Home Cart 0 Sign in  
X

[ CAS No. 109-83-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
3d Animation Molecule Structure of 109-83-1
Chemical Structure| 109-83-1
Chemical Structure| 109-83-1
Structure of 109-83-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 109-83-1 ]

Related Doc. of [ 109-83-1 ]

Alternatived Products of [ 109-83-1 ]

Product Details of [ 109-83-1 ]

CAS No. :109-83-1 MDL No. :MFCD00002839
Formula : C3H9NO Boiling Point : -
Linear Structure Formula :HNCH3(CH2CH2OH) InChI Key :OPKOKAMJFNKNAS-UHFFFAOYSA-N
M.W : 75.11 Pubchem ID :8016
Synonyms :

Calculated chemistry of [ 109-83-1 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 5
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 2.0
Molar Refractivity : 20.5
TPSA : 32.26 Ų

Pharmacokinetics

GI absorption : Low
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.43 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.19
Log Po/w (XLOGP3) : -0.94
Log Po/w (WLOGP) : -0.8
Log Po/w (MLOGP) : -0.63
Log Po/w (SILICOS-IT) : -0.54
Consensus Log Po/w : -0.35

Druglikeness

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

Water Solubility

Log S (ESOL) : 0.42
Solubility : 197.0 mg/ml ; 2.62 mol/l
Class : Highly soluble
Log S (Ali) : 0.75
Solubility : 419.0 mg/ml ; 5.58 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.42
Solubility : 28.4 mg/ml ; 0.378 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 109-83-1 ]

Signal Word:Danger Class:8
Precautionary Statements:P210-P260-P264-P270-P271-P273-P280-P301+P312+P330-P301+P330+P331-P303+P361+P353-P304+P340+P310-P305+P351+P338+P310-P314-P362+P364-P370+P378-P403+P233-P403+P235-P405-P501 UN#:2735
Hazard Statements:H227-H302+H312-H314-H335-H373-H402 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 109-83-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 109-83-1 ]
  • Downstream synthetic route of [ 109-83-1 ]

[ 109-83-1 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 109-83-1 ]
  • [ 131543-46-9 ]
  • [ 18424-96-9 ]
Reference: [1] Patent: US5066804, 1991, A,
[2] Bulletin de la Societe Chimique de France, 1994, vol. 131, p. 188 - 199
  • 2
  • [ 109-83-1 ]
  • [ 131543-46-9 ]
  • [ 18424-96-9 ]
  • [ 67992-27-2 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1978, vol. <II>, p. 83 - 88
  • 3
  • [ 109-83-1 ]
  • [ 74-88-4 ]
  • [ 38256-93-8 ]
Reference: [1] Phosphorus and Sulfur and the Related Elements, 1986, vol. 28, p. 327 - 336
  • 4
  • [ 109-83-1 ]
  • [ 24424-99-5 ]
  • [ 57561-39-4 ]
YieldReaction ConditionsOperation in experiment
100% at 20℃; for 1 h; To a solution of 2-(methylamino)ethanol (500 mg, 0.53 ml, 6.66 mmol) in CH2Cl2 (20 ml) was added Boc2O (1.48 g, 6.79 mmol), followed by stirring at room temperature for 1 hour.
The reaction solution was extracted with brine and CH2Cl2.
The organic layer thus obtained was dried over MgSO4 and filtered.
Then, the filtrate was concentrated in vacuo to obtain the object compound (colorless oil, quantitative);
1H NMR (200 MHz, CDCl3) δ 3.74 (q, J= 10.5, 5.2 Hz, 2H) 3.25 (t, J= 5.2 Hz, 2H) 2.91 (s, 3H) 1.45 (s, 9H);
mass spectrum m/e (relative intensity) 144 (20) 102 (24) 57 (70) 44 (100).
100% at 20℃; for 4 h; Example 38; N1-(3-Fluoro-4-(2-(1-(2-(methylamino)ethyl)-1H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(2-methoxyphenyl)malonamide (96); Step 1: tert-Butyl 2-hydroxyethyl(methyl)carbamate (97) (J. Med. Chem., 1999, 42, 11, 2008) To a solution of 2-(methylamino)ethanol (5.0 g, 67 mmol) in THF (50 ml) at RT was added Boc2O (15.7 g, 72 mmol) and the reaction mixture was stirred at RT for 4 hours. The reaction mixture was concentrated to dryness and the title compound 97 was used directly in the next step with no additional purification (11.74 g, 100percent yield). MS (m/z): 176.2 (M+H).
100% at 20℃; for 1 h; Preparation of l-2-[4-Bromo-2-(4-oxo-2-ftιioxo1hiazolidin-5-ylidenemefliyl)phenoxy]efliyl-3-efliyl-l- methylurea(Compoιmd 161)Step 1 : Synthesis of t-butyl2-hydroxyethylmethylcarbamate; To a solution of 2-(methylamino)ethanol (500 mg, 0.53 ml, 6.66 mmol) in CH2Cl2 (20 ml) was added BoC2O (1.48 g,6.79 mmol), followed by stirring at room temperature for 1 hour. The reaction solution was extracted with brine and CH2Cl2. The organic layer thus obtained was dried over MgSO4 and filtered. Then, the filtrate was concentrated in vacuo to obtain the object compound (colorless oil, quantitative);1HNMR (200 MHz, CDCl3) δ 3.74 (q, J= 10.5, 5.2 Hz, 2H) 3.25 (t, J= 5.2 Hz, 2H) 2.91 (s, 3H) 1.45 (s, 9H); mass spectrum m/e (relative intensity) 144 (20) 102 (24) 57 (70) 44 (100).
100% at 0 - 20℃; for 3 h; 2-(methylamino)ethanol (90.1 g, 1.2 mol) was dissolved in 1.2 L of methylene chloride, and BoC2O (218 g, 1 mol) was slowly added thereto while stirring at 00C, followed by at room temperature for 3 hours. The reaction mixture was sequentially washed with 700 mL of an aqueous solution of saturated ammonium chloride, and 300 mL of water. The washed mixture was dehydrated using anhydrous sodium sulfate and concentrated under a reduced pressure, to obtain the compound (a) (175 g, 1 mol, 100percent) as an oil with no color.TLC : Rf = 0.5 (50percent EtOAc in Hex) visualized with Ce-Mo stain1H NMR (600MHz, CDCl3) δ 1.47 (s, 9H), 2.88 (br s, IH), 3.41 (br s, 2H), 3.76 (br s, 2H)
100% at 0 - 20℃; for 3 h; 90.1 g (1.2 mol) of 2-(methylamino)ethanol was dissolved in 1.2 L of methylene chloride, 218 g (1 mol) of Boc2O was slowly added thereto while the resulting solution was stirred at 0°C, and the resulting solution was stirred at room temperature for 3 hours. The reaction mixture was sequentially washed with 700 mL of an aqueous saturated ammonium chloride solution and 300 mL of water, dehydrated using anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 175 g (1 mol) of an achromic oil compound protected by the Boc group (yield: 100percent). [0140] 1H NMR (600MHz, CDCl3) δ 7.84 (br s, 2H), 7.76 (br s, 2H), 4.34 (d, J = 15.0 Hz, 2H), 3.63 (br s, 2H), 3.04 (d, J = 15.0 Hz, 3H), 1.46 (d, J = 16.2 Hz, 9H) [0141] 90 g (0.514 mol) of the obtained compound was dissolved in 1.5 L of tetrahydrofuran, 88.0 g (539 mol) of N-hydroxyphthalimide and 141 g (0.539 mol) of triphenylphosphine were added thereto, 106 mL (0.539 mol) of diisopropyl azodicarboxylate was slowly added thereto while stirring the resulting solution at 0°C, and the resulting solution was stirred for 3 hours while the temperature thereof was raised to room temperature. After concentration of the reaction mixture under reduced pressure, 600 mL of isopropylether was added thereto, the resulting solution was stirred at 0°C for 1 hour, and white solid-type triphenylphosphine oxide was filtered. The solid was washed with 200 mL of isopropylether cooled to 0°C and collected with the first filtrate, and the resulting filtrate was concentrated under reduced pressure to obtain 198 g of a mixture of Compound XX and diisopropyl hydrazodicarboxylate in a mixing ratio of 10 to 15percent (yield: 120percent). [0142] 1H NMR (600MHz, CDCl3) δ 7.84 (br s, 2H), 7.76 (br s, 2H), 4.34 (d, J = 15.0 Hz, 2H), 3.63 (br s, 2H), 3.04 (d, J = 15.0 Hz, 3H), 1.46 (d, J= 16.2 Hz, 9H)
100% at 0 - 20℃; Preparation of Compound XX 90.1 g (1.2 mol) of 2-(methylamino)ethanol was dissolved in 1.2 L of methylene chloride, 218 g (1 mol) of Boc2O was slowly added thereto while the resulting solution was stirred at 0° C., and the resulting solution was stirred at room temperature for 3 hours. The reaction mixture was sequentially washed with 700 mL of an aqueous saturated ammonium chloride solution and 300 mL of water, dehydrated using anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain 175 g (1 mol) of an achromic oil compound protected by the Boc group (yield: 100percent). [0152] 1H NMR (600 MHz, CDCl3) δ 7.84 (br s, 2H), 7.76 (br s, 2H), 4.34 (d, J=15.0 Hz, 2H), 3.63 (br s, 2H), 3.04 (d, J=15.0 Hz, 3H), 1.46 (d, J=16.2 Hz, 9H)
100% With triethylamine In dichloromethane at 20℃; for 16 h; Boc2O (8.0 g, 36.6 mmol, 1.1 eq.) and triethylamine (6.75 g, 66.5 mmol, 2.0 eq.) were added to a solution of 2-(methylamino)ethanol (2.5 g, 33.3 mol, 1.0 eq.) in dichloromethane (50 mL).
The reaction was stirred at 20° C. for 16 hours and washed with water (30 mL*2) and brine (30 mL).
The organic phase was dried over anhydrous sodium sulfate, and concentrated to give the title compound (5.8 g, yield: 100percent).
99% at 20℃; for 3 h; Cooling with ice In a 100 mL round-bottom flask, 1.1 mL (13.62 mmol) of 2-(methylamino)ethanol were dissolved in 10 mL of anh. dichloromethane. The reaction flask was then cooled in an ice bath and a solution of 2.5 g (11.4 mmol) of Boc anhydride in 3.6 mL of dichloromethane was added. The reaction mixture was stirred for 3 h at rt. Afterwards, dichloromethane was added to the crude reaction mixture and the organic phase was washed first with 8 mL of a saturated solution of NH4Cl and then with 4 mL of water. The organic phase was washed over anh. Na2SO4, filtered, and concentrated under reduced pressure to yield 1.97 g of 2-[N-(tert-Butyloxycarbonyl)-N-methylamino]ethanol as a colorless oil in 99percent yield. Rf=0.4 (Hex: EtOAc (1:1)). 1H NMR (300MHz, CDCl3) δ (ppm): 3.72 (t, 2H, J=5.2 Hz, H1), 3.37 (d, 2H, J=5.4 Hz, H2), 2.90 (s, 3H, N CH3), 2.59 (br s, 1H, OH), 1.44 (s, 9H, 3 x CH3, tBu); 13C NMR (75 MHz, CDCl3) δ (ppm): 157.1 (CO), 79.7 (Cq, t-Bu), 61.1 (C1), 51.2 (C2), 35.3 (N-CH3), 28.0 (3 x CH3, tBu).
97% With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 4.5 h; A 100 mL round-bottomed flask (rbf) equipped with a magnetic stirbar was charged withTHF (15 mL), water (15 mL) and 2-(methylamino)ethanol (2.00 mL, 25.0 mmol). To thestirred solution exposed to air Boc2O (5.9 g, 27 mmol) was added in 4 portions within 10min resulting in gas evolution. Several drops of sat. aq. NaHCO3 were added 40 min laterto keep the pH around 8. Most of THF was removed on a rotary evaporator 4.5 h after theBoc2O addition. The residue was transferred into a separatory funnel using EtOAc,washed with aq. 2.5 M NH4Cl (20 mL) and brine. The organic phase was dried overMgSO4, filtered into a 500 mL rbf and stripped of volatiles on the rotary evaporator.Using hexane transferred the crude product into a pre-weighed 100 mL rbf, removedvolatiles on the rotary evaporator (20 mm Hg). N-Methyl-N-Boc-aminoethanol wasobtained as colorless oil: 4.26 g (97percent). A 3-neck rbf equipped with a magnetic stirbar, arubber septum, a glass stopcock (Teflon tape, central neck) and connected to a vacuumline was charged with 4.26 g of the protected amine (24.3 mmol). After evacuation andrefill with nitrogen 90 mL of THF freshly distilled from sodium-benzophenone ketyl wasadded. The flask was placed in an ice-water bath. Approx. 25 min later quickly added1.09 g of 60percent NaH (27.2 mmol) in paraffin via the central neck. Approx. 20 min lateradded allyl bromide (2.15 mL, 24.8 mmol) with a syringe via the rubber septum followedby 0.4487 g of tetrabutylammonium iodide (1.21 mmol, 5 molpercent) via the central neck.Approx. 2.5 h later removed the cold bath and let the reaction mixture stirring for 16 hunder nitrogen. The flask was immersed in ice-water bath followed by careful addition ofwater (20 mL, audible sound). The mixture was transferred into a 250 mL separatoryfunnel followed by addition of EtOAc (50 mL) and extraction. The organic phase was setaside and the aqueous phase was extracted with fresh portion of EtOAc (40 mL). Theorganic phases were combined, washed with aq. 2.5 M NH4Cl (50 mL) and brine, driedover MgSO4, filtered into a 500 mL rbf and stripped of volatiles on the rotary evaporatorleaving behind yellow oil, which was chromatographed on silica (normal phase, EtOAchexane,1:3) furnishing 3.7916 g of N-Methyl-N-Boc-aminoethanol O-allyl ether ascolorless oil (72percent yield). N-Boc deprotection was achieved according to the method ofStrazzolini et al.1 To a 200 mL rbf charged with a magnetic stirbar and CH2Cl2 (22 mL)and immersed in an ice-water bath added 1.48 mL of conc. H2SO4 (assumed to be 17.9 M,26.5 mmol) with stirring. The central neck was plugged with a glass stopcock while adropping funnel was attached to the side-neck. A solution of 3.79 g of N-Methyl-N-BocaminoethanolO-allyl ether (17.6 mmol) in 65 mL CH2Cl2 was added to the solution ofacid dropwise from the addition funnel within 45 min followed by removal of cold bathand stirring at rt for 6 h. The dark purple mixture was transferred into a separatory funneland extracted with water (40 mL). The organic phase was extracted with additional 40mL of water, after which the aqueous extracts were combined in a 200 mL Erlenmeyerflask and basified by addition of NaOH (3.245 g in 15 mL water) with stirring. Theresulting solution was saturated with NaCl and extracted with three 50 mL portions ofCH2Cl2. Combined extracts were dried over Na2SO4, filtered into a 500 mL rbf andstripped of the solvent on the rotary evaporator (200 mm Hg). The resulting yellowish oilwas fractionated in vacuo using a one-piece distillation head and a receiving flask held at-50 °C. The title compound was obtained as colorless oil (1.2208 g, 60percent yield).
97% at 20℃; for 0.166667 h; N-methylethanol (6.0 g, 0.08 mol) was added to alumina (12.4 g, 0.12 mol). Then 9.6 g (0.09 mol, 1 .1 eq) of (Boc) 2O were added. The reaction was stirred for 10 min at room temperature. The residue was diluted in EtOAc (2x150 mL), filtered and evaporated. Mono protected compound (13.6 g, 97percent) was obtained as an oil. Rf : 0.25 (cyclohexane/EtOAc 8:2). 1H NMR (300 MHz, CDCl3): 3.72 (t, 2H, J = 5,2 Hz, H2), 3.37 (d, 2H, J = 5,4 Hz, H1 ), 2.90 (s, 3H, H3), 2.59 (bs, 1 H, OH), 1 .44 (s, 9H, (CH3)3). 13C NMR (75 MHz, CDCl3) : 157.1 (C4), 79,7 (C(CH3)3), 61 .1 (C2), 51 .2 (C1 ), 35.3 (C3), 28.0 ((CH3)3). MS (IC/NH3): m/z = 176 [M+H]+
97% With aluminum oxide In ethyl acetate at 20℃; for 0.166667 h; A.
Synthesis of 2-[N-(tert-butyloxycarbonyl)-N-methylamino]ethanol
N-methylethanol (6.0 g, 0.08 mol) was added to alumina (12.4 g, 0.12 mol).
Then 9.6 g (0.09 mol, 1.1 eq) of (Boc) 20 were added.
The reaction was stirred for 10 min at room temperature.
The residue was diluted in EtOAc (2x150 mL), filtered and evaporated.
Mono protected compound (13.6 g, 97percent) was obtained as an oil.
Rf : 0.25 (cyclohexane/EtOAc 8:2).
1H NMR (300 MHz, CDCl3): 3.72 (t, 2H, J = 5,2 Hz, H2), 3.37 (d, 2H, J = 5,4 Hz, H1), 2.90 (s, 3H, H3), 2.59 (bs, 1H, OH), 1.44 (s, 9H, (CH3)3).
13C NMR (75 MHz, CDCl3) : 157.1 (C4), 79,7 (C(CH3)3), 61.1 (C2), 51.2 (C1), 35.3 (C3), 28.0 ((CH3)3).
MS (IC/NH3): m/z = 176 [M+H]+.B. Synthesis of 2-[N-(tert-butyloxycarbonyl)-N-methylamino]ethanol [0128] N-methylethanol (6.0 g, 0.08 mol) was added to alumina (12.4 g, 0.12 mol). Then 9.6 g (0.09 mol, 1.1 eq) of (Boc)2O were added. The reaction was stirred for 10 min at room temperature. The residue was diluted in EtOAc (2x150 mL), filtered and evaporated. Mono protected compound (13.6 g, 97percent) was obtained as an oil. Rf : 0.25 (cyclohexane/EtOAc 8:2).1H NMR (300 MHz, CDCl3): 3.72 (t, 2H, J = 5,2 Hz, H2), 3.37 (d, 2H, J = 5,4 Hz, H1), 2.90(s, 3H, H3), 2.59 (bs, 1H, OH), 1.44 (s, 9H, (CH3)3).13C NMR (75 MHz, CDCl3) : 157.1 (C4), 79,7 (C(CH3)3), 61.1 (C2), 51.2 (C1), 35.3 (C3), 28.0 ((CH3)3).MS (IC/NH3): m/z = 176 [M+H]+.
97% With aluminum oxide In dichloromethane at 20℃; for 0.166667 h; Inert atmosphere N-methylethanol (6.0 g, 0.08 mol) was added to alumina (12.4 g, 1.5 eq), followed by (Boc)2O (9.6 g, 1.1 eq) in DCM (150 mL). The reaction was stirred for 10 min at room temperature. The residue was diluted in EtOAc, filtered and evaporated. Mono-protected compound (13.6 g, ρ=97percent) was obtained as an oil. Rf (EtOAc/Cyclohexane 20percent)=0.25 1H NMR (300MHz, CDCl3): 3.72 (t, 2H, J=5.2Hz), 3.37 (d, 2H, J=5.4Hz), 2.90 (s, 3H), 2.59 (bs, 1H), 1.44 (s, 9H). 13C NMR (75MHz, CDCl3): 157.1, 79.7, 61.1, 51.2, 35.3, 28.0. MS (IC+): m/z=176 [M+H+], calculated 176.
97% at 0 - 20℃; A solution of 2-(methylamino)ethanol (9.01 g, 120 mmol, 1.20 eq.) in dichloromethane (50 mL) was cooled to 0 °C followed by dropwise addition of a solution of di-tert-butyl dicarbonate (21.83 g, 100.00 mmol, 1.00 eq.) in dichloromethane (40 mL) over a period of 1 h. The reaction mixture was stirred overnight at room temperature. After removal of the solvent under reduced pressure, brine (35 mL) was added and the resulting aqueous phase was extracted with ethyl acetate (5 × 30 mL). The collected organic layers were washed with brine (2 × 30 mL) and dried over MgSO4. Removal of the solvent under reduced pressure afforded BocN-MP as a pale yellow oil (17.00 g, 97.02 mmol, 97percent). 1H-NMR (300 MHz, CDCl3, 300 K): δ (ppm) = 1.45 (s, 9H, C(CH3)3), 2.91 (s, 3H, NCH3), 3.38 (t, 2H, HOCH2CH2N), 3.73 (t, 2H, HOCH2CH2N).
97%
Stage #1: for 0.666667 h;
Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water at 20℃; for 4.5 h;
Di-tert-butyl dicarbonate (5.9 g, 27.03 mmol) was added to the mixture in THF, distilled water and 2-methylamino ethanol (2 ml, 24.90 mmol) After stirring for 40 minutes, saturated aqueous NaHCO3 solution was added to adjust pH to 8. Thereafter, the mixture was stirred at room temperature for 4 hours and 30 minutes. The reaction was terminated by evaporation of THF, followed by addition of EtOAc, washing with 2.5 M Ammonium chloride and aqueous NaCl solution, and drying over MgSO4. EtOAc was evaporated and redissolved in hexane and evaporated, and the reaction product (Boc-methylamino ethanol) was dried in a vacuum oven (yield = 97percent).
92% With triethylamine In dichloromethane at 20℃; for 2 h; Synthesis of 219.1 To a solution of 2-(methylamino)ethanol (750 mg, 10 mmol, 1.0 eq) and Et3N (1.1 g, 11 mmol, 1.1 eq) in DCM (100 mL), Boc20 (2.3 g, 10.5 mmol, 1.05 eq) was added. The mixture was stirred at room temperature for 2 h and then washed with H20 (80 mL x 3). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 219.1 (1.6 g, yield: 92percent) as a yellow oil; ESI-MS (M+H)+: 176.2.
90% at 20℃; for 2 h; Cooling with ice bath Example 82Synthesis of te/*-butyl 2-(4-isocyanatophenoxy)ethyl(methyl)carbamate[00236] To a mixture 2-(methylamino) ethanol (5.0 g, 66.5 mmol) in 15ml of ethyl acetate was added a solution of (BoC)2O (14.5 g, 66.5 mmol) in 5 mi of ethyl acetate dropwise with cooling in an ice bath The resulting mixture was stirred at room temperature for 2 hours, and the solvent was removed by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, dried over Na^SO4 and filtered. After removing the solvent, the crude tert-butyl 2-hydroxyethyl(methyl)carbamate was used without further purification for the next reaction (10.5 g, 90percent) A solution of diisopropyl azodicarboxylate (5.22 g, 25.9 mmol) in 5 ml of THF was added dropwise to a solution of 4-nitryl phenol (3.0 g, 21 56 mmol), tert-butyl 2-hydroxyethyl(methyl)carbamate (4.53 g, <n="101"/>25.9 minol) and triphenylphosphine (6.78 g, 25.9 mtnol) in 60 ml of THF with ice-bath cooling under nitrogen atmosphere. The resulting mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure by evaporation. The residue was mixed with ether and filtered. The filtrate was concentrated and purified by flashing silica gel column (Petroleum ether/Ethyl acetate=10/l~8/l) to afford the intermediate /ert-butyl methyl(2-(4-nitrophenoxy)ethyl)carbamate (2.48 g. 39percent) To a solution of this intermediate tert-butyl methyl(2-(4- nitrophenoxy)ethyl)carbamate (2.48 g, 8.4 mmol) in methanol was added Pd/C under hydrogen atmosphere. The mixture was heated to 50 0C for 1 hour, and then cooled down to room temperature and filtered. The filtrate was concentrated to give the crude tert-butyl 2-(4-amuiophenoxy)ethyl(methyl)carbamate which was used without further purification for the next reaction (2.10 g, 95percent). To a solution of tπphosgene (206 mg, 0.695 mmol) in DCM was added tert-butyl 2-(4-aminophenoxy)ethyl(methyl)carbamate (500 mg, 1.88 mmol) with ice-bath cooling followed by dropwise addition of TEA (380 mg, 3,76 mmol). After that, the mixture was stirred at room temperature for 2 hours. Tbe solvent was removed under reduced pressure without heating. The residue mixed with ether and filtered, The filtrate was concentrated to give tert-butyl 2-(4-isocyanatophenoxy)ethyl(methyI)carbamate (500 mg).
86% at 20℃; for 2 h; Step 1:
To a mixture of 2-(methylamino)ethanol (5.0 g, 66.6 mmol) in DCM (100 mL) was added a solution of (Boc)2O (15.0 g, 67.9 mmol) in DCM (20 mL).
The mixture was stirred at rt for 2 h, diluted with EA (100 mL) and washed with water.
The organic layer was separated, dried over Na2SO4, filtered and concentrated to give tert-butyl 2-hydroxyethyl(methyl)carbamate 112a (10.0 g, 86percent) as colorless oil.
78% at 0 - 20℃; for 2 h; A solution of Boc2O (5.80 g, 26.6 mmol) in dry EtOAc (10 ml) was added dropwise to a 0 °C cooled solution of 2-(methylamino)ethanol (2.14 ml, 26.6 mmol) in dry EtOAc (9 ml).
The mixture was stirred at room temperature for 2 h, and then concentrated under reduced pressure.
The oil residue was partitioned between EtOAc (100 ml) and water (300 ml), and the collected organic phases dried over anhydrous Na2SO4, filtered and evaporated in vacuum to furnish t-butyl 2-hydroxyethyl(methyl)carbamate in 78percent yield (3.66 g) of as a colorless oil. IR (liquid film, cm-1): 3444, 2977, 1673, 1394, 1225, 1156, 1074, 877, 774. 1H NMR (CDCl3) δ 3.72-3.80 (m 3H), 3.40 (t, J = 5.0, 2H), 2.92 (s, 3H), 1.47 (s, 9H).
66% With dmap; triethylamine In dichloromethane at 20℃; for 17 h; A mixture of 2-(methylamino)ethanol (2.0 g, 27 mmol), triethylamine (4.4 mL, 33 mmol), di-tert-butyl dicarbonate (6.1 g, 28 mmol) and 4-dimethylaminopyridine (160 mg, 1.3 mmol) in CH2C12 (200 mL) was stirred at ambient temperature. After 17 h, the reaction mixture was diluted with H20 (50 mL). The aqueous layer was separated and extracted with CH2Cl2 (25 mL). The combined organic layers were washed with saturated NaCl (25 mL) , dried (Na2S04) and concentrated under reduced pressure. Purification by column chromatography (silica gel, 75: 25 CH2Cl2/MeOH) gave tert-butyl (2- hydroxyethyl) methylcarbamate (3.1 g, 66percent) as a colorless oil: 1H NMR (300 MHz, DMSO-d6) 81.38 (9H, s), 2.80 (3H, br s), 3.17 (2H, t, J = 8.8 Hz), 3.42-3.48 (2H, m), 4.65 (1H, br s).
62% With dmap In acetonitrile at 20℃; for 16 h; A mixture of 2-methylamino-ethanol (2.5 g; 33.3 mmol; 1 eq.), di-tert-butyl dicarbonate (7.99 g; 36.6 mmol; 1.1 eq.) and dimethyl-pyridin-4-yl-amine (813 mg; 6.66 mmol; 0.2 eq.) in ACN (50 mL) and the resulting mixture was stirred at room temperature for 16 hours. After dilution with EA, the solution was washed with sat. aq. NH4CI, dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography (25percent to 70percent EA in cyclohexane) afforded the title compound (4 g, 62percent) as a colourless oil. 1H NMR (DMSO-de) δ 4.70-4.61 (m, 1 H), 3.46 (q, J = 5.8 Hz, 2H), 3.18 (t, J = 6.1 Hz, 2H), 2.80 (br s, 3H), 1.38 (br s, 9H).
13.29 g at 20℃; for 48 h; Inert atmosphere 2-(Methylamino)ethanol (5.32 ml, 66.6 mmol) was dissolved in dry dichioromethane (DCM) (30 ml). Boc2O (17.00 ml, 73.2 mmol) was added portion-wise and reaction mixture stirred under N2 at rt. The reaction mixture was left stirring at rt for a further 2 days. The reaction mixture was diluted with water, the organic layer separated and the aq. layer further extracted with DCM. The combinedorganic layers were dried (Na2SO4) and concentrated to give the product (13.29 g, 76 mmol, 114percent)as a colourless oil. LCMS (2 mm Formic): Rt = 0.66 mi [MH] = 176.
6.6 g With potassium carbonate In water at 20℃; for 16 h; To a stirred suspension of 2-(methylamino)ethanol (5.0 g) in water (75 mL)was added potassium carbonate (15.3 g) and di-tert-butyl dicarbonate (12.1 g)and the mixture was stirred at room temperature for 16 hours. The mixture was extracted with dichloromethane. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Aminophase-silica-gel chromatography gave 6.6 g of thetitle compound.
66.19 g at 20℃; for 2 h; Cooling with ice Reference Example 1 tert-Butyl 2-hydroxyethyl(methyl)carbamate (0384) (0385) To a mixture of 2-(methylamino)ethanol (30.04 g) and ethyl acetate (90 mL) was dropwise added a mixture of di-tert-butyl dicarbonate (87.30 g) and ethyl acetate (10 mL) under ice-cooling. After stirring at room temperature for 2 hrs., the mixture was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (150 mL), washed with water (100 mL) and dried over anhydrous magnesium sulfate. Concentration under reduced pressure gave the title compound (66.19 g) as a colorless oil. (0386) 1H-NMR (CDCl3): 1.47 (9H, s), 2.92 (3H, s), 3.40 (2H, t, J=5.1 Hz), 3.72-3.80 (2H, m).
2.4 g With triethylamine In dichloromethane at 20℃; TEA (3.52 mL, 25.00 mmol) was added to a solution of Boc2O (3.00 g, 13.77 mmol) and 2-(methylamino)ethanol (1.00 mL, 12.52 mmol) in DCM (80 ml) and stirred at rt overnight. The mixture was washed with brine, dried on MgSO4, filtrated and concentrated to afford 2.40 g of intermediate 158 (colorless oil).
20 g at 25℃; for 16 h; To a solution of 2-(methylamino)ethanol (10 g, 133.14 mmol) in DCM (10 mL) was added B0C2O (34.87 g, 159.77 mmol) at 25 °C. The mixture was stirred at 25°C for 16 hrs and then concentrated. The residue was purified by column chromatography to afford ie/t-butyl N-(2- hydroxyethyl)-N-methyl-carbamate (20 g, Compound BE-1) as a colorless oil.

Reference: [1] Journal of Organic Chemistry, 2000, vol. 65, # 20, p. 6368 - 6380
[2] Patent: US2009/42872, 2009, A1, . Location in patent: Page/Page column 19
[3] Patent: US2007/4675, 2007, A1, . Location in patent: Page/Page column 92-93
[4] Patent: WO2007/81091, 2007, A1, . Location in patent: Page/Page column 26
[5] Patent: WO2011/5028, 2011, A2, . Location in patent: Page/Page column 11
[6] Patent: EP2692727, 2014, A2, . Location in patent: Paragraph 0139-0142
[7] Patent: US2014/179691, 2014, A1, . Location in patent: Paragraph 0150-0152
[8] Patent: US2016/200730, 2016, A1, . Location in patent: Paragraph 0792; 0793
[9] Bioorganic and Medicinal Chemistry Letters, 1997, vol. 7, # 19, p. 2491 - 2496
[10] ChemMedChem, 2015, vol. 10, # 3, p. 470 - 489
[11] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 16, p. 3938 - 3944
[12] Journal of Organic Chemistry, 2004, vol. 69, # 2, p. 577 - 580
[13] Tetrahedron, 2011, vol. 67, # 11, p. 2139 - 2148
[14] Patent: WO2014/86952, 2014, A1, . Location in patent: Page/Page column 41; 42; 43
[15] Patent: EP2740493, 2014, A1, . Location in patent: Paragraph 0126; 0127; 0128; 0129
[16] European Journal of Medicinal Chemistry, 2015, vol. 95, p. 483 - 491
[17] Molecules, 2015, vol. 20, # 3, p. 4764 - 4779
[18] Patent: KR101826496, 2018, B1, . Location in patent: Paragraph 0160; 0165-0167
[19] Synthetic Communications, 1993, vol. 23, # 17, p. 2443 - 2449
[20] Patent: WO2011/133039, 2011, A2, . Location in patent: Page/Page column 202
[21] Chirality, 2010, vol. 22, # 7, p. 675 - 683
[22] Patent: WO2014/143672, 2014, A1, . Location in patent: Page/Page column 187
[23] Angewandte Chemie - International Edition, 2012, vol. 51, # 8, p. 1835 - 1839
[24] Chemical Communications, 2014, vol. 50, # 53, p. 7071 - 7074
[25] RSC Advances, 2015, vol. 5, # 115, p. 95300 - 95306
[26] Journal of Medicinal Chemistry, 2018, vol. 61, # 7, p. 2753 - 2775
[27] Patent: WO2009/85562, 2009, A1, . Location in patent: Page/Page column 99-100
[28] Angewandte Chemie - International Edition, 2007, vol. 46, # 34, p. 6469 - 6472
[29] Patent: US2011/152252, 2011, A1, . Location in patent: Page/Page column 16
[30] Patent: US2015/158846, 2015, A1, . Location in patent: Paragraph 0295
[31] Patent: US5962458, 1999, A,
[32] Journal of Medicinal Chemistry, 1999, vol. 42, # 11, p. 2007 - 2020
[33] European Journal of Pharmaceutical Sciences, 2015, vol. 72, p. 69 - 80
[34] Journal of Medicinal Chemistry, 1990, vol. 33, # 1, p. 97 - 101
[35] Acta Pharmacologica Sinica, 2012, vol. 33, # 2, p. 279 - 288
[36] Journal of the American Chemical Society, 2013, vol. 135, # 1, p. 309 - 314
[37] Organic and Biomolecular Chemistry, 2016, vol. 14, # 25, p. 6071 - 6078
[38] Patent: WO2005/97129, 2005, A2, . Location in patent: Page/Page column 83
[39] Patent: WO2013/91773, 2013, A1, . Location in patent: Page/Page column 79
[40] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 21, p. 3219 - 3225
[41] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 6, p. 1547 - 1551
[42] Patent: US2003/27836, 2003, A1,
[43] Patent: US5523302, 1996, A,
[44] Patent: US4753933, 1988, A,
[45] Patent: EP1752457, 2007, A1, . Location in patent: Page/Page column 198
[46] Patent: US2008/287477, 2008, A1, . Location in patent: Page/Page column 19
[47] Patent: WO2003/105845, 2003, A1, . Location in patent: Page 62-63
[48] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 1, p. 170 - 174
[49] Patent: WO2009/29439, 2009, A1, . Location in patent: Page/Page column 16
[50] Patent: EP1602362, 2005, A1, . Location in patent: Page/Page column 33-34
[51] Patent: EP1607088, 2005, A1, . Location in patent: Page/Page column 44
[52] Patent: WO2007/47432, 2007, A1, . Location in patent: Page/Page column 39
[53] Patent: US2004/24057, 2004, A1, . Location in patent: Page/Page column 49
[54] Journal of Medicinal Chemistry, 2011, vol. 54, # 11, p. 3839 - 3853
[55] Tetrahedron, 2011, vol. 67, # 34, p. 6131 - 6137
[56] Patent: WO2011/86125, 2011, A1, . Location in patent: Page/Page column 86
[57] Journal of Medicinal Chemistry, 2011, vol. 54, # 23, p. 8030 - 8050
[58] Patent: WO2011/140009, 2011, A1, . Location in patent: Page/Page column 76
[59] Patent: WO2014/140076, 2014, A1, . Location in patent: Page/Page column 120; 121
[60] Patent: WO2014/198647, 2014, A2, . Location in patent: Page/Page column 134
[61] Patent: US2016/128945, 2016, A1, . Location in patent: Paragraph 0384; 0385; 0386
[62] Patent: WO2017/3639, 2017, A2, . Location in patent: Page/Page column 52
[63] Patent: WO2017/125530, 2017, A1, . Location in patent: Page/Page column 270
[64] Patent: WO2018/41763, 2018, A1, . Location in patent: Page/Page column 45
[65] Biomacromolecules, 2018, vol. 19, # 7, p. 2759 - 2771
[66] Bioconjugate Chemistry, 2018, vol. 29, # 7, p. 2181 - 2194
  • 5
  • [ 109-83-1 ]
  • [ 41840-28-2 ]
  • [ 57561-39-4 ]
Reference: [1] Patent: US4962113, 1990, A,
  • 6
  • [ 109-83-1 ]
  • [ 57561-39-4 ]
Reference: [1] Patent: US6362336, 2002, B1, . Location in patent: Example 54
  • 7
  • [ 109-83-1 ]
  • [ 34619-03-9 ]
  • [ 57561-39-4 ]
Reference: [1] Journal of Materials Chemistry B, 2017, vol. 5, # 46, p. 9102 - 9113
  • 8
  • [ 109-83-1 ]
  • [ 6000-44-8 ]
YieldReaction ConditionsOperation in experiment
96.7% With sodium hydroxide In water at 160℃; 10 g (calculated on the basis of the dry substance) of a Pd-doped copper catalyst on active carbon (Degussa AG, CE 1015 OY/W) suspended in water was placed first analogously to example 1 in an autoclave and 61 g ethanolamine and 272 g sodium hydroxide solution (15percent by weight) were added. The autoclave was closed and the contents were heated to 160° C. The pressure was kept at 12 bar (absolute) and the hydrogen that formed was continuously discharged by a pressure control valve. After the end of the reaction (which is evident from the decrease in gas release) it was cooled to 90° C. and the catalyst was removed from the product solution by filtration. 315 g filtrate which contained 29.8 g percent by weight Na glycinate was obtained (corresponds to a yield of 96.7percent of theory).The filtered catalyst was suspended in 10 g water and fed back into subsequent batches.
Reference: [1] Patent: US2009/163739, 2009, A1, . Location in patent: Page/Page column 2-3
  • 9
  • [ 109-83-1 ]
  • [ 4535-90-4 ]
YieldReaction ConditionsOperation in experiment
96% With thionyl chloride In dichloromethane EXAMPLE 2
N-Methyl-N-(2-chloroethyl)amine, hydrochloride salt
Hydrogen chloride was bubbled into a stirred solution of 2-(methylamino)ethanol (10 g, 133 mmol) in CH2 Cl2 (25 ml) until the mixture turned wet litmus paper red.
The mixture was cooled to 0° C., and thionyl chloride (15.82 g, 133 mmol) was added dropwise.
The mixture was allowed to stir overnight at room temperature.
The solvent was removed under reduced pressure to give product as a white solid (16.60 g, 96percent yield): mp 95°-100° C.; 1 H NMR (DMSO-d6) 4.00(t, 2H, J=6.28 Hz), 3.36(t, 2H, J=6.29 Hz), 2.81(s, 3H)ppm; IR (KBr) 3400, 2960, 2750, 2420, 1730, 1580, 1460, 1390, 1310, 1270, 1200, 1150, 1165, 1005, 990, 900, 860, 710 cm-1.
87% With thionyl chloride In chloroform at 0 - 50℃; for 17 h; Inert atmosphere To a solution of 2-(methylamino)ethanol (400 pL, 5.00 mmol, 1.0 equiv.) in chloroform (50 mL)was added, under argon at 0°C, thionyle chloride (1.09 mL, 15.0 mmol, 3.0 equiv.). After 17 h of stirring at 50°C, the solvent was concentrated until approximatively 10 mL, then diethyl ether (40 mL) was added to precipitate the compound which was collected on a fritglass, washed several times diethyl ether and dried with a vane pump during one night to afford compound A0219 (567 mg, 4.36 mmol) as a white solid in 87percent yield which was used in the next step without further purification. 1H NMR (400 MHz, MeOD) 5 3.91 (t, J = 5.4 Hz, 2H, CH2CI), 3.42 (t, J = 5.4 Hz, 2H, CH2N), 2.77 (s, 3H, CH3N). 13C NMR (100 MHz, MeOD) 551.46 (CH2N), 40.22 (CH2CI), 33.64 (CH3N).
Reference: [1] Journal of Medicinal Chemistry, 1995, vol. 38, # 14, p. 2672 - 2680
[2] Patent: US5233031, 1993, A,
[3] Chemical and Pharmaceutical Bulletin, 2002, vol. 50, # 7, p. 941 - 959
[4] Journal of the Chemical Society. Dalton Transactions, 2001, # 8, p. 1306 - 1318
[5] Journal of medicinal chemistry, 1992, vol. 35, # 17, p. 3246 - 3253
[6] Patent: WO2015/140337, 2015, A1, . Location in patent: Page/Page column 33
[7] Journal of Medicinal Chemistry, 1998, vol. 41, # 27, p. 5429 - 5444
[8] Journal of the American Chemical Society, 2008, vol. 130, # 15, p. 5052 - 5053
[9] Organometallics, 2012, vol. 31, # 21, p. 7427 - 7433,7
[10] Chemische Berichte, 1905, vol. 38, p. 3132
[11] Patent: WO2007/25889, 2007, A2, . Location in patent: Page/Page column 37; 39-40; 42
[12] Journal of Polymer Science, Part A: Polymer Chemistry, 2014, vol. 52, # 5, p. 671 - 679
  • 10
  • [ 109-83-1 ]
  • [ 40052-63-9 ]
YieldReaction ConditionsOperation in experiment
320.3 g at 0 - 5℃; Add 860.0 gr of 47percent HBr to a three-necked flask connected to a thermometer, cool to 0 ~ 5 and slowly drop 180.0 gr of N-methylaminoethanol. When the addition is completed, the temperature of the reaction solution is raised, and water is continuously removed while keeping the temperature higher than 100 ° C.When a certain amount of water is removed, 2000 mL of cold acetone is added, followed by heating to reflux. When the reaction solution becomes a clear solution, the solution is slowly cooled and crystallized.The mixture was further stirred at 0 ° C for 1 hour, filtered and dried to obtain 320.3 g of 2-bromo-N-methylethanamine-bromate as a white solid.
Reference: [1] Journal of the American Chemical Society, 2009, vol. 131, # 21, p. 7447 - 7455
[2] Journal of the American Chemical Society, 2003, vol. 125, # 34, p. 10319 - 10326
[3] Soft Matter, 2011, vol. 7, # 12, p. 5627 - 5637
[4] Chemical Communications, 2018, vol. 54, # 66, p. 9174 - 9177
[5] Chemische Berichte, 1905, vol. 38, p. 3132
[6] Journal of Organic Chemistry, 1982, vol. 47, # 8, p. 1513 - 1518
[7] Journal of the American Chemical Society, 2013, vol. 135, # 41, p. 15306 - 15309
[8] Chemistry - An Asian Journal, 2011, vol. 6, # 6, p. 1520 - 1524
[9] Patent: KR2018/54180, 2018, A, . Location in patent: Paragraph 0098; 0099
  • 11
  • [ 109-83-1 ]
  • [ 4316-73-8 ]
YieldReaction ConditionsOperation in experiment
97.2% With sodium hydroxide In water at 160℃; for 4 h; 10 g (calculated on the basis of the dry substance) of a Cu/Ni-based Raney catalyst (Degussa AG, BOO 111) was placed first as a suspension in water in a 600 ml autoclave with stirrer, pressure control valve and jacket heating and 75 g N-methyl-ethanolamine as well as 204 g of a 20percent by weight sodium hydroxide solution were added. The autoclave was closed and the contents were heated to a temperature of 160° C. with the aid of the jacket heating. An increasing pressure of hydrogen was generated in this process which was kept at 10 bar (absolute) by the controlled opening of the pressure control valve. The release of gas was completely finished after 4 hours and the reactor was cooled to 90° C. After the stirrer was switched off, the catalyst sedimented within one hour and a portion of the supernatant clear solution of Na sarcosinate was moved from the autoclave through a plunge pipe. The catalyst remained in the reactor and could be used again in further batches.For each further cycle the suspension of catalyst remaining in the reactor was admixed with the said amounts of N-methylethanolamine and sodium hydroxide solution and the reaction was started by heating.With the exception of the initial batch, 270 g of a colourless solution of Na sarcosinate containing 40.0percent by weight (corresponds to a yield of 97.2percent of theory) was obtained per cycle.
Reference: [1] Patent: US2009/163739, 2009, A1, . Location in patent: Page/Page column 2
[2] Journal of the American Chemical Society, 2016, vol. 138, # 19, p. 6143 - 6146
  • 12
  • [ 109-83-1 ]
  • [ 18162-48-6 ]
  • [ 204580-28-9 ]
YieldReaction ConditionsOperation in experiment
71.39% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 16 h; To a stirred solution of 2-methylamino-ethanol (18-a) (10 g, 133.13 mmol) in dichloromethane (200 mL) were added diisopropylethylamine (30.8 ml, 186.39 mmol) and tert-butyl-chloro-dimethyl-silane (20.06 g, 133.13 mmol) at room temperature. The mixture was stirred for 16 h. After completion of the reaction, water was added and the mixture was extracted with dichloromethane. The separated organic part was washed with water and was dried over sodium sulfate and concentrated under reduced pressure to get [2-(tert-butyl-dimethylsilanyloxy)-ethyl]-methyl-amine (8-a) (18 g, 71.39percent) as a yellow liquid.
56% With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; Inert atmosphere Preparation of 2-((te -butyIdimethylsilyl)oxy)-N-methyIethanamine a. 2-((tert-butyldimethylsilyl)oxy)~N-methytethanamine 2-(methylamino)ethanol (1.0 g, 13.3 mmol) was stirred in DCM (25.0 ml) under atmosphere of nitrogen. DIEA (3.23 ml, 18.6 mmol) followed by tert-butylchlorodimethylsilane (2.0 g, 13.3 mmol) was added and the reaction mixture was stirred at room temperature over night. The reaction mixture was poured into ether/water. The aqueous layer was extracted with ether three times. The combined organic layer was dried over MgS0 and evaporated and remaining material was dried under high vacuum to afford title compound (1.4 g, yield: 56percent), 1H-NMR (400 MHz, CDCla) δ 0.08 (s, 6 H) 0.91 (s, 9 H) 1.93 (br. s., 1 H) 2.48 (s, 3 H) 2.71 (t, 2 H) 3.75 (t, 2 H).
Reference: [1] Organic and Biomolecular Chemistry, 2009, vol. 7, # 4, p. 655 - 659
[2] Patent: US2014/194431, 2014, A1, . Location in patent: Paragraph 0160-0161
[3] Organic Letters, 2016, vol. 18, # 15, p. 3878 - 3881
[4] Patent: WO2015/57938, 2015, A1, . Location in patent: Page/Page column 119-120
[5] Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 2, p. 328 - 333
[6] Patent: WO2013/79505, 2013, A1, . Location in patent: Page/Page column 62
[7] Patent: WO2006/125972, 2006, A1, . Location in patent: Page/Page column 51
  • 13
  • [ 109-83-1 ]
  • [ 1408327-48-9 ]
YieldReaction ConditionsOperation in experiment
75%
Stage #1: With dimethyl sulfoxide In dichloromethane; N,N-dimethyl-formamide at -5 - 50℃;
Stage #2: With triethylamine In N,N-dimethyl-formamide at 20 - 60℃;
To a solution of 5-nitro-lH-pyrazole-3-carboxyhc acid (5.0 g, 31.8mmol) and 2-(methylamino)ethanol (3.58 g, 47.7 mmol) in DCM (50 mL) was added dropw1se SOCh (ll.SmL, 159 nunmol) and DMF ( 4 drops) at -5 °C for 1 0 min. Then the reaction mixture was stirredat 50 °C overnight. The reaction mixture was concentrated in vacuo. The residue was added intoDMF (50 mL) and TEA (13.3 mL, 95.4 mmol). The reaction was then stirred at 60 °C overmght. After removal of solvent in vacuo, the residue was purified by silica gel column chromatography(DCM/MeOH '" 50/1 -~ 10/1) to give 5-methyl-2-nitro-6,7-dihydropyrazolo[1,5-a]pyrazm-4(5H)one(4.66 g, 75percent) as a yellow solid.[00991] 1H NNIR (400 MHz, DMSO-d6): 8 '" 7.42 (s, 1H), 4.53 (t, J "' 6.0 Hz, 2H), 3.87 (t, J '"6.8 Hz, 2H), 3.03 (s, 3H).
Reference: [1] Patent: WO2018/136890, 2018, A1, . Location in patent: Paragraph 00989; 00990; 00991
  • 14
  • [ 109-83-1 ]
  • [ 1408327-48-9 ]
Reference: [1] Organic Process Research and Development, 2012, vol. 16, # 11, p. 1870 - 1873
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 109-83-1 ]

Aliphatic Chain Hydrocarbons

Chemical Structure| 110-73-6

[ 110-73-6 ]

2-(Ethylamino)ethan-1-ol

Similarity: 0.92

Chemical Structure| 111-42-2

[ 111-42-2 ]

2,2'-Azanediyldiethanol

Similarity: 0.92

Chemical Structure| 14426-21-2

[ 14426-21-2 ]

Diethanolamine hydrochloride

Similarity: 0.86

Chemical Structure| 108-01-0

[ 108-01-0 ]

2-(Dimethylamino)ethanol

Similarity: 0.86

Chemical Structure| 111-41-1

[ 111-41-1 ]

N-(2-Hydroxyethyl)ethylenediamine

Similarity: 0.80

Alcohols

Chemical Structure| 110-73-6

[ 110-73-6 ]

2-(Ethylamino)ethan-1-ol

Similarity: 0.92

Chemical Structure| 111-42-2

[ 111-42-2 ]

2,2'-Azanediyldiethanol

Similarity: 0.92

Chemical Structure| 14426-21-2

[ 14426-21-2 ]

Diethanolamine hydrochloride

Similarity: 0.86

Chemical Structure| 108-01-0

[ 108-01-0 ]

2-(Dimethylamino)ethanol

Similarity: 0.86

Chemical Structure| 111-41-1

[ 111-41-1 ]

N-(2-Hydroxyethyl)ethylenediamine

Similarity: 0.80

Amines

Chemical Structure| 110-73-6

[ 110-73-6 ]

2-(Ethylamino)ethan-1-ol

Similarity: 0.92

Chemical Structure| 111-42-2

[ 111-42-2 ]

2,2'-Azanediyldiethanol

Similarity: 0.92

Chemical Structure| 14426-21-2

[ 14426-21-2 ]

Diethanolamine hydrochloride

Similarity: 0.86

Chemical Structure| 108-01-0

[ 108-01-0 ]

2-(Dimethylamino)ethanol

Similarity: 0.86

Chemical Structure| 111-41-1

[ 111-41-1 ]

N-(2-Hydroxyethyl)ethylenediamine

Similarity: 0.80