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Product Details of [ 1251011-05-8 ]

CAS No. :1251011-05-8 MDL No. :MFCD14581202
Formula : C11H20N2O3 Boiling Point : -
Linear Structure Formula :- InChI Key :MYPAWHOIUKGJIE-UHFFFAOYSA-N
M.W :228.29 Pubchem ID :71305257
Synonyms :

Safety of [ 1251011-05-8 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338 UN#:
Hazard Statements:H302-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1251011-05-8 ]

* 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 [ 1251011-05-8 ]

[ 1251011-05-8 ] Synthesis Path-Downstream   1~27

  • 1
  • [ 1008526-71-3 ]
  • tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate [ No CAS ]
  • 2
  • [ 1972659-50-9 ]
  • [ 1251011-05-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: sodium hydride / 1,4-dioxane / 22 h / 0 - 80 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 2 h / 20 °C
Multi-step reaction with 2 steps 1.1: sodium hydride / 1,4-dioxane; mineral oil / 16 h / 0 - 80 °C 2.1: borane-THF / tetrahydrofuran / 16 h / 0 - 25 °C 2.2: 5 h / 0 - 70 °C
Multi-step reaction with 2 steps 1: sodium hydride / 1,4-dioxane / 12 h / 80 °C 2: borane-THF / tetrahydrofuran / 12 h / 0 - 25 °C / Inert atmosphere
  • 3
  • [ 1363381-20-7 ]
  • [ 1251011-05-8 ]
YieldReaction ConditionsOperation in experiment
90% Stage #1: tert-butyl 7-oxo-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate With borane-THF In tetrahydrofuran at 0 - 25℃; for 16h; Stage #2: With methanol In tetrahydrofuran at 0 - 70℃; for 5h; 38.5 Step 5: Synthesis of tert-butyl 5-oxa-2, 8-diazaspiro [3.5] nonane-2-carboxylate To a solution of tert-butyl 7-oxo-5-oxa-2, 8-diazaspiro [3.5] nonane-2-carboxylate (2.7 g, 11.2 mmol) in THF (30 mL) was added borane-tetrahydrofuran complex (33.6 mL, 33.6 mmol) dropwise at 0 and the mixture was stirred at 25 for 16 hrs. The mixture was quenched with MeOH (10 mL) at 0 and stirred at 70 for 5 hrs. The resulting mixture was concentrated to dryness and the residue was purified bysilica gel chromatography (DCM: MeOH = 25: 1) to give desired product (2.3 g, 90%yield) as yellow oil. MS (ESI) m/z: 229 (M+H) +.
50% With lithium aluminium tetrahydride In tetrahydrofuran at 20℃; for 2h;
87.76 % With borane-THF In tetrahydrofuran at 0 - 25℃; Inert atmosphere; 3 Step 3 To a solution of tert-butyl 7-oxo-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (520 mg, 2.15 mmol, 1 eq) in THF (8 mL) was added BH3.THF (1 M, 6.44 mL, 3 eq) at 0°C under N2. After addition, the reaction solution was stirred at 25°C for 12h. TLC (dichloromethane: methanol= 10:1) showed several new spots. The solution was quenched by 15% sodium hydroxide solution (10 mL) was added drop-wise over a 5 minute period to control gas evolution. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane) to afford tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.88 mmol, 87.76% yield) as a white solid.
87.76 % With borane-THF In tetrahydrofuran at 0 - 25℃; Inert atmosphere; 3 Step 3 To a solution of tert-butyl 7-oxo-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (520 mg, 2.15 mmol, 1 eq) in THF (8 mL) was added BH3.THF (1 M, 6.44 mL, 3 eq) at 0°C under N2. After addition, the reaction solution was stirred at 25°C for 12h. TLC (dichloromethane: methanol= 10:1) showed several new spots. The solution was quenched by 15% sodium hydroxide solution (10 mL) was added drop-wise over a 5 minute period to control gas evolution. The mixture was diluted with water (10 mL) and extracted with ethyl acetate (20 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0 to 10% methanol in dichloromethane) to afford tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.88 mmol, 87.76% yield) as a white solid.

  • 5
  • [ 1251011-05-8 ]
  • [ 128071-98-7 ]
  • [ 2366182-98-9 ]
YieldReaction ConditionsOperation in experiment
69% With triethylamine In 1-methyl-pyrrolidin-2-one at 110℃; for 21h; Sealed tube; 141.1 Step 1: tert-Butyl 8-(4-bromopyridin-2-yl)-5-oxa-2,8-diazaspiro[3.5]nonane-2- carboxylate A solution of 4-bromo-2-fluoro-pyridine (50 mg, 0.284 mmol), tert-butyl 5-oxa- 2,8-diazaspiro[3.5]nonane-2-carboxylate (97.3 mg, 0.426 mmol) and Et3N (120 μL, 0.861 mmol) in NMP (1 mL) was heated at 110 °C in a sealed tube for 21 hours. The reaction mixture was cooled to ambient temperature and partitioned between EtOAc and brine. The layers were separated and the organic phase washed with brine (x 3), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica, 0 to 30% EtOAc/Petroleum Ether gradient elution) to give tert-butyl 8-(4-bromo-2-pyridyl)-5-oxa-2,8-diazaspiro[3.5]nonane- 2-carboxylate (75.8 mg, 0.197 mmol, 69%) as a colourless oil; 1H NMR (500 MHz, Chloroform- d) δ 8.03 (d, J = 5.3 Hz, 1H), 6.86 (d, J = 5.2 Hz, 1H), 6.83 (s, 1H), 3.90 (d, J = 9.3 Hz, 2H), 3.84 (d, J = 9.2 Hz, 2H), 3.80 (t, J = 5.0 Hz, 2H), 3.66 (s, 2H), 3.47 (dd, J = 5.7, 4.6 Hz, 2H), 1.47 (s, 9H); MS m/z: 384.1 (M+H)+
With potassium carbonate In dimethyl sulfoxide at 90℃; 4 Step 4 To a solution of 4-bromo-2-fluoropyridine (331.49 mg, 1.88 mmol, 1 eq) in DMSO (5 mL) was added tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.88 mmol, 1 eq) and K2CO3 (520.65 mg, 3.77 mmol, 2 eq). After addition, the reaction solution was stirred at 90°C for 12h. TLC (petroleum ether: ethyl acetate= 3:1) showed several new spots. After cooling, the reaction mixture was filtered and filtrate was diluted with ethyl acetate (50 mL) and washed with brine (3 x 30 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0 to 20% ethyl acetate in petroleum ether) to afford tert-butyl 8-(4-bromo-2-pyridyl)-5-oxa-2,8- diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.05 mmol, 55.84% yield, 94% purity) as a colorless oil.
With potassium carbonate In dimethyl sulfoxide at 90℃; 4 Step 4 To a solution of 4-bromo-2-fluoropyridine (331.49 mg, 1.88 mmol, 1 eq) in DMSO (5 mL) was added tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.88 mmol, 1 eq) and K2CO3 (520.65 mg, 3.77 mmol, 2 eq). After addition, the reaction solution was stirred at 90°C for 12h. TLC (petroleum ether: ethyl acetate= 3:1) showed several new spots. After cooling, the reaction mixture was filtered and filtrate was diluted with ethyl acetate (50 mL) and washed with brine (3 x 30 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (0 to 20% ethyl acetate in petroleum ether) to afford tert-butyl 8-(4-bromo-2-pyridyl)-5-oxa-2,8- diazaspiro[3.5]nonane-2-carboxylate (430 mg, 1.05 mmol, 55.84% yield, 94% purity) as a colorless oil.
  • 6
  • [ 1251011-05-8 ]
  • [ 2366182-99-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: triethylamine / 1-methyl-pyrrolidin-2-one / 21 h / 110 °C / Sealed tube 2: trifluoroacetic acid / dichloromethane / 17 h / 20 °C
  • 7
  • [ 1251011-05-8 ]
  • [ 2366183-00-6 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: triethylamine / 1-methyl-pyrrolidin-2-one / 21 h / 110 °C / Sealed tube 2: trifluoroacetic acid / dichloromethane / 17 h / 20 °C 3: triethylamine / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere
  • 8
  • [ 1251011-05-8 ]
  • [ 2366182-97-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: triethylamine / 1-methyl-pyrrolidin-2-one / 21 h / 110 °C / Sealed tube 2: trifluoroacetic acid / dichloromethane / 17 h / 20 °C 3: triethylamine / tetrahydrofuran / 16 h / 20 °C / Inert atmosphere 4: potassium acetate / 1,4-dioxane / 2 h / 90 °C / Inert atmosphere
  • 9
  • tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate [ No CAS ]
  • [ 35251-99-1 ]
  • tert-butyl 8-(3-chloropyrido[3,4-b]pyrazin-2-yl)-5-oxa-2,8-diazaspiro[3.5] nonane-2-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
550 mg With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 40℃; for 2h; 50.1 Step 1: preparation of tert- butyl 8-(3-chloropyrido[3,4-b]pyrazin-2-yl)-5-oxa-2,8- diazaspiro[3.5] nonane-2-carboxylate (compound 50a) To the solution of 2,3-dichloropyrido[3,4-b]pyrazine (CAS: 35251-99-1, Vendor: Aldrich, 300 mg, 1.51 mmol) in l,4-dioxane (10 mL) was added V,V-diisopropylethylamine (0.39 mL, 2.26 mmol) and ferf-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate (CAS: 1251011-05-8, Vendor: PharmaBlock, 348 mg, 1.52 mmol). After being stirred at 40 °C for 2 hrs, the reaction mixture was concentrated to give compound 50a (550 mg) as a yellow oil. MS calc’d 392 (MH+), measured 392 (MH+).
  • 10
  • [ 1251011-05-8 ]
  • [ 2403784-44-9 ]
  • [ 2403784-45-0 ]
YieldReaction ConditionsOperation in experiment
140 mg With tris-(dibenzylideneacetone)dipalladium(0); (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl; sodium t-butanolate In toluene at 110℃; for 3h; Inert atmosphere; 47.2 Step 2: preparation of tert-butyl 8- [6- (2-trimethylsilylethoxycarbonyl)-7,8-dihydro- 5H- 1,6-naphthyridin-3-yl]-5-oxa-2,8-diazaspiro [3.5]nonane- 2-carboxylate (compound 47b) To a solution of 2-trimethylsilylethyl 3 -bromo-7, 8-dihydro-5H- 1 ,6-naphthyridine-6- carboxylate (compound 47a, 150 mg, 0.42 mmol), tert-butyl 5-oxa-2,8-diazaspiro[3.Slnonane-2- carboxylate (CAS: 1251011-05-8, Vendor: PharmaBlock, 105 mg, 0.46 mmol), sodium tertbutoxide (101 mg, 1.05 mmol), R-BINAP (52 mg, 0.08 mmol) in toluene (4 mL) was added Pd2(dba)3 (38 mg, 0.04 mmol). The solution was stirred at 110 °C under N2 atmosphere for 3 hrs.After being cooled down, the mixture was quenched by addition of saturated NH4C1 (aq. 20 mL), diluted with 50 mL water, extracted with EA (30 mL) three times. The combined organic layer was washed with water (30 mL) twice and brine (20 mL) once, dried over Na2SO4 and concentrated to give crude product which was purified by flash column (PE/EA = 1/1) to give compound 47b (140 mg) as a yellow oil. MS calc’d 419 (MW), measured 419 (MW).
  • 11
  • [ 1251011-05-8 ]
  • [ 2403784-52-9 ]
  • [ 2403784-53-0 ]
YieldReaction ConditionsOperation in experiment
140 mg With N-ethyl-N,N-diisopropylamine In butan-1-ol at 140℃; for 2h; 51.3 Step 3: preparation of tert- butyl 8-[6-(2-trimethylsilylethoxycarbonyl)-7,8-dihydro- 5//-pyrido[4,3-d]pyrimidin-2-yl]-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate(compound 51c) To the solution of 2-trimethylsilylethyl 2-chlo ro-7,8-di hydro-57/-pyrido[ 4, 3-d Ipyrimidine- 6-carboxylate (compound 51b, 200 mg, 0.64 mmol) in l-butanol (3 mL) was added N,N- diisopropylethylamine (0.22 mL, 1.27 mmol) and ferf-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2- carboxylate (CAS: 1251011-05-8, Vendor: PharmaBlock; 218 mg, 0.96 mmol). The solution was reacted under microwave at 140 °C for 2 hrs. After concentration, the residue was purified by prep-TLC (PE/EA = 2/1) to give compound 51c (140 mg) as a yellow gum. MS calc’d 506 (MEL), measured 506 (MEL).
  • 12
  • [ 1251011-05-8 ]
  • [ 2403784-46-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl / toluene / 3 h / 110 °C / Inert atmosphere 2: toluene-4-sulfonic acid / methanol / 5 h / 55 °C
  • 13
  • [ 1251011-05-8 ]
  • [ 2403784-47-2 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl / toluene / 3 h / 110 °C / Inert atmosphere 2: toluene-4-sulfonic acid / methanol / 5 h / 55 °C 3: potassium carbonate / acetonitrile / 2 h / 55 °C
  • 14
  • [ 1251011-05-8 ]
  • [ 2403782-92-1 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; (R)-2,2'-bis(diphenylphosphanyl)-1,1'-binaphthyl / toluene / 3 h / 110 °C / Inert atmosphere 2: toluene-4-sulfonic acid / methanol / 5 h / 55 °C 3: potassium carbonate / acetonitrile / 2 h / 55 °C 4: trifluoroacetic acid / dichloromethane / 1 h / 0 - 25 °C
  • 15
  • [ 1008526-70-2 ]
  • tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate [ No CAS ]
  • 16
  • [ 398489-26-4 ]
  • [ 1251011-05-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: triethylamine / ethanol / 16 h / 20 °C 2.1: palladium 10% on activated carbon; hydrogen / ethanol / 1650 °C 3.1: triethylamine / dichloromethane / 2 h / 0 - 20 °C 4.1: sodium hydride / 1,4-dioxane; mineral oil / 16 h / 0 - 80 °C 5.1: borane-THF / tetrahydrofuran / 16 h / 0 - 25 °C 5.2: 5 h / 0 - 70 °C
  • 17
  • [ 50-00-0 ]
  • [ 1251011-05-8 ]
  • [ 2414057-54-6 ]
YieldReaction ConditionsOperation in experiment
82% With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 16h; 38.6 Step 6: Synthesis of tert-butyl 8-methyl-5-oxa-2, 8-diazaspiro [3.5] nonane-2-carboxylate To a degassed mixture oftert-butyl 5-oxa-2, 8-diazaspiro [3.5] nonane-2-carboxylate (2.3g, 10.1mmol) and paraformaldehyde (1.52 g, 50.5 mmol) in MeOH (25mL) was added Pd/C (150 mg, 10%wt) and the mixture was degassed under N 2 atmosphere for three times and stirred under a H 2 balloon at 25 for 16 hrs. The mixture was filtered and the filtrate was concentrated to dryness to give desired product (2.0g, 82%yield) as colorless oil. MS (ESI) m/z: 243 (M+H) +.
  • 18
  • [ 1251011-05-8 ]
  • [ 1366647-33-7 ]
YieldReaction ConditionsOperation in experiment
100% With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 70℃; for 16h; Inert atmosphere; 2-Methyl-5-oxa-2,8-diazaspiro[3.5]nonane (127B) Lithium aluminium hydride (1M solution in tetrahydrofuran, 1.97 mL, 1.97 mmol, 3.0 eq) was added dropwise under nitrogen to a 0°C cooled solution of /er/-butyl 5-oxa-2,8- diazaspiro[3.5]nonane-2-carboxylate (127A) (150 mg, 0.657 mmol, 1.0 eq) in tetrahydrofuran (4.0 mL). The reaction was stirred at 0°C for 5 minutes, the cooling bath was removed and the reaction was then heated to 70°C for 16 h (effervescence was observed at 0°C and 35°C). The reaction mixture was cooled to 0°C and quenched by the slow addition of water (0.075 mL), aqueous sodium hydroxide solution (15%, 0.075 mL) and then water (0.22 mL). The cooling bath was removed and the reaction mixture was stirred for 15 minutes, magnesium sulfate was added and stirred for a further 40 minutes. The mixture was dried passing through a phase separator, washed with tetrahydrofuran and diethyl ether and then concentrated to dryness under reduced pressure to afford 2-methyl-5-oxa-2,8- diazaspiro[3.5]nonane (127B) as a pale brown oil. The sample was taken on into the next reaction without further purification. Yield: assumed 100%. NMR (400 MHz, CDCb) d 3.63 - 3.56 (m, 2H), 3.47 - 3.43 (m, 2H), 3.00 (s, 2H), 2.94 - 2.86 (m, 2H), 2.83 - 2.79 (m, 2H), 2.40 (s, 3H), Ntf not observed.
With lithium aluminium tetrahydride In tetrahydrofuran at 0 - 70℃; for 16h; 2-Methyl-5-oxa-2,8-diazaspiro[3.5]nonane (127B) Lithium aluminium hydride (1M solution in tetrahydrofuran, 1.97 mL, 1.97 mmol, 3.0 eq) was added dropwise under nitrogen to a 0°C cooled solution of tert- butyl 5-oxa-2,8- diazaspiro[3.5]nonane-2-carboxylate (127A) (150 mg, 0.657 mmol, 1.0 eq) in (0775) tetrahydrofuran (4.0 mL). The reaction was stirred at 0°C for 5 minutes, the cooling bath was removed and the reaction was then heated to 70°C for 16 h (effervescence was observed at 0°C and 35°C). The reaction mixture was cooled to 0°C and quenched by the slow addition of water (0.075 mL), aqueous sodium hydroxide solution (15%, 0.075 mL) and then water (0.22 mL). The cooling bath was removed and the reaction mixture was stirred for 15 minutes, magnesium sulfate was added and stirred for a further 40 minutes. The mixture was dried passing through a phase separator, washed with tetrahydrofuran and diethyl ether and then concentrated to dryness under reduced pressure to afford 2- methyl-5-oxa-2,8-diazaspiro[3.5]nonane (127B) as a pale brown oil. The sample was taken on into the next reaction without further purification. (0776) Yield: assumed 100%. NMR (400 MHz, CDCb) d 3.63 - 3.56 (m, 2H), 3.47 - 3.43 (m, 2H), 3.00 (s, 2H), 2.94 - 2.86 (m, 2H), 2.83 - 2.79 (m, 2H), 2.40 (s, 3H), Nif not observed.
  • 19
  • [ 1251011-05-8 ]
  • [ 2309427-01-6 ]
  • [ 2309427-10-7 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 70℃; for 17h; 15.1 First Step Compound 1h (70 mg, 176 μmol, 1 eq), 15a (40.2 mg, 176 μmol, 1 eq) and diisopropylethylamine (22.7 mg, 176 μmol, 30.7 μL, 1 eq) were dissolved in dimethyl sulfoxide (5 mL). The mixed solution was allowed to react at 70° C. for 17 hours. After the reaction was complete and the reaction solution was cooled, 10 mL water and 30 mL ethyl acetate were added to the reaction solution for extraction. Then, the organic phase was added with water to extract excess dimethyl sulfoxide. The organic phase was dried over anhydrous sodium sulfate, concentrated, and subjected to planar chromatography (0/1 petroleum ether/ethyl acetate) to give compound 15b. MS-ESI calculated for [M+H]+:590, found: 590.
  • 20
  • [ 1251011-05-8 ]
  • [ 2648950-00-7 ]
  • [ 2648952-91-2 ]
YieldReaction ConditionsOperation in experiment
36 mg With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate at 20℃; for 1h; 1.8 Synthesis of tert-butyl 8-{2-[4-(4-chlorophenyl)-5-(pyridin-4-yl)-1H-imidazol-1-yl]acetyl}-5-oxa-2,8- diazaspiro[3.5]nonane-2-carboxylate / Intermediate 58 tert-Butyl 5-oxa-2,8-diazaspiro[3.5]nonane- 2-carboxylate (45 mg, 0.197 mmol) and 2-[4-(4-chlorophenyl)-5-(4-pyridyl)imidazol-1-yl]acetic acid;2,2,2-trifluoroacetic acid (Intermediate 2a) (100 mg, 0.183 mmol) were dissolved in a solution of EtOAc (2 mL) and DIPEA (160 uL, 0.916 mmol) then T3P (50%, 220 uL, 0.370 mmol) was added. The reaction was stirred at RT for 1 h. The reaction was concentrated in vacuo. The crude product was purified via preparative HPLC (Method A1) to afford the title compound (36 mg, 37% yield) as a brown solid.1H NMR (500 MHz, Chloroform-d) δ 8.72 - 8.69 (m, 2H), 7.65 (s, 1H), 7.39 - 7.35 (m, 2H), 7.25 - 7.23 (m, 2H), 7.23 - 7.20 (m, 2H), 4.67 - 4.58 (m, 2H), 3.85 - 3.76 (m, 2H), 3.73 - 3.59 (m, 3H), 3.58 - 3.48 (m, 3H), 3.41 - 3.37 (m, 1H), 3.31 - 3.26 (m, 1H), 1.45 (s, 9H). LCMS (Analytical Method H) Rt = 0.56 min, MS (ESIpos): m/z 524.4, 526.2 [M+H]+, Purity = 100%.
  • 21
  • [ 1600960-38-0 ]
  • [ 1251011-05-8 ]
  • [ 2758809-41-3 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine In tetrahydrofuran at 65℃; for 16h; Intermediate _ 30: tert- butyl 4-{2-[(4-bromopyridin-2- yl)carbamoyl]ethyl}piperazine-1-carboxylate General procedure: Intermediate 29 (150 mg, 0.66 mmol) was dissolved in THF (5 mL), 1- piperazinecarboxylic acid tert-butyl ester (2701 mg, 1.45 mmol) was added and the reaction solution was stirred at 65 °C for 16 hrs. Volatiles were removed under vacuum and the residue was purified by flash chromatography on Biotage silica cartridge (from cHex to EtOAc) to afford Intermediate 30 (125 mg, 0.30 mmol, 46% yield) as foam. (0372) LC-MS (ESI): mlz (M+1): 415.2 (Method 1)
100% With triethylamine In tetrahydrofuran at 65℃; for 16h; Intermediate _ 30: tert- butyl 4-{2-[(4-bromopyridin-2- yl)carbamoyl]ethyl}piperazine-1-carboxylate General procedure: Intermediate 29 (150 mg, 0.66 mmol) was dissolved in THF (5 mL), 1- piperazinecarboxylic acid tert-butyl ester (2701 mg, 1.45 mmol) was added and the reaction solution was stirred at 65 °C for 16 hrs. Volatiles were removed under vacuum and the residue was purified by flash chromatography on Biotage silica cartridge (from cHex to EtOAc) to afford Intermediate 30 (125 mg, 0.30 mmol, 46% yield) as foam. (0372) LC-MS (ESI): mlz (M+1): 415.2 (Method 1)
  • 22
  • [ 1251011-05-8 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C 1.2: 20 °C 2.1: trifluoroacetic acid / dichloromethane / 0 - 25 °C
  • 23
  • [ 1251011-05-8 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C 1.2: 20 °C 2.1: trifluoroacetic acid / dichloromethane / 0 - 25 °C 3.1: Cs2CO3 / N,N-dimethyl-formamide / 16 h / 90 °C
  • 24
  • [ 1251011-05-8 ]
  • [ 2839409-34-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: Cs2CO3 / N,N-dimethyl-formamide / 16 h / 90 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 25 °C
  • 25
  • [ 1251011-05-8 ]
  • [ 2839407-39-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: Cs2CO3 / N,N-dimethyl-formamide / 16 h / 90 °C 2.1: trifluoroacetic acid / dichloromethane / 2 h / 25 °C 3.1: N-ethyl-N,N-diisopropylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate / N,N-dimethyl-formamide / 0.17 h / 20 °C 3.2: 20 °C
  • 26
  • [ 4472-44-0 ]
  • [ 1251011-05-8 ]
  • [ 2839409-33-3 ]
YieldReaction ConditionsOperation in experiment
68.3% With Cs2CO3 In N,N-dimethyl-formamide at 90℃; for 16h; 28.1 first step To a solution of 28a (1 g, 4.39 mmol) in DMF (20 mL) was added Cs2CO3 (2.9 g, 8.8 mmol) and 2-chloro-4,6-dimethylpyrimidine (0.69 g, 4.84 mmol), the mixture was 90°C After stirring for 16 hours, the reaction solution was quenched by adding water (30 mL), extracted with dichloromethane (30 mL*3), the organic phases were combined, dried and concentrated, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate system) to obtain 8-(4). ,6-Dimethylpyrimidin-2-yl)-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate tert-butyl ester (Compound 28b) (1g, pale yellow solid, 68.3%).
  • 27
  • [ 1186050-58-7 ]
  • [ 1251011-05-8 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
59.6% Stage #1: 6-fluoro-2-(2H-1,2,3-triazol-2-yl)benzoic acid; tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate 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 0.166667h; Stage #2: tert-butyl 5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate In N,N-dimethyl-formamide at 20℃; 27.1 first step Combine 2-fluoro-6-(2H-1,2,3-triazol-2-yl)benzoic acid (1.0 g, 4.83 mmol) and HATU (2.8 g, 7.2 mmol), DIEA (1.25 g, 9.6 mmol) A mixture of DMF (30 mL) was stirred at room temperature for 10 minutes. 27a (1.1 g, 4.82 mmol) was then added and the resulting mixture was stirred at room temperature overnight. After cooling, the reaction solution was diluted with 100 mL of ethyl acetate, washed with water (50 mL*3), the organic phases were combined, dried and concentrated, and the residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate system) to obtain 8-(2-fluoro- 6-(2H-1,2,3-triazol-2-yl)benzoyl)-5-oxa-2,8-diazaspiro[3.5]nonane-2-carboxylate tert-butyl ester ( Compound 27b) (1.2 g, white solid, 59.6%).
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