Home Cart 0 Sign in  
X

[ CAS No. 2435-36-1 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 2435-36-1
Chemical Structure| 2435-36-1
Chemical Structure| 2435-36-1
Structure of 2435-36-1 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 2435-36-1 ]

Related Doc. of [ 2435-36-1 ]

Alternatived Products of [ 2435-36-1 ]

Product Details of [ 2435-36-1 ]

CAS No. :2435-36-1 MDL No. :MFCD01735429
Formula : C9H14O4 Boiling Point : -
Linear Structure Formula :- InChI Key :SQFQEQDRLAZVJQ-UHFFFAOYSA-N
M.W :186.21 Pubchem ID :200652
Synonyms :

Calculated chemistry of [ 2435-36-1 ]

Physicochemical Properties

Num. heavy atoms : 13
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.78
Num. rotatable bonds : 4
Num. H-bond acceptors : 4.0
Num. H-bond donors : 0.0
Molar Refractivity : 45.83
TPSA : 52.6 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) : -6.87 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.36
Log Po/w (XLOGP3) : 0.79
Log Po/w (WLOGP) : 0.75
Log Po/w (MLOGP) : 0.86
Log Po/w (SILICOS-IT) : 1.02
Consensus Log Po/w : 1.16

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.23
Solubility : 11.0 mg/ml ; 0.0591 mol/l
Class : Very soluble
Log S (Ali) : -1.48
Solubility : 6.23 mg/ml ; 0.0335 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.96
Solubility : 20.4 mg/ml ; 0.109 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.61

Safety of [ 2435-36-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P305+P351+P338 UN#:N/A
Hazard Statements:H227-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 2435-36-1 ]

* 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.

  • Upstream synthesis route of [ 2435-36-1 ]
  • Downstream synthetic route of [ 2435-36-1 ]

[ 2435-36-1 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 67-56-1 ]
  • [ 4056-78-4 ]
  • [ 2435-36-1 ]
YieldReaction ConditionsOperation in experiment
100% at 7 - 12℃; for 16 h; Reflux A 5-L, 3-neck, roundbottom flask was equipped with a mechanical stirrer, a J-KEM temperature controller, and a reflux condenser. The flask was charged with cyclopentane-l,3-dicarboxylic acid(357 g, 2.262 mol) and methanol (1.75 L). The solution was cooled to 7 °C using anice/water bath. Concentrated sulfuric acid (70 mL) was added dropwise over 30 minresulting in an exotherm up to 12 °C. The reaction mixture was heated to reflux andstirred for 16 h when TLC analysis (10 percent methanol/ethyl acetate) indicated that thereaction was complete. The reaction mixture was concentrated, redissolved in methyl- 179 -ATI-2514175vl tert-butyl ether, and washed with saturated aqueous sodium bicarbonate (2 x 150 mL) and brine (2 x 150 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The resulting clear oil was dissolved in hexane (2 L) and treated with a 2 N aqueous sodium hydroxide solution (950 mL) until the pH ~ 10. The layers were separated and the aqueous layer was extracted with hexane (4 x 1 L). The organic layers were combined, dried over sodium sulfate, filtered, and concentrated to provide 360 g (100percent) of dimethyl cyclopentane-l,3-dicarboxylate as a clear oil. 1H NMR (500 Hz, CDCls) δ ppm 3.67 (s, 6H), 2.75-2.83 (m, 2H), 2.20-2.26 (m, 1H), 2.05-2.12 (m, 1H), 1.90-2.0 (m, 4H).
88% With sulfuric acid In water at 0 - 90℃; Step A:
Dimethyl cyclopentane-1,3-dicarboxylate.
A solution of cyclopentane-1,3-dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0° C. in an ice water bath.
Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at <15° C.
After the addition, the reaction was heated to 90° C. and stirred overnight.
The reaction was cooled to room temperature and concentrated to dryness.
The residue was treated with MTBE (500 mL) and H2O (100 mL).
The aqueous layer was separated and extracted with MTBE (2*100 mL).
The combined organic extracts were washed with saturated sodium bicarbonate (2*100 mL), brine (100 mL), dried over anhydrous MgSO4, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88percent) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H), 2.11-2.02 (m, 1H), 1.96-1.88 (m, 4H).
88% at 15 - 90℃; . A solution of cyclopentane-1,3- dicarboxylic acid (70.0 g, 443 mmol) and anhydrous methanol (300 mL) was cooled to 0 °C in an ice water bath. Concentrated sulfuric acid (14 mL) was added dropwise, maintaining the temperature at < 15 °C. After the addition, the reaction was heated to 90 °C and stirred overnight. The reaction was cooled to room temperature and concentrated to dryness. Theresidue was treated with MTBE (500 mL) and H20 (100 mL). The aqueous layer was separated and extracted with MTBE (2 x 100 mL). The combined organic extracts were washed with saturated sodium bicarbonate (2 x 100 mL), brine (100 mL), dried over anhydrous Mg504, filtered, and concentrated to dryness to provide the title compound (72.5 g, 88percent) as a pale yellow oil. ‘HNMR(400 IVIFIz, CDC13) 3.65 (s, 6H), 2.84-2.72 (m, 2H), 2.26-2.17 (m, 1H),2.11 -2.02(m, 1H), 1.96- 1.88(m,4H).
64% at 20℃; for 15 h; Heating / reflux To a solution of the title compound from Step A above (11.2 g) in MeOH (250 mL) was added concentrated H2SO4 (0.5 mL) at room temperature. The mixture was heated to reflux for 15 h, cooled to room temperature, filtrated and concentrated. The remaining residue was diluted with EtOAc (100 mL), washed with saturated aqueous NaHCO3 (3 x 50 mL) and saturated aqueous NaCl (50 mL), dried (MgSO4), filtered, concentrated and purified by chromatography (silica, cyclohexane/EtOAc) to afford the title compound as a colorless solid (8.43 g, 64percent). [MH]+ = 187.

Reference: [1] Patent: WO2012/145569, 2012, A1, . Location in patent: Page/Page column 179; 180
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 10, p. 3480 - 3491
[3] Patent: US2018/170931, 2018, A1, . Location in patent: Paragraph 0188
[4] Patent: WO2018/112382, 2018, A1, . Location in patent: Page/Page column 174
[5] Tetrahedron Letters, 2005, vol. 46, # 18, p. 3201 - 3203
[6] Patent: WO2006/128184, 2006, A2, . Location in patent: Page/Page column 167
[7] Australian Journal of Chemistry, 1985, vol. 38, # 11, p. 1705 - 1718
[8] Patent: WO2016/106623, 2016, A1, . Location in patent: Page/Page column 113
[9] Patent: WO2016/106624, 2016, A1, . Location in patent: Page/Page column 64
  • 2
  • [ 67-56-1 ]
  • [ 84545-00-6 ]
  • [ 2435-36-1 ]
Reference: [1] Patent: WO2016/106623, 2016, A1, . Location in patent: Page/Page column 69
[2] Patent: WO2016/106624, 2016, A1, . Location in patent: Page/Page column 46
[3] Patent: WO2016/109219, 2016, A1, . Location in patent: Page/Page column 47
  • 3
  • [ 498-66-8 ]
  • [ 2435-36-1 ]
Reference: [1] Patent: WO2012/145569, 2012, A1,
  • 4
  • [ 2435-36-1 ]
  • [ 107-04-0 ]
  • [ 15448-76-7 ]
YieldReaction ConditionsOperation in experiment
54%
Stage #1: With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; for 0.5 h;
Stage #2: at 20℃; for 12 h;
Dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate. n-Butyllithium (2.5 M in hexane, 419.0 mL, 1048 mmol) was added slowly to a solution of diisopropylamine (152 mL, 1090 mmol) and anhydrous THF (1000 mL) at −78° C. (dry ice/acetone) under N2. Next, the reaction was stirred for 0.5 hours at 0° C. before cooling to −78° C. DMPU (404 mL, 3350 mmol) was added via an addition funnel. Then a solution of dimethyl cyclopentane-1,3-dicarboxylate (78.0 g, 419 mmol) and anhydrous THF (300 mL) was added slowly via an addition funnel. The reaction was warmed to 0° C. and stirred for 30 minutes, then cooled to −78° C. and treated with a solution of 1-bromo-2-chloroethane (59.0 mL, 712 mmol) and anhydrous THF (200 mL). The reaction was allowed to warm slowly to room-temperature and was stirred for 12 hours at room-temperature. The reaction was quenched with saturated aqueous ammonium chloride (400 mL). The reaction was diluted with ethyl acetate (500 mL), the organic layer separated, and the aqueous layer was further extracted with ethyl acetate (2×500 mL). The combined organic extracts were washed with brine (2×300 mL), dried over anhydrous MgSO4, filtered, and concentrated to dryness. The residue was filtered through a pad of silica gel and washed with ethyl acetate (2000 mL). The filtrate was concentrated to dryness and the residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 30:1 to 20:1, gradient elution) to provide the title compound (48.5 g, 54percent) as white solid. 1H NMR (400 MHz, CDCl3): δ 3.69 (s, 6H), 2.08-1.99 (m, 4H), 1.91 (s, 2H), 1.73-1.63 (m, 4H).
54%
Stage #1: With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; for 0.5 h; Inert atmosphere
Stage #2: at -78 - 20℃; for 12 h;
Step B: Dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate. n-Butyllithium (2.5 M in hexane, 419.0 mL, 1048 mmol) was added slowly to a solution of diisopropylamine (152 mL, 1090 mmol) and anhydrous THF (1000 mL) at -78 °C (dry ice/acetone) underN2. Next, the reaction was stirred for 0.5 hours at 0 °C before cooling to -78 °C. DIVIPU (404 mL, 3350mmol) was added via an addition funnel. Then a solution of dimethyl cyclopentane-1,3- dicarboxylate (78.0 g, 419 mmol) and anhydrous THF (300 mL) was added slowly via an addition funnel. The reaction was warmed to 0 °C and stirred for 30 minutes, then cooled to -78°C and treated with a solution of 1-bromo-2-chloroethane (59.0 mL, 712 mmol) and anhydrous THF (200 mL). The reaction was allowed to warm slowly to room-temperature and was stirred for 12 hours at room-temperature. The reaction was quenched with saturated aqueous ammonium chloride (400 mL). The reaction was diluted with ethyl acetate (500 mL), the organic layer separated, and the aqueous layer was further extracted with ethyl acetate (2 x 500 mL). The combined organic extracts were washed with brine (2 x 300 mL), dried overanhydrous MgSO4, filtered, and concentrated to dryness. The residue was filtered through a pad of silica gel and washed with ethyl acetate (2000 mL). The filtrate was concentrated to dryness and the residue was purified by flash column chromatography (petroleum ether/ethyl acetate, 30 :1 to 20 :1, gradient elution) to provide the title compound (48.5 g, 54percent) as white solid. ‘H NIVIR (400MHz, CDC13): 3.69 (s, 6H), 2.08 - 1.99 (m, 4H), 1.91 (s, 2H), 1.73 - 1.63 (m, 4H)
Reference: [1] Patent: US2018/170931, 2018, A1, . Location in patent: Paragraph 0189
[2] Patent: WO2018/112382, 2018, A1, . Location in patent: Page/Page column 1714; 175
[3] Patent: US2010/267738, 2010, A1, . Location in patent: Page/Page column 32
[4] Patent: WO2012/145569, 2012, A1, . Location in patent: Page/Page column 180; 181
[5] Patent: WO2016/106623, 2016, A1, . Location in patent: Page/Page column 80
[6] Patent: WO2016/106624, 2016, A1, . Location in patent: Page/Page column 52
  • 5
  • [ 2435-36-1 ]
  • [ 107-04-0 ]
  • [ 15448-76-7 ]
  • [ 106004-07-3 ]
Reference: [1] Australian Journal of Chemistry, 1985, vol. 38, # 11, p. 1705 - 1718
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 2435-36-1 ]

Aliphatic Cyclic Hydrocarbons

Chemical Structure| 15448-76-7

[ 15448-76-7 ]

Dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate

Similarity: 0.93

Chemical Structure| 32811-75-9

[ 32811-75-9 ]

Methyl 3-oxocyclopentanecarboxylate

Similarity: 0.93

Chemical Structure| 28269-03-6

[ 28269-03-6 ]

(1R,2R)-rel-Dimethyl 4-oxocyclopentane-1,2-dicarboxylate

Similarity: 0.93

Chemical Structure| 25090-39-5

[ 25090-39-5 ]

3-(Methoxycarbonyl)cyclohexanecarboxylic acid

Similarity: 0.93

Chemical Structure| 3399-22-2

[ 3399-22-2 ]

Dimethyl trans-1,4-Cyclohexanedicarboxylate

Similarity: 0.93

Esters

Chemical Structure| 6138-26-7

[ 6138-26-7 ]

Trimethyl propane-1,2,3-tricarboxylate

Similarity: 0.96

Chemical Structure| 15448-76-7

[ 15448-76-7 ]

Dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate

Similarity: 0.93

Chemical Structure| 32811-75-9

[ 32811-75-9 ]

Methyl 3-oxocyclopentanecarboxylate

Similarity: 0.93

Chemical Structure| 28269-03-6

[ 28269-03-6 ]

(1R,2R)-rel-Dimethyl 4-oxocyclopentane-1,2-dicarboxylate

Similarity: 0.93

Chemical Structure| 15177-67-0

[ 15177-67-0 ]

trans-4-(Methoxycarbonyl)cyclohexanecarboxylic acid

Similarity: 0.93