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Chemical Structure| 593-56-6 Chemical Structure| 593-56-6
Chemical Structure| 593-56-6

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Methoxyamine hydrochloride is an orally active and effective inhibitor of base excision repair (BER). It inhibits BER activity by binding to the 3' hydroxyl left after the removal of damaged bases by 3-methylpurine-DNA glycosylase (MPG). Additionally, methoxyamine hydrochloride can directly bind to apurinic (AP) sites. Furthermore, it can synergistically enhance the therapeutic effects of DNA damaging agents.

Synonyms: O-Methylhydroxylamine hydrochloride

4.5 *For Research Use Only !

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Product Details of Methoxyamine HCl

CAS No. :593-56-6
Formula : CH6ClNO
M.W : 83.52
SMILES Code : NOC.[H]Cl
Synonyms :
O-Methylhydroxylamine hydrochloride
MDL No. :MFCD00012951
InChI Key :XNXVOSBNFZWHBV-UHFFFAOYSA-N
Pubchem ID :521874

Safety of Methoxyamine HCl

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H290-H302+H312-H315-H319-H351-H372-H410
Precautionary Statements:P201-P202-P234-P260-P264-P270-P272-P273-P280-P301+P312+P330-P302+P352+P312-P305+P351+P338-P308+P313-P333+P313-P337+P313-P390-P391-P405-P406-P501
Class:8
UN#:1759
Packing Group:

Application In Synthesis of Methoxyamine HCl

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

  • Downstream synthetic route of [ 593-56-6 ]

[ 593-56-6 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 41602-56-6 ]
  • [ 593-56-6 ]
  • 4-dimethylamino-2-hydroxy-benzaldehyde-(<i>O</i>-methyl oxime ) [ No CAS ]
  • 2
  • [ 27644-00-4 ]
  • [ 593-56-6 ]
  • 2-Biphenyl-4-yl-1-phenyl-ethanone O-methyl-oxime [ No CAS ]
  • 3
  • [ 2592-18-9 ]
  • [ 593-56-6 ]
  • [ 80543-39-1 ]
  • 4
  • [ 593-56-6 ]
  • [ 63874-95-3 ]
  • [ 132549-05-4 ]
  • [ 132549-06-5 ]
  • 5
  • [ 593-56-6 ]
  • [ 153559-46-7 ]
  • cis-4-<(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl>benzoic acid O-methyloxime [ No CAS ]
  • 4-[[(E)-Methoxyimino]-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-naphthalen-2-yl)-methyl]-benzoic acid [ No CAS ]
  • 6
  • [ 51716-63-3 ]
  • [ 593-56-6 ]
  • cis-bicyclo[3.3.0]octane-3,7-dione bis(O-methyloximme) [ No CAS ]
  • 7
  • [ 593-56-6 ]
  • [ 143211-10-3 ]
  • [ 143390-89-0 ]
  • [ 248582-68-5 ]
  • 8
  • [ 593-56-6 ]
  • [ 107819-90-9 ]
  • N1,N2-bis(tert-butoxycarbonyl)-N3-methoxyguanidine [ No CAS ]
  • 9
  • [ 593-56-6 ]
  • [ 13395-36-3 ]
  • [ 1001420-17-2 ]
YieldReaction ConditionsOperation in experiment
75% In ethanol; at 20℃; for 15h;Molecular sieve; To a solution of <strong>[13395-36-3]ethyl trimethylacetopyruvate</strong> (205 mg, 1.02 mmol) in dry EtOH (1 mL) was added O-methylhydroxylamine hydrochloride (90 mg, 1.07 mmol) and 3A mol. sieves. The reaction was stirred at RT for 15 h, then was filtered and washed with EtOH. The filtrated was concentrated in vacuo, and the residue was partitioned between Et2O and sat. aqueous NaHCO3. The Et2O layer was washed with water and brine, dried (MgSO4) and concentrated in vacuo to give Part A compound (176 mg, 75%) as a red-orange oil.
  • 10
  • [ 97-08-5 ]
  • [ 593-56-6 ]
  • 4-chloro-N-methoxy-3-nitrobenzenesulfonamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.02 g (76%) In pyridine; water; (1) Methoxylamine hydrochloride(0.90 g (10.8 mmol) was suspended in pyridine (3.0 ml). To this, under cooling with ice and with stirring, 4-chloro-3-nitrobenzenesulfonylchloride (2.56 g (10.8 mmol)) was added and the mixture was stirred under cooling with ice for one hour and at room temperature for 3 hours. Water (50.0 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was washed with dilute hydrochloric acid and water successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 2.02 g (76%) of 4-chloro-N-methoxy-3-nitrobenzenesulfonamide as pale yellow-white crystals. mp: 69.5-71.0 C.; NMR (CDCl3) delta: 3.86 (3H, s), 7.29 (1H, s), 7.77 (1H, d, J=8.4 Hz), 8.05 (1H, dd, J=8.4 & 2.1 Hz), 8.41(1H, d, J=2.1 Hz).
  • 11
  • [ 593-56-6 ]
  • [ 26638-43-7 ]
  • [ 179730-98-4 ]
YieldReaction ConditionsOperation in experiment
71% With triethylamine; In chloroform; at 0 - 20℃; for 16h; (1) Production of methyl 2-[(N-methoxyamino)sulfonyl]benzoate 1.8 g (21.3 mmole) of methoxyamine hydrochloride was suspended in 100 ml of chloroform. Thereto was dropwise added 5.4 g (53.8 mmole) of triethylamine at 0C or lower. Further was dropwise added, at 0C or lower, 5.0 g (21.3 mmole) of <strong>[26638-43-7]methyl 2-(chlorosulfonyl)benzoate</strong> dissolved in 30 ml of chloroform. The mixture was stirred at room temperature for 16 hours to give rise to a reaction. After confirmation of the completion of the reaction, the reaction mixture was poured into water, followed by extraction with chloroform. The resulting organic layer was washed with water and dried over anhydrous magnesium sulfate. The inorganic matter was removed by filtration. The filtrate was subjected to distillation under reduced pressure to remove the solvent. The resulting solid was washed with n-hexane to obtain 3.7 g (yield: 71%) of methyl 2-[(N-methoxyamino)sulfonyl]benzoate as a white powder.
  • 12
  • [ 593-56-6 ]
  • [ 90176-80-0 ]
  • 4-fluoro-2-trifluoromethyl-benzaldehyde O-methyloxime [ No CAS ]
YieldReaction ConditionsOperation in experiment
93% EXAMPLE 29 Compound 29-A: 4-Fluoro-2-trifluoromethyl-benzaldehyde O-methyloxime Reaction of <strong>[90176-80-0]4-fluoro-2-trifluoromethyl-benzaldehyde</strong> with methoxylamine hydrochloride as described in the preparation of compound 3-A gave the title oxime ether as a clear oil (93% yield). 1H-NMR indicated a 92:8 mixture of E- and Z-isomers. 1H-NMR 400 MHz (CDCl3) delta (ppm): (E-isomer) 4.00 (3H, s, OCH3), 7.25 (1H, m, aromatic), 7.37 (1H, m, aromatic), 8.08 (1H, m, aromatic), 8.36 (1H, broad s, CH).
  • 13
  • [ 593-56-6 ]
  • [ 51814-19-8 ]
  • [ 886435-83-2 ]
YieldReaction ConditionsOperation in experiment
187.5 g (589.1 mmol, 98.2%) With hydrogenchloride; In pyridine; REFERENCE EXAMPLE 2 1-Benzyloxycarbonyl-4-ethoxycarbonyl-3-methoxyiminopyrrolidine <strong>[51814-19-8]1-Benzyloxycarbonyl-4-ethoxycarbonyl-3-oxopyrrolidine</strong> (196.7 g, 600.0 mmol) was dissolved in pyridine (700 ml) and mixed with O-methylhydroxylamine hydrochloride (76.55 g, 916.5 mmol) under ice-cooling, and the mixture was stirred at the same temperature for 10 minutes and then at room temperature for 5 hours. Pyridine was evaporated under a reduced pressure, the residue was mixed with 1 N hydrochloric acid and ethyl acetate and then the mixture was shaken and subjected to separation of layers. The organic layer was washed with saturated brine, and the water layer was further extracted with ethyl acetate. The organic layers were dried over anhydrous sodium sulfate and filtered, the solvent was evaporated under a reduced pressure and then the residue was purified by a silica gel column chromatography (n-hexane:ethyl acetate=1:1) to obtain 187.5 g (589.1 mmol, 98.2%) of the title compound. 1H-NMR (400 MHz, CDCl3) delta (ppm): 1.15-1.32 (3 H, m), 3.55-4.05 (5 H, m), 4.05-4.25 (4 H, m), 5.09-5.20 (2 H, m), 7.28-7.40 (5 H, m).
  • 14
  • [ 60-29-7 ]
  • [ 593-56-6 ]
  • tetra(n-butyl)ammonium hydrogen sulfate [ No CAS ]
  • [ 148625-35-8 ]
  • methyl 3-methoxyiminomethyl-4-nitrobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxyamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 l of ethyl ether. The organic phase was separated and washed sequentially with water (1*500 mL), 2percent aqueous hydrochloric acid (2*500 mL), water (2*250 mL), and brine (1*250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 l of ethyl ether. The organic phase was separated and washed sequentially with water (1*500 mL), 2percent aqueous hydrochloric acid (2*500 mL), water (2*250 mL), and brine (1*250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 l of ethyl ether. The organic phase was separated and washed sequentially with water (1*500 mL), 2percent aqueous hydrochloric acid (2*500 mL), water (2*250 mL), and brine (1*250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 l of ethyl ether. The organic phase was separated and washed sequentially with water (1x500 mL), 2percent aqueous hydrochloric acid (2x500 mL), water (2x250 mL), and brine (1x250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 l of ethyl ether. The organic phase was separated and washed sequentially with water (1x500 mL), 2percent aqueous hydrochloric acid (2x500 mL), water (2x250 mL), and brine (1x250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.

  • 15
  • [ 66389-80-8 ]
  • [ 593-56-6 ]
  • Boc-Pab(OMe) [ No CAS ]
YieldReaction ConditionsOperation in experiment
With mercaptoacetic acid; triethylamine; In ethanol; water; at 55 - 90℃; Methoxyamidination of Boc-CBA (to give Boc-Pab(OMe) A 5 L reactor was flushed with N2 and EtOH (1.75 L, 7 vol) was added. The N2 was allowed to flow through the reactor while the following additions were made. Boc- CBA (25Og, 1.08 mol) was added to the EtOH and the temperature was raised to 55 0C. After almost complete dissolution, triethylamine (525 mL, 3.5 eq.) was added, and then a 30% w/w solution OfNH2OMe hydrochloride in water (599 g, 2 eq.) was added drop-wise at a rate of ~20 mL/min. (the NH2OMe salt solution used had a 5% wt. excess of HCl in it so 3 eq. of base was needed to neutralize all the HCl in the reagent). A small exotherm was noted, and during the addition, the solution cleared.alpha-Mercaptoacetic acid (77mL, 1 eq.) was added to produce a slightly opaque mixture of total volume ~3 L. The mantle was heated carefully to 90 0C, and when reflux (internal temp = 78 C) was obtained, the N2 was turned off and the reaction stirred overnight.After 21 hours of stirring at reflux, the reaction was at 96% conversion (HPLC column: Symmetry Shield RP8, 3.5 mum, 50 mm; 230 nm - see Example 3 for more details). The reaction mixture was then cooled to 40 0C and acetone (160 mL, 2 eq.) added over one minute. The mixture was allowed to stand for 1 hour in order to quench any remaining NH2OMe. The mixture was then poured into round-bottomed flasks and the solvent removed by rotary evaporation at 40 0C under vacuum. The remaining residues were dissolved in 3 L of a 2:1 mixture of nBuOAc: H2O and placed in a reactor at 25 0C (total volume = 4.5 L) and stirred for 10 minutes for efficient mixing of the layers.After the phases separated on standing, the aqueous layer (2 L, pH 6) was removed. The organic layer was washed with 1 L of water and the aqueous layer removed (pH=4). EPO <DP n="18"/>This was followed by a wash with a solution OfK2CO3 (297 g, 2 eq.) in 1 L of water (this helps remove the mercaptoacetic acid). The basic water layer was removed and a final wash with 1 L of water was performed. After removal of the aqueous layer, the organic layer was removed from the reactor and stored overnight (total vol -2.3 L). The organic layer was azeotropically dried by removal of approximately half of the nBuOAc (925 mL) on a rotary evaporator. The resulting mixture was placed in a reactor (mantle temp. = 30 C) and 425 mL of nBuOAc was added (total volume of nBuOAc = 2 L - 0.925 + 0.425 = 1.5 L = 6 vol). This was followed by addition of 440 mL (1.75 vol.) of EtOH. The mixture was heated to 30 C to obtain a solution of Boc-Pab(OMe).The above reaction can be repeated using n-butanol as solvent in place of ethanol.The Boc-CBA obtained by the step 1 reaction above can also be used without isolation or purification in the step 2 methoxyamidation reaction.
  • 16
  • [ 143390-88-9 ]
  • [ 593-56-6 ]
  • [ 143211-10-3 ]
  • [ 143390-89-0 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In methanol; dichloromethane; EXAMPLE 2 Methyl E-2-(2-methylphenoxymethyl)phenylglyoxylate O-methyloxime STR22 Variant 2.1 129 g of a mixture composed of 80 % by weight of methyl 2-(2-methylphenoxymethyl)phenylglyoxylate and 13 % by weight of methyl 2-(2-methylphenoxymethyl)phenylglyoxylate dimethyl acetal were refluxed together with 41.7 g (0.5 mol) of O-methylhydroxylamine hydrochloride and 450 ml of methanol for 7 hours. The mixture was cooled to 20 C. and then 450 ml of methylene chloride were added and 219 g (6 mol) of gaseous hydrogen chloride were passed in. The mixture was stirred at this temperature for 15 hours and then the solvent was removed under reduced pressure. The residue was washed first with cold methanol and then with petroleum ether and subsequently dried. Yield: 106.8 g (colorless solid).
  • 17
  • 1-ethyl-3,3-(dimethylaminopropyl)carbodiimide.HCl [ No CAS ]
  • [ 2592-18-9 ]
  • [ 593-56-6 ]
  • N-Methoxy-t-boc-1-allothreonine amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; In water; (B) N-Methoxy-t-boc-1-allothreonine amide t-Boc-1-allothreonine (9.13 g) is dissolved in 85 ml of water and 41 ml of 1N potassium hydroxide solution. Methoxyamine hydrochloride (5.22 g) and 8.67 g of 1-ethyl-3,3-(dimethylaminopropyl)carbodiimide.HCl are added. The mixture is stirred at room temperature for 4 hours and then saturated with sodium potassium tartarate. The resulting mixture is extracted with ethyl acetate (four 150 ml portions) and the organic layer is dried over anhydrous sodium sulfate and stripped of solvent to give 7.38 g of the title compound as a solid.
  • 18
  • [ 67936-72-5 ]
  • [ 593-56-6 ]
  • [ 5780-66-5 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate; In chloroform; Petroleum ether; EXAMPLE 13 Pyrazine carboxaldehyde, O-methyl oxime A solution of pyrazine carboxaldehyde diethyl acetal (3.6 g) and O-methylhydroxylamine hydrochloride (1.7 g) in 25 ml of alcohol was refluxed for 8 hours. The solvent was evaporated and the residue treated with chloroform and an aqueous solution of sodium bicarbonate. The chloroform layer was separated and dried over magnesium sulphate. Evaporation of the solvent and crystallization of the residual oil from petroleum ether (b.p. 40°-60° C.) afforded the title compound (1.3 g), m.p. 40°-41° C.
  • 19
  • [ 593-56-6 ]
  • tetra(n-butyl)ammonium hydrogen sulfate [ No CAS ]
  • [ 148625-35-8 ]
  • methyl 3-methoxyiminomethyl-4-nitrobenzoate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 1 methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 1 of ethyl ether. The organic phase was separated and washed sequentially with water (1x500 mL), 2percent aqueous hydrochloric acid (2x500 mL), water (2x250 mL), and brine (1x250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
With sodium acetate; In dichloromethane; water; f) Preparation of methyl 3-methoxyiminomethyl-4-nitrobenzoate. To a well stirred mixture of 195 g of <strong>[148625-35-8]methyl 3-formyl-4-nitrobenzoate</strong>, 1 l methylene chloride and 370 mL of water was added sequentially 77.6 g of methoxylamine hydrochloride, 76.2 g of sodium acetate and 6.8 g of tetra-n-butylammonium hydrogen sulfate. The resulting mixture was stirred overnight at room temperature, then diluted with 2 1 of ethyl ether. The organic phase was separated and washed sequentially with water (1x500 mL), 2percent aqueous hydrochloric acid (2x500 mL), water (2x250 mL), and brine (1x250 mL); then dried over anhydrous magnesium sulfate. The solvent was removed using a rotary evaporator yielding 218.6 g of the expected methyl 3-methoxyiminomethyl-4-nitrobenzoate as a reddish oil that solidified upon standing, and which was used as such in the next step.
  • 20
  • [ 593-56-6 ]
  • [ 231958-04-6 ]
  • [ 607738-98-7 ]
YieldReaction ConditionsOperation in experiment
98% To a stirred solution of compound 7 (5.0 g, 19.9 mmol) in DMF (30 mL) was added EDC (3.9 mL, 21.9 mmol), HOBt (3.35 g, 21.9 mmol). After stirring at rt for 30 min, methoxyamine hydrochloride (1.83 g, 21.9 mmol) was added. The resulting mixture was stirred for another 10 min, and cooled to 0 C. DIPEA (8.09 mL, 46.4 mmol) was added slowly to maintain the internal reaction temperature below 25 C. After finishing the addition, the reaction mixture was allowed to warm to rt and stirred at rt overnight. The resulting mixture was poured into water and extracted with EtOAc. The combined organic layer was washed with cold 0.5 N HCl and water. The organic layer was then extracted with cold 0.5 N NaOH, and the combined basic aqueous extract was adjusted pH to 8 by a slow addition of cold 0.5 N HCl. The resulting precipitate was collected by filtration, and washed with cold water. The crude product was recrystallized in EtOH to afford 8a (5.17 g, 98 %) as a white solid. 1H NMR (DMSO-d6): delta 11.65 (s, 1H), 8.65 (s, 1H), 7.75 (s, 1H), 7.40 (dd, J=1.5, 8.0Hz, 1H), 7.25 (d, J=8.0Hz, 1H), 3.69 (s, 3H), 2.23 (s, 3H), 1.47 (s, 9H).
A mixture of commercially-available 4-amino-3-methylbenzoic acid (100 g, 0.66 mol) and di-tertbutyl dicarbonate (150 g, 0.68 mol) in THF (1000 mL) was slowly heated to 50C overnight. The resulting mixture was cooled to rt and the solvent was removed on a rotary evaporator. The resulting solids were triturated with hexanes and dried in vacuo to afford 151 g (91%) of the crude <strong>[231958-04-6]BOC-protected aniline intermediate</strong> as a light pink solid. To the above, light-pink solid was added 1- (3- dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (127 g, 0.66 mol), HOBt (90 g, 0.66 mol), and DMF (1000 ml), and the resulting mixture was stirred at rt for 30 minutes followed by addition of methoxyamine hydrochloride (55 g, 0.66 mol) in one portion. After stirring for 10 min, the mixture was cooled using an ice bath. Diisopropyl-ethylamine (250 ml, 1.4 mol) was added at such a rate so as to maintain the internal reaction temperature below 25C. After the addition was complete, the ice bath was removed and the reaction was stirred overnight at rt. The reaction mixture was partitioned between 0.5 L of water and 1.5 L of EtOAc and the resulting layers were separated. The aqueous portion was extracted with additional EtOAc (400 mL x 3), and the combined organic extracts were washed with, water (300 mL x 3), cold 0.5 N aqueous HC1 (400 mL x 2), and water (500 mL). The product was then extracted with cold 0.5 N aqueous NaOH (300 mL x 3) and the combined basic aqueous extracts were neutralized to pH = 8 by a slow addition of cold 0.5 N aqueous HC1. The resulting solid which precipitated was collected by filtration and washed with cold water.'The wet solid was decolorized in hot EtOH with active charcoal to give 106 g of white solid as the BOC-protected N-methoxyamide intermediate. To a slurry of the above solid (91 g, 0.32 mol) in 1,4-dioxane (400 mL) at rt was added a 4M solution of HC1 in dioxane (400 mL), and the resulting mixture was stirred at rt overnight. Diethyl ether (1000 mL) was added and the precipitated solid was collected by filtration and triturated with a hot EtOH/H20 mixture (4: 1 v/v). Drying the resulting solid in vacuo afforded 53 g of the pure hydrochloride salt (1D) as a white solid. 1H NMR (d6-DMSO) : 6 9.5-9. 9 (br. s, 1H), 7.75 (s, 1H), 7.55 (d, 1H), 7.36 (d, 1H), 3.70 (s, 3H), 2.38 (s, 3H).
  • 21
  • [ 19090-04-1 ]
  • [ 593-56-6 ]
  • [ 1034770-39-2 ]
YieldReaction ConditionsOperation in experiment
With pyridine; at 20℃; Methoxylamine hydrochloride (1.23 g, 14.8 mmol) was added to a solution of Example 1C (1.99 g, 13.4 mmol) in pyridine (30 mL) and stirred overnight at ambient temperature. The mixture was concentrated to a yellow residue and ethyl acetate (200 mL) and 1N hydrochloric acid (200 mL) were added. The organic layer was washed with brine, dried with anhydrous sodium sulfate and filtered. The solvent was concentrated under reduced pressure and the residue chromatographed on silica gel eluding with 0-to-20% ethyl acetate in hexane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) delta ppm 3.72 (s, 2H), 3.85 (s, 3H), 4.51 (s, 2H), 6.89 (dd, J=8.14, 1.36 Hz, 1H), 6.96 (td, J=7.46, 1.36 Hz, 1H), 7.14 (m, 1H), 7.21 (d, J=7.46 Hz, 1H). MS (DCI) m/z 178.07 (M+H)+.
  • 22
  • [ 593-56-6 ]
  • [ 2840-44-0 ]
  • [ 1384839-45-5 ]
  • 23
  • [ 593-56-6 ]
  • [ 1180-71-8 ]
  • [ 476330-99-1 ]
  • 25
  • [ 21080-80-8 ]
  • [ 593-56-6 ]
  • [ 1254716-82-9 ]
YieldReaction ConditionsOperation in experiment
79% In ethanol; at 20℃; for 1h; Methoxyl amine hydrochloride (30percent solution in water, 0.4 mL, 0.651 mmol, 1.2 equiv.) was added at room temperature to the product obtained from step a (200 mg, 0.543 mmol, 1 equiv.) in EtOH (8 mL), and the reaction mixture was stirred for 1 h at RT. EtOH was evaporated under reduced pressure and the remaining aqueous phase was extracted with EA (15 mL). The organic phase was washed with water (10 mL), saturated sodium chloride solution (10 mL), dried over Na2SO4 and concentrated under reduced pressure. A pale yellow liquid was obtained as product (180 mg, 79percent yield).
78% In ethanol; water; at 20℃; for 1h; To a solution of step-a product (200 mg, 0.543 mmol, 1 eq) in EtOH (8 mL), methoxylamine hydrochloride (30percent solution in water, 0.4 mL, 0.651 mmol, 1.2 eq) was added at room temperature and the reaction mixture stirred for 1 h. EtOH was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78percent).
78% In ethanol; water; at 23℃; for 1h; To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30 percent solution in water, 0.4 mL, 0.651 mmol, 1.2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78 percent).
78% In ethanol; water; at 20℃; for 1h; Step b: To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30percent solution in water, 0.4 mL, 0.651 mmol, 1.2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78percent).
78% In ethanol; water; at 20℃; for 1h; To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30 percent solution in water, 0.4 mL, 0.651 mmol, 1 .2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78 percent).
78% In ethanol; water; at 23℃; for 1h; Step b: To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30 percent solution in water, 0.4 mL, 0.651 mmol, 1 .2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78 percent).
78% In ethanol; water; at 23℃; for 1h; To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30 percent solution in water, 0.4 mL, 0.651 mmol, 1 .2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78 percent).
78% In ethanol; water; at 23℃; for 1h; Step b: To a solution of step-a product (200 mg, 0.543 mmol, 1 equivalent) in ethanol (8 mL), methoxylamine hydrochloride (30 percent solution in water, 0.4 mL, 0.651 mmol, 1 .2 equivalents) was added at room temperature and the reaction mixture stirred for 1 h. ethanol was evaporated under reduced pressure and the residual aqueous layer was extracted with ethyl acetate (15 mL). The organic layer was washed with water (10 mL), brine solution (10 mL), dried over sodium sulphate, filtered and concentrated under reduced pressure to give a pale yellow liquid (180 mg, 78 percent).

  • 26
  • [ 615-06-5 ]
  • [ 593-56-6 ]
  • methyl (Z)-3-(furan-2-yl)-3-(methoxyimino)propanoate [ No CAS ]
  • [ 1257649-01-6 ]
  • 27
  • [ 149057-19-2 ]
  • [ 593-56-6 ]
  • [ 1312705-49-9 ]
YieldReaction ConditionsOperation in experiment
With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; To a solution of <strong>[149057-19-2]piperazine-1,2,4-tricarboxylic acid 4-benzyl ester 1-tert-butyl ester</strong> (0.364 g, 1 mmol) in dichloromethane (3 mL) was added O-Methyl Hydroxylamine HCl (95 mg, 1.13 mmol), EDC HCl (0.3 g, 1.57 mmol) and DIEA (0.28 g, 2.17 mmol). The resulting mixture was stirred at room temperature overnight and partitioned between dichloromethane and water. The combined organic extracts were washed with brine, dried, and evaporated. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc/n-Hexane (30/70) to afford the title product.LC/MS (m/z) [M]+ 394.2 (calculated for C19H27N3O6, 393.19).
  • 29
  • [ 5779-93-1 ]
  • [ 593-56-6 ]
  • C10H13NO [ No CAS ]
  • 30
  • [ 593-56-6 ]
  • [ 51012-64-7 ]
  • C10H12BrNO [ No CAS ]
  • 31
  • [ 6967-82-4 ]
  • [ 593-56-6 ]
  • C9H10BrNO2 [ No CAS ]
  • 32
  • [ 54413-93-3 ]
  • [ 593-56-6 ]
  • C9H10INO3 [ No CAS ]
  • 33
  • [ 50-00-0 ]
  • [ 593-56-6 ]
  • [ 51814-19-8 ]
  • C17H22N2O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
The compound shown in Formula 3 was dissolved in 640 ml of absolute ethanol,After clarification, 68.2 g of sodium carbonate and 41.2 g of 37% formaldehyde solution were added, and the mixture was stirred for 3 hours while warming to 25-30 C.,TLC (thin layer chromatography) showed the reaction was completed;42.4 g of methoxyamine hydrochloride was added, and the mixture was stirred for 2 hours at 25-30 C. TLC (thin layer chromatography) showed that the reaction was completed.Suction filtration, to the filter cake was added 110ml dichloromethane, stirred for 20 minutes, filtered,The filtrate is concentrated at 30-40 degrees. After evaporating, 110 ml of methylene chloride was added thereto and concentrated to dryness at 40-45 C.After evaporation to dryness, 410 ml of methylene chloride and 144 ml of water are added, the mixture is stirred for 5 minutes at 20 to 25 C., left standing for 0.5 hours,The organic layers were collected in layers; the methylene chloride layer was washed twice with 144 ml of water each time,Each 20 ~ 25 for 5 minutes, allowed to stand for 0.5 hours, the organic layer was separated and collected,Adding 200g Yuan Ming powder to it, stirring at 20 ~ 25 for 5 ~ 6 hours;The filtrate was evaporated under reduced pressure at 35 ~ 40 C to give the compound shown in Formula 2, the reaction is as follows
  • 34
  • [ 37718-11-9 ]
  • [ 593-56-6 ]
  • N-methoxy-1H-pyrazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
94% Under inert atmosphere 1H-pyrazol-3-carboxylic acid (250 mg, 2.23 mmol) was diluted in anhydrous DMF (7.4 mL) and HOBt H20 (444 mg, 2.90 mmol) and EDC.HCl (556 mg, 2.90 mmol) were successively added. The reaction mixture was stirred at rt for 10 min. Methoxyamine hydrochloride (335 mg, 4.01 mmol) and DIPEA (1 .17 mL, 6.69 mmol) were added and the reaction mixture was stirred at rt for 16h. The reaction mixture was concentrated in vacuo and purified by flash chromatography on silica gel (DCM/methanol: 100/0 to 90/10) then by C-18 reverse phase (H2O/ACN: 98/2 to 50/50) to give intermediate (27a) (297.5 mg, 2.1 1 mmol, 94percent) as a white solid. MS m/z ([M+H]+) 142. MS m/z ([M-H]-) 140. 1 H NMR (300 MHz, DMSO-d6): (ppm) 3.65 (s, 3H), 6.63 (t, J = 2.2 Hz, 1 H), 7.82 (dd, J = 2.4, 1 .4 Hz, 1 H), 1 1 .49 (s, 1 H), 13.27 (s, 1 H).
  • 35
  • [ 593-56-6 ]
  • [ 143211-10-3 ]
  • [ 143390-89-0 ]
YieldReaction ConditionsOperation in experiment
84.8% In methanol; for 6h;Reflux; In a 500 ml three-necked bottle, 63.1 g (0.2 mol) of 2- (2-methylphenoxymethyl) phenyl oxalate with a content of 90% and 18.7 g of methoxyamino hydrochloride with a content of 98% ( 0.22 mol) and 150 ml of methanol. After refluxing for 6 hours, cool to 20 C, and uniformly pass 71 g (2 mol) of dry hydrogen chloride gas into the reaction kettle within 1 hour. After passing through the hydrogen chloride, react at room temperature for 5 hours. It was filtered, the solid was washed with 100 ml of cold methanol, and dried, the mass was 55.9 g, the content was 95.0%, and the yield was 84.8%
 

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