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CAS No. : | 118-31-0 | MDL No. : | MFCD00004048 |
Formula : | C11H11N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NVSYANRBXPURRQ-UHFFFAOYSA-N |
M.W : | 157.21 | Pubchem ID : | 8355 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 10 |
Fraction Csp3 : | 0.09 |
Num. rotatable bonds : | 1 |
Num. H-bond acceptors : | 1.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 51.62 |
TPSA : | 26.02 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.76 cm/s |
Log Po/w (iLOGP) : | 1.78 |
Log Po/w (XLOGP3) : | 2.11 |
Log Po/w (WLOGP) : | 2.15 |
Log Po/w (MLOGP) : | 2.56 |
Log Po/w (SILICOS-IT) : | 2.61 |
Consensus Log Po/w : | 2.24 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 2.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.69 |
Solubility : | 0.318 mg/ml ; 0.00202 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.29 |
Solubility : | 0.812 mg/ml ; 0.00516 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -4.11 |
Solubility : | 0.0123 mg/ml ; 0.0000785 mol/l |
Class : | Moderately soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.0 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | at 16 - 45℃; for 40 h; | In the is provided with a stirrer, thermometer, condenser, dropping funnel in the reaction container, adding the mass fraction is 85percent third eyeball 130 ml, methylamine (3) 210 ml, reducing the temperature of the solution to 16 °C, control the stirring speed 130rpm, slowly adding amine methylnaphthalene (2) 0.31mol, dropping time control in 4h, the temperature of the solution elevated to 45 °C, and 36h, evaporate third eyeball, the mass fraction of the residue to 70percent cyclohexane 230 ml, are sequentially used for quality fraction is 35percent potassium sulfite washing solution, sodium bromide solution, phosphorus pentoxide dehydration, 1.8kPa vacuum distillation, collecting 110 - - 115 °C fraction, the mass fraction of the 95percent nitromethane recrystallizing, to obtain crystal N-methyl-1-naphthalene methylamine 45.06g, yield 85percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With copper(I) chloride; 4 A molecular sieve; oxygen In pyridine at 60℃; for 24h; | |
98% | With dmap; copper(l) iodide; 9-azabicyclo[3.3.1]nonane N-oxyl; oxygen; 4,4'-di-tert-butyl-2,2'-bipyridine In acetonitrile at 20℃; for 15h; | |
90% | With potassium hydroxide; nickel copper formate; (Bu4N)2S2O8 In 1,2-dichloro-ethane at 20℃; for 12h; |
90% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; free radical; trichloroisocyanuric acid In dichloromethane at 10℃; for 1.5h; | |
89% | With sodium hypochlorite In ethanol for 0.25h; Ambient temperature; | |
89% | With 1-methyl-1H-imidazole; oxygen; copper(ll) bromide In dimethyl sulfoxide at 100℃; for 24h; | 1 Typical procedure for CuBr2/NMI catalyzed aerobic oxidation of primary amines General procedure: To a 100 mL eggplant type Schlenk flask were added CuBr2 (67.0 mg, 0.3 mmol), corresponding amine (3 mmol) and a solution of NMI (73.8 mg, 0.9 mmol) in DMSO (6 mL). The flask was evacuated and purged with oxygen for three times before the flask was attached to a balloon filled with oxygen. Then the flask was heated at 100 °C for 24 h. After the flask was cooled down and the reaction mixture turned into green color, water (15 mL) and dichloromethane (15 mL) was added into the mixture. The water layer was extracted with dichloromethane (5 mL x 3) and the organic layers were combined. After removing the solvent, residue was purified by column chromatography (PE/EA = 100:1) to give the product. |
83% | With tris(2,2’-bipyridine)dichlororuthenium(II) hexahydrate; oxygen; copper(I) bromide; lithium tert-butoxide In dimethyl sulfoxide at 20℃; for 18h; Schlenk technique; Irradiation; | |
81% | With pyridine; tert.-butylhydroperoxide; iodine; potassium carbonate In water at 80℃; for 0.0666667h; | |
79% | With tert.-butylhydroperoxide; ammonium fluoride; iodine; oxygen In water; dimethyl sulfoxide at 70℃; for 2h; Schlenk technique; Sealed tube; | |
70% | With fluorosulfonyl fluoride; dihydrogen peroxide; caesium carbonate In ethanol; water at 20℃; for 3h; | General procedure: In this case, optimized reaction conditions are a littlebit different from those for the oxidation of anilines: 30% H2O2(6.0 equiv), Cs2CO3 (10.0 equiv), SO2F2 (balloon), EtOH/H2O = 3/1(v/v), room temperature for 3 h. |
With pyridine; copper(l) iodide; oxygen at 60℃; for 24h; mol. sieves; Yield given; | ||
Multi-step reaction with 2 steps 1: dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](benzylidene) (tricyclohexylphosphine) ruthenium(II); oxygen / toluene / 12 h / 110 °C / 760.05 Torr / Sealed tube 2: dichloro[1,3-bis(2-methylphenyl)-2-imidazolidinylidene](benzylidene) (tricyclohexylphosphine) ruthenium(II); oxygen; ammonium acetate / 5,5-dimethyl-1,3-cyclohexadiene / 1 h / 130 °C / 760.05 Torr / Sealed tube | ||
99 %Chromat. | With C68H64Cl2N6P2Ru2(4+)*2F6P(1-)*2Cl(1-); caesium carbonate In N,N-dimethyl-formamide at 100℃; for 24h; Inert atmosphere; Green chemistry; | |
With sodium periodate; C31H29Br2N3Ru In water; ethyl acetate at 80℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With N,N'-bis(salicylidene)-1,2-phenylene-diaminocobalt(II); ammonia; hydrogen In tetrahydrofuran; water at 120℃; for 24h; Autoclave; | |
With lithium borohydride; Rink amine resin; water; trifluoroacetic acid; trimethyl orthoformate solid phase synthesis; 1) RT, 2) THF, 70 deg C, 5 h, 3) CH2Cl2, RT, 5 h; Yield given. Multistep reaction; | ||
Multi-step reaction with 3 steps 1: NaBH4 / ethanol; H2O / 20 °C 2: 2.7 g / PPh3; DEAD / tetrahydrofuran / 22 h / 0 - 20 °C 3: NaBH4; AcOH / propan-1-ol; H2O / 5 h / 80 - 90 °C |
Multi-step reaction with 2 steps 1: hydroxylamine hydrochloride; sodium carbonate / ethanol / 20 °C 2: palladium 10% on activated carbon; hydrogen / ethanol / 20 °C | ||
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C 2: acetic acid; hydrogen bromide / 0.5 h / 0 °C 3: ammonia / ethanol; water / 4 h / 20 °C | ||
Multi-step reaction with 3 steps 1: sodium tetrahydroborate / methanol / 1 h / 0 - 20 °C 2: hydrogen bromide / acetic acid / 0.5 h / 0 °C 3: ammonium hydroxide / ethanol / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 1-naphthalene methanol With resin-bound CH2OCONHCOOtBu; diethylazodicarboxylate In tetrahydrofuran for 12h; Stage #2: With trifluoroacetic acid In 1,2-dichloro-ethane for 4h; | |
59% | With potassium <i>tert</i>-butylate; ammonia In toluene at 150℃; for 24h; | |
Multi-step reaction with 2 steps 1: 2.7 g / PPh3; DEAD / tetrahydrofuran / 22 h / 0 - 20 °C 2: NaBH4; AcOH / propan-1-ol; H2O / 5 h / 80 - 90 °C |
Multi-step reaction with 2 steps 1: acetic acid; hydrogen bromide / 0.5 h / 0 °C 2: ammonia / ethanol; water / 4 h / 20 °C | ||
Multi-step reaction with 2 steps 1: hydrogen bromide / acetic acid / 0.5 h / 0 °C 2: ammonium hydroxide / ethanol / 4 h / 20 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With (pyridine)(tetrahydroborato)zinc In tetrahydrofuran for 0.4h; Heating; | |
97% | With sodium hydrogensulfate monohydrate; molybdenum(V) chloride; sodium cyanoborohydride In ethanol for 2h; Reflux; | |
96% | With sodium tetrahydroborate at 20℃; for 0.0333333h; neat (no solvent, solid phase); |
92% | With iron oxide; zirconium(IV) chloride; sodium cyanoborohydride In neat (no solvent) at 75 - 80℃; for 0.333333h; | A typical procedure for solvent-free reductionof benzaldehyde oxime to benzylamine with NaBH3CN/ZrCl4/nano Fe3O4 system General procedure: A mixture of benzaldehyde oxime (0.121 g, 1 mmol) and nano Fe3O4 (0.046 g, 0.2 mmol) (nano particle size≈70 nm) was ground in a porcelain mortar. ZrCl4 (0.233 g,1 mmol) was then added and grinding the mixture was continued for a moment at room temperature. The mortar was heated in an oil bath until the temperature of reaction mixture reaches 75-80 °C. NaBH3CN (0.314 g, 5 mmol) wasthen added portion wisely and the mixture was ground for15 min at 75-80 °C. After completion of the reaction, H2O(5 mL) was added and the mixture was stirred for 5 min. The mixture was extracted with EtOAc (2 × 5 mL) and then dried over anhydrous Na2SO4. Evaporation of the solvent affords the pure liquid benzylamine in 93 % yield (0.1 g, Table 2, entry 1). |
83% | With zirconium(IV) chloride; sodium cyanoborohydride In neat (no solvent) at 75 - 80℃; for 0.333333h; | |
With hydrogen; acetic acid In ethanol at 20℃; for 2h; | ||
With palladium 10% on activated carbon; hydrogen In ethanol at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
15% | In N,N-dimethyl acetamide; | 6-[(Naphthalen-1-yl-methyl)-amino]-methyl}-2,4-pteridinediamine To a solution of 6-bromomethyl-2,4-pteridinediamine hydrobromide (51 mg, 0.2 mmol) in anhydrous N,N dimethylacetamide was added 1-aminomethyl-naphthalene (31.67 ul, 0.22 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. 9 mg product was obtained. Yield: 15%; 1H NMR (500 MHz, DMSO-d6): delta 4.6479 (s, 2H), 4.7893 (s, 2H), 7.575-7.6244 (m, 3H), 7.74232-7.7570 (d, J=6.91 Hz, 1H), 7.9935-8.0276 (dd, J1=8.06 Hz, J2=8.995 Hz, 2H), 8.1670-8.1831 (d, J=8.04 Hz, 1H), 8.8430 (s, 1H); ESI-MS: m/z 332 (M++1) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethylmorpholine;; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20.0℃; for 20.0h; | Example 110 1-methyl-N-(1-naphthalenylmethyl)-5-oxoprolinamide (E110) 1-methyl-5-oxoproline (0.050 g, 0.35 mmol, prepared in a manner analogous to that described above for example 51), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (0.081 g, 0.42 mmol), 1-hydroxybenzotriazole (0.057 g, 0.42 mmol), N-ethyl morpholine (0.166 ml, 1.05 mmol) and (1-naphthalenylmethyl)amine were combined in dichloromethane (~8 ml) and the mixture was stirred for ~20 hrs at room temperature. The mixture was then washed with 2M aqueous hydrogen chloride (5 ml) and the organic layer was separated using a phase separator. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, separated as before, and then evaporated. The residue was purified by mass-directed automated HPLC to give pure 1-methyl-N-(1-naphthalenylmethyl)-5-oxoprolinamide as a white solid (0.062 g). LC/MS [M+H]+=283, retention time=2.1 minutes. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 16h; | Synthesis Example 61-1: Synthesis of (S)-2-(N-Fmoc amino)-3-(N-Boc amino) propionate 1-naphthalenemethylamide (Compound X-4) 201.6 mg of commercially available (S)-2-(N-Fmoc amino)-4-(N-Boc amino) propionate was dissolved in 2.0 ml of DMF, and then 110.0 mg of WSCI hydrochloride and 75.6 mg of HOBt were added and dissolved therein. Then, 29 mul of 1-naphthalene methylamine was added to the solution and the whole was stirred for 16 hours at room temperature. On completion of the reaction, the solvent was distilled off. The residue was purified by means of silica gel column chromatography (10 g, chloroform/methanol = 30/1), and 226.3 mg of the above-mentioned compound was obtained as a white solid product. MS(FAB,Pos.):m/z=566[M+1]+ 1H-NMR(500MHz,DMSO-d6):delta=1.37(9H,s),3.26-3.29(2H,m),4.10-4.25 (2H,m),4.27-4.29(2H,m),4.76(2H,d,J=5.6Hz),6.80(1H,t,J=5.6Hz),7.30-7.37(2H,m),7.43(2H,t,J=7.3Hz),7.44(2H,d,J=5.8Hz),7.71(2H, d,J=7.7Hz),7.88(1H,t,J=4.3Hz),7.90(2H,d,J=7.6Hz),7.93(1H,m),8.03(1H,d,J=6.8Hz),8.51(1H,t,J=5.6Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In N,N-dimethyl-formamide; at 20℃; for 12h; | Synthesis Example 23-1: Synthesis of Nalpha-Fmoc-Ndelta- Boc-L-ornithine 1-naphthalenemethylamide (Compound IX-3) 501.7 g of commercially available Nalpha-Fmoc-Ndelta-Boc-L-ornithine was dissolved in 10 ml of DMF, and then 166.4 g of HOBt, 328.0 mg of WSCI hydrochloride and 0.195 ml of 1-naphthalenemethylamine were added to the solution and the whole was stirred for 12 hours at room temperature. On completion of the reaction, the solvent was distilled off. Then, the residue was dissolved in chloroform, and the extraction was performed by the addition of a 1 mol/l hydrochloric acid, followed by washing an organic layer with a saturated sodium hydrogencarbonate aqueous solution. The solvent was distilled off, and 631.7 mg of the above-mentioned compound was obtained as a white solid product. MS(FAB,Pos.):m/z=594[M+1]+ |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With benzotriazol-1-ol; diisopropyl-carbodiimide; In DMF (N,N-dimethyl-formamide); dichloromethane; at 50℃; | Fmoc-Dbu (Boc) -OH (100 mg, 440.5 G/MOL, 0.23 mmol, 1 eq), DIC (36 mul, 126.20 G/MOL, 0.806 G/CM3, 0.23 mmol, 1 eq) and HOBt (31 mg, 135.12 G/MOL, 0.23 MMOL, 1 eq) were dissolved in dry DMF/DCM (1/1,3 ML). After 5 minutes 1-NAPHTHYLMETHYLAMINE (33 1LL, 157.22 g/mol, 1.092 G/CM3, 0.23 MMOL, 1 eq, Fluka) was added to the reaction mixture. After overnight stirring at 50°C, solvent was evaporated and the residue was dissolved in 30 ML ETHYL acetate and washed three times with 20 ml water. Organic phase was dried with NA2SO4 and evaporated. Residue was purified with flash chromatography. 78.5 mg of 4-N-BOC-AMINO- (S)-2-N -FMOC-AMINO-N"-1-NAPHTHYLMETHYLBUTAN- amide was obtained, yield 60percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrogen;palladium; In ethanol; | A. L-Alanyl-L-Proline To a dry 5 mL flask was added N-pyruvyl-L-proline (0.085 g., 0.46 mmoles, 1.0 eq.), naphth-1-ylmethylamine (0.144 g., 0.92 mmoles, 2.0 eq.), and 2.0 mL absolute ethanol. After 3.0 hours at 25 C., the reaction mixture and 100 mL of ethanol were transferred under nitrogen to a 500 mL Parr shaker flask previously flushed with nitrogen. Palladium-on-carbon (0.02 g., 0.18 mmoles, 0.4 eq.) was added together with 50 mL absolute ethanol. Nitrogen was bubbled through the suspension for 5 minutes and the mixture then hydrogenated at 50 psi for 22 hours using three alternating vacuum/hydrogen gas cycles. The reaction mixture was filtered through Celite and concentrated to a yellow oil which was analyzed by HPLC to show an 88% conversion (yield) and a 31% diastereomeric excess of L-alanyl-L-proline. Unreacted imine is the other major peak (5%). The N-pyruvyl-L-proline utilized as starting material can be conveniently obtained from 2,2-dichloropropionic acid according to the following procedure. | |
With nitrogen;palladium; In ethanol; | A. L-alanyl-L-proline To a dry 5 mL flask was added N-pyruvyl-L-proline (0.085 g., 0.46 mmoles, 1.0 eq.), naphth-1-ylmethylamine (0.144 g., 0.92 mmoles, 2.0 eq.), and 2.0 mL absolute ethanol. After 3.0 hours at 25 C., the reaction mixture and 100 mL of ethanol were transferred under nitrogen to a 500 mL Parr shaker flask previously flushed with nitrogen. Palladium-on-carbon (0.02 g., 0.18 mmoles, 0.4 eq.) was added together with 50 mL absolute ethanol. Nitrogen was bubbled through the suspension for 5 minutes and the mixture then hydrogenated at 50 psi for 22 hours using three alternating vacuum/hydrogen gas cycles. The reaction mixture was filtered through Celite and concentrated to a yellow oil which was analyzed by HPLC to show an 88% conversion (yield) and a 31% diastereomeric excess of L-alanyl-L-proline. Unreacted imine is the other major peak (5%). The N-pyruvyl-L-proline utilized as starting material can be conveniently obtained from 2,2-dichloropropionic acid according to the following procedure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Step A N-t-Butoxycarbonyl-4(R)-benzyloxyproline naphth-1-ylmethylamide The title compound was prepared using the procedure in Example 1 step H using N-t-butoxycarbonyl-4(R)-benzyloxyproline and naphth-1-ylmethylamine. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; | 1-Ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (7.5 g), was added in portions to a solution of 2-nitrobenzoic acid (5.01 g) in methylene chloride (300 ml) cooled to 0 C. The mixture (containing ethyl 2-nitrobenzoyl carbonate) was stirred for 15 minutes and then 1-naphthylmethylamine (4.7 g) was added dropwise at 0-5 C. The mixture was then stirred for 1 hour at ambient temperature and then washed successively with M hydrochloric acid, M sodium hydroxide and then with water. The organic phase was dried (MgSO4) and evaporated. The residue was purified by column chromatography, eluding with methylene chloride/ether (80/20 v/v) to give N-(1-naphthylmethyl)-2-nitrobenzamide as a white solid (7.9 g), of satisfactory purity. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis Example 51-1: Synthesis of Nα-(4-(N-Cbz-aminomethyl) benzoyl)-NG- Pmc-L-arginine 1-naphthalenemethylamide (Compound XXX-1) 2.187 g of the compound obtained in Synthesis Example 42-1, 0.95 g of WSCI and 0.67 g of HOBt were dissolved in 33 ml of DMF, and then 0.51 ml of 1-naphthalenemethylamine was added to the solution. After 18 hours, the reaction solution was concentrated and a 1 mol/l hydrochloric acid was added thereto, followed by extraction with chloroform. A saturated sodium bicarbonate solution was added to an organic layer and extraction was performed with chloroform, followed by washing the organic layer with a saturated salt solution. The organic layer was driedwith anhydrous sodium sulfate and concentrated. The residue thus obtained was dissolved in 50 ml of DMF and 5 ml of diethylamine was added to the solution. After 1 hour, the residue obtained by concentrating the reaction solution was suspended in 40 ml of DMF, followed by the addition of 0.95 g of WSCI, 0.60 g of DMAP, and 0.75 g of the compound obtained in Synthesis Example 41-1 to the suspension. After 3 days, the reaction solution was concentrated and then a 1 mol/l hydrochloric acid was added thereto. Then, it was extracted with chloroform and an organic layer was washed with a saturated salt solution. The organic layer was dried with anhydrous sodium sulfate and concentrated. The residue thus obtained was purified by means of silica gel column chromatography (80 g, chloroform/methanol = 20/1), and 2.47 g of the above-mentioned compound was obtained as a light-yellow solid product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Synthesis Example 19-2: Synthesis of Nalpha-(4-(N-Boc-aminomethyl) benzoyl-N delta-Boc-L-ornithine 1-naphthalenemethylamide (Compound XVIII-1) 501.7 mg of commercially available Nalpha-Fmoc-Ndelta-Boc-ornithine was dissolved in 6.0ml of DMF, and then 328.0mg of WSCI hydrochloride and 166.4 mg of HOBt were added and dissolved. Then, 195 ml of 1-naphthalene methylamine was added to the solution and the whole was stirred for 20 hours at room temperature. On completion of the reaction, the solvent was distilled off. Then, the residue was dissolved in chloroform and washed with a 1 mol/l hydrochloric acid and a saturated salt solution. An organic layer was dried with anhydrous sodium sulfate, followed by distilling the solvent off to obtain 631.7 mg of a crude product as a white frothy product. 499.9 mg of the product was dissolved in 10 ml of DMF, and then 1.0 ml of diethylamine was added to the solution and the whole was stirred for 180 minutes at room temperature. On completion of the reaction, the solvent was distilled off and then the product was dried by a vacuum pump. 509.2 mg of the dried product was dissolved in 10 ml of DMF, and then 241.9 mg of WSCI hydrochloride, 113.8 mg of HOBt, and 253.9 mg of the compound obtained in Synthesis Example 19-1 were added to the solution and the whole was stirred for 13.5 hours at room temperature. On completion of the reaction, the solvent was distilled off. The residue was dissolved in chloroform and washed with a 1 mol/l hydrochloric acid, a 1 mol/l sodium hydroxide aqueous solution, and a saturated salt solution. An organic layer was dried with anhydrous sodium sulfate and then the solvent was distilled off. The residue was purified by means of silica gel column chromatography (25 g, chloroform/methanol = 25/1), and 310.8 mg of the above-mentioned compound was obtained as a white solid product. MS(FAB,Pos.):m/z=605[M+1]+ 1H-NMR(500MHz,DMSO-d6): delta=1.36 (9H,s), 1.39 (9H,s), 1.35-1.45 (2H,m), 1.60-1.80 (2H,m), 2.91 (2H,m), 4.17 (2H,d,J=7.7Hz), 4.48 (1H.m), 4.7 5 (2H,d,J=5.9Hz), 6.80 (1H,t,J=5.6Hz), 7.31 (2H,d,J=8.3Hz), 7.4-7.4 5 (3H,m), 7.5-7.6 (2H,m), 7.8-7.9 (3H,m), 7.95 (1H,m), 8.06 (1H,m), 8.4 5(1H,d,J=5.9Hz),8.51(1H,d,J=5.4Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 80℃; for 3.08333h; | 4.2. General procedure for the synthesis of 4-substituted-2-chloropyrimidin-4-amines (7-9) General procedure: To a mixture of 2,4-dichloropyrimidine (6) (5.00 g, 33.60 mmol) and primary amines (33.60 mmol) in 65 mL of EtOH, kept at 0 °C (ice-bath), DIPEA (6.08 mL, 36.80 mmol) was added. The reaction was allowed to stir on the ice-bath for 5 minutes and was refluxed at 75-80 °C for 3 h. After cooling to 25 °C, the EtOH was evaporated in vacuo and the residue was re-dissolved in a solvent mixture of EtOAc and dichloromethane (DCM) in 3:1 ratio and successfully washed with a concentrated NaHCO3 and NaCl solution (1 × 15 mL). Aqueous layer was washed with EtOAc (3 × 15 mL) and the combined organic layer was dried over anhydrous MgSO4 and filtered. The organic layer is evaporated in vacuo and the resulting residue was further purified using either one of the following two methods: (1) Method A: Silica gel column chromatography using EtOAc/hexanes twice (3:1 and 1:3, respectively) to afford solid products (60-65%); (2) Method B: Differential melting point separation-the collected organic layers are evaporated in vacuo and the oily residue is washed with a solution of hexanes and ether (3:1) to afford a precipitate that was dried on filter paper at 80-85 °C for 2 h to afford solid products. Some physical and spectroscopy data are provided below for 7, 8 and 9. |
With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 80℃; for 3.08h; | ||
With N-ethyl-N,N-diisopropylamine In ethanol at 0 - 85℃; for 4.08333h; | General procedure for the synthesis of 4-substituted-2-chloropyrimidin-4-amines (6-7) General procedure: To a mixture of 2,4-dichloropyrimidine (5) (5.00 g, 33.60 mmol) and primary amines (R1 = naphth-1-ylmethanamine and diphenylmethanamine; 33.60 mmol) in 65 mL of EtOH, kept at 0 °C (ice-bath), DIPEA (6.08 mL, 36.80 mmol) was added. The reaction was allowed to stir on the ice-bath for 5 min and was refluxed at 80-85 °C for 4 h. After cooling to 25 °C, 20 mL of EtOAc was added and solution was neutralized with drop-wise addition of ~6 M HCl (pH = 7-7.5), washed with a saturated NaHCO3 and NaCl solution (1 x 50 mL). Aqueous layer was re-washed with EtOAc (3 x 25 mL) and the combined organic layer was dried over anhydrous MgSO4 and filtered. The organic layer is evaporated in vacuo and the resulting residue was further purified using either one or both of the following methods: (1) Method A: Silica gel column chromatography using EtOAc: hexanes twice (3:1 and 1:3 v/v, respectively) or 9:1 DCM: EtOAc to afford solid products (60-65%); (2) Method B: The collected organic layers were evaporated in vacuo and the oily residue was vigorously mixed with a solution of hexanes to afford a precipitate that was dried on filter paper at 80-85 °C for ~2-3 h to afford solid products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere; | |
91% | With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere; | 2 Representative Procedure for the preparation of 4,5-dichloro-7V(aryl/alkyl)thiophene-2-sulfonamidesTo a solution of 4,5-dichlorothiophene-2-sulfonyl chloride ( 1.000 g, 4.002 mmol) in anhydrous CH2CI2 (20 mL) was added 1-naphthylmethylamine (0.630 g, 4.007 mmol) followed by Et3N (0.84 mL, 6.027 mmol) and stirred at room temperature for 2 h. The reaction mixture was diluted with water (20 mL) and extracted with CH2C12 (100 mL), washed with brine, dried (Na2S04) and concentrated under vacuo. The residue was purified by recrystallization from CH2Cl2-hexane to afford the pure 4,5-dichloro-N-(naphthalen-l -ylmethyl)thiophene-2-sulfonamide (1.350 g, 91 %) as a white crystalline product. |
91% | With triethylamine In dichloromethane at 20℃; for 2h; Inert atmosphere; | 2 To a solution of 4,5-dichlorothiophene-2-sulfonyl chloride (1.000 g, 4.002 mmol) in anhydrous CH2C12 (20 mL) was added 1-naphthylmethylamine (0.630 g, 4.007 mmol) followed by Et3N (0.84 mL, 6.027 mmol) and stirred at room temperature for 2 h. The reaction mixture was diluted with water (20 mL) and extracted with CH2C12 (100 mL), washed with brine, dried (Na2S04) and concentrated under vacuo. The residue was purified by recrystallization from CH2Clr-hexane to afford the pure 4,5-dichloro-N-(naphthalen-l-ylmethyl)thiophene-2-sulfonamide (1.350 g, 91%) as a white crystalline product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: 4-methyl-N-(naphthalen-1-ylmethyl)benzenesulfonamide With n-butyllithium In tetrahydrofuran at 0℃; for 0.166667h; Inert atmosphere; Stage #2: With naphthalene; lithium In tetrahydrofuran at -78 - 25℃; Stage #3: With water In tetrahydrofuran | 4.5. General procedure for synthesis of amines 17 General procedure: To a solution of the corresponding sulfonamide 16 (1 mmol) in anhydrous THF (10 mL) was added n-buthyl lithium (1 mmol, 0.625 mL) at 0 °C under inert argon atmosphere. After 10 min, the resulting solution was added to a suspension of lithium powder (7.2 mmol, 50 mg) and naphthalene (0.08 mmol, 10 mg) in anhydrous THF (5 mL) at -78 °C. The mixture was stirred during 12 h, reaching temperature to rise to 25 °C, and finally was hydrolyzed with water (10 mL). The mixture was extracted with AcOEt (3×10 mL) and washed with brine (10 mL), after drying with anhydrous MgSO4, ands filtering on Celite, the solvents were removed under low pressure(15-18 Torr). The resulting mixture was purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 20℃; for 6.5h; Inert atmosphere; | 5.2.18. N-(4-Fluorobenzyl)-2,3-dihydroxybenzamide (5a) General procedure: A solution of 2,3-dihydroxybenzoic acid (154 mg, 1 mmol), EDCI (380 mg, 2 mmol), DIPEA (2 mmol), and HOBt (290 mg, 2 mmol) in dry THF (15 mL) was stirred at rt under N2. To this solution was added 90% (4-fluorophenyl)methanamine (0.152 mL, 1.2 mmol). The reaction mixture was stirred for 6.5 h at rt. After removal of most of THF, 20 mL of EtOAc was added to the residue. The solution was washed by 1 N HCl, satd NH4Cl and dried over Na2SO4. The concentration provided the residue which was purified by chromatography using petroleum ether/ethyl acetate (1:1) as eluent to give compound 5a as a white solid (51 mg, 57% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With tert.-butylhydroperoxide; sodium chloride In water at 70℃; Green chemistry; | |
91% | With F,N,S tri-doped hierarchical nanocarbon (FNSHC-700); air In acetonitrile at 85℃; for 18h; | |
89% | With oxygen; iron(II) bromide In neat (no solvent) at 110℃; for 8h; Green chemistry; |
72% | With 5,5-dihydroxy-pyrimidine-2,4,6-trione; dimethylsulfide; 7-(trifluoromethyl)-1,10-ethyleneisoalloxazinium chloride In 2,2,2-trifluoroethanol at 20℃; for 5h; | |
70% | With basolite C300; oxygen In neat (no solvent) at 80℃; for 12h; | |
65% | With pyrimidine-2,4,5,6(1H,3H)-tetraone; oxygen; copper(l) chloride at 30℃; for 3h; | |
85 %Chromat. | With oxygen In water for 12h; Reflux; | |
81 %Spectr. | With 2-tert-butyl-5-hydroxy-1,4-benzoquinone; oxygen In acetonitrile at 20℃; for 20h; chemoselective reaction; | |
81 %Spectr. | With dihydrogen peroxide In water at 100℃; for 16h; Sealed tube; | General reaction procedure: General procedure: In a 25 mL pressure tube equipped with a stirring bar, benzyl amine (1 mmol) and H2O2 (30% in water; 1 mmol) were injected by syringe under air atmosphere. Then the tube was closed and heated to 100 °C for 16 h. After the reaction was complete, the reaction mixture was cooled down and extracted with diethyl ether. The product was obtained after evaporation and NMR spectra were recorded. 1,4-Dimethoxybenzene was added as the internal standard. |
84 %Chromat. | With oxygen In dimethyl sulfoxide at 100℃; for 24h; | |
85 %Chromat. | With Cu/Al2O3 In para-xylene at 140℃; for 48h; Inert atmosphere; | 5 Example 5 1 mmol of an amine compound substrate having the structure shown in the following table was added to the reaction flask.The Cu/Al2O3 (7 mol%) obtained in Example 1 was prepared.P-xylene 5ml,Raise the temperature to 140 ° C under nitrogen protection conditions, sample detection,The detection method is a GC method in which twelve n-hexane is an internal standard.The reaction is over,The reaction solution was filtered, and the filter cake was washed with toluene (3×5 mL).Wash with K2CO3 aqueous solution (3×5 mL), and concentrate the filtrate.The target product was purified by column purification. The experimental results are as follows: |
71.0 %Spectr. | With tetrabutylammonium tetrafluoroborate In acetonitrile at 20℃; for 3h; Electrochemical reaction; | |
98 %Spectr. | With vinylene bridged donor-acceptor type porous organic polymer prepared from tris(4-formylphenyl)amine and tricyanomesitylene In acetonitrile for 8h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine In dichloromethane at 20℃; for 2h; | 4.2.1. Methyl N-[(1-naphthalenyl)methyl]carbamate (17) Methyl chloroformate (58 μL, 0.73 mmol) and triethylamine (183 μL, 1.3 mmol) were added to a solution of 1-naphthalenylmethanamine (21, 100 mg, 0.64 mmol) in CH2Cl2 (5 mL), and the reaction mixture was stirred at rt for 2 h. The reaction mixture was diluted with water, extracted with EtOAc, the combined organic extract was dried over Na2SO4 and concentrated to dryness. Purification of the crude product (SiO2, EtOAc-hexanes) afforded methyl 1-naphthalenylmethyl)carbamate (17) as a white solid (134 mg, 0.62 mmol, 97% yield; mp 74-75 °C). 1H NMR (500.3 MHz, CD3OD): (two rotamers 0.2:0.8) δ 8.09 (d, J = 8.2 Hz, 0.2H), 8.04 (d, J = 8.2 Hz, 0.8H), 7.84 (d, J = 7.5 Hz, 1H), 7.81-7.75 (m, 1H), 7.53-7.38 (m, 4H), 5.06 (s, 0.4H), 4.72 (s, 1.6), 3.65 (br s, 3H).1413C NMR (125.8 MHz, CD3OD): (two rotamers) δ 159.6, 138.1, 135.6, 135.4, 132.8, 132.7, 129.8, 129.7, 129.2, 129.1, 127.4, 127.2, 126.9, 126.8, 126.5, 126.4, 126.2, 124.8, 124.4, 63.5, 52.7, 43.6. HRMS-EI: m/z (%) 215.0950 (15) (215.0946 calcd for C13H13NO2), 158 (60), 141 (21), 129 (100). |
With triethylamine at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | [0083j Carboxylic acid (1 .0 eq.), O-(7-Azabenzotriazol- 1 -yl)-N,N,N,N? - tetramethyluronium hexafluorophosphate (HATU) (1.2 eq.) and 1 -Hydroxy-7-Azabenzotriazole (HOAt) 0.6M in DMF (1.0 eq.) were dissolved in DMF under argon atmosphere. The solution was cooled to 0 C and amine (1.1 eq.) was added. After stirring for 5 minutes at 0 C, Hunig?sbase (3 - 4 eq.) was added. The reaction mixture was stirred at 0 C. After completion of reaction (1 h; monitored by LCMS), water was added to reaction mixture and stirred 30 minutes. Product was isolated either by filtration or ethyl acetate extraction:_DPLG-2122 was prepared following the general procedure for HATU mediatedcoupling of Boc-4-F-Phe-OH (2.OOg, 7.06 mmol) and 1-naphthylmethylamine (1.17 mL, 7.77mmol). After completion of reaction (1 h), 100 mL water was added to the reaction mixture. Aprecipitate was formed. The mixture was stirred for 15 minutes and filtered. The precipitate waswashed with water and dried to give 2.96 g (99%) product. ?H NMR (500 MHz, DMSO-d6) oe8.47 (t, J 5.8 Hz, 1H), 8.03 (dd, J 6.3, 3.4 Hz, 1H), 7.94 (dd, J 6.2, 3.4 Hz, 1H), 7.84 (d, J= 8.1 Hz, 1H), 7.55 - 7.52 (m, 2H), 7.44 - 7.41 (m, 1H), 7.38 - 7.36 (m, 1H), 7.28 - 7.25 (m,2H), 7.07 -7.00 (m, 3H), 4.74 (d, J= 5.6 Hz, 2H), 4.25 -4.15 (m, 1H), 2.93 (dd, J 13.6, 5.1Hz, 1H), 2.77 (dd,J= 13.6, 10.0 Hz, 1H), 1.30 (s, 9H). | |
99% | General procedure: Carboxylic acid (1.0 eq.), O-(7-Azabenzotriazol-1-yl)-N,N,N,N?-tetramethyluronium hexafluorophosphate(HATU) (1.2 eq.) and 1-Hydroxy-7-Azabenzotriazole(HOAt) 0.6M in DMF (1.0 eq.) were dissolved in DMF under argon atmosphere. The solution was cooled to 00 C. and amine (1.1 eq.) was added. Afier stirring for 5 minutes at 00 C., Huenig?s base (3-4 eq.) was added. The reaction mixture was stirred at 00 C. Afier completion of reaction (1 h; monitored by LCMS), water was added to reaction mixture and stirred 30 minutes. Product was isolated either by filtration or ethyl acetate extraction; DPLG-2122 was prepared following the general procedure for HATU mediated coupling of Boc-4-F-Phe-OH (2.00 g, 7.06 mmol) and 1-naphthylmethylamine (1.17 mL, 7.77 mmol). After completion of reaction (1 h), 100 mL water was added to the reaction mixture. A precipitate was formed. The mixture was stirred for 15 minutes and filtered. The precipitate was washed with water and dried to give 2.96 g (99%) product. 1H NMR (500 MHz, DMSO-d6) delta 8.47 (t, J=5.8 Hz, 1H), 8.03 (dd, J=6.3, 3.4 Hz, 1H), 7.94 (dd, J=6.2, 3.4 Hz, 1H), 7.84 (d, J=8.1 Hz, 1H), 7.55-7.52 (m, 2H), 7.44-7.41 (m, 1H), 7.38-7.36 (m, 1H), 7.28-7.25 (m, 2H), 7.07-7.00 (m, 3H), 4.74 (d, J=5.6 Hz, 2H), 4.25-4.15 (m, 1H), 2.93 (dd, J=13.6, 5.1 Hz, 1H), 2.77 (dd, J=13.6, 10.0 Hz, 1H), 1.30 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With iron(III) chloride; 3-methyl-4-oxa-5-azahomoadamantane; oxygen In water at 100℃; for 10h; | Typical procedure for oxidative synthesis of benzimidazoles, benzoxazolesor benzothiazoles General procedure: A mixture of 1.2 mmol o-phenylenediamine, 2-aminophenol or 2-aminothiophenol and 1 mmol primary amine, 10 mol % FeCl3, 1 mol % 3-methyl-4-oxa-5-azahomoadamantane, 5 ml H2O were mixed in a 10-ml three-necked flask, then O2 was bubbled into the flask at flow rate of 20 ml/min. The reaction mixture was stirred at 100 C for several hours, and reaction progress was monitored by TLC. The final reaction mixture was cooled to room temperature and extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was directly purified by column chromatography on silica gel using hexane/ethyl acetate (7:3) as eluent to afford the pure product. |
87% | With 2,2,6,6-tetramethyl-piperidine-N-oxyl; ferric nitrate In neat (no solvent) at 110℃; for 24h; Green chemistry; | |
83% | With tert.-butylhydroperoxide In water at 100℃; for 9h; | Experimental General procedure: A mixture of 1.5 mmol aromatic amines, 1 mmol o-phenylenediamine, and 4 mmol TBHP were prepared in a 10-ml, three-necked flask, stirred at 100 °C for several hours, and the reaction progress was monitored by TLC. After completionof the reaction, the reaction mixture was cooled to room temperature. The pure product was isolated after a simple filtration. When necessary, the crude product was purified by chromatography using hexane/ethyl acetate (7:3) as eluent. |
69% | With Al cations incorporated into the Si framework; open air In neat (no solvent) at 100℃; for 15h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With ammonium iodide In 1-methyl-pyrrolidin-2-one at 160℃; for 10h; | Synthesis of E-2-styrylquinolines (3aselected as an example); general procedure General procedure: A mixture of 2-methylquinoline (1a) (0.14 g, 1 mmol), benzylamine(0.32 g, 3.0 mmol), and NH4I (0.17 g, 1.2 mmol)in NMP (4 mL) was stirred at 160 °C for 10 h until the totalconsumption of 1a. After cooling, the reaction mixture waswashed with brine (20 mL) and extracted with CH2Cl2(2 × 20 mL). The combined organic extract was dried overNa2SO4 and concentrated under vacuum. The residue waspurified by column chromatography (petroleum ether/EtOAc = 6:1) to afford the target product 3a (pale yellowsolid, 85%, 0.20 g). |
85% | With tert.-butylhydroperoxide; N-Bromosuccinimide In water; acetonitrile at 100℃; for 48h; Schlenk technique; Darkness; Green chemistry; | |
75% | With tert.-butylhydroperoxide; water; sodium chloride at 100℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With Acetaldehyde oxime; oxygen; 1N,3N,5N-trihydroxy-1,3,5-triazin-2,4,6[1H,3H,5H]-trione In water at 100℃; for 38h; Green chemistry; | Typical Procedure for the Aerobic Oxidative Synthesis of Oximes General procedure: A mixture of primary amine (1 mmol), THICA (5 mol%), acetaldoxime(10 mol%), and H2O (5 mL) was placed in a three-neckedflask. O2 was stirred into the flask at a flow rate of 20 mL/min. The reaction mixture was stirred at 100 °C for several hours, and the reaction progress was monitored by TLC. When the final reaction mixture was cooled to r.t. and extracted with Et2O, the organic layer was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was pure enough. When necessary,the crude product was purified by chromatography using EtOAc-PE (1:8) as eluent. |
84% | With diperoxydodecanedioic acid In N,N-dimethyl-formamide at 20 - 55℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With potassium carbonate; In acetonitrile; at 160.0℃; for 1h;Microwave irradiation; Inert atmosphere; | General procedure: 4-Methyl-N-phenylquinazolin-2-amine (17a). A mixture of 16 (20 mg, 0.11 mmol), aniline (0.012 mL, 0.13 mmol) and K2CO3 (23 mg, 0.17 mmol) in CH3CN (0.90 mL) was placed in sealed vial. The mixture was heated using microwave irradiation at 160 C for 1 h. The reaction mixture was filtered and concentrated and the residue was purified by chromatography on SiO2 (benzene/ether, 4:1) to afford 17a (17 mg, 65%) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With Acetaldehyde oxime; 3-methyl-4-oxa-5-azahomoadamantane; oxygen In water at 100℃; for 9h; Green chemistry; | |
89% | With indium(III) chloride; Acetaldehyde oxime; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; oxygen In toluene at 100℃; for 4h; | General procedure for the aerobic oxidative synthesis of oximes General procedure: A mixture of 2 mmol primary amine, acetaldoxime (6.2 mmol),InCl3 (0.1 mmol), TEMPO (0.2 mmol), and Toluene (10 ml) was placed in a 20 ml three-necked flasks. O2 was bubbled into the flask at a flow rate of 20 ml/min. The reaction mixture was stirred at 100 °C for several hours and the reaction progress was monitored by TLC. After cooling to room temperature, the solution was directly evaporated to dryness and the residue was purified by column chromatography on silica gel (ethyl acetate/n-hexane = 1:8)to give the corresponding oximes. |
88% | With 3-chloro-benzenecarboperoxoic acid In ethyl acetate at 20℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | With triphenylphosphine; bis(dibenzylideneacetone)-palladium(0); In N,N-dimethyl-formamide; at 20℃; under 760.051 Torr; for 48h;Inert atmosphere; | General procedure: An argon-filled 1L round bottomflask was charged with: 5-iodo-2-deoxycytidine (30 g, 85 mmol); benzylamine (109.3 g, 1020 mmol, 12 eq); and anhydrous N,N-dimethylformamide (DMF, 205 mL). The mixture was rapidly magnetically stirred until all the solids had dissolved. The resulting solution was degassed by two cycles of evacuation to 50 mm and refilling with argon. A mixture of bis(dibenzylidineacetone)palladium(0) (978 mg, 1.7 mmol, 0.02 eq) and triphenylphosphine (1.92 g, 7.3 mmol, 0.086 eq) was added and the resulting fine black suspension was rapidly stirred, evacuated to 50 mm and filled with carbon monoxide (1 atm) from a rubber balloon. The mixture was stirred at room temperature (?20 C) and periodically refilled with carbon monoxide. After 26 hours, the reaction was found to be complete by TLC analysis (silica gel, eluent: 15% methanol/85% dichloromethane (v/v), Rf(SM) = 0.3, Rf(5a) = 0.4). The reaction mixture was diluted with ethyl acetate (205 mL), filtered, and rinsed forward with 65% ethyl acetate/35%DMF (100 mL). The clear green filtrate was concentrated on a rotary evaporator (50-80 C, 1-2 mm) until all the solvents and most of the benzylamine had distilled. The dark orange residue (?75 g) was dissolved in hot abs. ethanol (650 mL) and rapidly hot-filtered to remove a small amount of insoluble flakes (?2 g). The clear filtrate was allowed to cool with slow stirring and the product crystallized as needles. After stirring overnight, the slurry was filtered and the cake washed with ice-cold ethanol (100 mL). After drying in vacuo, the product 5a was obtained as a white, crystalline solid: 22.0 g,72% yield, mp 193-4 C. |
40% | With triphenylphosphine; bis(dibenzylideneacetone)-palladium(0); In N,N-dimethyl-formamide; at 20℃; under 760.051 Torr; for 48h; | Prepared as described for (4a), using 1-naphthylmethylamine (6 eq) in place of benzylamine, with a reaction time of 48 hours at room temperature. After concentrating the reaction mixture, the residue was extracted with diisopropyl ether (~40 mL/g) to remove most of the excess 1- naphthylmethylamine. The residue was crystallized from hot methanol (50 mL/g), with hot filtration, to afford the product (4b; Scheme 1; Example 1) as a white solid, 40% yield. 1H NMR (500 MHz, d6-DMSO): delta = 8.81 (t, J= 5.5 Etaz, 1Eta), 8.43 (s, 1H), 8.14 (d, J= 4.4, 1H), 8.09 (bs, 1H), 7.96 (m, 1H), 7.79 (m, 1H), 7.75 (bs, 1H), 7.53 (m, 4H), 6.14 (t, J= 6.6 Hz, 1H), 5.24 (d, J= 4.3 Hz, 1H), 5.01 (t, J= 5.6 Hz, 1H), 4.90 (dd, J= 15.6, 13.4 Hz, 1H), 4.89 (dd, J= 15.5, 13.2 Hz, 1H), 4.26 (m, J= 4.1 Hz, 1H), 3.84 (dd, J= 8.4, 4.4 Hz, 1H), 3.58 (m, 2H), 2.20 (m, 2H). 13C NMR (500 MHz, d6-DMSO): delta = 165.45 (IC), 163.58 (IC), 153.57 (IC), 143.93 (IC), 136.07 (IC), 134.20 (IC), 133.32 (IC), 128.61 (IC), 127.59 (IC), 126.34 (IC), 125.89 (IC), 125.53 (IC), 125.07 (IC), 123.36 (IC), 98.82 (IC), 87.71 (IC), 85.99 (IC), 70.13 (IC), 61.16 (IC), 42.42 (IC), 40.14 (IC). MS m/z: [M"] calcd for C2iH2iN405, 409.42; found, 409.1 (EST). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With oxygen; acetic acid In chlorobenzene Heating; Green chemistry; | |
85% | With iron(II) triflate; oxygen In chlorobenzene at 110℃; for 11h; Schlenk technique; | Bis(indolyl)methanes 3 and 4; General Procedure General procedure: To a Schlenk tube were added benzylamine 1 (1.3 mmol), indole 2(2.0 mmol), Fe(OTf)2 (10 mol%), and anhydrous chlorobenzene (2 mL).The tube was equipped with an O2 balloon, and the mixture wasstirred at 110 °C until complete consumption of indole (TLC monitoring).When the reaction was complete, the mixture cooled to r.t., dilutedwith CH2Cl2 (10 mL), and washed with H2O (2 × 10 mL). The organicextract was dried (anhyd Na2SO4) and concentrated under reducedpressure, and the resulting residue was purified by columnchromatography (silica gel, hexane-EtOAc) to afford the correspondingbis(indolyl)methane products 3 and 4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: (naphth-1-yl)methylamine; N<SUP>4</SUP>-(tert-butoxy)-N<SUP>2</SUP>-(tert-butoxycarbonyl)-L-asparaginyl-L-alanine With 1-hydroxy-7-aza-benzotriazole; HATU In N,N-dimethyl-formamide at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 6h; | 36 Example 36 - Preparation of tert-butyl ((4S,7S)-4,12, 12-trimethyl- 1-(naphthalen-1-yl)-3,6,9-trioxo- 1 1-oxa-2,5, 1 O-triazatridecan-7-yl)carbamate (DPLG-2095) [0118j DPLG-2095 was prepared following the general procedure for HATU mediated coupling of 1V4-Qert-butoxy)-N2-Qert-butoxycarbonyl)-L-asparaginyl-L-alanine (120 mg, 0.32mmol) and 1-naphthylmethylamine (56 tl, 0.38 mmol). After completion of reaction (6 h), themixture was precipitated with water. The precipitate was filtered and dried to give product (153mg, 93%). ‘H NMR (500 MHz, DMSO-d6) ö 10.26 (s, 1H), 8.47 (t, J 5.7 Hz, 1H), 8.06 - 8.04(m, 1H), 8.01 (d, J= 7.4 Hz, 1H), 7.96 - 7.94 (m, 1H), 7.86 - 7.84 (m, 1H), 7.57 - 7.52 (m, 2H),7.48 - 7.43 (m, 2H), 6.94 (d, J 8.1 Hz, 1H), 4.74 (d, J 5.8 Hz, 2H), 4.32 - 4.26 (m, 2H), 2.46(dd,J= 14.6, 5.5 Hz, 1H), 2.29 (dd,J= 14.6, 8.5 Hz, 1H), 1.37 (s, 9H), 1.24 (d,J= 7.0 Hz, 3H),1.13 (s, 9H). |
93% | Stage #1: (naphth-1-yl)methylamine; N<SUP>4</SUP>-(tert-butoxy)-N<SUP>2</SUP>-(tert-butoxycarbonyl)-L-asparaginyl-L-alanine With 1-hydroxy-7-aza-benzotriazole; 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 0℃; for 0.0833333h; Inert atmosphere; Stage #2: With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 6h; | 36 Example 36-Preparation of tert-butyl ((4S,7S)-4, 12,1 2-trimethyl- 1 -(naphthalen- 1 -yl)-3,6,9-trioxo-1 1- oxa-2,5, 10-triazatridecan-7-yl)carbamate (DPLG2095) General procedure: Carboxylic acid (1.0 eq.), O-(7-Azabenzotriazol-1-yl)-N,N,N,N’-tetramethyluronium hexafluorophosphate(HATU) (1.2 eq.) and 1-Hydroxy-7-Azabenzotriazole(HOAt) 0.6M in DMF (1.0 eq.) were dissolved in DMF under argon atmosphere. The solution was cooled to 00 C. and amine (1.1 eq.) was added. Afier stirring for 5 minutes at 00 C., Hünig’s base (3-4 eq.) was added. The reaction mixture was stirred at 00 C. Afier completion of reaction (1 h; monitored by LCMS), water was added to reaction mixture and stirred 30 minutes. Product was isolated either by filtration or ethyl acetate extraction; DPLG-2095 was prepared following the general procedure for HATU mediated coupling of N4-(tert-butoxy)- N2-(tert-butoxycarbonyl)-L-asparaginyl-L-alanine (120 mg, 0.32 mmol) and 1 -naphthylmethylamine (56 pi, 0.38 mmol). Afier completion of reaction (6 h), the mixture was precipitated with watet The precipitate was filtered and dried to give product (153 mg, 93%). ‘H NMR (500 MHz, DMSOd 5) ö 10.26 (s, 1H), 8.47 (t, J=5.7 Hz, 1H), 8.06-8.04 (m, 1H), 8.01 (d, J=7.4 Hz, 1H), 7.96-7.94 (m, 1H), 7.86-7.84 (m, 1H), 7.57-7.52 (m, 2H), 7.48-7.43 (m, 2H), 6.94 (d, J=8.1 Hz, 1H), 4.74 (d, J=5.8 Hz, 2H), 4.32-4.26 (m, 2H), 2.46 (dd, J=14.6, 5.5 Hz, 1H), 2.29 (dd, J=14.6, 8.5 Hz, 1H),1.37 (s, 9H), 1.24 (d, J=7.0 Hz, 3H), 1.13 (s, 9H). |
93% | With 1-hydroxy-7-aza-benzotriazole; 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 for 6h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dipotassium peroxodisulfate; potassium carbonate at 20℃; for 12h; Green chemistry; | |
76% | With 2,8-dibromo-10-(4-bromophenyl)-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2′,1′-f ][1,3,2]diazaborinin-4-ium-5-uide In acetonitrile at 50℃; for 5h; Irradiation; Green chemistry; | Typical Procedures for Photocatalytic Oxidation of Amine with 2-Aminothiophenol General procedure: Amine (1 mmol), 2-aminothiophenol (2 mmol), BODIPY photosensitizer (0.01 mmol, 1.0 mol%), and acetonitrile (5 mL) were added to a dry 10-mL flask. The flask was pressurized with air (2 bar) and then heated to 50 C. The solution was then irradiated using a 35-W xenon lamp through a cutoff filter (0.72M NaNO2 aqueous solution, which is transparent for light >385nm, because lamps could emit a small amount of ultraviolet light). After the reaction was completed, the solvent was evaporated under reduced pressure. The crude product was further purified using column chromatography. |
72% | With acide 2,4,6-trihydroxybenzoique; oxygen In para-xylene at 140℃; for 24h; Green chemistry; | Experimental Procedure for the Synthesis of Benzothiazole Derivatives 9 General procedure: To a two-necked flask, benzylamine derivatives 1 (4.0 mmol), o-aminothiophenol (8a) (3.0 mmol), 4,6-dihydroxysalicylic acid (10 mol%), and distilled p-xylene (2.0 mL) were added, and then the reaction vessel was connected to an O2 balloon at room temperature. The mixture was stirred in 140 °C under O2 atmosphere for 24 h. The resulting mixture was transferred into a round-bottom flask using ethyl acetate (EtOAc) and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluent: hexane/EtOAc) to give product 9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | General procedure: Example 6 - Preparation of tert-butyl (S)-(4-((naphthalen-l-ylmethyl)amino)-4-oxobutan- 2-yl)carbamate (PKS2241, PKS2261)The title compound was synthesized by following the general protocol for HATU mediated coupling of Boc-L-P-homoalanine and 1-naphthylmethylamine on a 1.5 mmol scale. After completion of reaction, water was added to reaction mixture to give white precipitate. Precipitate was filtered, washed with water and dried in air to give product (490 mg, 95%) as a white solid. 1H NMR (500 MHz, DMSO-d6) delta 8.38 (t, J= 5.7 Hz, 1H), 8.06 - 8.04 (m, 1H),7.95 - 7.93 (m, 1H), 7.86 - 7.84 (m, 1H), 7.56 - 7.52 (m, 2H), 7.48 - 7.42 (m, 2H), 6.72 (d, J = 8.3 Hz, 1H), 4.76 - 4.68 (m, 2H), 3.89 - 3.80 (m, 1H), 2.35 (dd, J= 13.9, 5.7 Hz, 1H), 2.18 (dd, J= 13.9, 8.2 Hz, 1H), 1.37 (s, 9H), 1.01 (d, J= 6.5 Hz, 3H). Carboxylic acid (1.0 eq.), O-(7-Azabenzotriazol- 1 -yl)-N,N,N,N'- tetramethyluronium hexafluorophosphate (HATU) (1.2 eq.), and l-Hydroxy-7-Azabenzotriazole (HO At) 0.6M in DMF (1.0 eq.) were dissolved in DMF under argon atmosphere. The solution was cooled to 0 C and amine was added. After stirring for 5 minutes at 0 C, Hunig's base (3 - 4 eq.) was added. The reaction mixture was stirred at 0 C for 1 hour. After completion of reaction (1 hour, monitored by LCMS), water (10 mL) was added to reaction mixture and stirred 30 minutes. Product was isolated either by ethyl acetate extraction or filtering the precipitate. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine; In dichloromethane; at 0 - 20℃; for 2h; | Example 63 - Preparation of PKS21204Boc- -Ala-OSu (286.28 mg, 1.00 mmol) was dissolved in dichloromethane (5.00 mL) and 1-naphthylmethanamine (157.21 mg, 1.00 mmol) was added. The solution was cooled to 0 C and triethylamine (101.19 mg, 1.00 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for 2 hours. After completion of reaction, dichloromethane was evaporated and water was added. A white precipitate appeared. Precipitate was filtered, washed with water and dried in air to give product (320 mg, 97%) as a white solid. Product was used in next step without further purification. 1H NMR (500 MHz, Chloroform-i ) delta 7.99 (d, J= 8.3 Hz, IH), 7.88 (d, J= 8.0 Hz, IH), 7.85 - 7.78 (m, IH), 7.59 - 7.48 (m, 2H), 7.45 - 7.40 (m, 2H), 5.90 (bs, IH), 5.14 (bs, IH), 4.93 - 4.85 (m, 2H), 3.48 - 3. (m, 2H), 2.45 - 2.36 (m, 2H), 1.39 (s, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With C19H35Cl2CoN2P; potassium <i>tert</i>-butylate; sodium triethylborohydride In tetrahydrofuran; toluene at 150℃; for 36h; Inert atmosphere; Molecular sieve; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | at 16 - 45℃; for 40h; | In the is provided with a stirrer, thermometer, condenser, dropping funnel in the reaction container, adding the mass fraction is 85% third eyeball 130 ml, methylamine (3) 210 ml, reducing the temperature of the solution to 16 C, control the stirring speed 130rpm, slowly adding amine methylnaphthalene (2) 0.31mol, dropping time control in 4h, the temperature of the solution elevated to 45 C, and 36h, evaporate third eyeball, the mass fraction of the residue to 70% cyclohexane 230 ml, are sequentially used for quality fraction is 35% potassium sulfite washing solution, sodium bromide solution, phosphorus pentoxide dehydration, 1.8kPa vacuum distillation, collecting 110 - - 115 C fraction, the mass fraction of the 95% nitromethane recrystallizing, to obtain crystal N-methyl-1-naphthalene methylamine 45.06g, yield 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
>99% | With triethylamine; In tetrahydrofuran; at 0℃; for 3h; | General procedure: Naphthylamine (0.13 g, 3.0 eq) and triethylamine (0.16 g,5.0 eq) was dissolved in THF (10 mL), and then, the mixturewas reacted with the 3,3?,4,4?-benzophenonetetracarboxylic dianhydride (1) (0.1 g, 0.031 mol) with constant stirring. After3 h a 5% hydrochloric acid was added and extracted withethyl acetate. Then, the organic solvent was evaporated.4,4?-carbonylbis(2-(naphthalen-1-ylcarbamoyl)benzoicacid) (2a). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: (naphth-1-yl)methylamine; cyclohexanone In ethanol at 40 - 70℃; for 0.333333h; Stage #2: formaldehyd In ethanol at 80℃; for 3h; Stage #3: decyl chloride In ethanol at 42 - 100℃; for 4h; | 1 Embodiment 1: degreasers L1And its preparation method (1) degreasers L1The composition, the components and the molecular formula is as follows:Degreasers L1By the 1 - naphthyl methyl amine, formaldehyde, cyclohexanone and chlorine in accordance with the molar ratio of 1:5: 1.0: 2.0 proportion reaction, molecular formula as follows:Wherein R is C10Of the straight-chain alkane.(2) degreasers L1Preparation method is as follows:(1) in the mounted electric stirrer, reflux condensation tube, thermometer is added in three-mouth flask 1 µM of 1 - naphthyl methyl amine, then adding solvent 10 µM ethanol, heating up to 40 °C, in the stirring rate is 300 rpm stirring 10min, then add 1.0 µM cyclohexanone, the temperature is raised to 70 °C, the stirring rate is 500 rpm, continuous stirring 20min after lowering the temperature to 32 °C, then 15% hydrochloric acid to adjust the pH value to 2, the mixture obtained from A;(2) the 5 µM formaldehyde and 5 µM ethanol mixed is put into the constant pressure dropping in the funnel, adjust the mixture A temperature to 80 °C, constant voltage to formaldehyde in the dropping funnel with ethanol is added to the mixture in the mixture drop A, side drop edge added stirring, drop acceleration is 2 drops/min, stirring rate 500 rpm, constant temperature reaction 3h after natural cooling to room temperature to obtain solution B;(3) solution B in the stirring rate is 300 rpm lower, temperature is adjusted to 42 °C, adding 2.0 µM of chlorine, then heating up to 100 °C, the stirring rate is adjusted to 350 rpm, constant temperature reflux reaction 2h, then cooling down to 50 °C to continue after the reaction 2h, obtaining mixture C;(4) the mixture C cooling to room temperature, then transferred to a round bottom flask, reduced pressure distillation to remove the solvent and the excess formaldehyde, then put into the drying in the vacuum drying box 24h, to obtain the degreasers L1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile at 0 - 20℃; for 4h; | |
93% | With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile at 20℃; for 4h; Cooling with ice; | 69 Example 69 Preparation of naphthyl-1-methylsulfonyl fluoride Dissolve 1-naphthylmethylamine [Compound 145] (157 mg, 1 mmol) in acetonitrile (3 mL).1-(Fluorosulfonyl)-2,3-dimethyl-1H-imidazole trifluoromethanesulfonate [Compound 4] (328 mg, 1 mmol) was added under ice-cooling.After the completion of the ice bath, the reaction at room temperature for 4 hours,After the reaction was completed with LC-MS, water (30 mL) was addedThe reaction mixture was extracted with ethyl acetate (20 mL×3).After combining the organic phases with water (20 mL),Saturated brine (20mL) was washed and dried over anhydrous sodium sulfate.Filter paper, the filtrate was concentrated by rotary evaporator.The oil pump dries the solvent,Obtained light yellow solid naphthyl-1-methylsulfonyl fluoride[Compound 146] (223 mg, 93%) (Scheme 69). |
34% | With 1-(fluorosulfuryl)-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate In acetonitrile at 0 - 20℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50.9% | Stage #1: 3-Furoic acid With 4-methyl-morpholine In tetrahydrofuran at -20℃; Inert atmosphere; Stage #2: (naphth-1-yl)methylamine With isobutyl chloroformate In tetrahydrofuran at -15 - 20℃; for 1.5h; Inert atmosphere; | General procedure for synthesis of amides General procedure: The compounds 5-13 were synthesized using the mixed anhydrides method (21) of peptide synthesis. The suitable acid (10 mmol) was dissolved in dry tetrahydrofuran (THF) or a mixture of dimethylformamide (DMF)/tetrahydrofuran (30 mL). Next, N-methylmorpholine (NMM) (10 mmol, 1.1 mL) was added and the mixture was stirred under nitrogen and chilled to -20°C. Isobutyl chloroformate (IBCF) (10 mmol, 1.3 mL) was added dropwise to keep the temperature below -15°C. Then the suitable amine: 2- or 4-fluorobenzylamine; 2- trifluoromethoxybenzylamine; 2-trifluoromethylbenzylamine, 4-bromobenzylamine or 1-naphthylmethylamine (10 mmol) in THF was added in small portions and the reaction mixture was stirred at -15°C for 30 min. and at room temperature for 1 h. The solution was concentrated in vacuo and the residue was dissolved in CHCl3 (40 mL). This solution was washed with 20 mL portions of 1 M HCl, saturated NaHCO3 solution and saturated NaCl solution, then dried with anhydrous MgSO4, filtered and concentrated in vacuo. The obtained compounds were purified as follows: 5, 6, 8, 11, 12 and 13 by crystallization from ethyl acetate/hexane, 10 by crystallization from ethyl acetate and 7, 9 by column chromatography in chloroform as eluent and then by crystallization from ethyl acetate/hexane. All stages of the synthesis were controlled by the thin-layer chromatography. The general procedure for the synthesis of the obtained compounds is shown in Scheme 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | General procedure: Formaldehyde (2.0mmol), trifluoroacetic acid (2.0mmol) and different commercially available amine (2.0mmol) were dissolved in dichloromethane and the solution was stirred at room temperature for 30min. Then, a solution in dichloromethane of the opportune 1,5-disubstituted indole derivatives 2, 3, 19, 32-34 (1.0mmol) was added and the mixture was stirring for 4-6h, following the course of reaction by TLC. When the starting compound disappeared, the reaction was quenched by 10% aqueous solution of sodium bicarbonate and washed with brine, dried over anhydrous Na2SO4 and filtered. Organic phase was evaporated in vacuum and 3-aminomethyl indole derivatives were obtained after flash chromatography using a mixture of dichloromethane/methanol (95/5 v:v) as eluent with 65-77% of yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With tris(pentafluorophenyl)borate; oxygen In neat (no solvent) at 120℃; for 12h; | General procedure for the synthesis of triarylpyridines General procedure: A mixture of ketone (2.0 mmol), amine (1.6 mmol), and B(C6F5)3 (0.01 mmol) was stirred at 120°C under 0.1 MPa of O2 for 12 hours. Then, the mixture was quenched by saturated NaHCO3 solution and extracted with CH2Cl2 (20 mL x 2). The combined organic phase was dried over Na2SO4 and filtered. After evaporation of the solvents, the residue was purified by silica gel chromatography (Hexane/AcOEt = 25:1) to afford triarylpyridines. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
148 mg | Stage #1: 2-Methylcyclopentanone; (naphth-1-yl)methylamine at 80℃; for 0.666667h; Inert atmosphere; Stage #2: ethylene glycol With [RhCl2(p-cymene)]2; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene at 145℃; for 24h; Stage #3: squaric acid In ethanol at 80℃; for 2.5h; Sealed tube; | 1.26 Example 1.26 (Synthesis of SQL-26) 0.42 g 2-methylcyclopentanone was dissolved in 10 mL 1-methylcyclohexanol under argon. 0.74 g 1-naphthylmethylamine was added and the resulting solution heated in an 80 °C-oil bath for 40 minutes. 26 mg dichloro(p-cymene)ruthenium (II) dimer, 50 mg XantPhos, and 0.53 mL ethylene glycol were added and the oil bath heated to 145 °C for 24 hours. Concentrated free of most 1-methylcyclohexanol then purified the residue using silica gel chromatography with an ethyl acetate-hexanes gradient. This provided 180 mg of pyrrole product which was dissolved with 2.5 mL ethanol and added to 39 mg squaric acid in a vial. The vial was sealed and its contents stirred and heated at 80 °C for 2.5 hours. The resulting slurry was cooled and filtered. The filter cake was dried under vacuum at 75 °C to 148 mg of squaraine product. HPLC-MS (APCI, +) 601. Amorphous polycarbonate film: l max = 594 nm, FWH M = 23 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With (1,3,5-triaza-7-phosphaadamantan-1-ium-1-yl)butane-1-sulfonate; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 20 - 60℃; for 24h; Inert atmosphere; Autoclave; chemoselective reaction; | Carbonylative Amidation; General Procedure General procedure: 5′-O-(4,4′-Dimethoxytrityl)-5-iodo-2′-deoxyuridine (5′-O-DMT-5-IdU) (1a) (1.0 mmol, 656mg), the corresponding amine 2 (2.0 mmol), Pd(OAc)2 (2 mol%), PTABS ligand (4 mol%), Et3N (10 mmol) and N2-purged DMF (10 mL) were added to a 100 mL stainless steel autoclave reaction flask at room temperature. The autoclave was closed and flushed with nitrogen gas and then pressurized with CO gas (40 psi). Caution. Carbon monoxide (CO) is an odorless, colorless and highly toxic gas. The reactions should be carried out in efficient fume hoods fitted with CO detectors. The reaction mixture was stirred with a mechanical stirrer (500 rpm) and heated at 60 °C for 24 h. The mixture was then allowed to cool to room temperature and the CO was vented carefully in a fume hood by adding KMnO4 solution. The reaction mass was diluted in cold water and subsequently extracted with EtOAc (3 × 25 mL). The combined organic layer was dried over Na2SO4 and concentrated in vacuo. A slurry was prepared from the residue using silica gel and the product was isolated by column chromatography (60-120 neutralized silica gel; CHCl3/MeOH/Et3N, 97.5:2.0:0.5). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With glacial acetic acid In ethyl acetate; propan-2-one at 20℃; for 16h; UV-irradiation; Green chemistry; | 2-Aminobenzamides 4-6; General Procedure General procedure: A mixture of 2-nitrobenzaldehyde 1 (0.2 mmol, 1.0 equiv), primary amine 2 or 3 (0.8 mmol, 4.0 equiv), acetic acid (19.2 L, 0.4 mmol, 2.0 equiv), and EtOAc/acetone (6:1, 3.0 mL) in a 5-mL glass bottle (equipped with a magnetic stirring bar) at r.t. was irradiated with UV light (24-W, 365-375 nm) for 16 h. Purification was by column chromatography (silica gel). |
77% | With glacial acetic acid In ethyl acetate; propan-2-one at 20℃; for 16h; UV-irradiation; | 11 preparation example 11 In a 10 mL reaction tube, add 0.2 mmol of 2-nitrobenzaldehyde, 0.8 mmol of 1-naphthylmethylamine, and 0.4 mmol of acetic acid, and add 3.0 mL of a solution with a mixing ratio of ethyl acetate and acetone of 6:1 as a solvent. Irradiate with 365-375nm ultraviolet light and react for 16h.2-amino-N-(naphthalen-1-ylmethyl)benzamide was obtained by column chromatography as a pale yellow solid with a yield of 77%. |
Tags: 118-31-0 synthesis path| 118-31-0 SDS| 118-31-0 COA| 118-31-0 purity| 118-31-0 application| 118-31-0 NMR| 118-31-0 COA| 118-31-0 structure
[ 2241-98-7 ]
Naphthalen-2-ylmethanamine hydrochloride
Similarity: 0.96
[ 10420-89-0 ]
(S)-(-)-1-(1-Naphthyl)ethylamine
Similarity: 0.90
[ 76532-33-7 ]
N-Methyl-1-(naphthalen-2-yl)methanamine
Similarity: 0.90
[ 3886-70-2 ]
(R)-1-(Naphthalen-1-yl)ethanamine
Similarity: 0.90
[ 2241-98-7 ]
Naphthalen-2-ylmethanamine hydrochloride
Similarity: 0.96
[ 10420-89-0 ]
(S)-(-)-1-(1-Naphthyl)ethylamine
Similarity: 0.90
[ 76532-33-7 ]
N-Methyl-1-(naphthalen-2-yl)methanamine
Similarity: 0.90
[ 3886-70-2 ]
(R)-1-(Naphthalen-1-yl)ethanamine
Similarity: 0.90
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H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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