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CAS No. : | 17078-28-3 | MDL No. : | MFCD00075591 |
Formula : | C10H13NO2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | KQGHTOZUPICELS-UHFFFAOYSA-N |
M.W : | 179.22 | Pubchem ID : | 152203 |
Synonyms : |
|
Num. heavy atoms : | 13 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.3 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 52.19 |
TPSA : | 40.54 Ų |
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) : | -6.16 cm/s |
Log Po/w (iLOGP) : | 1.5 |
Log Po/w (XLOGP3) : | 1.74 |
Log Po/w (WLOGP) : | 1.38 |
Log Po/w (MLOGP) : | 1.67 |
Log Po/w (SILICOS-IT) : | 1.14 |
Consensus Log Po/w : | 1.49 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.19 |
Solubility : | 1.15 mg/ml ; 0.00644 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.21 |
Solubility : | 1.11 mg/ml ; 0.00619 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.29 |
Solubility : | 0.93 mg/ml ; 0.00519 mol/l |
Class : | Soluble |
PAINS : | 1.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.22 |
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 |
---|---|---|
90% | With borane-THF In tetrahydrofuran at 0℃; for 5 h; | As shown in Scheme 5, the bromide synthons used (41a-41c) were synthesized from the corresponding acids first by reduction to alcohols followed by bromination using PPh3/CBr4 (for 41a) or PPh3/Br2 (for 41b and 41c).; To a flame-dried, three-neck, 100 mL round-bottomed flask equipped with a condenser and argon line was added the appropriate carboxylic acid (10 mmol) dissolved in dry THF (25 mL). After cooling to 0°C, 1M BH3*THF (20 mmol) was added drop- wise to the stirred mixture and the reaction was then left at 0°C for 5h. The reaction mixture was diluted with cold water, washed with a saturated solution of NaHC03, and extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with brine (1 x 25 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with 25percent ethyl acetate-hexanes to afford the corresponding alcohols. p- (N, N-dimethylamino) phenethyl Alcohol (40a). Yield, 90percent; mp. 56-57°C ;'H NMR (CDCl3) : 8 2.77 (t, 2H, J = 6.6 Hz), 2.92 (s, 6H, NMe2), 3.80 (t, 2H, J = 6.5 Hz), 6.72 (d, 2H, J = 8.53 Hz), 7.10 (d, 2H, J = 8.51 Hz). 13C NMR (CDC13) : 8 38.21, 40.93 (NMe2), 64.01, 113.20 (2C, Ar), 126.43 129.72 (2C, Ar), 149.51 ; IR (neat): 3284,2855, 1617, 1527, 1352,1049, 1021, 804. HRMS (ESI) m/z : Calcd for CloHlsNO [M+H] + 166.1232, found 166.1225 [M+H] +. |
69% | With borane-THF In tetrahydrofuran at 0 - 20℃; for 1 h; Inert atmosphere | BH3.THF (5 mL, 1M in THF) was added dropwise into a mixture of 2-[4- (dimethylamino)phenyl] acetic acid (300 mg, 1.67 mmol) and tetrahydrofuran (10 mL) under nitrogen. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by water, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1 :4) to afford the title compound (190 mg, 69percent) as a white solid. LCMS [M+H+] 166. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride at 60℃; for 1h; | ||
With thionyl chloride for 1h; Heating; | ||
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h; |
With oxalyl dichloride; N,N-dimethyl-formamide In toluene at 20℃; for 2h; Inert atmosphere; | ||
With oxalyl dichloride In dichloromethane at 20℃; for 0.5h; | 28.1 Step 128A 28BTo a solution of 4-(dimethylamino)-phenylacetic acid 28A (155 mg, 0.862 mmol) in DCM (2 mL) was added oxalyl chloride (115 mg, 0.905 mmol) and catalytic amount of DMF. The mixture was stirred at RT for 30 min. Without further work-up, the mixture was concentrated in vacuo to give 28B (used directly in Step 2). | |
With phosgene; N,N-dimethyl-formamide In dichloromethane at 25℃; for 0.5h; | 52.1 Step 1. 2-(4-(Dimethylamino)phenyl)acetyl chloride To a solution of 2-(4-(dimethylamino)phenyl)acetic acid (200 mg, 1.12 mmol) in DCM (4 mL) was added (COCl)2 (212.47 mg, 1.67 mmol, 146.53 uL) and one drop of DMF (815.71 ug, 11.16 umol), then the mixture was stirred at 25 °C for 0.5 hr. The reaction mixture was concentrated under vacuum to afford the product (230 mg, crude) as a yellow liquid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 1-hydroxybenzotriazol-hydrate; triethylamine; dicyclohexyl-carbodiimide In N,N-dimethyl-formamide for 48h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 4℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 4-methyl-morpholine; benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 25℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 29h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
31% | With pyridine; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 55℃; for 12h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With borane-THF; In tetrahydrofuran; at 0℃; for 5h; | As shown in Scheme 5, the bromide synthons used (41a-41c) were synthesized from the corresponding acids first by reduction to alcohols followed by bromination using PPh3/CBr4 (for 41a) or PPh3/Br2 (for 41b and 41c).; To a flame-dried, three-neck, 100 mL round-bottomed flask equipped with a condenser and argon line was added the appropriate carboxylic acid (10 mmol) dissolved in dry THF (25 mL). After cooling to 0C, 1M BH3*THF (20 mmol) was added drop- wise to the stirred mixture and the reaction was then left at 0C for 5h. The reaction mixture was diluted with cold water, washed with a saturated solution of NaHC03, and extracted with ethyl acetate (3 x 25 mL). The combined organic layers were washed with brine (1 x 25 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with 25% ethyl acetate-hexanes to afford the corresponding alcohols. p- (N, N-dimethylamino) phenethyl Alcohol (40a). Yield, 90%; mp. 56-57C ;'H NMR (CDCl3) : 8 2.77 (t, 2H, J = 6.6 Hz), 2.92 (s, 6H, NMe2), 3.80 (t, 2H, J = 6.5 Hz), 6.72 (d, 2H, J = 8.53 Hz), 7.10 (d, 2H, J = 8.51 Hz). 13C NMR (CDC13) : 8 38.21, 40.93 (NMe2), 64.01, 113.20 (2C, Ar), 126.43 129.72 (2C, Ar), 149.51 ; IR (neat): 3284,2855, 1617, 1527, 1352,1049, 1021, 804. HRMS (ESI) m/z : Calcd for CloHlsNO [M+H] + 166.1232, found 166.1225 [M+H] +. |
69% | With borane-THF; In tetrahydrofuran; at 0 - 20℃; for 1h;Inert atmosphere; | BH3.THF (5 mL, 1M in THF) was added dropwise into a mixture of 2-[4- (dimethylamino)phenyl] acetic acid (300 mg, 1.67 mmol) and tetrahydrofuran (10 mL) under nitrogen. The resulting solution was stirred for 1 h at room temperature. The reaction was then quenched by water, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The residue was purified by a silica gel column eluting with ethyl acetate/petroleum ether (1 :4) to afford the title compound (190 mg, 69%) as a white solid. LCMS [M+H+] 166. |
With lithium aluminium tetrahydride;Inert atmosphere; | General procedure: The majority of alcohols were commercially available. Alcohols 9c,26 9i,27 9j28 and 9k29 were prepared by LiAlH4 reduction of the corresponding carboxylic acids and gave spectral data consistent with those in the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With mercury(II) fluoride; oxygen In acetonitrile at 25℃; for 24h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With 1-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride; benzotriazol-1-ol; triethylamine In dichloromethane at 20℃; | 25 [Example 25]; (R)-3-Chloro-5,11-dihydro-5-[1-(4-dimethylaminophenethyl)pyrrolidin-2-ylmethyl]dibenzo[b,e][1,4]oxazepine dihydrochloride (= compound of Example 8) Methyl ester of N-[(4-dimethylaminophenyl)acetyl]-D-proline: 1-Hydroxybenzotriazole monohydrate (6.1 g, 45.4 mmol) and N-dimethylaminopropyl-N'-ethylcarbodiimide hydrochloride (8.7 g, 45.4 mmol) were added to a solution of (4-dimethylaminohenyl)acetic acid (7.4 g, 41.3 mmol) and methyl ester hydrochloride of D-proline (7.19 g, 43.4 mmol) in methylene chloride (150 ml). The obtained mixture was stirred at room temperature for 6 hours. Triethylamine (6.3 ml, 45.4 mmol) was added to the mixture. They were stirred at room temperature overnight and the reaction mixture was successively washed with water (200 ml), 5 % aqueous sodium hydrogencarbonate solution (200 ml) and water (200 ml). The solvent was evaporated under reduced pressure. The obtained residue was subjected to the silica gel column chromatography. After the elution with methylene chloride and methanol (10:1), suitable fractions were collected and the solvent was evaporated under reduced pressure to obtain the title compound in the form of a brown oily substance (11.0 g, 83 %). ESI/Mass : 291 [M+H+] NMR (CDCl3) δ : 1.82-2.26(4H, m), 2.82-2.98 (6H, m), 3.40-3.76 (2H, m), 3.60(3H, s), 3.73(2H, s), 4.41-4.52(1H, m), 6.64-6.74 (2H, m), 7.07-7.19(2H, m) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | 221 6-[2-(4-Dimethylamino-phenyl)-acetylamino]-hexanoic acid methyl ester (3/58) Example 221 6-[2-(4-Dimethylamino-phenyl)-acetylamino]-hexanoic acid methyl ester (3/58) The title compound was obtained from (4-dimethylamino-phenyl)-acetic acid (1/58) and methyl 6-aminohexanoate hydrochloride (2c) by the following method. Yield 73%. 1H NMR (CDCl3, HMDSO), δ: 1.16-1.92(m, 6H); 2.34(t, J=7.0 Hz, 2H); 3.03(s, 6H); 3.22(s, 2H); 3.43(q, J=6.0 Hz, 2H); 3.65(s, 3H); 6.00(bs, 1H); 6.69(d, J=9.0 Hz, 2H); 7.79(d, J=9.0 Hz, 2H). | |
73% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With triethylamine In tetrahydrofuran Inert atmosphere; Cooling with ice; Stage #2: With isobutyl chloroformate In tetrahydrofuran for 0.333333h; Cooling with ice; Stage #3: methyl 6-aminocaproate hydrochloride With triethylamine In tetrahydrofuran at 20℃; for 1.25h; Cooling with ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 71h; | 160 Synthesis of methyl (4-dimethylaminophenyl)acetate Iodomethane (0.382 mL) and potassium carbonate (848 mg) were added to a solution of (4-dimethylaminophenyl)acetic acid (1 g) in DMF (10 mL), and the reaction solution was stirred at room temperature for 71 hours. Thereafter, ethyl acetate and water were added to the reaction solution, and the organic layer was separated. The resulting organic layer washed with brine, dried over anhydrous magnesium sulfate and then concentrated under reduced pressure to obtain 468 mg of the title compound. The property values of the compound are as follows. 1H-NMR (CDCl3) δ (ppm): 2.92 (s, 6H), 3.52 (s, 2H), 3.67 (s, 3H), 6.69 (d, J=8.4 Hz, 2H), 7.13 (d, J=8.4 Hz, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium azide; TEA; triethylphosphine In dichloromethane; dimethyl sulfoxide at 0℃; for 60h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With 1,10-Phenanthroline; oxygen; copper(II) oxide; potassium ferrocyanide; In dimethyl sulfoxide; at 120℃; under 11251.1 Torr; for 40h;Autoclave; | General procedure: The reaction was carried out in a 40 mL stainless steel autoclave lined with Teflon. Typically, 0.5 mmol substrate, 0.6 mmol K4Fe(CN)6, 0.1mmol CuO, 0.5 mmol 1,10-phenanthroline and 2 mL DMSO were added into the reactor and 1.5MPa of oxygen was filled. Then the reaction system was heated under magnetic stirring at 120C for 40h. Once the reaction time was reached, the mixture was cooled to room temperature. GC analysis of the reaction mixture provided the GC yields of the products. In addition, the crude product from another parallel experiment was purified by column chromatography, and identified by 1H NMR and 13C NMR. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With tetra(n-butyl)ammonium hydroxide In methanol; ethanol ligand and a soln. of (C4H9)4NOH in MeOH dissolved in EtOH, kept for 15 min, this soln. and Re complex added to EtOH, deaerated with N2, refluxed for 7 h; evapd., recrystd. twice from CH2Cl2 by addn. of chilled isooctane, dried(vac.); elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 0.333333h; Stage #2: 5'-isopropyl-2',4'-dimethoxybiphenyl-3-amine In tetrahydrofuran; N,N-dimethyl-formamide | 76 4-Dimethylaminophenylacetic acid (24.6 mg, 0.14 mmol) was dissolved in dry DMF (5 mL). TBTU (48 mg, 0,19 mmol) and DIPEA (65 μl_, 3 eq) was added and the mixture was stirred for 20 minutes. Then 5'-lsopropyl-2',4'-dimethoxybiphenyl-3-amine (0.25 M in THF, 0.50 mL, 0.125 mmol) was added and the mixture left stirring over night. The solvents were evaporated in vacuo and the ccrude product was purified on preperative HPLC to yield 26.8 mg pure material (HPLC). The product was used without further purification or analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example 31 2-[4-(dimethylamino)phenyl]-N-(4-[(trifluoromethyl)thio]phenyl}acetamide The product was prepared from 2-(4-(dimethylamino)phenyl)acetic acid (23 mg) and 4-trifluoromethylthioaniline (28 mg) according to Method C: 1H NMR (300 MHz, CDCl3) delta ppm 2.98 (s, 6 H), 3.66 (s, 2 H). 6.72 - 6.78 (m, 2 H), 7.14 - 7.19 (m, 2 H), 7.19 (s, 1 H), 7.43 - 7.51 (m, 2 H), 7.52 - 7.57 (m, 2 H); MS (ESI-pos) m/z 355.0 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With pyridine; 1,3,5-trichloro-2,4,6-triazine In dichloromethane at 0℃; for 0.25h; Stage #2: benzoic acid hydrazide With indium In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With pyridine; 1,3,5-trichloro-2,4,6-triazine In dichloromethane at 0℃; for 0.25h; Stage #2: 2-Amino-2-methyl-1-propanol With indium In dichloromethane at 20℃; for 40h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 63% 2: 8% | With indium; deuterated ammonium chloride In tetrahydrofuran-d8; water-d2 at 20℃; for 22h; Reflux; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With 1-hydroxy-7-aza-benzotriazole; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane Stage #2: α,α-bis(trifluoromethyl)-2,3,4,5-tetrahydro-1H-1-benzazepine-7-methanol In dichloromethane at 60℃; | 49 2-(4-Dimethylamino-phenyl)-1-[7-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-2,3,4,5-tetrahydro-1-benzazepin-1-yl]-ethanone To a solution of 2-(4-(dimethylamino)phenyl)acetic acid (36 mg, 0.2 mmol) in anhydrous CH2Cl2 (1 mL) were added HOAt (27.0 mg, 0.2 mmol) and EDC-HCl (40 mg, 0.21 mmol). The mixture was stirred until a clear solution was observed, and then 1D (31 mg, 0.1 mmol) was added and the mixture was stirred at 60° C. overnight. The solvent was removed in vacuo and the product was purified by prep-HPLC to yield Example 49 (14.5 mg, 30%). HRMS m/z 475.1819 (M+H)+. 1H NMR (500 MHz, Acetone-D6) δ 7.71 (d, 1H), 7.59 (s, 1H), 7.51 (d, 1H), 7.22 (d, 2H), 6.92 (d, 2H), 4.62 (dd, 1H), 3.57 (d, 1H), 3.50 (d, 1H), 3.13 (s, 6H), 2.54 (m, 2H), 2.20 (t, 1H), 1.84 (m, 1H), 1.72 (m, 2H), 1.28 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane for 0.5h; Stage #2: tert-Butyl N-hydroxycarbamate In dichloromethane for 18h; | 4 [(tert-Butoxy)carbonyl]amino 2-[4-(dimethylamino)phenyl]acetateTo a solution of 4-dimethylamino phenyl acetic acid (2.0 g, 11.6 mmol) in DCM (20 ml) is added EDCI.HCl (3.2 g, 16.74 mmol) and triethylamine (4.7 ml, 33.48 mmol). The reaction is stirred for 30 minutes before addition of N-tert-butoxycarbonyl hydroxylamine (2.2 g, 16.74 mmol). The reaction is stirred for 18 hours then quenched with water (10 ml). The organics are separated, washed twice with water (2×5 ml), dried over sodium sulfate and concentrated in vacuo. Purification of the title compound is achieved by silica gel column chromatography eluting with heptane: ethyl acetate (4:1, v:v). (2.08 g, 63%), 1H NMR (250 MHz, CHLOROFORM-d) δ ppm 7.89 (1H, s), 7.11-7.23 (2H, m), 6.63-6.76 (2H, m), 2.94 (6H, s), 1.47 (9H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 20℃; for 1.08333h; Inert atmosphere; Stage #2: ethyleneglycol sulfate In tetrahydrofuran; 1,2-dimethoxyethane; hexane for 16h; Inert atmosphere; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid; 3-tropanol With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 20h; Stage #2: With sodium hydrogencarbonate | 5.1.7. 8-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-(4-(dimethylamino)phenyl)acetate (6) Tropine (0.30 g, 2.12 mmol), 4-(dimethylamino)phenylacetic acid (0.31 g, 1.70 mmol), 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (0.49 g, 2.54 mmol) and 4-dimethylaminopyridine (0.21 mmol, 0.026 g) were dissolved in DCM (12 mL) and stirred for 20 h at room temperature. The reaction mixture was washed with NaHCO3 (2 × 15 mL), H2O (2 × 15 mL), brine (20 mL), dried over Na2SO4, and concentrated in vacuo. The product was purified by silica gel flash column (DCM/MeOH/NH4OH, 4:1:0.1) to yield 6 as a yellow oil (0.37 g, 71%). FTIR (neat, cm-1) ν 2933, 2873, 2848, 1726, 1567; 1H NMR (500 MHz, CDCl3) δ 7.19 (m, 2H), 6.66 (m, 2H), 4.97 (t, J = 5.4, 1H), 3.50 (s, 2H), 3.05 (s, 2H), 2.94 (s, 6H), 2.26 (s, 3H), 2.09 (dt, J = 14.7, 4.8 Hz, 2H), 1.92 (m, 2H), 1.78 (m, 2H), 1.66 (d, J = 14.4 Hz); 13C NMR (125.7 MHz, CDCl3) δ 171.4, 149.8, 129.9, 122.0, 112.9, 67.6, 59.8, 41.3, 40.8, 40.4, 36.5, 25.5; ESI-HRMS m/z calcd for C18H26N2O2: 303.2067 [M+H+], found 303.2067. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere; | |
With dmap; dicyclohexyl-carbodiimide In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.1% | With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 16h; | Ethyl 3-cinnamamidopropanoate (7-ester). General procedure: trans-Cinnamic acid (1.49, 10.0 mmol) and HOBt (2.263 g, 15 mmol) were dissolved in DMF (50 mL). EDC.HCl (2.865 g, 15 mmol) was added, followed by β-alanine ethyl ester hydrochloride (1.53 g, 10 mmol) and DIPEA (5.3 mL, 30 mmol) and the solution was stirred at RT for 16 h. The solvent was removed in vacuo and the residual oil was re-dissolved in EtOAc (100 mL), the organic phase was washed with 5% w/v aqueous sodium hydrogen carbonate solution (2 ×100 mL) then 5% w/v citric acid solution (2× 30 mL) and brine, before being dried on MgSO4. The solvent was evaporated in vacuo to afford the product (1.48 g, 59.8% yield). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diphenyl phosphoryl azide; triethylamine In toluene at 20 - 80℃; for 1.25h; Inert atmosphere; | 5.2.1 General procedure for synthesis of isocyanates from acid General procedure: To a suspension of acid (1.5 g, 6.25 mmol, 1.0 equiv) in toluene, under inert atmosphere, was added triethylamine (0.76 g, 7.5 mmol, 1.2 equiv) followed by slow addition of diphenylphsophoryl azide (1.90 g, 6.87 mmol, 1.1 equiv). Reaction mixture was stirred at room temperature for 15 min., followed by heating to 80 °C for 1 h during which evolution of nitrogen was observed. Solvent was removed at reduced pressure. Unless otherwise mentioned, isocyanate was extracted by the following method. Residue was stirred in hexane (10 mL/mmol) and supernatant was collected. Hexane extraction was repeated twice. Combined hexane layer was evaporated to get crude isocyanate, which was used for next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 12h; | 12; 97 GENERAL METHOD 12 GENERAL METHOD 12To a solution of the appropriate carboxylic acid (1.2 eq.) in DMF (2 mL) maintained at 0°C were added HATU (1.5 eq.) and DIPEA (2 eq.). To the reaction mixture was added the appropriate 4-(piperazin-l-yl)thieno[2,3- | |
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 0 - 20℃; for 12h; | 97 General procedure: General Method 12 [0416] To a solution of the appropriate carboxylic acid (1.2 eq.) in DMF (2 mL) maintained at 0° C. were added HATU (1.5 eq.) and DIPEA (2 eq.). To the reaction mixture was added the appropriate 4-(piperazin-1-yl)thieno[2,3-c]pyrimidine or 4-(2,5-diazabicyclo[2.2.1]heptan-2-yl)thieno[2,3-d]pyrimidine derivative (1 eq.) and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was then diluted with water and extracted with EtOAc. The organic layer was washed with water and brine, then dried over sodium sulphate. The organic layer was concentrated under vacuum and the crude residue was purified by column chromatography (silica gel 100-200 mesh, MeOH:DCM 1:9) to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid; 1,1,1-trifluoro-4-phenylbut-3-en-2-one With pivaloyl chloride; N-ethyl-N,N-diisopropylamine Stage #2: With (2S,3R)-3-isopropyl-2-phenyl-3,4-dihydro-2H-benzo[4,5]thiazolo[3,2-a]pyrimidine In dichloromethane at -78℃; for 16h; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With dmap; dicyclohexyl-carbodiimide In dichloromethane at 0 - 20℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 18h; | 32 4-[1-(2,5-Dimethylbenzyl)-1H-benzimidazol-2-yl]methyl}-N,N-dimethylaniline Example 32 4-[1-(2,5-Dimethylbenzyl)-1H-benzimidazol-2-yl]methyl}-N,N-dimethylaniline 2-[4-(Dimethylamino)phenyl]acetic acid (0.18 mg, 1.0 mmol) was added to a stirred solution of Intermediate 6 (0.20 g, 0.88 mmol) in DCM (6 mL), EDC (0.19 g, 0.97 mmol) and triethylamine (0.37 mL, 2.65 mmol) at 0° C., and stirred at r.t. for 18 h. The reaction was diluted with water (60 mL) and extracted with ethyl acetate (3*10 mL). The organic layer was separated, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by preparative HPLC, yielding the title compound. LCMS (ES+) 370 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; chloroform at 70℃; for 20h; Overall yield = 80 %; diastereoselective reaction; | (4) General procedure for β-lactam synthesis (Table 1 and Table 2) General procedure: The appropriate imine (0.762 mmol) and carboxylic acid (0.915 mmol, 1.2 eq.) were stirred in theappropriate solvent. NEt(i-Pr)2 (182 mg, 246 μL, 1.410 mmol, 1.85 eq.) and [T3P (364 mg, 1.14 mmol,1.5 eq. (728 mg of 50% wt. solution in THF)] were added by syringe and the reaction mixture stirred at70 °C for 20 h. The reaction was poured into sat. NaHCO3 (10 mL) and extracted with CH2Cl2 (3 × 10mL). The combined organic phases were dried (MgSO4), filtered, and concentrated to give the crudematerial. At this stage the diastereoselectivity was determined using 1H NMR. The material was purifiedby column chromatography (see individual entries for eluting solvent systems). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; In acetic anhydride; at 30℃; for 2h; | General procedure: General procedure A Step-a: Synthesis of 2-(4-fluorophenyl)-3-(4-((E)-3-methoxy-3-oxoprop-1-en-1-yl) phenyl) acrylic acid (C). A mixture of 4-fluorophenylacetic acid (2.5 g, 13.2 mmol) and methyl (E)-3-(4-formylphenyl)acrylate (2.03 g, 13.2 mmol) were dissolved under stirring with acetic anhydride (8 ml). To this mixture diisopropylethylamine (DIPEA) (3.4 ml, 19.7 mmol) was added and stirred at 30 C for 2 h. Upon completion (as monitored by TLC using 100% ethyl acetate as eluent), the reaction mixture was poured into water and the pH was adjusted to 1 using dil. HClaq (1:1). The aqueous layer was extracted with ethyl acetate (2 * 150 ml). The combined ethyl acetate layer was washed with water till the washings were neutral and dried over anhydrous Na2SO4. The ethyl acetate layer was evaporated to dryness to obtain a sticky compound, which was triturated with cold dichloromethane (DCM) to furnish a white solid. It was filtered and dried under vacuum to afford the title compound (2 g, 47%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With pivaloyl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 0.0833333h; Inert atmosphere; Stage #2: methyl 2-(phenyl(tosylimino)methyl)acrylate With (+)-Tetramisole hydrochloride In dichloromethane at -78 - 20℃; for 16h; Inert atmosphere; enantioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | 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 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [bis(acetoxy)iodo]benzene; iodine; palladium diacetate In N,N-dimethyl-formamide at 60℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; triethylamine In acetonitrile at 20℃; for 5h; Inert atmosphere; | 5.1.9. (2S)-N-{(1R)-2-Hydroxy-1-[4-(2-methylpentyloxy)phenyl]ethyl}-2-phenylpropanamide (3) General procedure: To a solution of 8a (90 mg, 0.33 mmol) in MeCN (10 mL) at room temperature under nitrogen was added TEA (0.14 mL,0.99 mmol), followed by (S)-2-phenylpropionic acid (50 mg,0.33 mmol) and HBTU (152 mg, 0.4 mmol). After stirring for 5 h, the reaction was quenched by H2O (5 mL), followed by addition of EtOAc (50 mL). The layers were separated. The organic layer was washed with saturated NaHCO3 (10 mL), brine (10 mL), dried (Na2-SO4) and concentrated under reduced pressure. Flash column chromatography of the crude product on silica gel using 0-30% EtOAc in hexanes afforded 3 (65 mg, 53%) as an off-white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20 - 25℃; for 16h; | |
45% | With dmap; dicyclohexyl-carbodiimide In dichloromethane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; HATU In N,N-dimethyl acetamide at 20℃; for 1h; | 221 Example 221: 2-(4-chloro-3-fluorophenoxy)-iV-(4-{2-[4- (dimethylamino)phenyl]acetamido}-3-hydroxybicyclo[2.2.2]octan-l-yl)acetamide (Compound 320) Example 221: 2-(4-chloro-3-fluorophenoxy)-iV-(4-{2-[4- (dimethylamino)phenyl]acetamido}-3-hydroxybicyclo[2.2.2]octan-l-yl)acetamide (Compound 320) 4 mL vial was charged with a stir bar, a 500 solution of Example 1981 (47.74 mg, 0.13 mmol) in N,N-dimethylacetamide, a 395.7 of a 0.35 mmol pre-weighed vial with a solution of 2-(4-(dimethylamino)phenyl)acetic acid (25.2 mg, 0.14 mmol) in 1000 of NN- dimethylacetamide, a 500 μ. solution of 2-(3H-[l,2,3]triazolo[4,5-Z>]pyridin-3-yl)-l, 1,3,3- tetramethylisouronium hexafluorophosphate(V) (57.4 mg, 0.15 mmol) in NN- dimethylacetamide, and triethylamine (53.01 μ., 0.38 mmol). This was capped and placed to stir at room temperature for 1 hour. Upon completion the mixture was concentrated to dryness, and the residue was purified by reverse phase HPLC (Phenomenex Luna C8(2) 5 μιτι ΙΟθΑ AXIA column (50 mm χ 30 mm). A gradient of acetonitrile (A) and 0.1 % CF3C02H in H20 (B) was used at a flow rate of 40 mL/minute (0-0.5 minute 5% A, 0.5-6.5 minutes linear gradient 5-100% A, 6.5-8.5 minutes 100% A, 8.5-9.0 minutes linear gradient 100-5% A, 9.0- 10.0 minutes 5% A). Detection methods are diode array (DAD) under positive APCI ionization conditions.) to yield the title compound. l NMR (400 MHz, DMSO-ce) S ppm 7.47 (td, J = 8.9, 1.1 Hz, 1H), 7.43 - 7.32 (m, 3H), 7.36 - 7.26 (m, 1H), 7.00 (dd, J = 1 1.4, 2.9 Hz, 1H), 6.81 (ddd, J = 9.0, 3.0, 1.3 Hz, 1H), 4.43 (d, J = 6.5 Hz, 2H), 4.06 (dd, J = 8.6, 1.9 Hz, 1H), 3.50 - 3.34 (m, 2H), 3.10 (d, J = 5.9 Hz, 6H), 2.26 (ddd, J = 12.4, 9.2, 2.6 Hz, 1H), 2.01 - 1.71 (m, 9H); MS (ESI+) m/z 504.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: DL-leucine ethyl ester hydrochloride In chloroform at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: glycine ethyl ester hydrochloride In chloroform at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: ethyl pyrrolidine-2-carboxylate hydro chloride In chloroform at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine In chloroform at 0℃; for 0.5h; Stage #2: ethyl 2-amino-3-phenylpropanoate hydrochloride In chloroform at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | With 1H-imidazole at 100℃; for 1h; Microwave irradiation; | N-(Diaminomethylene)-2-(4-(dimethylamino)phenyl)acetamide hydrochloride (3e) The mixture of N-(diaminomethylene)-2-(4-(dimethylamino)phenyl carboxylic acid 2 (1 mM),guanidine hydrochloride (2 mM) and imidazole (1mM) was exposed to microwave irradiation withsolvent free condition (100OC), power of MW oven(200 W) for 1 h (in 15 min intervals). The resultingcrude product (3e) extracted was purified by columnchromatography using solvents A system.Yield 21%; Rf = 0.87 (C);1H-NMR (CDCl3, δ,ppm): 8.83-8.71 (m, 5H), 8.67-8.52 (m, 3H), 3.94 (s,2H), 3.24 (s, 6H), 13C NMR (DSMO-d6, δ, ppm):169.36, 150.98, 144.61, 144.37, 142.06, 134.6,132.1, 114.9, 110.3, 41.0; ESI-MS (m/z) 221.27(M+H)+. Analysis: calcd for C11H17ClN4O0: C,51.45; H, 6.67; N, 21.82%; found: C, 51.24; H, 6.63;N, 21.74%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dicyclohexyl-carbodiimide In N,N-dimethyl-formamide at 50℃; for 22h; | 1.g; 1.h; 1.i; 1.j; 1.k; 1.l g) The first step of the dimethylation reaction product was transferred to a clean 25 mL round bottom flask, and the water was directly removed using a rotary evaporator (rotational evaporation condition: 50 ° C, 60 rpm);h) Weigh 12 mg of N-hydroxysuccinimide (NHS) and 30 mgN,N-dicyclohexylcarbodiimide (DCC) is added to the round bottom flask;i) 4 mL of dry N,N-dimethylformamide (DMF) (LC-MS grade) was added to the round bottom flask;j) stirring and heating in an oil bath, the temperature is controlled at 50 ° C,Control the rotation speed of 1000 rpm (the reaction equation is as follows);k) the reaction time is 22h;l) Freeze centrifugation, stored at -18 ° C for cryopreservation for labeling reactions. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium cyanoborohydride In water for 0.00277778h; Sonication; | 1.a; 1.b; 1.c; 1.d; 1.e; 1.f a) directly weigh 10 mg (0.066 mmol) of p-aminophenylacetic acid using a 1.5 mL centrifuge tube;b) dissolving p-aminophenylacetic acid with 500 μL of ultrapure water,It can be dissolved by oscillating or ultrasonic means;c) Add 7.4% CH2O 100μL, mix well during the shock period of 10s;d) adding 0.6 mol/L of catalyst NaBH3CN 150 μL,The shock is fully mixed during the 10s period;e) using 0.5% formic acid (FA) to control the solution pH=5,And make up to 1mL with ultrapure water;f) Reaction at room temperature, 500 rpm for 1 h.Through the above six steps, a total of p-dimethylaminophenylacetic acid can be obtained.(The reaction equation is as follows); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In N,N-dimethyl acetamide at 20℃; for 1h; Sealed tube; | 221 Example 221: 2-(4-chloro-3-fluorophenoxy)-N-(4-{2-[4-(dimethylamino)phenyl]acetamido}-3-hydroxybicyclo[2.2.2]octan-l-yl)acetamide(Compound 320) A 4 mL vial was charged with a stir bar, a 500 μL· solution of Example 1981 (47.74 mg, 0.13 mmol) in N,N-dimethylacetamide, a 395.7 μL· of a 0.35 mmol pre-weighed vial with a solution of 2-(4-(dimethylamino)phenyl)acetic acid (25.2 mg, 0.14 mmol) in 1000 μL· of N,N- dimethylacetamide, a 500 μL· solution of 2-(3H-[l,2,3]triazolo[4,5-]pyridin-3-yl)- l , 1 ,3,3- tetramethylisouronium hexafluorophosphate(V) (57.4 mg, 0.15 mmol) in N,N- dimethylacetamide, and triethylamine (53.01 μ., 0.38 mmol). This was capped and placed to stir at room temperature for 1 hour. Upon completion the mixture was concentrated to dryness, and the residue was purified by reverse phase HPLC (Phenomenex Luna C8(2) 5 μπι 100A AXIA column (50 mm x 30 mm). A gradient of acetonitrile (A) and 0.1 % CF3C02H in H20 (B) was used at a flow rate of 40 mL/minute (0-0.5 minute 5% A, 0.5-6.5 minutes linear gradient 5- 100% A, 6.5-8.5 minutes 100% A, 8.5-9.0 minutes linear gradient 100-5% A, 9.0-10.0 minutes 5% A). Detection methods are diode array (DAD) under positive APCI ionization conditions.) to yield the title compound.JH NMR (400 MHz, DMSO-+) m/z 504.1 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With pyridine; dicyclohexyl-carbodiimide In dichloromethane at 20 - 25℃; for 20h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h; | |
70% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h; | 1261.4 Step 4: Preparation of rac-N-((3R,4S)-1-benzyl-4-(4-(trifluoromethyl)phenyl)pyrrolidin-3-yl)-2-(4-(dimethylamino)phenyl)acetamide To a suspension of rac-(3R,4S)-1-benzyl-4-(4-(trifluoromethyl)phenyl)pyrrolidin-3-amine (430 mg, 1.25 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (269 mg, 1.50 mmol), HATU (570 mg, 1.50 mmol) in dichloromethane (10mL) was added trimethylamine (0.35 ml, 2.50 mmol). The reaction mixture was stirred at room temperature for 16 h. The mixture was diluted with dichloromethane (50 mL) and washed with satd-sodium carbonate solution then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate: 1/1) to give (420 mg, 70% yield) of the title compound as a white solid. MS: m+1=482.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h; | |
75% | With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate In dichloromethane at 20℃; for 16h; | 1397.4 Step 4: Preparation of N-((3S,4R)-1-benzyl-4-(4-(trifluoromethyl)phenyl)pyrrolidin-3-yl)-2-(4-(dimethylamino)phenyl)acetamide To a suspension of (3S,4R)-1-benzyl-4-(4-(trifluoromethyl)phenyl)pyrrolidin-3-amine (430 mg, 1.34 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (288 mg, 1.61 mmol), HATU (611 mg, 1.61 mmol) in dichloromethane (10mL) was added triethylamine (0.37 ml, 2.68 mmol). The reaction mixture was stirred at room temp for 16 h. The mixture was diluted with dichloromethane (50mL) and washed with satd sodium carbonate solution then brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash column chromatography (petroleum ether/ethyl acetate: 1/1) to give (483 mg, 75% yield) of the title compound as a white solid. MS: m+1=482.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | 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 0 - 20℃; | General procedure: To a solution of N-(5-(2-(5-amino-1,3,4-thiadiazol-2-yl)ethylthio)-1,3,4-thiadiazol-2-yl)-2-phenylacetamide 8 (770mg, 2.03mmol) in DMF (30mL) was added phenylacetic acid (304mg, 2.24mmol) and diisopropylethylamine (1.05g, 8.14mmol). The mixture was cooled to 0°C and HATU (773mg, 2.03mmol) was added. The reaction was allowed to warm to rt overnight, and the solvent was removed in vacuo. The resultant residue was taken up in DCM (100mL) and washed with 10% KHSO4, (50mL), sat’d NaHCO3 (50mL), and brine (50mL). The organic layer was dried over MgSO4, filtered, and concentrated. The residual product was triturated with 20% ethylacetate/hexanes to afford 450mg of 3a as a tan solid (45% yield) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85 mg | 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 acetamide at 20℃; for 18h; | 84 N-[4-(3-anilino-5-methyl-4-oxo-4,5,6,7-tetrahydro-1 H-pyrrolo[3,2-c]pyridin-2-yl)pyridin-2-yl]-2-[4-(dimethylamino)phenyl]acetamide A solution of 2-(2-aminopyridin-4-yl)-3-anilino-5-methyl-1 ,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one (see Intermediate 3, 0.1 g, 0.30 mmol, 1 eq) in DMA (2 ml.) was treated with N,N-diisopropylethylamine (0.37 mL, 7 eq; CAS-RN:[7087-68-5]), [4-(dimethylamino)phenyl]-acetic acid (161 mg, 3 eq), and benzotriazol-1- yloxytripyrrolidinophosphonium hexafluorophosphate (0.468 g, 3 eq; CAS-RN:[128625-52-5]), and stirred for 18 h at r.t..OThen a sodium bicarbonate solution in water was added, and the mixture was extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate), filtered, concentrated under reduced pressure, and purified by column chromatography (column silica gel, 25 g, gradient: ethanol/dichloromethane 0-12%), and triturated with hexane to give 85 mg of the title compound as a yellow solid.LC-MS (Method 2): Rt= 1.14 min; MS (ESIpos): m/z = 495 [M+H]+1H NMR (400 MHz, DMSO-d6) d ppm 2.85 (s, 6 H) 2.86 (s, 3 H) 2.91 (t, 2 H) 3.54 (s, 4 H) 6.53 - 6.58 (m, 2 H) 6.61 (t, 1 H) 6.66 - 6.70 (m, 2 H) 7.01 (dd, 2 H) 7.1 1 (dd, 1 H) 7.15 (d, 2 H) 7.35 (s, 1 H) 8.03 (d, 1 H) 8.19 (s, 1 H) 10.39 (s, 1 H) 11.73 (s, 1 H)). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid 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 0.25h; Stage #2: 6-(piperazin-1-yl)pyridazine-3-carbonitrile hydrochloride In N,N-dimethyl-formamide for 3h; | a a.SYNTHESIS OF PZ-4060 To a mixture of 4-(Dimethylamino)phenylacetic acid (100 mg, 0.558 mmol) and DIPEA (292 m, 1.674 mmol) in DMF (3 mL) at room temperature HATU (318 mg, 0.837 mmol) DIPEA (292 m, 1.674 mmol) were added and allowed to stirr for 15 min. then followed by addition of 6-(piperazin-1-yl)pyridazine-3-carbonitrile, HCl (139 mg, 0.614 mmol). The reaction mixture was stirred for 3 hrs. After completion of reaction the mixture was diluted with water (4 mL) and the seperated solids were collected by Liberation. The crude solid was purified by flash column chromatography using using a gradient of methanol in methylene chloride (0 to 15%) as eluant to afford title compound 6-(4-(2-(4- (dimethylamino)phenyl)acetyl)piperazin-l-yl)pyridazine-3-carbonitrile. 1H NMR (500 MHz, DMSO-d6) d 7.89 (d, J= 9.6 Hz, 1H), 7.34 (d , J= 9.7 Hz, 1H), 7.07 (d, J= 8.3 Hz, 2H), 6.68 (d, J= 8.3 Hz, 2H), 3.81 - 3.54 (m, 10H), 2.86 (s, 6H). 13C NMR (126 MHz, DMSO) d 170.26, 159.12, 149.60, 131.52, 129.78, 129.25, 123.30, 117.82, 113.01, 111.82, 45.05, 44.39, 44.15. ESI-MS (M+1): 352.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.49 g | With tetrabutylammomium bromide; potassium hydroxide at 80℃; for 6h; Inert atmosphere; | 1.2; 12 (2) Under Ar protection, add methyl 2-(4-aminophenyl)acetate (1.65g, 10mmol) and methyl p-toluenesulfonate (7.45g, 40mmol) into a 50mL flask, and add 2N KOH solution (30mL), warm to 80°C and stir, quickly add tetrabutylammonium bromide (0.13g, 0.4mmol), react for 6h, wait for the reaction solution to cool to room temperature, extract with ether, combine the organic phases, and dry with anhydrous magnesium sulfate Treatment, spin off most of the solvent, purify by silica gel column chromatography, eluting with ethyl acetate/petroleum ether (V/V=1:20) to obtain 2-(4-(dimethylamino)phenyl)acetic acid ( 1.49g), the yield was 83%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With tetrabutylammomium bromide; potassium hydroxide at 80℃; for 6h; Inert atmosphere; | 13 Example 13 Under Ar protection, in a 50mL flask, add methyl 2-(4-aminophenyl)acetate (1.65g, 10mmol), trimethyl phosphate (5.60g, 40mmol), add 2N KOH solution (30mL), and increase the temperature. After stirring at 80°C, tetrabutylammonium bromide (0.13g, 0.4mmol) was quickly added. After 6 hours of reaction, the reaction solution was cooled to room temperature, extracted with ether, and the organic phases were combined, dried over anhydrous magnesium sulfate, and removed by spinning. Part of the solvent was purified by silica gel column chromatography and eluted with ethyl acetate/petroleum ether (V/V=1:20) to obtain 2-(4-(dimethylamino)phenyl)acetic acid (1.31g) as The rate is 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With pyridine; potassium <i>tert</i>-butylate Reflux; | 4.1.3 Synthesis of (E)-3-styryl-4H-1-benzopyran-4-ones (1-24) General procedure: Compounds 2, 3, 5-8, 10, 11, and 13-16 were synthesized as described in a previous report11. Compounds 1, 9, and 17 were synthesized using a previously reported method with a small modification, involuving the use of phenylmalonic acids. Briefly, the corresponding 3-formylchromone (II, 2mmol) and phenylmalonic acid (IIIa, 8mmol) were dissolved in dry pyridine (20mL). tert-BuOK (3mmol) was added to the solution, and the mixture was refluxed until complete disappearance of 3-formylchromone. After the reaction mixture was diluted with ice-water and acidified to pH 4 with 5M HCl, the sample was extracted with CHCl3. The combined organic layer was washed with a saturated NaHCO3 solution followed by brine. The organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-AcOEt solvent system) to obtain the corresponding 3-styryl-4H-1-benzopyran-4-one derivative. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With pyridine; potassium <i>tert</i>-butylate Reflux; | 4.1.3 Synthesis of (E)-3-styryl-4H-1-benzopyran-4-ones (1-24) General procedure: Compounds 2, 3, 5-8, 10, 11, and 13-16 were synthesized as described in a previous report11. Compounds 1, 9, and 17 were synthesized using a previously reported method with a small modification, involuving the use of phenylmalonic acids. Briefly, the corresponding 3-formylchromone (II, 2mmol) and phenylmalonic acid (IIIa, 8mmol) were dissolved in dry pyridine (20mL). tert-BuOK (3mmol) was added to the solution, and the mixture was refluxed until complete disappearance of 3-formylchromone. After the reaction mixture was diluted with ice-water and acidified to pH 4 with 5M HCl, the sample was extracted with CHCl3. The combined organic layer was washed with a saturated NaHCO3 solution followed by brine. The organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-AcOEt solvent system) to obtain the corresponding 3-styryl-4H-1-benzopyran-4-one derivative. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With pyridine; potassium-t-butoxide Reflux; | 4.1.3 Synthesis of (E)-3-styryl-4H-1-benzopyran-4-ones (1-24) General procedure: Compounds 2, 3, 5-8, 10, 11, and 13-16 were synthesized as described in a previous report11. Compounds 1, 9, and 17 were synthesized using a previously reported method with a small modification, involuving the use of phenylmalonic acids. Briefly, the corresponding 3-formylchromone (II, 2mmol) and phenylmalonic acid (IIIa, 8mmol) were dissolved in dry pyridine (20mL). tert-BuOK (3mmol) was added to the solution, and the mixture was refluxed until complete disappearance of 3-formylchromone. After the reaction mixture was diluted with ice-water and acidified to pH 4 with 5M HCl, the sample was extracted with CHCl3. The combined organic layer was washed with a saturated NaHCO3 solution followed by brine. The organic layer was dried over Na2SO4, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane-AcOEt solvent system) to obtain the corresponding 3-styryl-4H-1-benzopyran-4-one derivative. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With dmap; diisopropyl-carbodiimide In tetrahydrofuran at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: 2-[4-(dimethylamino)phenyl]acetic acid; 3-Ode-[(2,6-dideoxy-3-methyl-3-O-methyl-α-L-ribohexopyranosyl)oxy]-6-O-methylerythromycin 2¢-acetate With dmap In dichloromethane at 20℃; Stage #2: In methanol at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
19% | 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 5h; | 97.1 Step 1. 1-(1-(2-(4-(dimethylamino)phenyl)acetyl)piperidin-4-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (GEN1-118) Compound 1-(piperidin-4-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (71 mg, 0.25 mmol), HATU (140 mg, 0.37 mmol), DIEA (129 mg, 1.00 mmol) were dissolved in DMF (1.5 mL) and 2-(4-(dimethylamino)phenyl)acetic acid (46 mg, 0.25 mmol) was added. After the addition, the resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was added dropwise to water (50 mL) and the mixture was filtered to obtain a white solid. The crude product was purified by Prep-TLC (MeOH/(MeOH + DCM)=60%). The desired compound (21.1 mg, yield 19%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.45 (s, 1H), 7.36 (d, J = 8.2, 1H), 7.27 (d, J = 7.8 Hz, 1H), 7.16 (t, J = 7.9 Hz, 1H), 7.06 (d, J = 8.6 Hz, 2H), 6.67 (d, J= 8.4 Hz, 2H), 4.67 - 4.54 (m, 1H), 4.29-4.07 (m, 2H), 3.74-3.49 (m, 2H), 2.93 (t, J = 13.1 Hz, 1H), 2.86 (s, 6H), 2.56-2.51 (m, 1H), 2.49-2.33 (m, 2H), 1.75-1.59 (m, 2H). MS (ESI): Rt = 1.62 min, m/z 446.9 [M+H]+, Purity: 100% 254 nm, 100% 214 nm. |
With N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate | 97.1 Step 1. Step 1. 1-(1-(2-(4-(dimethylamino)phenyl)acetyl)piperidin-4-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (GEN1-118) Compound 1-(piperidin-4-yl)-7-(trifluoromethyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (71 mg, 0.25 mmol), HATU (140 mg, 0.37 mmol), DIEA (129 mg, 1.00 mmol) were dissolved in DMF (1.5 mL) and 2-(4-(dimethylamino)phenyl)acetic acid (46 mg, 0.25 mmol) was added. After the addition, the resulting mixture was stirred at room temperature for 5 hours. The reaction mixture was added dropwise to water (50 mL) and the mixture was filtered to obtain a white solid. The crude product was purified by Prep-TLC (MeOH/(MeOH + DCM)=60%). The desired compound (21.1 mg, yield 19%) was obtained as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.45 (s, 1H), 7.36 (d, J = 8.2, 1H), 7.27 (d, J = 7.8 Hz, 1H), 7.16 (t, J = 7.9 Hz, 1H), 7.06 (d, J = 8.6 Hz, 2H), 6.67 (d, J= 8.4 Hz, 2H), 4.67 - 4.54 (m, 1H), 4.29-4.07 (m, 2H), 3.74-3.49 (m, 2H), 2.93 (t, J = 13.1 Hz, 1H), 2.86 (s, 6H), 2.56-2.51 (m, 1H), 2.49-2.33 (m, 2H), 1.75-1.59 (m, 2H). MS (ESI): Rt = 1.62 min, m/z 446.9 [M+H]+, Purity: 100% 254 nm, 100% 214 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With anhydrous sodium carbonate; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate | 87.1 Step 1. Step 1. Synthesis of 1-(1-(2-(4-(dimethylamino)phenyl)acetyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (GEN1-097) HATU (263 mg, 0.692 mmol) was added to a solution of 3-(4-piperidinyl)-1H-benzimidazol-2-one (100 mg, 0.460 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (99 mg, 0.55 mmol) and DIEA (179mg, 1.38mmol) in DMF (1.5mL). The mixture was stirred at room temperature for 16 hours. The resulting mixture was purified by preparation. HPLC (Waters-Large-prep-2 Xbridge C18 5um 19 * 150mm, 2%-40%B; A: H2O(0.1%TFA), B: CH3CN; UV: 214 nm, flow rate: 15mL / min). Then saturated Na2CO3 was added to basify the solution to pH=8. The mixture was extracted with EtOAc (20 mL*3), and the combined organic layer was concentrated to obtain the desired compound (64 mg, yield 36%) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 10.82 (s, 1H), 7.12 (d, J= 8.8 Hz, 2H), 6.95-6.93 (m, 4H), 6.72 (d, J= 8.4 Hz, 2H), 4.57 (d, J= 12.4 Hz, 1H), 4.42-4.36 (m, 1H), 4.07 (d, J= 13.2 Hz, 1H), 3.70-3.58 (m, 2H), 3.14-3.08 (m, 1H), 2.85 (s, 6H), 2.68-2.62 (m, 1H), 2.05-1.96 (m, 1H), 1.91-1.83 (m, 1H), 1.66 (d, J = 11.6 Hz, 1H), 1.55 (d, J= 10.8 Hz, 1H). MS (ESI): Rt = 3.286 min, m/z 379.2 [M+H]+; Purity: 99.37% 254 nm, 99.34% 214 nm. |
36% | 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 16h; | 87.1 Step 1. Synthesis of 1-(1-(2-(4-(dimethylamino)phenyl)acetyl)piperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one (GEN1-097) HATU (263 mg, 0.692 mmol) was added to a solution of 3-(4-piperidinyl)-1H-benzimidazol-2-one (100 mg, 0.460 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (99 mg, 0.55 mmol) and DIEA (179mg, 1.38mmol) in DMF (1.5mL). The mixture was stirred at room temperature for 16 hours. The resulting mixture was purified by preparation. HPLC (Waters-Large-prep-2 Xbridge C18 5um 19 * 150mm, 2%-40%B; A: H2O(0.1%TFA), B: CH3CN; UV: 214 nm, flow rate: 15mL / min). Then saturated Na2CO3 was added to basify the solution to pH=8. The mixture was extracted with EtOAc (20 mL*3), and the combined organic layer was concentrated to obtain the desired compound (64 mg, yield 36%) as a white solid. 1HNMR (400 MHz, DMSO-d6): δ 10.82 (s, 1H), 7.12 (d, J= 8.8 Hz, 2H), 6.95-6.93 (m, 4H), 6.72 (d, J= 8.4 Hz, 2H), 4.57 (d, J= 12.4 Hz, 1H), 4.42-4.36 (m, 1H), 4.07 (d, J= 13.2 Hz, 1H), 3.70-3.58 (m, 2H), 3.14-3.08 (m, 1H), 2.85 (s, 6H), 2.68-2.62 (m, 1H), 2.05-1.96 (m, 1H), 1.91-1.83 (m, 1H), 1.66 (d, J = 11.6 Hz, 1H), 1.55 (d, J= 10.8 Hz, 1H). MS (ESI): Rt = 3.286 min, m/z 379.2 [M+H]+; Purity: 99.37% 254 nm, 99.34% 214 nm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With benzotriazol-1-ol | 3 Step 3. Step 3. Synthesis of 2-(4-(dimethylamino)phenyl)-1-(4-((2-nitrophenyl)amino)piperidin-1-yl)ethan-1-one (GEN1-121-3) EDCI (260 mg, 1.356 mmol) was added to a solution of N-(2-nitrophenyl)piperidin-4-amine (200 mg, 0.904 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (194.4 mg, 1.085 mmol), HOBT (183.2 mg, 1.356), DIEA (233.2 mg, 1.808 mmol) in DMF (5 mL). The resulting mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with water (300 mL), and it was extracted with EtOAc (100 mL*3). The combined organic phase was washed with brine (150 mL), dried over anhydrous Na2SO4 and it was filtered. The filtrate was concentrated to obtain the crude product (310 mg), which was used directly in the next step without purification. | |
With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 1h; | 99.3 Step 3. Synthesis of 2-(4-(dimethylamino)phenyl)-1-(4-((2-nitrophenyl)amino)piperidin-1-yl)ethan-1-one (GEN1-121-3) EDCI (260 mg, 1.356 mmol) was added to a solution of N-(2-nitrophenyl)piperidin-4-amine (200 mg, 0.904 mmol), 2-(4-(dimethylamino)phenyl)acetic acid (194.4 mg, 1.085 mmol), HOBT (183.2 mg, 1.356), DIEA (233.2 mg, 1.808 mmol) in DMF (5 mL). The resulting mixture was stirred at room temperature for 1 h. The reaction mixture was diluted with water (300 mL), and it was extracted with EtOAc (100 mL*3). The combined organic phase was washed with brine (150 mL), dried over anhydrous Na2SO4 and it was filtered. The filtrate was concentrated to obtain the crude product (310 mg), which was used directly in the next step without purification. |
Tags: 17078-28-3 synthesis path| 17078-28-3 SDS| 17078-28-3 COA| 17078-28-3 purity| 17078-28-3 application| 17078-28-3 NMR| 17078-28-3 COA| 17078-28-3 structure
[ 132864-53-0 ]
2-(3-(Dimethylamino)phenyl)acetic acid
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[ 1373223-10-9 ]
2-(3-(Dimethylamino)phenyl)acetic acid hydrochloride
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[ 132864-53-0 ]
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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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