Home Cart 0 Sign in  
X

[ CAS No. 23794-16-3 ] {[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 23794-16-3
Chemical Structure| 23794-16-3
Chemical Structure| 23794-16-3
Structure of 23794-16-3 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 23794-16-3 ]

Related Doc. of [ 23794-16-3 ]

Alternatived Products of [ 23794-16-3 ]

Product Details of [ 23794-16-3 ]

CAS No. :23794-16-3 MDL No. :MFCD09702373
Formula : C7H5BrClNO Boiling Point : -
Linear Structure Formula :- InChI Key :BZWBRLWSWBQIBX-UHFFFAOYSA-N
M.W : 234.48 Pubchem ID :16720431
Synonyms :

Calculated chemistry of [ 23794-16-3 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 2
Num. H-bond acceptors : 2.0
Num. H-bond donors : 0.0
Molar Refractivity : 47.31
TPSA : 29.96 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.1 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.61
Log Po/w (XLOGP3) : 2.29
Log Po/w (WLOGP) : 2.31
Log Po/w (MLOGP) : 1.2
Log Po/w (SILICOS-IT) : 2.84
Consensus Log Po/w : 2.05

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.01
Solubility : 0.23 mg/ml ; 0.000982 mol/l
Class : Soluble
Log S (Ali) : -2.56
Solubility : 0.651 mg/ml ; 0.00278 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.85
Solubility : 0.0328 mg/ml ; 0.00014 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.86

Safety of [ 23794-16-3 ]

Signal Word:Danger Class:8
Precautionary Statements:P501-P260-P270-P264-P280-P303+P361+P353-P301+P330+P331-P363-P301+P312+P330-P304+P340+P310-P305+P351+P338+P310-P405 UN#:3261
Hazard Statements:H302-H314 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 23794-16-3 ]

* 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 [ 23794-16-3 ]

[ 23794-16-3 ] Synthesis Path-Downstream   1~50

  • 1
  • [ 14294-11-2 ]
  • [ 23794-16-3 ]
  • [4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-pyridin-2-yl-amine [ No CAS ]
  • 3
  • [ 948914-01-0 ]
  • [ 23794-16-3 ]
  • 4-nitro-1<i>H</i>-indole-2-carboxylic acid <i>N</i>'-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-hydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% In methanol Heating;
  • 4
  • [ 948914-03-2 ]
  • [ 23794-16-3 ]
  • 6-nitro-1<i>H</i>-indole-2-carboxylic acid <i>N</i>'-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-hydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In methanol Heating;
  • 5
  • [ 948914-04-3 ]
  • [ 23794-16-3 ]
  • 7-nitro-N'-[4-(2-chloropyridin-4-yl)-1,3-thiazol-2-yl]-1H-indole-2-carbohydrazide [ No CAS ]
YieldReaction ConditionsOperation in experiment
73% In methanol Heating;
  • 6
  • [ 23794-16-3 ]
  • [ 622-52-6 ]
  • [4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-<i>p</i>-tolyl-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
70% In ethanol for 6h; Heating;
  • 7
  • [ 23794-16-3 ]
  • [ 614-78-8 ]
  • [4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-<i>o</i>-tolyl-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% In ethanol for 6h; Heating;
  • 8
  • [ 23794-16-3 ]
  • [ 4947-89-1 ]
  • (3-chloro-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]
  • 9
  • [ 23794-16-3 ]
  • [ 117174-84-2 ]
  • (3-chloro-4-methyl-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]
  • 10
  • [ 23794-16-3 ]
  • [ 41440-07-7 ]
  • [4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-(3-methyl-pyridin-2-yl)-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% In ethanol for 6h; Heating;
  • 12
  • [ 23794-16-3 ]
  • [ 3696-23-9 ]
  • (4-chloro-phenyl)-[4-(2-chloro-pyridin-4-yl)-thiazol-2-yl]-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% In ethanol for 6h; Heating;
  • 13
  • [ 23794-16-3 ]
  • [ 1015242-47-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: Ethyl isobutyrate With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 2h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In tetrahydrofuran at -78 - 20℃; 141.a a) 2-[2-(2-Chloro-pyridin-4-yl)-2-oxo-ethyl]-4-methyl-3-oxo-pentanoic acid ethyl ester. 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (500 mg) is stirred in a mixture of 20 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Ethyl isobutyrate (337 mg) in 5 ml THF is added drop wise to a solution of LiHMDS (2.1 ml 1.0 M solution) in 5 ml THF at - 78 0C. After stirring for 2 hours at -78 0C 2-bromo-1-(2- chloro-pyridin-4-yl)-ethanone (see above) dissolved in 3 ml THF is added drop wise. The reaction mixture is allowed to warm to room temperature overnight. Aqueous NH4Cl solution is added and the mixture is extracted with ethyl acetate. After removal of the solvent the title compound is obtained as a pale yellow oil. 1H-NMR (400 MHz, DMSO-d6): 1.07 (d, 3H), 1.10 (d, 3H), 1.19 (t, 3H), 2.98 (sept, 1 H), 3.50- 3.68 (m, 2H), 4.13 (q, 2H), 4.33 (t, 1H), 7.84 (d, 1H), 7.96 (s, 1H), 8.63 (d, 1H). MS (ESI+) m/z: 312 [MH]+.
  • 14
  • [ 23794-16-3 ]
  • 4-(5-(2-chloropyridin-4-yl)-3-ethoxycarbonyl-1H-pyrrol-2-yl)-piperidine-1-carboxylic acid tert-butyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: 4-(2-ethoxycarbonylacetyl)piperidine-1-carboxylic acid tert-butyl ester With sodium hydride In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In tetrahydrofuran at 0 - 20℃; Stage #3: With ammonium acetate In ethanol at 20℃; 144.b b) 4-[5-(2-Chloro-pyridin-4-yl)-3-ethoxycarbonyl-1 H-pyrrol-2-yl]-piperidine-1 -carboxylic acid tert-butyl ester. NaH (660 mg, 14.5 mmol) is added to a solution of 4-(2-ethoxycarbonyl-acetyl)-piperidine-1- carboxylic acid tert-butyl ester in 150 ml of THF at 0 0C the mixture is allowed to react for 15 min at room temperature to give a clear solution. A solution of 3.5 g (14.9 mmol) 1-(2-chloro- pyridin-4-yl)-ethanone (free base, example 1c) in THF is added. The reaction is stirred for 1 h at 0 0C and at room temperature over night. Ice is added, followed by extraction with ethyl acetate. The combined organic layers are washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. The residue is dissolved in 50 ml of ethanol. After adding 4.20 g(54.5 mmol) NH4OAc the reaction is stirred at room temperature over night. Ice is added, followed by extraction with ethyl acetate. The combined organic layers are washed with sat. NaHCO3 and brine, dried over Na2SO4 and concentrated. The crude product is purified by silica gel chromatography (hexanes-ethyl acetate gradient).1H-NMR (400 MHz, DMSO-d6): 1.27 (t, 3H), 1.47 (s, 9H), 1.75-1.81 (m, 2H), 1.90-1.97 (m,2H), 2.85-2.95 (m, 2H), 3.86 (t, 1H), 4.09-4.14 (m, 2H), 4.31 (q, 2H), 7.09 (s, 1H), 7.39 (d,1H), 7.52 (s, 1H), 8.28 (d, 1 H), 9.91 (s, 1H, NH).MS (ESI+) m/z: 434 [MH]+.
  • 15
  • [ 286440-10-6 ]
  • [ 23794-16-3 ]
  • BrCH3OC6H3CON2H2C3HNSC5H3NCl [ No CAS ]
YieldReaction ConditionsOperation in experiment
64% In ethanol for 10h; Heating;
  • 16
  • [ 23794-16-3 ]
  • [ 151094-90-5 ]
  • C10H10N3OS2CH2COC5H3NCl [ No CAS ]
YieldReaction ConditionsOperation in experiment
65% With sodium acetate In methanol Heating;
  • 18
  • [ 23794-16-3 ]
  • [ 933986-15-3 ]
YieldReaction ConditionsOperation in experiment
Stage #1: carbethoxyacetamidine hydrochloride With sodium ethanolate In ethanol at 0℃; for 0.333333h; Stage #2: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one In ethanol at 0 - 20℃; for 16h; 1.b b) 2-Amino-5-(2-chloro-pyridin-4-yl)-1 H-pyrrole-3-carboxylic acid ethyl ester2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (3.0 g, 12.8 mmol) is stirred in a mixture of 35 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Carbamimidoyl-acetic acid ethyl ester hydrochloride (4.26 g, 25.6 mmol) (Liebigs Ann. Chem. 1977, 1895) is suspended in 10 ml ethanol and cooled to 0 oC. To this mixture sodium ethoxide (1.74 g, 25.6 mmol) is added. The mixture is stirred for 20 minutes, then 2- bromo-1-(2-chloro-pyridin-4-yl)-ethanone in 10 ml ethanol is added dropwise. After stirring at r.t. for 16 hours the reaction is stopped by adding 100 ml water and the mixture is extracted with ethylacetate. The material obtained after removal of the solvent is used for further steps without purification.1H-NMR (400 MHZ1 DMSO-d6): 1.27 (t, 3H), 4.16 (q, 2H), 5.97 (s, 2H), 6.98 (d, 1 H), 7.44 (dd, 1H), 7.55 (d, 1 H), 8.14 (d, 1H), 11.1 (s, 1 H). MS (ESI+) m/z: 266 [MH]+
  • 19
  • [ 23794-16-3 ]
  • [ 56-06-4 ]
  • [ 933986-22-2 ]
YieldReaction ConditionsOperation in experiment
With sodium ethanolate; In ethanol; for 16h;Heating / reflux; To a solution of <strong>[56-06-4]2,6-diamino-4-hydroxypyrimidine</strong> (269 mg, 2.1 mmol) and sodium ethoxide (159 mg, 2.3 mmol) in 8 ml ethanol is added 2-bromo-1-(2-chloro-pyridin-4-yl)-ethanone (500 mg, 2.1 mmol) (free base prepared as described in example 1 b). The mixture is heated under reflux for 16 hours and then quenched by addition of water. The white precipitate which forms is filtered and titurated with ether to give the target molecule.1H-NMR (400 MHZ, DMSO-d6): 6.34 (s, 2H), 7.17 (s, 1H), 7.65 (d, 1 H), 7.77 (s, 1 H), 8.22 (d, 1 H), 10.41 (brs, 1 H), 11.7 (brs, 1 H). MS (ESI+) m/z: 262 [MH]+
  • 20
  • 2-bromo-1-(2-chloro-4-pyridinyl)-ethanone hydrobromide [ No CAS ]
  • [ 23794-16-3 ]
YieldReaction ConditionsOperation in experiment
With sodium hydrogencarbonate In diethyl ether; water 1.b 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (3.0 g, 12.8 mmol) is stirred in a mixture of 35 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Carbamimidoyl-acetic acid ethyl ester hydrochloride (4.26 g, 25.6 mmol) (Liebigs Ann. Chem. 1977, 1895) is suspended in 10 ml ethanol and cooled to 0 oC. To this mixture sodium ethoxide (1.74 g, 25.6 mmol) is added. The mixture is stirred for 20 minutes, then 2- bromo-1-(2-chloro-pyridin-4-yl)-ethanone in 10 ml ethanol is added dropwise. After stirring at r.t. for 16 hours the reaction is stopped by adding 100 ml water and the mixture is extracted with ethylacetate. The material obtained after removal of the solvent is used for further steps without purification.1H-NMR (400 MHZ1 DMSO-d6): 1.27 (t, 3H), 4.16 (q, 2H), 5.97 (s, 2H), 6.98 (d, 1 H), 7.44 (dd, 1H), 7.55 (d, 1 H), 8.14 (d, 1H), 11.1 (s, 1 H). MS (ESI+) m/z: 266 [MH]+
With sodium hydrogencarbonate In water 141.a a) 2-[2-(2-Chloro-pyridin-4-yl)-2-oxo-ethyl]-4-methyl-3-oxo-pentanoic acid ethyl ester. 2-Bromo-1-(2-chloro-pyridin-4-yl)-ethanone hydrobromide (500 mg) is stirred in a mixture of 20 ml aqueous NaHCO3 solution and ether to liberate the free base. The aqueous phase is extracted two more times with ether, the ether phase dried and concentrated. Ethyl isobutyrate (337 mg) in 5 ml THF is added drop wise to a solution of LiHMDS (2.1 ml 1.0 M solution) in 5 ml THF at - 78 0C. After stirring for 2 hours at -78 0C 2-bromo-1-(2- chloro-pyridin-4-yl)-ethanone (see above) dissolved in 3 ml THF is added drop wise. The reaction mixture is allowed to warm to room temperature overnight. Aqueous NH4Cl solution is added and the mixture is extracted with ethyl acetate. After removal of the solvent the title compound is obtained as a pale yellow oil. 1H-NMR (400 MHz, DMSO-d6): 1.07 (d, 3H), 1.10 (d, 3H), 1.19 (t, 3H), 2.98 (sept, 1 H), 3.50- 3.68 (m, 2H), 4.13 (q, 2H), 4.33 (t, 1H), 7.84 (d, 1H), 7.96 (s, 1H), 8.63 (d, 1H). MS (ESI+) m/z: 312 [MH]+.
  • 21
  • [ 23794-16-3 ]
  • [ 5699-40-1 ]
  • C10H11ClN4O2 [ No CAS ]
  • 23
  • [ 23794-16-3 ]
  • [ 621-40-9 ]
  • [ 1187669-37-9 ]
YieldReaction ConditionsOperation in experiment
94% In ethanol for 1h; Reflux;
94% Stage #1: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one; (3-methylphenyl)thiourea In ethanol for 1h; Heating; Reflux; Stage #2: With ammonia In ethanol; water at 0 - 20℃; for 1h; 1-87 Example 1-87 4-(2-Chloro-4-pyridinyl)-7V-(3-methylphenyl)-l,3-thiazol-2-amine (150). [0359] 4-(2-Chloro-4-pyridinyl)-7V-(3-methylphenyl)-l,3-thiazol-2-amine (150). A mixture of 2-bromo-l-(2-chloro-4-pyridinyl)ethanone (0.51 g, 2.2 mmol) and 3-methylphenylthiourea (4) (0.36 g, 2.2 mmol) in EtOH (35 mL) was stirred at reflux temperature for 1 h. The mixture was cooled to 20 0C, diluted with water (80 niL), the pH adjusted to ca. 8 with aqueous NH3 and the mixture stirred at 0 °C for 1 h. The precipitate was filtered, washed with water (5 mL) and dried. The crude solid was purified by column chromatography, eluting with EtOAc, to give amine 150 (0.62 g, 94%) as a white powder: mp (EtO Ac/pet, ether) 195-197 0C; 1H NMR δ 10.30 (s, 1 H, NH), 8.45 (br d, J= 5.1 Hz, 1 H, H-6'), 7.93 (br d, J= 1.2 Hz, 1 H, H-3'), 7.87 (dd, J= 5.2, 1.4 Hz, 1 H, H-5'), 7.84 (s, 1 H, H-5), 7.55 (br d, J= 8.0 Hz, 1 H, H-6"), 7.47 (br s, 1 H, H-2"), 7.25 (br t, J= 7.8 Hz, 1 H, H-5"), 6.82 (br d, J= 7.4 Hz, 1 H, H-4"), 2.33 (s, 3 H, CH3); 13C NMR δ 163.6, 151.0 (2), 150.3, 146.2, 144.4, 140.6, 138.1, 128.8, 122.3, 119.7, 117.6, 114.2, 109.1, 21.9; MS m/z 302.5 (MH+, 100%). Anal, calcd for Ci5Hi2ClN3S: C, 59.70; H, 4.01; N, 13.92. Found: C, 59.75; H, 4.07; N, 13.82%.
  • 24
  • [ 23794-16-3 ]
  • [ 15827-84-6 ]
  • [ 1289555-46-9 ]
YieldReaction ConditionsOperation in experiment
Stage #1: 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one; 4-aminopyridine-3-carbonitrile In ethanol for 2h; Reflux; Stage #2: With sodium hydrogencarbonate In ethanol for 4h; Reflux; 1.3 6-Aminonicotinonitnle (2 g, 16.8 mmoi) and 2-bromo-1-(2-ch]oro-4-yl)-ethanone (3.9 g, 16.8 mmol) were refluxed in ethanol (100 ml) for 2h. Pale-yellow precipitate formed. NaHC03 (2 g) was added to the cooled reaction mixture and the mixture was refluxed for another 4h. After cooling, the precipitate was filtrated, washed with water and recrystalized from ethyl acetate to give the 2-(2-chloropyridin-4-yl)-6-cyano-imidazo[1 ,2-a]pyridine (1.7 g). 1 H NMR (300 MHz, D SO~cf6) δ: 8.70 (d, 1H) 8.30 (d, 1 H) 7.63 (s, 1 H) 7.35 (d, 1H) 7.29 (d, 1 H) 7.21 (dd, 1 H) 7.14 (dd, H) ; MS (ES) miz (M+H) 255.7
  • 25
  • [ 23794-16-3 ]
  • [ 1312814-59-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5
  • 26
  • [ 23794-16-3 ]
  • [ 1312814-77-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5
  • 27
  • [ 23794-16-3 ]
  • [ 1312814-47-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 28
  • [ 23794-16-3 ]
  • [ 1312814-67-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5
  • 29
  • [ 23794-16-3 ]
  • [ 1354531-07-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 30
  • [ 23794-16-3 ]
  • [ 1312814-64-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C 4: sodium cyanoborohydride / acetonitrile / 15 h / 20 °C / pH 5
  • 31
  • [ 23794-16-3 ]
  • [ 1312814-22-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 32
  • [ 23794-16-3 ]
  • [ 1312814-48-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 33
  • [ 23794-16-3 ]
  • [ 1312814-57-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 34
  • [ 23794-16-3 ]
  • [ 1312814-60-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 35
  • [ 23794-16-3 ]
  • [ 1312814-78-0 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 36
  • [ 23794-16-3 ]
  • [ 1312814-83-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 37
  • [ 23794-16-3 ]
  • [ 1312814-73-5 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 38
  • [ 23794-16-3 ]
  • [ 1312814-68-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1: ammonium acetate / ethanol 2: 4,5-bis(diphenylphosphono)-9,9-dimethylxanthene; palladium diacetate; sodium t-butanolate / N,N-dimethyl-formamide / Microwave irradiation 3: trifluoroacetic acid / 20 °C
  • 39
  • [ 23794-16-3 ]
  • [ 1260585-11-2 ]
  • [ 1523413-73-1 ]
YieldReaction ConditionsOperation in experiment
With potassium phosphate In acetonitrile at 20℃;
  • 40
  • [ 14222-60-7 ]
  • [ 23794-16-3 ]
  • 4-(2-chloropyridin-4-yl)-2-(2-propylpyridin-4-yl)thiazole [ No CAS ]
  • 41
  • [ 23794-16-3 ]
  • tert-butyl 9,11-dioxo-8-(2,4,6-trimethoxybenzyl)-2,8-diazaspiro[5.5]undecane-2-carboxylate [ No CAS ]
  • tert-butyl 2'-(2-chloropyridin-4-yl)-4'-oxo-5'-(2,4,6-trimethoxybenzyl)-1',4',5',6'-tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With ammonium acetate; acetic acid In ethanol at 0 - 80℃; for 5h; 2.9 tert-butyl-2,-(2-chloropyridin-4-yl)-4,-oxo-5,-(2,4,6-trimethoxybenzyl)-l,,4,,5,,6'- tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-l-carboxylate (9). tert-butyl-2,-(2-chloropyridin-4-yl)-4,-oxo-5,-(2,4,6-trimethoxybenzyl)-l,,4,,5,,6'- tetrahydro spiro[piperidine-3,7'-pyrrolo[3,2-c]pyridine]-l-carboxylate (9). To a solution of tert-butyl 9,1 l-dioxo-8-(2,4,6-trimethoxybenzyl)-2,8-diazaspiro[5.5]undecane-2-carboxylate 8 (1.0 g, 2.0 mmol) in ethanol (30 mL), 2-bromo-l-(2-chloropyridin-4-yl)ethanone INT-40 (1.0 g, 4.0 mmol) was added at 0 °C. To this ammonium acetate (499 mg, 6 mmol) and acetic acid (250 mg, 4.0 mmol) were added. The resulting mixture was heated at 80 °C and for 5 h. The reaction mixture was concentrated under reduced pressure and the residue was partitioned between water (100 mL) and ethyl acetate (150 mL). The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to afford 9 (350 mg, 27%) as a brown solid. 1H NMR (400 MHz, DMSO-d6) δ 1.36 (s, 9H), 1.56 (s, 2H), 3.0 (d, J = 12.8 Hz, 1H), 3.3 (brs, 1H), 3.72 (s, 7H), 3.76 (s, 4H), 3.82 (brs, 2H), 4.0 (d, J = 13.2 Hz, 1H), 5.0 (brs, 1H), 6.62 (s, 2H), 7.16 (d, J = 2.2 Hz, 1H), 7.68- 7.69 (dd, J = 1.4, 5.3 Hz, 1H), 7.82 ( d, J = 1.4 Hz, 1H), 8.3 (d, J = 4.5 Hz, 1H), 11.5 (s, 1H). MS m/z (M+H): 453.3.
  • 42
  • [ 23794-16-3 ]
  • [ 6228-73-5 ]
  • 4-(2-chloropyridin-4-yl)-2-cyclopropyloxazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
13.2 g With silver trifluoromethanesulfonate In ethyl acetate at 70℃; Darkness; Inert atmosphere; 2 Step 2: 4-(2-Chloropyridin-4-yl)-2-cyclopropyloxazole A mixture of 2-bromo-l-(2-chloropyridin-4-yl)ethanone (20 g, 85 mmol), cyclopropanecarboxamide (9.07 g, 106 mmol), AgOTf (43.83 g, 170.6 mmol), and EtOAc (300 mL) was stirred at 70 °C overnight in darkness under N2 and then allowed to cool to rt. Brine (300 mL) was added to the mixture, and the mixture was stirred for 3 h and filtered. The aqueous layer was separated and extracted with EtOAc (3x300 mL). The combined organic layers were washed (2x300 mL saturated NaHC03 and then 200 mL brine), dried (Na2S04), filtered, and concentrated. The residue was purified by silica gel chromatography (petroleum ether/EtOAc = 9/1) to give 4-(2-chloropyridin-4-yl)-2-cyclopropyloxazole (13.2 g, 70%) as a yellow solid. 1H NMR (400 MHz, CDCl3): d 8.38 (d, 1H), 7.92 (s, 1H), 7.66 (d, 1H), 7.49 (d, 1H), 2.17-2.09 (m, 1H), 1.18-1.07 (m, 4H); LCMS 220.9 [M+H]+.
  • 43
  • [ 23794-16-3 ]
  • [ 50607-30-2 ]
  • [ 724726-05-0 ]
YieldReaction ConditionsOperation in experiment
63% With ammonium acetate In ethanol at 20℃; for 18h;
  • 44
  • [ 23794-16-3 ]
  • C24H34N2O7 [ No CAS ]
  • C31H39ClN4O6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonium acetate In ethanol at 80℃; for 16h;
  • 45
  • [ 23794-16-3 ]
  • 5-(2,2-difluoroethyl)-1-methylpiperidine-2,4-dione [ No CAS ]
  • (rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere; Intermediate 131 (1167) (rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one (Racemate) (rac)-5-(2,2-Difluoroethyl)-1-methylpiperidine-2,4-dione (see Intermediate 130, 1.00 g), 2- bro o-1-(2-chloropyridin-4-yl)ethan-1-one (1.23 g, 5.23 mmol) and ammonium acetate (1.21 g, 15.7 mmol) were dissolved in 39 ml_ 1-propanol and stirred at 120°C for 4 hours under nitrogen atmosphere. Most of the 1 -propanol was removed under reduced pressure. The residue was diluted with ethyl acetate and 2 M aqueous sodiumhydroxide solution. The layers were separated and the aquoeus layer was extracted with ethyl acetate once. The combined organic layers were dried using a waterresistant filter and the clear filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane. A yellow solid precipitated and was filtered off under vacuo to provide batch 1 of the desired product in 95% purity: 593 mg. The clear filtrate was concentrated under reduced pressure and purified by flash chromatography (25g ultra column, gradient dichloromethane/ethanol 0-10) to provide batch 2 of the target compound in 88% purity: 340 mg. Batch 1 and 2 were combined and used for the following reaction: 932 mg in 90% purity. LC-MS (Method 2): Rt = 0.88 min; MS (ESIpos): m/z = 326 [M+H]+ (1169) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.10 - 2.28 (m, 1 H) 2.32 - 2.46 (m, 1 H) 2.93 (s, 3 H) 3.32 (br dd, 1 H) 3.43 - 3.52 (m, 1 H) 3.72 (dd, 1 H) 6.11 - 6.56 (m, 1 H) 7.17 (d, 1 H) 7.69 (dd, 1 H) 7.80 (d, 1 H) 8.30 (d, 1 H) 11.87 (br s, 1 H).
With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere; Intermediate 131 (1167) (rac)-2-(2-chloropyridin-4-yl)-7-(2,2-difluoroethyl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one (Racemate) (rac)-5-(2,2-Difluoroethyl)-1-methylpiperidine-2,4-dione (see Intermediate 130, 1.00 g), 2- bro o-1-(2-chloropyridin-4-yl)ethan-1-one (1.23 g, 5.23 mmol) and ammonium acetate (1.21 g, 15.7 mmol) were dissolved in 39 ml_ 1-propanol and stirred at 120°C for 4 hours under nitrogen atmosphere. Most of the 1 -propanol was removed under reduced pressure. The residue was diluted with ethyl acetate and 2 M aqueous sodiumhydroxide solution. The layers were separated and the aquoeus layer was extracted with ethyl acetate once. The combined organic layers were dried using a waterresistant filter and the clear filtrate was concentrated under reduced pressure. The residue was diluted with dichloromethane. A yellow solid precipitated and was filtered off under vacuo to provide batch 1 of the desired product in 95% purity: 593 mg. The clear filtrate was concentrated under reduced pressure and purified by flash chromatography (25g ultra column, gradient dichloromethane/ethanol 0-10) to provide batch 2 of the target compound in 88% purity: 340 mg. Batch 1 and 2 were combined and used for the following reaction: 932 mg in 90% purity. LC-MS (Method 2): Rt = 0.88 min; MS (ESIpos): m/z = 326 [M+H]+ (1169) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.10 - 2.28 (m, 1 H) 2.32 - 2.46 (m, 1 H) 2.93 (s, 3 H) 3.32 (br dd, 1 H) 3.43 - 3.52 (m, 1 H) 3.72 (dd, 1 H) 6.11 - 6.56 (m, 1 H) 7.17 (d, 1 H) 7.69 (dd, 1 H) 7.80 (d, 1 H) 8.30 (d, 1 H) 11.87 (br s, 1 H).
  • 46
  • [ 23794-16-3 ]
  • 1,5,5-trimethylpiperidine-2,4-dione [ No CAS ]
  • 2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere; Intermediate 141 (1218) 2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one 1,5,5-Trimethylpiperidine-2,4-dione (see Intermediate 140, 1.03 g), 2-bromo-1-(2-chloropyridin- 4-yl)ethan-1-one (1.56 g, 6.64 mmol) and ammonium acetate (1.53 g, 19.9 mmol) were dissolved in 49 mL propanol stirred at 120 °C for 4 hours under argon atmosphere. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane and water. Between both layers a yellow precipitate was formed. It was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 1 of the target compound in 98% purity: 697 mg. The filtrate was extracted with dichloromethane three times, the combined organic layers were washed with water and brine, filtered through a silicone coated filter and concentrated under reduced pressure. The crude product was treated with dichloromethane and sonicated. The undissolved precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 2 of the target compound in 98% purity: 184 mg. Filtrate II was suspended in ~1 mL dichloromethane and diluted with MTBE. The formed precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 3 of the target compound in 76% purity: 73 g. The batches were combined and used for the following reaction. batch 1: (1220) LC-MS (Method 2): Rt = 0.90 min; MS (ESIpos): m/z = 290 [M+H]+ (1221) -NMR (400 MHz, DMSO-d6) d [ppm] = 1.32 (s, 6 H), 2.93 (s, 3 H), 3.31 (s, 2 H), 7.13 (d, 1 H), 7.71 (dd, 1 H), 7.84 (d, 1 H), 8.29 (d, 1 H), 11.58 (br s, 1 H).
With ammonium acetate In propan-1-ol at 120℃; for 4h; Inert atmosphere; Intermediate 141 (1218) 2-(2-chloropyridin-4-yl)-5,7,7-trimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one 1,5,5-Trimethylpiperidine-2,4-dione (see Intermediate 140, 1.03 g), 2-bromo-1-(2-chloropyridin- 4-yl)ethan-1-one (1.56 g, 6.64 mmol) and ammonium acetate (1.53 g, 19.9 mmol) were dissolved in 49 mL propanol stirred at 120 °C for 4 hours under argon atmosphere. The reaction mixture was concentrated under reduced pressure and treated with dichloromethane and water. Between both layers a yellow precipitate was formed. It was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 1 of the target compound in 98% purity: 697 mg. The filtrate was extracted with dichloromethane three times, the combined organic layers were washed with water and brine, filtered through a silicone coated filter and concentrated under reduced pressure. The crude product was treated with dichloromethane and sonicated. The undissolved precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 2 of the target compound in 98% purity: 184 mg. Filtrate II was suspended in ~1 mL dichloromethane and diluted with MTBE. The formed precipitate was filtered off, washed with water and dichloromethane and dried at 50°C under vacuo to provide batch 3 of the target compound in 76% purity: 73 g. The batches were combined and used for the following reaction. batch 1: (1220) LC-MS (Method 2): Rt = 0.90 min; MS (ESIpos): m/z = 290 [M+H]+ (1221) -NMR (400 MHz, DMSO-d6) d [ppm] = 1.32 (s, 6 H), 2.93 (s, 3 H), 3.31 (s, 2 H), 7.13 (d, 1 H), 7.71 (dd, 1 H), 7.84 (d, 1 H), 8.29 (d, 1 H), 11.58 (br s, 1 H).
  • 47
  • [ 23794-16-3 ]
  • 1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione [ No CAS ]
  • 2-(2-chloropyridin-4-yl)-5-methyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With ammonium hydroxide In propan-1-ol at 120℃; for 8h; Intermediate 161 (1286) 2-(2-chloropyridin-4-yl)-5- ethyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one To a stirred solution of 1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione (960 mg, 4.59 mmol, see Intermediate 13) in 1-propanol (17 ml) in a microwave tube was added 2-bromo-1-(2- chloropyridin-4-yl)ethan-1-one (1.08 g, 4.59 mmol, see Intermediate 118) and ammonium acetate (1.06 g, 13.8 mmol; CAS-RN:[631-61-8]) and the mixture was stirred at 120° C for 4 h. The mixture was concentrated in vacuum and the residue was heated to 120° C for 4 h. Dichloromethane and an aqueous sodium hydroxide solution (10%, w/v) were added and the mixture was stirred resulting in the precipitation of a solid. The solid was collected by filtration and dried in vacuum to give 1.46 g (92 % yield) of the title compound as a crude product that was used without further purification. (1288) LC-MS (Method 1): Rt = 0.92 min; MS (ESIpos): m/z = 344 [M+H]+ (1289) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.518 (2.24), 2.523 (1.55), 2.669 (0.50), 2.673 (0.53), 2.841 (0.42), 2.871 (0.56), 2.934 (16.00), 3.424 (0.52), 3.440 (1.15), 3.454 (0.71), 3.462 (1.47), 3.468 (1.47), 3.477 (0.83), 3.720 (0.73), 3.740 (0.70), 7.189 (4.92), 7.681 (1.56), 7.685 (1.70), 7.695 (1.58), 7.698 (1.80), 7.800 (2.55), 7.803 (2.47), 8.309 (2.29), 8.323 (2.23).
With ammonium hydroxide In propan-1-ol at 120℃; for 8h; Intermediate 161 (1286) 2-(2-chloropyridin-4-yl)-5- ethyl-7-(2,2,2-trifluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2- c]pyridin-4-one To a stirred solution of 1-methyl-5-(2,2,2-trifluoroethyl)piperidine-2,4-dione (960 mg, 4.59 mmol, see Intermediate 13) in 1-propanol (17 ml) in a microwave tube was added 2-bromo-1-(2- chloropyridin-4-yl)ethan-1-one (1.08 g, 4.59 mmol, see Intermediate 118) and ammonium acetate (1.06 g, 13.8 mmol; CAS-RN:[631-61-8]) and the mixture was stirred at 120° C for 4 h. The mixture was concentrated in vacuum and the residue was heated to 120° C for 4 h. Dichloromethane and an aqueous sodium hydroxide solution (10%, w/v) were added and the mixture was stirred resulting in the precipitation of a solid. The solid was collected by filtration and dried in vacuum to give 1.46 g (92 % yield) of the title compound as a crude product that was used without further purification. (1288) LC-MS (Method 1): Rt = 0.92 min; MS (ESIpos): m/z = 344 [M+H]+ (1289) -NMR (400 MHz, DMSO-d6) d [ppm]: 2.518 (2.24), 2.523 (1.55), 2.669 (0.50), 2.673 (0.53), 2.841 (0.42), 2.871 (0.56), 2.934 (16.00), 3.424 (0.52), 3.440 (1.15), 3.454 (0.71), 3.462 (1.47), 3.468 (1.47), 3.477 (0.83), 3.720 (0.73), 3.740 (0.70), 7.189 (4.92), 7.681 (1.56), 7.685 (1.70), 7.695 (1.58), 7.698 (1.80), 7.800 (2.55), 7.803 (2.47), 8.309 (2.29), 8.323 (2.23).
  • 48
  • 1-methylpiperidine-2,4-dione [ No CAS ]
  • [ 23794-16-3 ]
  • 2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
4.01 g With ammonium acetate In ethanol at 20℃; for 2h; Intermediate 99 (1033) 2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-methylpiperidine-2,4-dione (CAS-RN:[118263-97-1], 3.80 g, 29.9 mmol), ammonium acetate (9.19 g, 119 mmol) was added 90.5 ml_ of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 7.00 g, 29.9 mmol). The reaction was stirred at rt for 2 h. To the reaction was added 90 ml_ of water and the mixture was cooled down to 0 °C, stirred for 1 h, filtered and rinsed with water, yielding the desired product as a grey solid. The mother liquor was concentrated under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 4.01 g of the title compound. (1035) LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m/z = 262 [M+H]+ (1036) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (d, 1H), 7.63 (dd, 1H), 7.14 (d, 1 H), 3.56 (t, 2H), 2.99 - 2.87 (m, 5H).
21 g With ammonium acetate In ethanol at 25℃; for 16h; Intermediate 119 (1129) 2-(2-chloropyridin-4-yl)-5- ethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a solution of 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one (see Intermediate 118, 32.0 g) in ethanol (320 ml_) were added ammonium acetate (42.1 g, 546 mmol) and 1-methylpiperidine- 2,4-dione (CAS-RN:[118263-97-1], 19.1 g, 150 mmol) in one portion. The mixture was stirred at 25 °C for 16 hours. The reaction mixture was diluted with water (1280 ml_) and filtered. The filter cake was dried to give 21.0 g of the title compound as a yellow solid. (1131) LC-MS (Method 6): Rt = 0.747 min; MS (ESIpos): m/z = 262.2 [M+H]+. (1132) 1H NMR (400 MHz, DMSO-de): d [ppm] = 12.00 (s, 1H) 8.29 (d, 1H), 7.74 (d, 1H), 7.64 (dd, 1.6 Hz, 1 H), 7.15 (d, 1H), 3.56 (t, 2H), 3.95 (t, 2H), 2.92 (s, 3H).
4.01 g With ammonium acetate In ethanol at 20℃; for 2h; Intermediate 99 (1033) 2-(2-chloropyridin-4-yl)-5-methyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-methylpiperidine-2,4-dione (CAS-RN:[118263-97-1], 3.80 g, 29.9 mmol), ammonium acetate (9.19 g, 119 mmol) was added 90.5 ml_ of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 7.00 g, 29.9 mmol). The reaction was stirred at rt for 2 h. To the reaction was added 90 ml_ of water and the mixture was cooled down to 0 °C, stirred for 1 h, filtered and rinsed with water, yielding the desired product as a grey solid. The mother liquor was concentrated under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 4.01 g of the title compound. (1035) LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m/z = 262 [M+H]+ (1036) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (d, 1H), 7.63 (dd, 1H), 7.14 (d, 1 H), 3.56 (t, 2H), 2.99 - 2.87 (m, 5H).
21 g With ammonium acetate In ethanol at 25℃; for 16h; Intermediate 119 (1129) 2-(2-chloropyridin-4-yl)-5- ethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a solution of 2-bromo-1-(2-chloropyridin-4-yl)ethan-1-one (see Intermediate 118, 32.0 g) in ethanol (320 ml_) were added ammonium acetate (42.1 g, 546 mmol) and 1-methylpiperidine- 2,4-dione (CAS-RN:[118263-97-1], 19.1 g, 150 mmol) in one portion. The mixture was stirred at 25 °C for 16 hours. The reaction mixture was diluted with water (1280 ml_) and filtered. The filter cake was dried to give 21.0 g of the title compound as a yellow solid. (1131) LC-MS (Method 6): Rt = 0.747 min; MS (ESIpos): m/z = 262.2 [M+H]+. (1132) 1H NMR (400 MHz, DMSO-de): d [ppm] = 12.00 (s, 1H) 8.29 (d, 1H), 7.74 (d, 1H), 7.64 (dd, 1.6 Hz, 1 H), 7.15 (d, 1H), 3.56 (t, 2H), 3.95 (t, 2H), 2.92 (s, 3H).

  • 49
  • [ 5239-39-4 ]
  • [ 23794-16-3 ]
  • 2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
3.91 g With ammonium acetate In ethanol at 20℃; for 1.5h; Intermediate 94 (1005) 2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 6,6-dimethylpiperidine-2,4-dione (CAS-RN:[5239-39-4], 2.65 g, 18.8 mmol), ammonium acetate (5.25 g, 68.2 mmol) was added 52 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 4.00 g, 17.1 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 120 mL of water. The mixture was stirred for 2 h at rt, cooled down to 0 °C for 30 min, filtered and rinsed with water, yielding 3.91 g. of the title compound as a green solid. (1007) LC-MS (Method 4): Rt = 1.74 min; MS (ESIpos): m/z = 276 [M+H]+ (1008) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (s, 1 H), 7.68 - 7.58 (m, 1H), 7.13 (t, 1H), 7.07 (s, 1H), 2.80 (s, 2H), 1.26 (s, 6H).
3.91 g With ammonium acetate In ethanol at 20℃; for 1.5h; Intermediate 94 (1005) 2-(2-chloropyridin-4-yl)-6,6-dimethyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 6,6-dimethylpiperidine-2,4-dione (CAS-RN:[5239-39-4], 2.65 g, 18.8 mmol), ammonium acetate (5.25 g, 68.2 mmol) was added 52 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS-RN: [23794-16-3], 4.00 g, 17.1 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 120 mL of water. The mixture was stirred for 2 h at rt, cooled down to 0 °C for 30 min, filtered and rinsed with water, yielding 3.91 g. of the title compound as a green solid. (1007) LC-MS (Method 4): Rt = 1.74 min; MS (ESIpos): m/z = 276 [M+H]+ (1008) -NMR (400 MHz, DMSO-de) d [ppm] = 11.97 (s, 1H), 8.28 (d, 1H), 7.74 (s, 1 H), 7.68 - 7.58 (m, 1H), 7.13 (t, 1H), 7.07 (s, 1H), 2.80 (s, 2H), 1.26 (s, 6H).
  • 50
  • [ 23794-16-3 ]
  • [ 1501330-86-4 ]
  • 2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
1.06 g With ammonium acetate In ethanol at 20℃; for 1.5h; Intermediate 108 (1071) 2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-cyclopropylpiperidine-2,4-dione (CAS-RN:[ 1501330-86- 4], 1.27 g, 8.28 mmol) and ammonium acetate (1.91 g, 24.8 mmol) was added 41.4 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS- RN:[23794-16-3], 1.94 g, 8.28 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 60 mL of water and the mixture was cooled down to 0 °C. The reaction was concentrated under vacuum to remove the organic solvent. The aqueous layer was extracted 3 times with ethyl acetate. The organic layers were combined, dried over MgSCL and dried under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 1.06 g of the title compound. (1073) LC-MS (Method 4): Rt = 1.83 min; MS (ESIpos): m/z = 288 [M+H]+ -NMR (400 MHz, DMSO-de) d [ppm] = 12.07 - 11.82 (m, 1H), 8.28 (d, 1H), 7.73 (s, 1H), 7.63 (dd, 1H), 7.14 (d, 1H), 3.53 (t, 2H), 2.87 (t, 2H), 2.61 (dt, 1H), 0.73 (dt, 2H), 0.58 (q, 2H).
1.06 g With ammonium acetate In ethanol at 20℃; for 1.5h; Intermediate 108 (1071) 2-(2-chloropyridin-4-yl)-5-cyclopropyl-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one To a round bottom flask charged with 1-cyclopropylpiperidine-2,4-dione (CAS-RN:[ 1501330-86- 4], 1.27 g, 8.28 mmol) and ammonium acetate (1.91 g, 24.8 mmol) was added 41.4 mL of ethanol. To the solution was added 2-bromo-1-(2-chloro-4-pyridyl)ethanone (CAS- RN:[23794-16-3], 1.94 g, 8.28 mmol). The reaction was stirred at rt for 90 min. To the reaction was added 60 mL of water and the mixture was cooled down to 0 °C. The reaction was concentrated under vacuum to remove the organic solvent. The aqueous layer was extracted 3 times with ethyl acetate. The organic layers were combined, dried over MgSCL and dried under vacuum. The residual crude product was purified by flash chromatography on silica gel (dichloromethane / methanol 2 to 15 %). The title compound containing fractions were concentrated under reduced pressure to provide 1.06 g of the title compound. (1073) LC-MS (Method 4): Rt = 1.83 min; MS (ESIpos): m/z = 288 [M+H]+ -NMR (400 MHz, DMSO-de) d [ppm] = 12.07 - 11.82 (m, 1H), 8.28 (d, 1H), 7.73 (s, 1H), 7.63 (dd, 1H), 7.14 (d, 1H), 3.53 (t, 2H), 2.87 (t, 2H), 2.61 (dt, 1H), 0.73 (dt, 2H), 0.58 (q, 2H).
Recommend Products
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 23794-16-3 ]

Bromides

Chemical Structure| 569667-89-6

[ 569667-89-6 ]

2-Bromo-1-(2-chloropyridin-4-yl)ethanone hydrobromide

Similarity: 1.00

Chemical Structure| 23794-13-0

[ 23794-13-0 ]

2-Bromo-1-(6-chloropyridin-3-yl)ethanone

Similarity: 0.89

Chemical Structure| 237384-43-9

[ 237384-43-9 ]

2-Bromo-1-(2-chloropyridin-3-yl)ethanone

Similarity: 0.82

Chlorides

Chemical Structure| 569667-89-6

[ 569667-89-6 ]

2-Bromo-1-(2-chloropyridin-4-yl)ethanone hydrobromide

Similarity: 1.00

Chemical Structure| 23794-13-0

[ 23794-13-0 ]

2-Bromo-1-(6-chloropyridin-3-yl)ethanone

Similarity: 0.89

Chemical Structure| 185319-20-4

[ 185319-20-4 ]

1-(2,6-Dichloropyridin-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 23794-15-2

[ 23794-15-2 ]

1-(2-chloropyridine-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 1381812-94-7

[ 1381812-94-7 ]

1-(3-Chloroisoquinolin-6-yl)ethanone

Similarity: 0.83

Ketones

Chemical Structure| 569667-89-6

[ 569667-89-6 ]

2-Bromo-1-(2-chloropyridin-4-yl)ethanone hydrobromide

Similarity: 1.00

Chemical Structure| 23794-13-0

[ 23794-13-0 ]

2-Bromo-1-(6-chloropyridin-3-yl)ethanone

Similarity: 0.89

Chemical Structure| 185319-20-4

[ 185319-20-4 ]

1-(2,6-Dichloropyridin-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 23794-15-2

[ 23794-15-2 ]

1-(2-chloropyridine-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 1381812-94-7

[ 1381812-94-7 ]

1-(3-Chloroisoquinolin-6-yl)ethanone

Similarity: 0.83

Related Parent Nucleus of
[ 23794-16-3 ]

Pyridines

Chemical Structure| 569667-89-6

[ 569667-89-6 ]

2-Bromo-1-(2-chloropyridin-4-yl)ethanone hydrobromide

Similarity: 1.00

Chemical Structure| 23794-13-0

[ 23794-13-0 ]

2-Bromo-1-(6-chloropyridin-3-yl)ethanone

Similarity: 0.89

Chemical Structure| 185319-20-4

[ 185319-20-4 ]

1-(2,6-Dichloropyridin-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 23794-15-2

[ 23794-15-2 ]

1-(2-chloropyridine-4-yl)ethanone

Similarity: 0.86

Chemical Structure| 237384-43-9

[ 237384-43-9 ]

2-Bromo-1-(2-chloropyridin-3-yl)ethanone

Similarity: 0.82