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CAS No. : | 91271-82-8 | MDL No. : | MFCD06655814 |
Formula : | C12H18N2O | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | NMFAEZHWSZZJOA-UHFFFAOYSA-N |
M.W : | 206.28 | Pubchem ID : | 4962390 |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | 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 |
---|---|---|
23.3% | With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In ISOPROPYLAMIDE; at 80℃; for 1h; | Example 92: 4-Chloro-6-(2-morpholin-4-ylmethyI-benzyIamino)-2H-phthalazin-l- one; A mixture 6-bromo-4-chloro-2H-phthalazin-l-one (150 mg, 0.58 mmol), 2- mophiholin-4-ylmethyl-benzylamine (132 mg, 0.64 mmol), Pd2(dba)3 (53 mg, 0.058 <n="87"/>mmol), rac-BINAP (132 mg, 0.17 mmol) and NaOt-Bu (140 mg, 1.45 mmol) in DMA (6 mL) was heated at 8O0C for Ih. The mixture was allowed to cool, diluted with EtOAc (25 mL) and washed with water (25 mL). The organic layer was dried over anhydrous sodium sulfate and concentrated. Chromatography on silica (EtOAc/hexanes) yielded the title compound. 4-Chloro-6-(2-morpholin-4-ylmethyl-benzylamino)-2H-phthalazin- 1 - one: 52 mg (23.3%): m/z (M+eta)=385. 1H-NMR (DMSO-J6) delta: 12.27 (s,lH), 7.85 (d,lH), 7.51 (m,lH), 7.22 (m,2H), 7.16 (m,2H), 7.11 (dd,lH), 6.73 (s,lH), 4.55 (d,2H), 3.50 (m,6H), 2.23 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With acetic acid; In acetonitrile; at 70℃;Inert atmosphere; | c) methyl [(4E)-1-(2-chloro-4-fluorophenyl)-4-(2-methoxy-1-[2-(morpholin-4-yl methyl)benzyl]amino}ethylidene)-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]acetate (Compound of Formula (VIII), Scheme 2).; [Show Image] The mixture of the above obtained methyl [1-(2-chloro-4-fluorophenyl)-5-hydroxy-4-(methoxyacetyl)-1H-pyrazol-3-yl]acetate (Compound of Formula (X), 400mg, 1.12mmol, leq), and <strong>[91271-82-8]1-[2-(morpholin-4-ylmethyl)phenyl]methanamine</strong> (347 mg, 1.68 mmol, 1.5eq.) in Acetonitrile and acetic acid (101 mg, 1.68 mmol, *1.5eq.) were stirred at room temperature under nitrogen in toluene/NMP(10/1) or Acetonitrile (3 mL). The reaction mixture was heated up to 70C and the reaction monitored by HPLC. After 1 hour the reaction was mostly starting material, so more acetic acid was added (0.5 eq.), and then after a further 30 minutes yet more acetic acid was added (0.5 eq.). After a further 30 minutes, 0.5 eq. of <strong>[91271-82-8]1-[2-(morpholin-4-ylmethyl)phenyl]methanamine</strong> was added. The reaction was stirred for a further 30 minutes and worked up even though not all of the starting material had been consumed. The solvent was evaporated and the residue was dissolved in ethyl acetate (containing 0.1% triethylamine) and passed through a silica gel plug (6 cm diameter, by 2 cm) eluting with 250ml of the same solvent. Evaporation of the solvent gave gave the pure methyl[(4E)-1-(2-chloro-4-fluorophenyl)-4-(2-methoxy-1-[2-(morpholin-4-ylmethyl) benzyl]amino}ethylidene)-5-oxo-4,5-dihydro-1H-pyrazol-3-yl]acetate (149 mg, quantitative yield) which was used in the following step without further purification. MS(ESI+): 546.3; MS(ESI-): 544.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | In ethanol; at 20℃;Inert atmosphere; Microwave irradiation; Sealed tube; Heating; | General procedure: To a solution containing S.I.-1 (0.20 g, 0.81 mmol) in 2 mL EtOH in a microwave reaction vial which could be sealed with a Teflon cap was added 4-amino-2,2,6,6-tetramethylpiperidine (0.13 g, 0.81 mmol). The tube was briefly flushed with an Argon stream (approximately 30 s) and sealed. The reaction was heated to 150 C for 1 hr in microwave and then allowed to cool to room temperature and stand for 12 hours, during which time a glassy solid formed. The solid was collected by filtration, washed with cold hexanes, and dried to give 140 mg (48%) of the product as a colorless crystalline solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 120℃; for 0.5h;Microwave irradiation; | General procedure: To a microwave vial containing a solution of Boc-L-glutamic acid tert-butyl ester (0.165 mmol, 1.0 equiv) and HATU (0.165 mmol, 1.0 equiv) in DMF (1.65 mL) was added the amine followed by DIPEA (57.5 muL, 2.0 equiv). The vial was sealed and heated under microwave irradiation for 30 min at 120 C. Upon completion, the reaction was partitioned between water and CH2Cl2, extracted 3× with CH2Cl2, dried over anhydrous Na2SO4, and concentrated under vacuum. Compounds were purified via reverse phase chromatography (5-95% acetonitrile/water) to afford the N-Boc-glutamylanilide-tert-butyl esters. The compounds were transferred to vials followed by the addition of 2.0 mL of 4.0 M HCl in dioxane. The reaction stirred at 40 C for 4 h. The reactions were concentrated under vacuum to afford the title compounds which were used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | General procedure: A solution of carboxylic acid (0.5 mmol) and HATU (0.55 mmol)in anhydrous DMF (2 mL) was stirred at ambient temperature for10 min. To this solution, DIPEA (0.6 mmol) and correspondingamine (0.54 mmol) were added successively and the mixture wasstirred for 18 h. After concentration under reduced pressure, thereaction mixture was treated with water (5 mL) and extracted withDCM (2 5 mL). After evaporation of the solvent, the residue wascrystallized from an appropriate solvent or subjected to columnchromatography on silica gel (DCM/MeOH) or preparative HPLC |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In N,N-dimethyl-formamide; at 20℃; | General procedure: Additional amide analogs were prepared by adding 1.5 equivalents of an amine which will provide the desired substituents into a 1 dram vial (1.5 eq.) along with lithium 5-amino-7- methoxyimidazo[1,2-c]quinazoline-2-carboxylate (30 mg, 0.114 mmol) and a DMF solution (1.0 ml) solution of DIPEA (0.079 ml, 0.454 mmol), shaking the vial for 5 minutes in a Bohdan Miniblock Shaker and then adding 1-propanephosphonic acid cyclic anhydride (50% w/w in EtOAc, 64.7 mul, 0.109 mmol), and continuing to shake the vial at RT overnight. The completed reaction was quenched with 1.0 ml water and the organic layer separated by filtering through a Varian 2 ml Reservior Frit and a Whatman 0.45mum syringe filter to remove emulsion, followed by solvent removal using a Genevac. The crude residue was dissolved in 1.0 ml DMSO and purified by LC/MS. |
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