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[ CAS No. 130761-99-8 ]

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3d Animation Molecule Structure of 130761-99-8
Chemical Structure| 130761-99-8
Chemical Structure| 130761-99-8
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Product Details of [ 130761-99-8 ]

CAS No. :130761-99-8 MDL No. :MFCD16036435
Formula : C13H14O3 Boiling Point : -
Linear Structure Formula :- InChI Key :UJDODTGHYKJEAA-UHFFFAOYSA-N
M.W :218.25 g/mol Pubchem ID :14530748
Synonyms :

Calculated chemistry of [ 130761-99-8 ]

Physicochemical Properties

Num. heavy atoms : 16
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.38
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 59.62
TPSA : 43.37 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.64 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.28
Log Po/w (XLOGP3) : 1.39
Log Po/w (WLOGP) : 1.95
Log Po/w (MLOGP) : 1.77
Log Po/w (SILICOS-IT) : 2.81
Consensus Log Po/w : 2.04

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.08
Solubility : 1.81 mg/ml ; 0.00827 mol/l
Class : Soluble
Log S (Ali) : -1.9
Solubility : 2.72 mg/ml ; 0.0125 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.54
Solubility : 0.0622 mg/ml ; 0.000285 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.45

Safety of [ 130761-99-8 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P264-P280-P302+P352-P305+P351+P338-P332+P313-P337+P313-P362 UN#:N/A
Hazard Statements:H315-H319 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 130761-99-8 ]

* 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 [ 130761-99-8 ]

[ 130761-99-8 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 130761-99-8 ]
  • (1R,3R)-3-Hydroxy-cyclopentanecarboxylic acid benzyl ester [ No CAS ]
  • (±)-cis-benzyl 3-hydroxycyclopentane-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium tetrahydroborate
  • 2
  • [ 98-78-2 ]
  • [ 100-39-0 ]
  • [ 130761-99-8 ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate In N,N-dimethyl-formamide at 20℃; Intermediate 29: Benzyl 3-oxocyclopentanecarboxylate To a solution of 3-oxocyclopentanecarboxylic acid (5.00 g, 39.1 mmol) in1VN-dimethylformamide (50 mL) was added potassium carbonate (16.2 g, 117 mmol) andbenzyl bromide (13.4 g, 78.2 mmol). After stirred at room temperature overnight, the mixture was poured into water (200 mL) and extracted with ethyl acetate (200 mL) twice. The combined organic layers were washed with water (200 mL) and brine (200 mL), dried over Na2SO4() and filtered. The filtrate was concentrated and purified bysilica gel column chromatography (petroleum ether: ethyl acetate = 10 : ito 8 : 1) to give the title compound (8.00 g, 94 % yield) as colorless oil. ‘H NIVIR (300 1VIHz, CDC13) 7.43 - 7.33 (m, 5H), 5.18 (s, 2H), 3.25 -3.14 (m, 1H), 2.61 -2.10 (m, 6H).
78% With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 18h; Inert atmosphere; Intermediate 332A: Benzyl 3-oxocyclopentanecarboxylate To a stirred solution of 3-oxocyclopentanecarboxylic acid (1.5 g, 11.71 mmol) in DMF (20 mL) was added K2CO3 (1.780 g, 12.88 mmol) followed by benzyl bromide (1.360 mL, 11.71 mmol) under nitrogen. The reaction mixture was then stirred for 18 h at RT. The reaction mixture was poured into water (100 mL) and extracted with ethyl acetate (2*100 mL). The combined organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (12 g REDISEP column, eluting with 20% EtOAc in hexane). Fractions containing the product were combined and evaporated to afford Intermediate 332A (2.1 g, 78% yield) as an oil. 1H NMR (400 MHz, chloroform-d) δ ppm 7.42-7.31 (m, 5H), 5.16 (s, 2H), 3.22-3.12 (m, 1H), 2.58-2.45 (m, 2H), 2.44-2.29 (m, 2H), 2.23 (s, 2H).
75% With caesium carbonate In N,N-dimethyl-formamide at 0 - 20℃; for 1.5h; 9.1 Step 1: Synthesis of benzyl 3-oxocyclopentanecarboxylate:A stirred solution of 3-oxocyclopentanecarboxylic acid (about 5 g, 39.06 mmol) in DMF (40 ml) at about O °C benzyl bromide (about 5.13 ml, 42.96 mmol) and cesium carbonate (about 4.63 g, 14.06 mmol) were added and allowed to stir at room temperature for about 90 minutes. After completion of the reaction (monitored by TLC), the reaction mixture was diluted with ethyl acetate (400 ml) and washed with water, brine and dried over Na2S04, the solvent was evaporated and combined with another batch (5.0 g) with same quantity and purified by silica gel column chromatography (100-200 mesh, Elution: 5 % EtOAc in Hexane) to afford the title compound as a liquid. Wt: 12.7 g; Yield: 75 %; NMR: (300 MHz, CDC13): δ 7.38-7.36 (m, 5H), 5.18 (s, 2H), 3.14-3.25 (m, 1H), 2.53-2.16 (m, 6H).
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 4h; 39 EXAMPLE 39; N-((lR)-l-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-3,3- difluoro- 1 -hydroxycyclopentanecarboxamide; To a solution of 3-carboxycyclopentanone (640 mg, 5.0 mmol) in 8 mL of degassedDMF was added potassium carbonate (828 mg, 5.99 mmol) and benzyl bromide (0.65 mL, 5.49 mmol). After 4 hours at room temperature, the reaction mixture was poured into 50 mL of water and extracted 3 times with EtOAc. The combined organic layers were washed with water and dried over sodium sulfate. Filtration and solvent removal provided material that was subjected to silica gel chromatography eluting with 10% EtOAc in hexanes to yield benzyl 3-oxocyclopentanecarboxylate.To a solution of benzyl 3-oxocyclopentanecarboxylate (1.03 g, 4.72 mmol) in 8 ml of 1,2-dichloroethane was added 3.34 g (7.55 mmol) of bis(2-methoxymethyl)amino-sulfur trifluoride. The mixture was heated at 50 0C for 20 hours and then slowly poured into 50 ml of saturated aqueous sodium bicarbonate solution. The mixture was extracted with one portion of chloroform and then two portions of ethyl acetate. The combined organic extracts were dried, filtered, concentrated, and subjected to silica gel chromatography eluting with 5-10% EtOAc in hexanes to yield benzyl 3,3-difluorocyclopentane- carboxylate.A solution of benzyl 3,3-difluorocyclopentanecarboxylate (13.1 g, 54.7 mmol) in 274 ml of TΗF was cooled to -78 0C under nitrogen. Potassium bis(trimethylsilyl)amide (175 ml of 0.5 M toluene solution, 87.5 mmol) was added via syringe over 15 minutes. The mixture was stirred for one hour, and then a solution of 3-phenyl-2-(phenylsulfonyl)oxaziridine (17.1 g, 65.6 mmol) in 50 ml of TBDF was added dropwise over 2 minutes. After 30 minutes at -78 0C, the reaction was quenched with the addition of 300 ml of saturated aqueous ammonium chloride solution. The reaction mixture was then warmed to room temperature, diluted with 100 ml of water, and extracted with EtOAc. The combined EtOAc extracts were washed with water and brine, and dried over sodium sulfate. Filtration and evaporation of solvent gave 35 g of an oily solid. The oily solid was stirred with 150 ml of chloroform and then filtered to remove the insoluble material. The filtrate was concentrated in vacuo and the residue EPO was subjected to chromatrography on silica gel eluting with 5 to 30% EtOAc in hexane to afford 8.2 g of racemic benzyl S^-difluoro-l-hydroxycyclopentanecarboxylate.The racemic material (5.3 g) was then applied to a ChiralPak AD column (5 cm x 50 cm, 20 μ ) to effect separation of enantiomers. The mobile phase gradient was 100 % hexane to 15% ethanol in hexane over 1 hour, and the flow rate was 100 ml per minute. The ultraviolet detector was set at 250 run. The (+)-enantiomer eluted first (retention time, 33.66 min) and the (-)-enantiomer eluted at 39.16 minutes.To a solution of (+)-benzyl 3,3-difluoro-l-hydroxycyclopentanecarboxylate (1.8 g, 7.0 mmol) in 45 ml of EtOAc was added a suspension of 10% Palladium on Carbon (720 mg) in 5 ml of EtOAc. The mixture was stirred at room temperature under hydrogen atmosphere for 1 hour (balloon). The reaction mixture was filtered through a glass micropore filter to remove the catalyst and the filtrate was concentrated under vacuum to give (+)-3,3-difluoro-l-hydroxycyclopentanecarboxylic acid.To a solution of the compound of Reference Example 4 (0.766 g, 2.18 mmol), (+)-3,3- difluoro-1-hydroxycyclopentanecarboxylic acid (0.454 g, 2.73 mmol), (lH-l,2,3-benzotriazol~l~yloxy)- [tris(dimethylamino)]phosphonium hexafluorophosphate (1.35 g, 3.06 mmol) in anhydrous dichloromethane (43 mL), was added triethylamine (0.553 g, 5.46 mmol). This reaction mixture was allowed to stir at ambient temperature for 1 hour. After the reaction was judged complete by LC/MS analysis, the volume of the reaction was reduced in vacuo. The residue was taken up in EtOAc, washed with water, 0.25 NΗC1 and saturated aqueous sodium bicarbonate solution. The organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude residue was subjected to silica gel chromatography eluting with 0-50% EtOAc in hexanes to provide the title compound as a foam, which gave proton ΝMR spectra consistent with theory and a mass ion (ES+) of 499.2 for M+Η+: 1H ΝMR (500 MHz, CDCI3) δ 8.13 (s, IH), 7.96 (bd, NH), 7.34 (d, J= 8.8 Hz, IH), 7.26 (m, 2H), 5.41 (m, IH),4.342 (s, 3H), 2.82 (m, IH), 2.46-2.25 (m, 4H), 1.92 (m, IH), 1.45 (d, J= 6.8 Hz, 3H).

  • 3
  • [ 130761-99-8 ]
  • benzyl 3,3-difluorocyclopentanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With diethylamino-sulfur trifluoride In cis-1,2-Dichloroethylene at 40℃; for 16h; Inert atmosphere; Intermediate 332B: Benzyl 3,3-difluorocyclopentanecarboxylate Intermediate 332B: Benzyl 3,3-difluorocyclopentanecarboxylate To a stirred ice-cooled solution of Intermediate 332A (0.2 g, 0.916 mmol) in anhydrous DCE (4 mL) was added DAST (0.303 mL, 2.291 mmol) under nitrogen. The reaction mixture was then allowed to heat to 40° C. and stir for 16 h. The reaction mixture was quenched with an aq. solution of NaHCO3 at 0° C. and extracted with DCM (2*50 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude compound was purified by silica gel chromatography (12 g REDISEP column, eluting with 10% EtOAc in hexanes). Fractions containing the product were combined and evaporated to afford Intermediate 332B as a colorless oil (0.07 g, 30% yield). 1H NMR (400 MHz, chloroform-d) δ ppm 7.41-7.31 (m, 5H), 5.15 (s, 2H), 3.05 (m, 1H), 2.49-2.33 (m, 2H), 2.26-2.00 (m, 4H).
With (bis-(2-methoxyethyl)amino)sulfur trufluoride In dichloromethane at 20℃;
With (bis-(2-methoxyethyl)amino)sulfur trufluoride In 1,2-dichloro-ethane at 50℃; for 20h; 39 EXAMPLE 39; N-((lR)-l-{5-[5-chloro-3-fluoro-2-(2-methyl-2H-tetrazol-5-yl)phenyl]-3-fluoropyridin-2-yl}ethyl)-3,3- difluoro- 1 -hydroxycyclopentanecarboxamide; To a solution of 3-carboxycyclopentanone (640 mg, 5.0 mmol) in 8 mL of degassedDMF was added potassium carbonate (828 mg, 5.99 mmol) and benzyl bromide (0.65 mL, 5.49 mmol). After 4 hours at room temperature, the reaction mixture was poured into 50 mL of water and extracted 3 times with EtOAc. The combined organic layers were washed with water and dried over sodium sulfate. Filtration and solvent removal provided material that was subjected to silica gel chromatography eluting with 10% EtOAc in hexanes to yield benzyl 3-oxocyclopentanecarboxylate.To a solution of benzyl 3-oxocyclopentanecarboxylate (1.03 g, 4.72 mmol) in 8 ml of 1,2-dichloroethane was added 3.34 g (7.55 mmol) of bis(2-methoxymethyl)amino-sulfur trifluoride. The mixture was heated at 50 0C for 20 hours and then slowly poured into 50 ml of saturated aqueous sodium bicarbonate solution. The mixture was extracted with one portion of chloroform and then two portions of ethyl acetate. The combined organic extracts were dried, filtered, concentrated, and subjected to silica gel chromatography eluting with 5-10% EtOAc in hexanes to yield benzyl 3,3-difluorocyclopentane- carboxylate.A solution of benzyl 3,3-difluorocyclopentanecarboxylate (13.1 g, 54.7 mmol) in 274 ml of TΗF was cooled to -78 0C under nitrogen. Potassium bis(trimethylsilyl)amide (175 ml of 0.5 M toluene solution, 87.5 mmol) was added via syringe over 15 minutes. The mixture was stirred for one hour, and then a solution of 3-phenyl-2-(phenylsulfonyl)oxaziridine (17.1 g, 65.6 mmol) in 50 ml of TBDF was added dropwise over 2 minutes. After 30 minutes at -78 0C, the reaction was quenched with the addition of 300 ml of saturated aqueous ammonium chloride solution. The reaction mixture was then warmed to room temperature, diluted with 100 ml of water, and extracted with EtOAc. The combined EtOAc extracts were washed with water and brine, and dried over sodium sulfate. Filtration and evaporation of solvent gave 35 g of an oily solid. The oily solid was stirred with 150 ml of chloroform and then filtered to remove the insoluble material. The filtrate was concentrated in vacuo and the residue EPO was subjected to chromatrography on silica gel eluting with 5 to 30% EtOAc in hexane to afford 8.2 g of racemic benzyl S^-difluoro-l-hydroxycyclopentanecarboxylate.The racemic material (5.3 g) was then applied to a ChiralPak AD column (5 cm x 50 cm, 20 μ ) to effect separation of enantiomers. The mobile phase gradient was 100 % hexane to 15% ethanol in hexane over 1 hour, and the flow rate was 100 ml per minute. The ultraviolet detector was set at 250 run. The (+)-enantiomer eluted first (retention time, 33.66 min) and the (-)-enantiomer eluted at 39.16 minutes.To a solution of (+)-benzyl 3,3-difluoro-l-hydroxycyclopentanecarboxylate (1.8 g, 7.0 mmol) in 45 ml of EtOAc was added a suspension of 10% Palladium on Carbon (720 mg) in 5 ml of EtOAc. The mixture was stirred at room temperature under hydrogen atmosphere for 1 hour (balloon). The reaction mixture was filtered through a glass micropore filter to remove the catalyst and the filtrate was concentrated under vacuum to give (+)-3,3-difluoro-l-hydroxycyclopentanecarboxylic acid.To a solution of the compound of Reference Example 4 (0.766 g, 2.18 mmol), (+)-3,3- difluoro-1-hydroxycyclopentanecarboxylic acid (0.454 g, 2.73 mmol), (lH-l,2,3-benzotriazol~l~yloxy)- [tris(dimethylamino)]phosphonium hexafluorophosphate (1.35 g, 3.06 mmol) in anhydrous dichloromethane (43 mL), was added triethylamine (0.553 g, 5.46 mmol). This reaction mixture was allowed to stir at ambient temperature for 1 hour. After the reaction was judged complete by LC/MS analysis, the volume of the reaction was reduced in vacuo. The residue was taken up in EtOAc, washed with water, 0.25 NΗC1 and saturated aqueous sodium bicarbonate solution. The organic extracts were dried over sodium sulfate, filtered, and concentrated. The crude residue was subjected to silica gel chromatography eluting with 0-50% EtOAc in hexanes to provide the title compound as a foam, which gave proton ΝMR spectra consistent with theory and a mass ion (ES+) of 499.2 for M+Η+: 1H ΝMR (500 MHz, CDCI3) δ 8.13 (s, IH), 7.96 (bd, NH), 7.34 (d, J= 8.8 Hz, IH), 7.26 (m, 2H), 5.41 (m, IH),4.342 (s, 3H), 2.82 (m, IH), 2.46-2.25 (m, 4H), 1.92 (m, IH), 1.45 (d, J= 6.8 Hz, 3H).
  • 5
  • [ 98-78-2 ]
  • [ 100-51-6 ]
  • [ 130761-99-8 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In tetrahydrofuran 17.1 Step 1 : 3-Oxo-cyclopentanecarboxylic acid benzyl ester: The mixture of 3-oxo- cyclopentanecarboxylic acid (750 mg), of benzyl alcohol (633 mg), l-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride 1(680 mg), and of 1-hydroxybenzotriazole (350 mg) in 50 ml tetrahydrofuran was stirred overnight. After addition of aq. Sodium bicarbonate (sat. 25 mL), the reaction mixture was extracted with of ethyl acetate (50 ml X 2). The organic layer was washed with brine, dried with anhydrous sodium sulfate and concentrated to yield 3-oxo-cyclopentanecarboxylic acid benzyl ester as oil.
With toluene-4-sulfonic acid In toluene for 4h; Reflux; Dean-Stark; 1 Step 1:benzyl 3-oxocyclopentanecarboxylate A mixture of 3-oxocyclopentanecarboxylic acid (5 g, 39.1 mmol) , phenylmethanol (4.2 g, 39.1 mmol) and TsOH·H2O (223 mg, 1.2 mmol) in toluene (50 mL) was heated to reflux and water was removed by Dean-Stark trap for 4 h. The reaction mixture was concentrated and the residue was purified by column chromatography on silica gel eluted with PE/EA20/1 to give benzyl 3-oxocyclopentanecarboxylate.[0684]1H NMR (CDCl3, 400 MHz) δ 2.05-2.57 (m, 6 H) , 3.09-3.22 (m, 1 H) , 5.14 (s, 2 H) , 7.27-7.41 (m, 5 H) ppm.
  • 6
  • [ 130761-99-8 ]
  • [ 62-53-3 ]
  • [ 1233927-24-6 ]
YieldReaction ConditionsOperation in experiment
Stage #1: benzyl 3-oxocyclopentanecarboxylate; aniline With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane Stage #2: With potassium carbonate In dichloromethane; water; ethyl acetate 17.2 Step2: 3-Phenylaminocyclopentanecarboxylic acid benzyl ester: The mixture of 3- oxocyclopentanecarboxylic acid benzyl ester (150 mg), aniline (75 mg), glacial acetic acid (200 μL), and sodium triacetoxyborohydride (230 mg) in DCM (20 mL) was stirred overnight. Upon the addtion of aq. potassium carbonate (IM, 30 mL), the mixture was extracted with ethyl acetate (30 ml X 2). Oragnic layers were combined, washed with brine, and concentrated. Flash chromatography on silica (50% ethyl acetate in hexane) gave the product as an oil: MS (m+1) = 282.3.
  • 7
  • [ 130761-99-8 ]
  • [ 762-72-1 ]
  • [ 1309166-43-5 ]
YieldReaction ConditionsOperation in experiment
33% Stage #1: benzyl 3-oxocyclopentanecarboxylate With titanium tetrachloride In dichloromethane at 0℃; Stage #2: allyl-trimethyl-silane In dichloromethane at 20℃; for 3h; 9.2 Step 2: Synthesis of benzyl 3-allyl-3 ntanecarboxylate:A stirred solution of benzyl 3-oxocyclopentanecarboxylate (step 1 , about 4.0 g, 18.39 mmol) in dry DCM (20 ml) at about 0 °C TiCL, (about 2.0 ml, 18.34 mmol) was added, after five minutes allyltrimethylsilane (about 11.7 ml, 73.39 mmol) was added slowly and allowed to stirred at room temperature for about 3 hours. After completion of the reaction (monitored by TLC), the reaction was quenched with water, extracted with EtOAc (200 ml x 2) and the organic layers were washed with brine, dried with Na2S04 and the solvent was evaporated. The resulting crude was combined with another batch (8.7 g) and purified by silica gel column chromatography (100-200 Mesh, Elution: 8-10 % EtOAc in Hexane) to afford the title compound as a pale yellow liquid. Wt: 5.0 g; Yield: 33 %; NMR: (300 MHz,CDC13): δ 7.36-7.34 (m, 5H), 5.96-5.86 (m, 1H), 5.15-5.14 (m, 4H), 2.98-2.93, 2.68 (brm, 1H), 2.37-2.34 (m, 2H), 2.10-1.65 (m, 4H), 1.65-1.62 (m, 2H); Mass: [M+Na]+: 283(100%), [M+H]+: 261 (18%).
  • 8
  • [ 130761-99-8 ]
  • [ 1309166-45-7 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: titanium tetrachloride / dichloromethane / 0 °C 1.2: 3 h / 20 °C 2.1: borane-THF / tetrahydrofuran / 3 h / 0 - 20 °C 2.2: 0.5 h
  • 9
  • [ 130761-99-8 ]
  • [ 1309166-47-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: titanium tetrachloride / dichloromethane / 0 °C 1.2: 3 h / 20 °C 2.1: borane-THF / tetrahydrofuran / 3 h / 0 - 20 °C 2.2: 0.5 h 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 10.5 h / 0 °C / Reflux
  • 10
  • [ 130761-99-8 ]
  • [ 1309166-41-3 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: titanium tetrachloride / dichloromethane / 0 °C 1.2: 3 h / 20 °C 2.1: borane-THF / tetrahydrofuran / 3 h / 0 - 20 °C 2.2: 0.5 h 3.1: triethylamine; methanesulfonyl chloride / dichloromethane / 10.5 h / 0 °C / Reflux 4.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 3 h / 20 °C
  • 11
  • C19H30O4Si [ No CAS ]
  • [ 130761-99-8 ]
YieldReaction ConditionsOperation in experiment
91% With methyl fluorosulfonate; 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 0.166667h;
  • 12
  • [ 619-42-1 ]
  • [ 130761-99-8 ]
  • C21H20O5 [ No CAS ]
  • C21H20O5 [ No CAS ]
  • C21H20O5 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With pyrrolidine; tert-Octylamine; sodium acetate; palladium diacetate; tris-(o-tolyl)phosphine In 1,4-dioxane at 110℃; for 12h; Inert atmosphere; Sealed tube; Glovebox; Overall yield = 56%; Overall yield = 59.0 mg; chemoselective reaction;
  • 13
  • [ 130761-99-8 ]
  • 2-(3-chloro-4-fluorophenyl)-N5-(3,3-difluorocyclopentyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide [ No CAS ]
  • 2-(3-chloro-4-fluorophenyl)-N5-(3,3-difluorocyclopentyl)-6,7-dihydropyrazolo[1,5-a]pyrazine-3,5(4H)-dicarboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: diethylamino-sulfur trifluoride / cis-1,2-Dichloroethylene / 16 h / 40 °C / Inert atmosphere 2.1: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 775.74 Torr 3.1: diphenyl phosphoryl azide; triethylamine / toluene / 2 h / 20 - 70 °C / Inert atmosphere 3.2: 16 h / 20 °C / Inert atmosphere
  • 14
  • [ 130761-99-8 ]
  • 3,3-difluorocyclopentanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: diethylamino-sulfur trifluoride / cis-1,2-Dichloroethylene / 16 h / 40 °C / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / ethyl acetate / 16 h / 20 °C / 775.74 Torr
  • 15
  • [ 130761-99-8 ]
  • 3-(2-ethoxy-2-oxoethyl)cyclopentanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr
  • 16
  • [ 130761-99-8 ]
  • ethyl 2-(3-(((3-chloropyrazin-2-yl)methyl)carbamoyl)cyclopentyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr 3.1: HATU; triethylamine / tetrahydrofuran / 20 °C
  • 17
  • [ 130761-99-8 ]
  • ethyl 2-(3-(8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclopentyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr 3.1: HATU; triethylamine / tetrahydrofuran / 20 °C 4.1: phosphorus pentachloride / acetonitrile / 1.5 h / 70 °C
  • 18
  • [ 130761-99-8 ]
  • ethyl 2-(3-(1-bromo-8-chloroimidazo[1,5-a]pyrazin-3-yl)cyclopentyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr 3.1: HATU; triethylamine / tetrahydrofuran / 20 °C 4.1: phosphorus pentachloride / acetonitrile / 1.5 h / 70 °C 5.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 1 h / 20 °C
  • 19
  • [ 130761-99-8 ]
  • ethyl 2-(3-(1-bromo-8-((2,4-dimethoxybenzyl)amino)imidazo[1,5-a]pyrazin-3-yl)cyclopentyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 6 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr 3.1: HATU; triethylamine / tetrahydrofuran / 20 °C 4.1: phosphorus pentachloride / acetonitrile / 1.5 h / 70 °C 5.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 1 h / 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 90 °C
  • 20
  • [ 130761-99-8 ]
  • ethyl 2-(3-(8-amino-1-bromoimidazo[1,5-a]pyrazin-3-yl)cyclopentyl)acetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 7 steps 1.1: sodium hydride / tetrahydrofuran / 0.25 h / 0 - 5 °C 1.2: 3 h / 0 - 20 °C 2.1: palladium on activated charcoal; hydrogen / ethyl acetate / 20 °C / 2585.81 Torr 3.1: HATU; triethylamine / tetrahydrofuran / 20 °C 4.1: phosphorus pentachloride / acetonitrile / 1.5 h / 70 °C 5.1: N-Bromosuccinimide / N,N-dimethyl-formamide / 1 h / 20 °C 6.1: potassium carbonate / N,N-dimethyl-formamide / 6 h / 90 °C 7.1: trifluoroacetic acid / 2 h / Reflux
  • 21
  • [ 867-13-0 ]
  • [ 130761-99-8 ]
  • benzyl 3-(2-ethoxy-2-oxoethylidene)cyclopentanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: diethoxyphosphoryl-acetic acid ethyl ester With sodium hydride In tetrahydrofuran at 0 - 5℃; for 0.25h; Stage #2: benzyl 3-oxocyclopentanecarboxylate In tetrahydrofuran at 0 - 20℃; for 3h; 2 Step 2:benzyl 3- (2-ethoxy-2-oxoethylidene) cyclopentanecarboxylate NaH (1.3 g, 33.7 mmol) was suspended in THF (130 mL) and cooled to 0-5 . Ethyl 2-(diethoxyphosphoryl) acetate (7.9 g, 35.3 mmol) was added and the mixture was stirred at 0-5 for 15 minutes. A solution of benzyl 3-oxocyclopentanecarboxylate (7 g, 32.1 mmol) in THF (20 mL) was then added, and the resulting mixture was allowed to warm to room temperature. After 3 h, the mixture was treated with EA and water. The organic layer was dried and concentrated. The residue was purified by column chromatography on silica gel eluted with PE/EA20/1 to give benzyl 3- (2-ethoxy-2-oxoethylidene) cyclopentanecarboxylate.[0687]1H NMR (CDCl3, 400 MHz) δ 1.25 (t, J7.04 Hz, 3 H) , 1.87-2.19 (m, 2 H) , 2.46-3.19 (m, 5 H) , 4.04-4.19 (m, 2 H) , 5.11 (s, 2 H) , 5.75-5.82 (m, 1 H) , 7.26-7.40 (m, 5 H) ppm.
  • 22
  • [ 130761-99-8 ]
  • (+)-3,3-difluoro-1-hydroxycyclopentanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 1,2-dichloro-ethane / 20 h / 50 °C 2.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 1.25 h / -78 °C 2.2: 0.53 h / -78 °C 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 1 h / 20 °C
  • 23
  • [ 130761-99-8 ]
  • [ 916736-25-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 1,2-dichloro-ethane / 20 h / 50 °C 2.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 1.25 h / -78 °C 2.2: 0.53 h / -78 °C 3.1: hydrogen / palladium 10% on activated carbon / ethyl acetate / 1 h / 20 °C 4.1: (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine / dichloromethane / 1 h / 20 °C
  • 24
  • [ 130761-99-8 ]
  • [ 916736-75-9 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 1,2-dichloro-ethane / 20 h / 50 °C 2.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 1.25 h / -78 °C 2.2: 0.53 h / -78 °C
  • 25
  • [ 130761-99-8 ]
  • benzyl 3,3-difluoro-(1S)-hydroxycyclopentanecarboxylate [ No CAS ]
  • benzyl 3,3-difluoro-(1R)-hydroxycyclopentanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: (bis-(2-methoxyethyl)amino)sulfur trufluoride / 1,2-dichloro-ethane / 20 h / 50 °C 2.1: potassium hexamethylsilazane / tetrahydrofuran; toluene / 1.25 h / -78 °C 2.2: 0.53 h / -78 °C 3.1: ethanol; hexane / Resolution of racemate
  • 26
  • [ 98-78-2 ]
  • [ 130761-99-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1: oxalyl dichloride / dichloromethane / 2.5 h / -10 - 20 °C 2: triethylamine; dmap / dichloromethane / 12 h / 0 - 20 °C
  • 27
  • 3-oxocyclopentanecarbonyl chloride [ No CAS ]
  • [ 100-51-6 ]
  • [ 130761-99-8 ]
YieldReaction ConditionsOperation in experiment
With dmap; triethylamine In dichloromethane at 0 - 20℃; for 12h; 2 Step 2: benzyl 3-oxocvclopentanecarboxylate To a solution of benzyl alcohol (4.80 g, 44.3 mmol) in DCM (30 ml)was added Et3N (4.75 ml, 34.1 mmol) and DMAP (0.834 g, 6.82 mmol). 3-Oxocyclopentanecarbonyl chloride (5 g, 34.1 mmol) was then added dropwise at 0 °C. The reaction mixture was stirred at 20 °C for 12h. Then the mixture was poured into water (45 mL) and extracted with three times with ethyl acetate. The combined organic layers were washed with brine (45 mL) , dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel (40% ethyl acetate in petroleum ether) to give the title compound. 1H NMR (400 MHz, CDC13): δ 7.35 (m, 5H), 5.15 (s, 2H), 3.12 (m, 1H), 2.60-2.10 (m, 6H).
  • 28
  • [ 130761-99-8 ]
  • benzyl spiro[2.4]heptane-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: -5 °C 2.1: diethylzinc / dichloromethane / 0.5 h / -10 °C 2.2: 12 h / 25 °C
  • 29
  • [ 130761-99-8 ]
  • spiro[2.4]heptan-5-ylmethanol [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: -5 °C 2.1: diethylzinc / dichloromethane / 0.5 h / -10 °C 2.2: 12 h / 25 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C
  • 30
  • [ 130761-99-8 ]
  • spiro[2.4]heptan-5-ylmethyl 4-methylbenzenesulfonate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: -5 °C 2.1: diethylzinc / dichloromethane / 0.5 h / -10 °C 2.2: 12 h / 25 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / dichloromethane / 1 h / 0 °C
  • 31
  • [ 130761-99-8 ]
  • 3-methoxy-7-(6-methyl-3-(1-(spiro[2.4]heptan-5-ylmethyl)-1H-pyrazol-4-yl)pyridin-2-yl)cinnoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 5 steps 1.1: potassium <i>tert</i>-butylate / tetrahydrofuran / 0.5 h / 0 °C 1.2: -5 °C 2.1: diethylzinc / dichloromethane / 0.5 h / -10 °C 2.2: 12 h / 25 °C 3.1: lithium aluminium tetrahydride / tetrahydrofuran / 1 h / 0 °C 4.1: triethylamine / dichloromethane / 1 h / 0 °C 5.1: caesium carbonate / N,N-dimethyl-formamide / 1.5 h / 60 °C
  • 32
  • [ 1779-49-3 ]
  • [ 130761-99-8 ]
  • benzyl 3-methylenecyclopentanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Stage #1: Methyltriphenylphosphonium bromide With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 0.5h; Stage #2: benzyl 3-oxocyclopentanecarboxylate In tetrahydrofuran at -5℃; 3 Step 3 : benzyl 3-methylenecyclopentanecarboxylate To a solution of bromo(methyl)triphenylphosphorane (7.37 g, 20.62 mmol) in THF (20 ml) was added 1 N potassium tert-butoxide (20.62 ml, 20.62 mmol) in THF dropwise at 0 °C for 30 min, then was added dropwise benzyl 3-oxocyclopentanecarboxylate (3 g, 13.75 mmol) in THF (10 mL). The resulting mixture was stirred at -5 °C for 1 hour. The reaction mixture was diluted with water (40 mL) and extracted with EtOAc (100 mL x 4). The combined organic layers were dried over anhydrous Na2SC"4, filtered and the filtrate was concentrated in vacuo. The residue was purified by Prep-TLC (20 % EtOAc in petroleum ether) to give the title compound. 1H NMR (400 MHz, CDC13): δ 7.34 (m, 5H), 5.12 (s, 2H), 4.87 (s, 2H), 2.88 (m, 1H), 2.59-2.29 (m, 4H), 2.05-1.90 (m, 2H).
  • 33
  • [ 130761-99-8 ]
  • benzyl 3-(N-methylacetamido)cyclopentanecarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine / 1,2-dichloro-ethane / 1 h / 20 °C 1.2: 20 °C 1.3: 3 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2.2: 2 h / 20 °C
  • 34
  • [ 130761-99-8 ]
  • 3-(N-methylacetamido)cyclopentanecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine / 1,2-dichloro-ethane / 1 h / 20 °C 1.2: 20 °C 1.3: 3 h / 20 °C 2.1: trifluoroacetic acid / dichloromethane / 1 h / 20 °C 2.2: 2 h / 20 °C 3.1: palladium 10% on activated carbon; hydrogen / methanol / 20 °C
  • 35
  • [ 24424-99-5 ]
  • methylamine hydrochloride salt [ No CAS ]
  • [ 130761-99-8 ]
  • benzyl 3-((tert-butoxycarbonyl)(methyl)amino)cyclopentane-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% Stage #1: methylamine hydrochloride salt; benzyl 3-oxocyclopentanecarboxylate With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃; for 1h; Stage #2: With sodium cyanoborohydride In 1,2-dichloro-ethane at 20℃; Stage #3: di-<i>tert</i>-butyl dicarbonate With N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane at 20℃; for 3h; Intermedaite 30: Benzyl 3-((tert-butoxycarbonyl)(methyl)amino)cyclopentane- carboxylate To a solution of benzyl 3-oxocyclopentanecarboxylate E08495_514.2 (4.20 g, 19.3 mmol) in i,2-dichloroethane (50 mL) was added methylamine hydrochloride (1.90 g, 28.6 mmol) and N,N-diisopropylethylamine (3.70 g, 28.7 mmol). The mixture was stirred at room temperature for 1 hour, and then sodium cyanoborohydride (3.00 g, 47.8 mmol) was added. After the reaction mixture was stirred at room temperature overnight,N,N-diisopropylethylamine (7.40 g, 57.4 mmol) and di-tert-butyl dicarbonate (10.5 g,48.2 mmol) was added. After stirred at room temperature for 3 hours, the mixture was diluted with dichloromethane (100 mL) and washed with water (100 mL) twice and brine (100 mL), dried over Na2SO4() and filtered. The filtrate was concentrated and purified by C 18 column (acetonitrile : water = 70 % to 75 %) to give the titlecompound (1.70 g, 22 % yield) as yellow oil. LC-MS (ESI): RT = 1.52 mm, mass calcd. for C,9H27N04 333.2, mlz found 334.3 [M+H]. ‘H N1.VIR (300 1VIHz, CDC13) 7.40 -7.30 (m, 5H), 5.13 (s, 2H), 2.96-2.77 (m, 1H), 2.73 (s, 3H), 2.20-2.03 (m, 2H), 1.95 -1.67 (m, 5H), 1.45 (s, 9H).
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