueous hydrochloric acid (1 M, 5 mL), then aqeuous sodium hydroxide (1 M, 5 ml_), then water (5 mL). The organic layer was dried (MgS04), filtered and evaporated to dryness by rotary evaporation. The resulting residue was subjected to flash chromatography (1 :3 ethyl acetate: hexane) to yield A/-(adamantan-1-ylmethyl)-2-chloro- 5-methoxybenzamides
  • 46
  • [ 7560-50-1 ]
  • [ 17768-41-1 ]
  • C22H27NO2 [ No CAS ]
  • 47
  • [ 698-27-1 ]
  • [ 17768-41-1 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-5-methylphenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 48
  • [ 17768-41-1 ]
  • [ 90-02-8 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)phenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 49
  • [ 673-22-3 ]
  • [ 17768-41-1 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-5-methoxyphenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 50
  • [ 38226-10-7 ]
  • [ 17768-41-1 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-3-fluorophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
77% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 51
  • [ 17768-41-1 ]
  • [ 146137-74-8 ]
  • 1-(adamantan-1-yl)-N-(2-fluoro-6-methoxybenzyl)methanamine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
72% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 52
  • [ 17768-41-1 ]
  • [ 100-52-7 ]
  • 1-(adamantan-1-yl)-N-benzylmethanamine hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 53
  • [ 17768-41-1 ]
  • [ 69-72-7 ]
  • N-(adamantan-1-ylmethyl)-2-hydroxybenzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20℃; for 12h;Inert atmosphere; To a stirred solution of <strong>[17768-41-1]adamantylmethylamine</strong> and salicylic acid in dry DMF was added DIPEA, HATU portionwise, stirred at RT for 12 h. Reaction mixture was diluted with water (10 ml) and extracted with ethyl acetate (2 x 10ml). The solvent was evaporated under vacuum and purified by Combiflash to afford the product 12 as pale yellow solid. 75% yield.
  • 54
  • [ 17768-41-1 ]
  • [ 635-93-8 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-4-chlorophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 55
  • [ 17768-41-1 ]
  • [ 1761-61-1 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-4-bromophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
85% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 56
  • [ 613-84-3 ]
  • [ 17768-41-1 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-4-methylphenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 57
  • [ 17768-41-1 ]
  • [ 210039-65-9 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-4-(trifluoromethyl)phenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% Stage #1: adamantylmethylamine; 2-hydroxy-5-(trifluoromethyl)benzaldehyde With acetic acid In ethanol at 20℃; for 0.5h; Inert atmosphere; Stage #2: With sodium tetrahydroborate In ethanol at 0 - 20℃; Inert atmosphere; General Procedure for Compounds (1-11 & 13-20) General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0°C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0°C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 58
  • [ 1450-75-5 ]
  • [ 17768-41-1 ]
  • 2-(1-((adamantan-1-ylmethyl)amino)ethyl)-4-bromophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
66% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 59
  • [ 17768-41-1 ]
  • [ 78443-72-8 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-3,5-dichlorophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 60
  • [ 17768-41-1 ]
  • [ 251300-28-4 ]
  • 2-(((adamantan-1-ylmethyl)amino)methyl)-4-bromo-6-fluorophenol hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% General procedure: To a solution of corresponding amine (1 mmol) and corresponding aldehyde (1.1 mmol) in EtOH (5ml) was added acetic acid (catalytic amount) and stirred under nitrogen for 30 minutes. The reaction mixture was brought to 0C then added sodium borohydride (1 mmol) portionwise and stirred at RT for 1-2 h. Upon completion, the reaction mixture was quenched with water and concentrated under vacuum. The crude product was basified with saturated sodium carbonate solution and extracted with ethylacetate (2 x 20 ml). The solvent was evaporated under reduced pressure, purified by Combiflash eluting with 5-30% (hexane:ethylacetate) solvent system to afford the final product. The obtained product (1 mmol) was dissolved in DCM (2 ml) and cooled to 0C and then 2M HCl in diethylether (2 mmol) was added dropwise and stirred for 15 minutes. The obtained solid was filtered, washed with diethylether and dried under vacuum to get product as HCl salt. (All the compounds were converted to hydrochloride salt except for compounds 11 & 18).
  • 61
  • [ 17768-41-1 ]
  • [ 114932-60-4 ]
  • pyrene butyric acid adamantanemethylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% In dichloromethane at 20℃; for 91h; Inert atmosphere;
  • 62
  • [ 5029-67-4 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)pyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With copper (I) iodide; 2-(2-methyl-1-oxopropyl)cyclohexanone; Cs2CO3 In dimethyl sulfoxide at 110℃; for 24h; Schlenk technique; Inert atmosphere; N-Pyridyl derivatives of adamantanamines 8-23and 26-29 and N-octylpyridin-2-amine (25). a.Homogeneous reaction. General procedure: A Schlenk flask (which is partof the reaction station for parallel synthesis) equippedwith a magnetic stirrer and preliminarily filled withargon was charged with copper(I) iodide (10-20 mol %,9.5-19 mg) and 2-isobutyrylcyclohexanone (L1)(20-40 mol %, 17-33 μL), after which 0.625 mmolof the corresponding pyridyl halide, 1 mL of DMSO,0.5 mmol of the corresponding amine (1-7, 24), and0.63 mmol (205 mg) of cesium carbonate were added.The reaction mixture was heated with stirring on anoil bath at 110°C for 24 h. The reaction products wereextracted in two ways: 1) 1 mL of dichloromethaneand 10 mL of water were added to the reaction mixtureand, after stirring, the aqueous layer was separated, andthe organic layer was dried over molecular sieves andevaporated; 2) 10 mL of dichloromethane were added tothe reaction mixture and extracted 3 times with 30 mL ofwater, the aqueous layer was separated, and the organiclayer was dried over molecular sieves and evaporated.The previously unknown compound 11 was isolated bycolumn chromatography, eluents CH2Cl2 and CH2Cl2-MeOH (100 : 1). The spectral data of compounds 8-10and 12-14 are described in [24, 25], compounds 15-19, in [11], compounds 20-23 and 26-29, in [12], andcompound 25, in [26].
With copper (I) iodide; 2-(2-methyl-1-oxopropyl)cyclohexanone; Cs2CO3 In N,N-dimethyl-formamide at 140℃; for 24h; Reflux; Inert atmosphere; N-Pyridyl-substituted adamantane-containing amines 2, 12-20, and 23-31 General procedure: A two-necked flask equipped with a reflux condenser and a magnetic stirrer was charged under argon with 0.5 mmol (103 mg) of 2- or 3-iodopyridine, 0.5 mmol of the corresponding adamantane-containing amine, 0.05 mmol (9.5 mg) of copper(I) iodide, 0.1 mmol (17 mg) of 2-(2-methyl-1-oxopropyl)cyclohexanone, 1 mmol (326 mg) of cesium carbonate, and 1 mL of DMF. The mixture was heated for 24 h at 140°C under stirring, cooled, and diluted with 5 mL of methylene chloride, and the precipitate was filtered off and washed with methylene chloride (5 mL). The filtrate was combined with the washings and evaporated under reduced pressure, the residue was dissolved in methylene chloride (5 mL), the solution was treated with water (5 mL), and the organic layer was separated, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. If necessary, the residue was subjected to silica gel chromatography using methylene chloride-petroleum ether (1 : 4 to 4 : 1), methylene chloride, or methylene chloride-methanol (100 : 1 to 3 : 1) as eluent. The products were isolated as slightly colored solids or oily substances.
With 2-(2-methyl-1-oxopropyl)cyclohexanone; Cs2CO3 In dimethyl sulfoxide at 110℃; for 24h;
  • 63
  • [ 7560-50-1 ]
  • [ 17768-41-1 ]
  • (E)-methyl 3-(4-((((3r,5r,7r)-adamantan-1-ylmethyl)amino)methyl)phenyl)acrylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% [0072] Adamantan-1 -ylmethanamine (1 in Fig. 2) (1g, 6.0 mmol) and (E)-methyl 3- (4-formylphenyl)acrylate (2 in Fig. 2) (1 g, 5.3 mmol) was dissolved in MeOH (30 ml_) and the mixture was stirred at room temperature for 2 hours. Sodium borohydride (0.61 g, 16 mmol) was then added, and the suspension was stirred overnight at room temperature. The white precipitate was filtered and dried to obtain the product (3 in Fig. 2) (1 .35 g, yield: 75%). 1 H-NMR (500 MHz, CDCI3): delta 7.69 (d, J = 16 Hz, 1 H), 7.48 (d, J = 7 Hz, 2H), 7.35 (d, J = 7 Hz, 2H), 6.43 (d, J = 16 Hz, 1 H), 3.81 (s, 2H), 3.80 (s, 3H), 2.23 (s, 3H), 1 .96 (s, 3H), 1 .63-1 .73 (m, 6H), 1 .53 (s, 6H); 13C-NMR (125 MHz, CDCI3): 167.55, 144.78, 143.81 , 132.87, 128.35 (2C), 128.08 (2C), 1 17.10, 62.15, 54.28, 51 .65, 40.85 (3C), 37.24 (3C), 33.49, 28.48 (3C). LC-MS calculated for C22H29NO2 expected [M]: 339.2; Found [M+H]+: 340.3.
75% Adamantan-1-ylmethanamine (1 g, 6.0 mmol) and (E)-methyl 3-(4-formylphenyl)acrylate (1 g, 5.3 mmol) was dissolved in MeOH (30 mL) and the mixture was stirred at room temperature for 2 h. Sodium borohydride (0.6 lg, 16 mmol) was then added, and the suspension was stirred overnight at room temperature. The white precipitate was filtered and dried to obtain (E)-methyl 3-(4-(((3r,5r,7r)-adamantan-1-ylmethyl)amino)methyl)phenyl)acrylate (1.35 g, yield: 75%).1H-NMR (500 MHz, CDC ): delta 7.69 (d, J= 16 Hz, 1H), 7.48 (d, J = 7 Hz, 2H), 7.35 (d, J = 7 Hz, 2H), 6.43 (d, J= 16 Hz, 1H), 3.81 (s, 2H), 3.80 (s, 3H), 2.23 (s, 3H), 1.96 (s, 3H), 1.63-1.73 (m, 6H), 1.53 (s, 6H); 13C-NMR (125 MHz, CDCb): 167.55, 144.78, 143.81, 132.87, 128.35 (2C), 128.08 (2C), 117.10, 62.15, 54.28, 51.65, 40.85 (3C), 37.24 (3C), 33.49, 28.48 (3C). LC- MS calculated for C22H29NO2 expected [M]: 339.2; Found [M+H]+: 340.3
  • 64
  • [ 17768-41-1 ]
  • 4-chloro-N-[4-(dimethylphosphoryl)phenyl]-5-(trifluoromethyl)pyrimidin-2-amine [ No CAS ]
  • N2-[4-(dimethylphosphoryl)phenyl]-N4-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% With triethylamine; In ethanol; at 120℃; for 0.333333h; Example 12 N2-[4-(dimethylphosphoryl)phenyl]-N4-(tricyclo[3.3.1.13,7]dec-1-ylmethyl)-5-(trifluoromethyl)pyrimidine-2,4-diamine (0425) (0426) To a solution of 4-chloro-N-[4-(dimethylphosphoryl)phenyl]-5-(trifluoromethyl)pyrimidin-2-amine (prepared as in Example 1: 40 mg, 0.12 mmol) in 2 mL of ethanol was added 50 muL of triethylamine and 1-Adamantanemethylamine (19 mg, 0.12 mmol). The mixture was microwave at 120 degrees for 20 minutes. The reaction mixture was filtered through a syringe filter and purified by prep-HPLC (Waters Sunfire C18 column with ACN/water mobile phases) to yield a white solid as product (40 mg, 73% yield.) MS/ES+: m/z=479
  • 65
  • [ 3565-26-2 ]
  • [ 17768-41-1 ]
  • N-[(adamantan-1-yl)methyl]-5-nitrosoquinolin-8-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% In pyridine at 20℃; for 72h; Amination of 5-nitrosoquinolin-8-ol with amines 1a-1d (general procedure). Amination of 5-nitrosoquinolin-8-ol with amines 1a-1d (general procedure). Amine 1a-1d, 23.6 mmol, was added at 20°C to a solution of 11.8 mmol of 5-nitrosoquinolin-8-ol in 60 mL of pyridine (amines 1a and 1b were preliminarily dissolved in 30 mL of pyridine). After 72 h, the mixture was poured into an ice-water mixture. The precipitate was filtered off, thoroughly washed in succession with water, a 0.5% solution of sodium hydrogen carbonate, and water again, and dried first in air and then in a vacuum desiccator over NaOH. N-[(Adamantan-1-yl)methyl]-5-nitrosoquinolin-8-amine (2a). The dry residue was washed with hot hexane (2 25 mL). Yield 2.58 g (68%), yellow crystals, mp 180°C. Electronic absorption spectrum (EtOH), λmax, nm (ε, L mol-1 cm-1): 446 (26 440), 689 (54). 1H NMR spectrum (CDCl3), δ, ppm: 1.711.80 m (6H, δ-CH2, β-CH2), 2.08 m (3H, γ-CH), 3.23 d (2H, NCH2, J = 5.0 Hz), 6.68 br.s (1H, 7-H), 6.93 br.s (1H, 6-H), 7.77 br.s (1H, NH), 8.04 br.s (1H, 3-H), 8.81 br.s (1H, 4-H), 9.87 br.s (1H, 2-H). 13C NMR spectrum (CDCl3), δC, ppm: 28.2 (CH, Ad), 34.8 (C1′, Ad), 36.8 (CH2, Ad), 40.6 (CH2, Ad), 55.1 (NCH2), 102.9 (C7), 148.1 (C4), 155.8 (C5). Found, %: C 74.42; H 6.92; N 12.73. C20H23N3O. Calculated, %: C 74.74; H 7.21; N 13.07.
  • 66
  • [ 3565-26-2 ]
  • [ 17768-41-1 ]
  • N8-[(adamantan-1-yl)methyl]quinoline-5,8-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: pyridine / 72 h / 20 °C 2: hydrazine hydrate; 0.5% Pd/C / dichloromethane / 1 h
  • 67
  • [ 17768-41-1 ]
  • [ 1571-08-0 ]
  • methyl 4-(((((3r,5r,7r)-adamantan-1-yl)methyl)amino)methyl)benzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90.1% With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 3h; A mixture of methyl 4-fomiylbenzoate (0.500 g, 3.046 mmol) and (adamantan-1-yl)methanamine (0.654 mL, 3.960 mmol) in dichloromethane (20 mL) was treated at the room temperature with sodium triacetoxyborohydride (1.291 g, 6.092 mmol), and stirred at the same temperature for 3 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 12 g cartridge; ethyl acetate / hexane = 30 % to 70 %) to give methyl 4-((((adamantan-1-yl)methyl)amino)methyl)benzoate as colorless oil (0.860 g, 90.1 %).
75% A solution of methyl 4-formylbenzoate (155 mg, 0.94 mol 1.1 eq.) and 1- adamantanemethylamine (140 mg, 0.85 mol, 1 eq.) in 3 mL methanol was stirred for 2 h at room temperature. Next, 210 mg sodium borohydride was added portionwise and the reaction was stirred until no starting material remained, approximately 3.5 h. The mixture was concentrated in vacuo, partitioned between ethyl acetate and water, the aqueous layer extracted two more times with ethyl acetate and the combined organic phases were dried over sodium sulfate. The solvent was removed under reduced pressure and the product was purified by column chromatography. The title product (221 mg, 0.71 mmol, 75%) was obtained as a clear oil that solidified upon standing. 1H NMR (chloroform-d) delta 7.99 (d, 2H), 7.41 (d, 2H), 3.90(s, 1H), 3.86 (s, 5H), 2.23 (s, 2H), 1.97 (s, 3H), 1.82-1.59 (m, 7H), 1.59-1.44 (m, 7H). MS (m/z) calc'd for C20H27NO2 [M+H]+ 313.20; found, 313.7.
  • 68
  • [ 17768-41-1 ]
  • [ 10165-86-3 ]
  • methyl 6-((((adamantan-1-yl)methyl)amino)methyl)nicotinate [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With sodium tris(acetoxy)borohydride; In dichloromethane; at 20℃; for 3h; A mixture of methyl 6-formylnicotinate (0.320 g, 1.938 mmol) and (adamantan-1-yl)methanamine (0.416 mL, 2.5 19 mmol) in dichloromethane (20 mL) was treated at the room temperature with sodium triacetoxyborohydride (0.821 g, 3.875 mmol), and stirred at the same temperature for 3 hr. Then, saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with dichloromethane. The organic layer was washed with aqueous saturated sodium chloride solution, dried with anhydrous Mg504, filtered, and concentrated in vacuo. The residue was chromatographed (5i02, 12 g cartridge; ethyl acetate / hexane = 30 percent to 70 percent) to give methyl 6-((((adamantan-1-yl)methyl)amino)methyl)nicotinate as yellow oil (0.530 g, 87.0 percent).
39% A solution of methyl 4-formylnicotinic acid (100 mg, 0.606 mol 1.0 eq.) and 1- adamantanemethylamine (100 mg, 0.606 mol, 1.0 eq.) in 2 mL methanol was stirred for 2 h at room temperature. Next, 150 mg sodium triacetoxyborohydride was added and the reaction mixture was stirred until no starting material remained. The mixture was concentrated in vacuo, partitioned between ethyl acetate and water, the aqueous layer extracted two more times with ethyl acetate and the combined organic phases were dried over sodium sulfate. The solvent was removed under reduced pressure and the product was purified by column chromatography. The title product (75 mg, 0.239 mmol, 39percent) was obtained as a clear oil. 1H NMR (500 MHz, Chloroform-d) delta 9.15 (d, J = 2.2 Hz, 1H), 8.26 (dd, J = 8.2, 2.1 Hz, 1H), 7.47 (d, J = 8.2 Hz, 1H), 3.97 (s, 2H), 3.96 (d, j = 1.6 Hz, 3H), 2.27 (s, 2H), 1.98 (s, 3H), 1.80 - 1.61 (m, 6H), 1.55 (d, j = 2.8 Hz, 6H).
  • 69
  • [ 17768-41-1 ]
  • [ 4774-14-5 ]
  • N-(1-adamantylmethyl)-6-chloropyrazin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
75% With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; General procedure: A corresponding chloro-substitutedeteroarene (0.2-0.5 mmol), finely powdered K2CO3 (173 mg,1.25 mmol), DMF (1 mL), and a corresponding adamantane-containing amine (0.2-0.5 mmol) were placed into a one-neckflask equipped with a magnetic stirrer and reflux condenser and filled with dry argon, and the reaction mixture was stirred for 24 h at 140 C. When the reaction was carried out with diamines 13 and 14 (0.5 mmol), 2,6-dichloropyrazine (186 mg, 1.25 mmol) and K2CO3 (345 mg, 2.5 mmol) were used. On the reaction completion, the mixture was cooled to room temperature, dichloromethane (5 mL) was added, a precipitate was filtered off and additionally washed with dichloromethane (5 mL), the commbined organic fractions were concentrated in vacuo, the residues were analyzed by NMR spectroscopy. If necessary, the products were purified by chromatography on silica gel, using the followwing sequence of eluents: light petroleum ether-CH2Cl2 (4 : 1 ?1 : 4), CH2Cl2, CH2Cl2-MeOH (500 : 1 ? 3 : 1). The target products were obtained as faintly colored or colorless dense oils or crystalline powders. The spectral data of compound 15 arer eported in the work.20
  • 70
  • [ 1448-87-9 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)quinoxalin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; General procedure: A corresponding chloro-substitutedeteroarene (0.2-0.5 mmol), finely powdered K2CO3 (173 mg,1.25 mmol), DMF (1 mL), and a corresponding adamantane-containing amine (0.2-0.5 mmol) were placed into a one-neckflask equipped with a magnetic stirrer and reflux condenser and filled with dry argon, and the reaction mixture was stirred for 24 h at 140 C. When the reaction was carried out with diamines 13 and 14 (0.5 mmol), 2,6-dichloropyrazine (186 mg, 1.25 mmol) and K2CO3 (345 mg, 2.5 mmol) were used. On the reaction completion, the mixture was cooled to room temperature, dichloromethane (5 mL) was added, a precipitate was filtered off and additionally washed with dichloromethane (5 mL), the commbined organic fractions were concentrated in vacuo, the residues were analyzed by NMR spectroscopy. If necessary, the products were purified by chromatography on silica gel, using the followwing sequence of eluents: light petroleum ether-CH2Cl2 (4 : 1 ?1 : 4), CH2Cl2, CH2Cl2-MeOH (500 : 1 ? 3 : 1). The target products were obtained as faintly colored or colorless dense oils or crystalline powders. The spectral data of compound 15 arer eported in the work.20
  • 71
  • [ 7742-73-6 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)-3-chloroisoquinolin-1-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; General procedure: A corresponding chloro-substitutedeteroarene (0.2-0.5 mmol), finely powdered K2CO3 (173 mg,1.25 mmol), DMF (1 mL), and a corresponding adamantane-containing amine (0.2-0.5 mmol) were placed into a one-neckflask equipped with a magnetic stirrer and reflux condenser and filled with dry argon, and the reaction mixture was stirred for 24 h at 140 C. When the reaction was carried out with diamines 13 and 14 (0.5 mmol), 2,6-dichloropyrazine (186 mg, 1.25 mmol) and K2CO3 (345 mg, 2.5 mmol) were used. On the reaction completion, the mixture was cooled to room temperature, dichloromethane (5 mL) was added, a precipitate was filtered off and additionally washed with dichloromethane (5 mL), the commbined organic fractions were concentrated in vacuo, the residues were analyzed by NMR spectroscopy. If necessary, the products were purified by chromatography on silica gel, using the followwing sequence of eluents: light petroleum ether-CH2Cl2 (4 : 1 ?1 : 4), CH2Cl2, CH2Cl2-MeOH (500 : 1 ? 3 : 1). The target products were obtained as faintly colored or colorless dense oils or crystalline powders. The spectral data of compound 15 arer eported in the work.20
  • 72
  • [ 17768-41-1 ]
  • [ 69887-12-3 ]
  • [ 27188-92-7 ]
YieldReaction ConditionsOperation in experiment
97% With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; General procedure: 1,4-Diisocyanatobutane (140 mg, 1 mmol) and triethylamine (200 mg, 2 mmol) were added to a solution of 3-(adamantan-1-yloxy)propan-1-amine (420 mg, 2 mmol) in DMF (5 mL). The mixture was stirred for 12 h at ~20 C, followed by the addition of an aqueous solution of 1 M HCl (25 mL) and stirring for another 30 min. A crystalline precipitate was collected by filtration, washed sequentially with water (25 mL) and ethyl acetate (15 mL), and dried in vacuo
  • 73
  • [ 17768-41-1 ]
  • [ 3356-89-6 ]
  • N-(1-adamantylmethyl)-3-phenylisoxazol-5-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With potassium carbonate; In N,N-dimethyl-formamide; for 1.5h;Reflux; General procedure: A mixture of <strong>[3356-89-6]5-chloro-3-phenylisoxazole</strong> (2) (5 mmol), amine (10 mmol) and K2CO3 (15 mmol) in DMF (25 mL) was refluxed under stirring for 1.5 h. The reaction mixture was cooled and diluted with cold H2O (40 mL). For 5a and 5b, the resulting precipitate was collected, washed with H2O and recrystallized from hexane-Et2O. For 5c-e, the reaction mixture was extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo. The residue was purified by column chromatography on silica gel (hexane-EtOAc, 5:1). 5-Aminoisoxazoles 5a and 5b are known compounds and have full characterization data.
  • 74
  • [ 13534-89-9 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)-3-bromopyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; bis(dibenzylideneacetone)-palladium(0); sodium t-butanolate In 1,4-dioxane Inert atmosphere; Reflux; Palladium-Catalyzed Amination of Dihalogenopyridines; GeneralProcedure General procedure: A flask flushed with dry argon and equipped with a magnetic stirrerand condenser was charged with appropriate dihalogenopyridine(0.25-1 mmol), Pd(dba)2 (2-8 mol%), the phosphine ligand (2.5-9mol%), the corresponding amine 1-5 (0.25-0.75 mmol), and absolute1,4-dioxane (2.5 mL). t-BuONa (0.37-0.75 mmol) was added, and themixture was stirred under reflux for 6-12 h (the progress of the reactionwas monitored by 1H NMR spectroscopy), cooled down to r.t.,1,4-dioxane was evaporated under vacuum, and the residue was chromatographedon silica gel using a sequence of eluents: PE, PE-CH2Cl2,4:1 to 1:2; CH2Cl2; CH2Cl2-MeOH, 200:1 to 50:1
  • 75
  • [ 52200-48-3 ]
  • [ 17768-41-1 ]
  • N-(1-adamantylmethyl)-3-bromopyridin-2-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With potassium carbonate; In N,N-dimethyl-formamide; at 140℃; This compound was also obtained in the non-catalytic reaction of <strong>[52200-48-3]3-bromo-2-chloropyridine</strong> (106 mg, 0.5 mmol) with amine 2 (82 mg,0.5 mmol) in DMF (1 mL) at 140 C in the presence of K2CO3 (276 mg,2 mmol); yield 85 mg (53%).1H NMR (400 MHz, CDCl3): delta = 1.57-1.58 (m, 6 H), 1.64-1.74 (m, 6 H),1.99 (br s, 3 H), 3.20 (d, J = 5.9 Hz, 2 H), 5.08 (br s, 1 H), 6.39 (dd, J =7.6, 4.8 Hz, 1 H), 7.57 (dd, J = 7.6, 1.2 Hz, 1 H), 8.02 (dd, J = 4.8, 1.2 Hz,1 H).13C NMR (100.6 MHz, CDCl3): delta = 28.3 (3 C), 33.7 (1 C), 37.0 (3 C), 40.4(3 C), 53.1 (1 C), 105.6 (1 C), 112.7 (1 C), 139.3 (1 C), 146.6 (1 C), 155.1(1 C).HRMS-MALDI-TOF: m/z [M + H]+ calcd for C16H22BrN2: 321.0966;found: 321.0944.
  • 76
  • [ 591-50-4 ]
  • [ 17768-41-1 ]
  • N-[(adamantan-1-yl)methyl]aniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With copper(l) iodide; caesium carbonate; 1,1'-bi-2-naphthol; In N,N-dimethyl-formamide; at 140℃; for 24h;Inert atmosphere; General procedure: A two-necked flask was charged under argon with 10 or 20 mol % of copper compound, 20 or 40 mol % of ligand L1-L7, 0.625 or 1.5 mmol of aryl iodide, 1 mL of DMF, 0.5 mmol of adamantane-containing amine, and 200-250 mg (0.6-0.75 mmol) of cesium carbonate. The mixture was heated for 24 h with stirring, cooled to room temperature, and diluted with methylene chloride (5 mL), the precipitate was filtered off, and the organic phase was thoroughly evaporated under reduced pressure (1 mm); if necessary, the product was purified by silica gel column chromatography. The spectral parameters of compounds 9 and 10 were consistent with those reported in [19].
  • 77
  • [ 2257-09-2 ]
  • [ 17768-41-1 ]
  • 1-((adamantan-1-yl)methyl)-3-phenethylthiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
  • 78
  • [ 404-72-8 ]
  • [ 17768-41-1 ]
  • N-[(adamantan-1-yl)methyl]-N′-(3-fluorophenyl)thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
88% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
88% With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; 3-Fluorophenyl isothiocyanate (2), 0.27 g (1.76 mmol), and triethylamine, 0.2 g (2 mmol), were added to a solution of 0.3 g (1.81 mmol) of (adamantan-1-yl)methanamine 1a in 5 mL of DMF. The mixture was stirred for 12 h, 5 mLof 1 N aqueous HCl was added, and the mixture was stirred for 30 min more. The white precipitate was filtered off, washed with 10 mL of water, and dried. Yield 0.49 g (88%), mp 154-155C. 1H NMR spectrum,delta, ppm: 1.451.67 m (12H, Ad), 1.94 s (3H, Ad),3.27 br.s (2H, CH2), 6.96 t (1H, 6-H, J = 8.1 Hz), 7.07 d (1H, 2-H, J = 8.1 Hz), 7.29 q (1H, 4-H, J =8.1 Hz), 7.53 d (1H, 5-H, J = 11.2 Hz), 7.63 br.s (1H, NHCH2), 9.58 br.s (1H, NHC6H4). 19F NMR spectrum: deltaF -113.04 ppm (1F). Mass spectrum, m/z (Irel, %): 318(2.7) [M]+, 135 (25) [Ad]+, 111 (32) [FC6H4NH2]+, 93(100), 79 (18). Found, %: C 67.92; H 7.25; N 8.77;S 10.09. C18H23FN2S. Calculated, %: C 67.89; H 7.28;N 8.80; S 10.07. M 318.45.
  • 79
  • [ 17768-41-1 ]
  • [ 1544-68-9 ]
  • N-[(adamantan-1-yl)methyl]-N′-(4-fluorophenyl)thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
81% With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 12h; General procedure: 3-Fluorophenyl isothiocyanate (2), 0.27 g (1.76 mmol), and triethylamine, 0.2 g (2 mmol), were added to a solution of 0.3 g (1.81 mmol) of (adamantan-1-yl)methanamine 1a in 5 mL of DMF. The mixture was stirred for 12 h, 5 mLof 1 N aqueous HCl was added, and the mixture was stirred for 30 min more. The white precipitate was filtered off, washed with 10 mL of water, and dried.
  • 80
  • [ 4411-26-1 ]
  • [ 17768-41-1 ]
  • [ 51334-15-7 ]
YieldReaction ConditionsOperation in experiment
83% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
  • 81
  • [ 17768-41-1 ]
  • 4-(adamantan-1-yl)phenyl isothiocyanate [ No CAS ]
  • 1-((adamantan-1-yl)methyl)-3-(4-(adamantan-1-yl)phenyl)thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
87% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
  • 82
  • [ 65068-86-2 ]
  • [ 17768-41-1 ]
  • 1-((adamantan-1-yl)methyl)-3-(adamantan-2-yl)thiourea [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine; In N,N-dimethyl-formamide; at 80℃; for 12h; General procedure: To the 1 equiv. of corresponding amine in 30 equiv. of DMF was added 1 equiv. of 1-isothiocyanatoadamantane and 1 equiv. (2 equiv. in case of amine hydrochloride) of Et3N at room temperature. The reaction mass was heated at 80 C for 12 h. After cooling down to room temperature 0.5N HCl and water was added and the resulting white precipitates were collected by suction filtration. The collected solid was thoroughly washed with water.
  • 83
  • [ 17768-41-1 ]
  • (x)C2HF3O2*C31H37N7O4 [ No CAS ]
  • [ 76-05-1 ]
  • 6-(6-(4-(3-(((adamantan-1-yl)methyl)amino)-3-oxopropyl)piperazin-1-yl)pyridin-3-yl)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-isopropyl-1H-indazole-4-carboxamide 2,2,2-trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
90% General procedure: Intermediate 1 (385 mg, 0.60 mmol) and N-Boc-2-aminoacetaldehyde (191 mg, 1.2 mmol, Sigma, 472654) were dissolved in DMF (5.0 mL) and acetic acid (0.5 mL). To the solution was added sodium triacetoxyborohydride (254 mg, 1.2 mmol) at 0 C. After being stirred overnight at room temperature, the mixture was filtered and purified by reverse-phase ISCO (10% - 100% methanol / 0.1% TFA in H20) to afford compound tert-butyl (2-(4-(5- (l-isopropyl-4-(((6-methyl-2-oxo-4-propyl-l,2-dihydropyridin-3-yl)methyl)carbamoyl)-lH- indazol-6-yl)pyridin-2-yl)piperazin-l-yl)ethyl)carbamate 2,2,2-trifluoroacetate. The obtained intermediate was dissolved in DCM (30 mL) and treated with trifluoroacetic acid (5.0 mL) at room temperature. After being stirred overnight at room temperature, the mixture was concentrated and purified by reverse-phase ISCO to afford intermediate 2 (302 mg, 73% over 2 steps). Intermediate 2 (100 mg, 0.15 mmol), HOAt (l-hydroxy-7-azabenzo-triazole) (31 mg, 0.23 mmol) and 1-adamantaneacetic acid (35 mg, 0.18 mmol, Sigma, 127272) were dissolved in DMSO (2.0 mL). To the solution were added NuMuMu (66 muL, 0.60 mmol), and EDCI (43 mg, 0.23 mmol) successively at room temperature. After being stirred overnight at room temperature, the mixture was concentrated under vacuum and purified by preparative HPLC (10% - 100% methanol / 0.1% TFA in H2O) to afford AM 16-1 OA as white solid in TFA salt form (75 mg, 58%). 1H NMR (600 MHz, CDC13) delta 8.47 (s, 1H), 8.37 (s, 1H), 7.85 (d, J= 7.8 Hz, 1H), 7.60 (brs, 4H), 6.75 (d, J = 8.3 Hz, 1H), 6.38 (s, 1H), 4.95 - 4.84 (m, 1H), 4.67 (s, 2H), 4.28 - 3.54 (m, 7H), 3.50 - 2.97 (m, 6H), 2.88 (t, J= 7.3 Hz, 2H), 2.40 (s, 3H), 1.92 (brs, 5H), 1.65 - 1.51 (m, 20H), 1.03 (t, J= 7.2 Hz, 3H).
  • 84
  • [ 17768-41-1 ]
  • [ 56961-30-9 ]
  • cis-(+/-)-5-[(3-Aminocyclopentyl)oxy]-2-chloro-N-(tricyclo[3.3.1.13.7]dec-1-ylmethyl)-benzamide [ No CAS ]
  • 85
  • [ 16744-98-2 ]
  • [ 17768-41-1 ]
  • N-[1-(adamantan-1-yl)methyl]-N'-(2-fluorophenyl)urea [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% With triethylamine; In N,N-dimethyl-formamide; at 20℃; for 8h; General procedure: 2-Fluorophenyl isocyanate (2), 0.97 equiv, and triethylamine, 0.2 g (2 mmol, unless otherwise stated), were added at room temperature to a mixture of 1 equiv of amine 1a-1i and 40 equiv of DMF. The mixture was stirred for 8 h, 5 mL of 1 N aqueous HCl was added, and the mixture was stirred for 30 min more. The white solid was filtered off, washed with 10 mL of water, and dried under reduced pressure.
With triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 8h; General procedure: To 1 equiv. of corresponding amine 2a-j in 40 equiv. of DMF was added 1 equiv. of 2-fluorophenyl isocyanate and 1 equiv. of Et3N (2 equiv. when amine used in form of hydrochloride) at 0C. The reaction mixture was stirred at room temperature overnight. After adding 1N HCl and water, the resulting white precipitates were collected by suction filtration.
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