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CAS No. : | 197142-34-0 | MDL No. : | MFCD08691405 |
Formula : | C11H17NO4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VXIIZQXOIDYWBS-PRJMDXOYSA-N |
M.W : | 227.26 | Pubchem ID : | 11020613 |
Synonyms : |
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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: |
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* 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 |
---|---|---|
3.6 g | With pyridine; oxalyl dichloride; at 20℃; for 1h; | Oxalyl chloride (2.9 mL, 33 mmol) was added drop wise to the mixture of compound PR-1 (5 g, 22 mmol), <strong>[112253-70-0]2-amino-4-bromobenzamide</strong> (4.7 g, 22 mmol) and pyridine (50 mL). The mixture was stirred for 1 hour at room temperature. The solvent was removed in vacuo. The obtained residue was purified by chromatography (petroleum ether: acetate ether=5: l) resulting in a intermediate (3.6 g). Method A2; Rt: 1.15 min. m/z=:447.7 (M+Na)+ Exact mass: 425.1 The above obtained intermediate (3.6 g,), Na2C03 (2.7 g. 25.4 mmol), H20 (20 mL) and CH3CH2OH (20 mL) were stirred for 2 hours under reflux. Most of CH3CH2OH was removed in vacuo. The residue was extracted with ethyl acetate (3 x 20 mL). The organic layer was dried over Na2S04 and concentrated in vacuo. The residue was washed with t-butyl methyl ether resulting in compound QA-6 (3.4 g) |
3.6 g | With pyridine; oxalyl dichloride; at 20℃; for 1h; | Oxalyl chloride (2.9 mL, 33 mmol) was added drop wise to the mixture of compound PR-1 (5 g, 22 mmol), <strong>[112253-70-0]2-amino-4-bromobenzamide</strong> (4.7 g, 22 mmol) and pyridine (50 mL). The mixture was stirred for 1 hour at room temperature. The solvent was removed in vacuo. The obtained residue was purified by chromatography (petroleum ether: acetate ether=5: l) resulting in a intermediate (3.6 g). Method A2; Rt: 1.15 min. m/z=:447.7 (M+Na)+ Exact mass: 425.1 The above obtained intermediate (3.6 g,), Na2C03 (2.7 g. 25.4 mmol), H20 (20 mL) and CH3CH2OH (20 mL) were stirred for 2 hours under reflux. Most of CH3CH2OH was removed in vacuo. The residue was extracted with ethyl acetate (3 x 20 mL). The organic layer was dried over Na2S04 and concentrated in vacuo. The residue was washed with t-butyl methyl ether resulting in compound QA-6 (3.4 g) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
To a stirred solution of (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid (261 mg, 1.16 mmole) in 15 mL of CH2Cl2, was added 1-methyl imidazole (0.23 mL, 2.5 equiv.) at 0-5° C. under nitrogen atmosphere. The reaction mixture was stirred for 10 min at 0-5° C. and then added methane sulfonyl chloride (0.11 mL, 1.2 equiv) at the same temperature. It was stirred for 1 h at 0-50° C. Then <strong>[89466-16-0]6-bromo-3-methylpyridin-2-amine</strong> (217 mg, 1 equiv) was added, and stirred for 18h at room temperature. Water (10 mL) was added to the reaction mixture, layers were separated and aqueous layer was extracted with DCM (3×10 mL). The combined organic layer was washed with 1N HCl (10 mL), followed by Sat NaHCO3 (10 mL) and then with brine (10 mL). Combined organic layer was dried over Na2SO4, concentrated and 371 mg (94percent yield) of titled compound was obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
22% | With 1-chloro-1-(dimethylamino)-2-methyl-1-propene; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 0 - 20℃; for 16.0h; | Compound 345a was prepared and purified according to the procedure reported in step-1 of scheme-344, from (lR,3S,5R)-2-(tm-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3- carboxylic acid (259a) (177 mg, 0.781 mmol) in DCM (5 mL) using l-chloro-N,N,2- trimethylprop- 1 -en- 1 -amine (0.114 mL, 0.859 mmol), 6-(difhioromethoxy)pyridin-2-amine (125 mg, 0.781 mmol) and DIPEA (202 mg, 1.561 mmol) to afford ( 1R,3 S,5R)-tert-butyl 3- (6-(difluoromethoxy)pyridin-2-ylcarbamoyl)-2-azabicyclo[3.1 ,0]hexane-2-carboxylate (345a) (170 mg, 59% yield) as a pale-yellow solid; NMR (300 MHz, DMSO-cfe) δ 10.44 (s, 1H), 8.04 - 7.85 (m, 2H), 7.57 (s, 1H), 6.88 - 6.64 (m, 1H), 4.34 - 4.05 (m, 1H), 3.35 (s, 1H), 2.38 - 2.21 (m, 1H), 2.21 - 2.02 (m, 1H), 1.71 - 1.53 (m, 1H), 1.32 (s, 9H), 0.84 - 0.64 (m, 1H), 0.50 - 0.33 (m, 1H);19F NMR (282 MHz, DMSO -de) δ -86.36; MS (ES+): 370 (M+l); (ES-): 368 (M-l). |
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