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[ CAS No. 3105-95-1 ] {[proInfo.proName]}

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Chemical Structure| 3105-95-1
Chemical Structure| 3105-95-1
Structure of 3105-95-1 * Storage: {[proInfo.prStorage]}
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Product Details of [ 3105-95-1 ]

CAS No. :3105-95-1 MDL No. :MFCD00005981
Formula : C6H11NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :HXEACLLIILLPRG-YFKPBYRVSA-N
M.W : 129.16 Pubchem ID :439227
Synonyms :
H-HoPro-OH

Calculated chemistry of [ 3105-95-1 ]

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.83
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 37.33
TPSA : 49.33 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -8.73 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.16
Log Po/w (XLOGP3) : -2.31
Log Po/w (WLOGP) : -0.17
Log Po/w (MLOGP) : -2.21
Log Po/w (SILICOS-IT) : 0.46
Consensus Log Po/w : -0.61

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : 0.88
Solubility : 981.0 mg/ml ; 7.59 mol/l
Class : Highly soluble
Log S (Ali) : 1.81
Solubility : 8340.0 mg/ml ; 64.6 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : -0.42
Solubility : 48.5 mg/ml ; 0.376 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.69

Safety of [ 3105-95-1 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 3105-95-1 ]

* 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 [ 3105-95-1 ]
  • Downstream synthetic route of [ 3105-95-1 ]

[ 3105-95-1 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 67-56-1 ]
  • [ 3105-95-1 ]
  • [ 18650-39-0 ]
YieldReaction ConditionsOperation in experiment
92% at 0 - 20℃; (S)-Piperidme-2-carboxylic acid (10.00 g, 77.46 mmol) in methanol (200ml) at 0°Cwas added thionyl chloride (15.0 ml, 205.61 mmol) under Ar. The mixture was stirred at 0°C for 30 min, then RT overnight, evaporated and crystallized with EtOH to afford the title product (9.90 g, 92percent yield). EIMS m/z 144.1 ( | M ]++I I ).
79.1% at 0 - 70℃; for 4 h; To a solution of (i)-piperidine-2-carboxylic acid ( 10.0 g. 77.4 mmol) in MeOH (50 mL) was added thionyl chloride (8.5 mL, 1 17.2 mmol) dropwise at 0 °C. The mixture was stirred at 0 °C for 1 hr and at 70 °C for another 3 hrs. After the reaction was completed, the mixture was concentrated in vacuo to give the title compound as a white solid (11.0 g, 79.1percent). The compound was characterized by the following spectroscopic data: MS (ESI, pos.ion) m/z: 144.1 [M+H] +; NMR (400 MHz, CDC13) δ (ppm): 5.02 (br, 1 H), 4.00 (br, 1 H), 3.85 (s, 3H), 3.63 (br, 1 H), 3.15 (br, 1 H), 2.28 (m, 1 H), 2.08 (m, 2H), 1.86 (m. 2H), 1.63 (br, 1H).
79.1% at 0 - 70℃; for 4 h; To a solution of L(-)-pipecolinic acid (10.0 g.77.4 mmol) in MeOH (50 mL) was added thionyl chloride (8.5 mL 117.2 mmol) dropwise at 0 °C. At the end of the addition, the mixture was stirred at 0 °C for 1.0 hr and then at 70 °C for another 3.0 hrs. After the reaction was completed, the mixture was concentrated in vacuo to give the title compound as a white solid (11.0 g.79.1percent). The compound was characterized by the following spectroscopic data:MS (LSI. pos.ion) w r: 144.1 [M+H] : and NMR (400 MHz. CDCl;,)i)(ppm): 5.02 (br. lH).4.00(br.1 H).3.85 (s.3H).3.63 (br. lH).3.15(br. lH). 2.28 (m.1H).2.08 (m.2H).1.86 (m.2H).1.63 (br.1H).
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 23, p. 7333 - 7342
[2] Chemistry - A European Journal, 2010, vol. 16, # 25, p. 7547 - 7553
[3] Patent: WO2015/28850, 2015, A1, . Location in patent: Page/Page column 88
[4] Tetrahedron Letters, 1991, vol. 32, # 49, p. 7183 - 7186
[5] Patent: WO2014/19344, 2014, A1, . Location in patent: Paragraph 00601
[6] Patent: WO2014/82379, 2014, A1, . Location in patent: Page/Page column 170; 171
[7] Tetrahedron Letters, 1990, vol. 31, # 16, p. 2341 - 2344
[8] Patent: US2015/79028, 2015, A1, . Location in patent: Paragraph 1638; 1654; 1655; 1656; 1657
  • 2
  • [ 3105-95-1 ]
  • [ 2133-33-7 ]
Reference: [1] Patent: US2006/276654, 2006, A1, . Location in patent: Page/Page column 3
  • 3
  • [ 102774-86-7 ]
  • [ 3105-95-1 ]
  • [ 101555-63-9 ]
YieldReaction ConditionsOperation in experiment
83% With potassium carbonate In 1,4-dioxane at 20℃; Synthesis of building blocks A Synthesis of (S)-1 -(((9H-fluoren-9-yl)methoxy)carbonyl)piperidine-2-carboxylic acid A solution of the L-pipecolic acid (3.6g, 38.7 mmol) in 40ml of 10percent sodium carbonate was dissolved in round bottom flask and allowed to stir for 5 min at rt. To this solution was added F-moc succinamide (8.5g, 34.8 mmol) dissolved in 35 ml dioxane and the reaction was stirred overnight. After overnight stirring water was added and the aqueous layer was extracted with ethyl acetate. The aqueous layer was made acidic (pH-2) by addition of concentrated HCI. The acidic layer was extracted with ethyl acetate (3x 40ml). The organic phase was washed with 1 N HCI followed by brine, dried over MgSO4 and concentrated under vacuo to yield a oily colorless liquid. The oily liquid was dissolved in ether and cooled to get fluffy white solid which was washed with hexane and dried to yield (S)-1 -(((9H-fluoren-9- yl)methoxy)carbonyl)piperidine-2-carboxylic acid ( 8.2g, 38.7mmol, 83percent). TLC (Hexane:EtOAc: TFA 1 : 1 : 0.2): RF = 0.60 HPLC (Gradient A) retention time= 24.6-24.8 min 1 H NMR (300 MHz, CDCI3) 5=1 .28-1 .53 (m, 2H), 1 .69-1 .82 (m, 3H), 2.19-2.37 (m, 1 H), 3.15 (t, 1 H, J= 13.2Hz), 4.05-4.33 (m, 2H), 4.37-4.49 (m, 2H), 4.76-5.05(m, 1 H), 7.28-7.41 (m, 4H), 7.55-7.62 (m, 2H), 1 .77 (s, 2H). 13C NMR (75 MHz, CDCI3) δ= 20.72, 24.70, 26.55, 41 .94, 47.25, 54.19, 67.86, 1 19.97, 125.08, 127.07, 127.68, 141 .33, 143.89, 156.65, 177.36 MS (ESI) m/z 352.66 [M + H] \ calculated 352.40 [M + H] +.
Reference: [1] Patent: WO2013/91900, 2013, A1, . Location in patent: Page/Page column 41
  • 4
  • [ 28920-43-6 ]
  • [ 3105-95-1 ]
  • [ 101555-63-9 ]
YieldReaction ConditionsOperation in experiment
1.41 g With sodium carbonate In 1,4-dioxane; water at 0 - 20℃; for 16 h; To a stirred mixture of (S)-piperidine-2-carboxylic acid (1.0 g, 7.75 mmol) and Na2C03 (1.65 g, 15.50 mmol) in water (10 mL) was added a solution of FMOC-C1 (3.0 g, 11.63 mmol) in 1,4-dioxane (10 mL) dropwise at 0°C and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with water (50 mL) and washed with MTBE (25 mL). The aqueous layer was acidified with 1M aqueous HC1 (10 mL) to pH 2 and extracted with EtOAc (3 x 50 mL). The combined organic extracts were washed with brine solution (50 mL), dried over anhydrous a2S04, filtered and concentrated to afford the title compound (1.41 g) as an off-white solid. The crude product was used in the next step without purification
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 4, p. 1111 - 1115
[2] Journal of the American Chemical Society, 2006, vol. 128, # 11, p. 3838 - 3847
[3] Patent: WO2013/148478, 2013, A1, . Location in patent: Page/Page column 23
  • 5
  • [ 82911-69-1 ]
  • [ 3105-95-1 ]
  • [ 101555-63-9 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 5, p. 1059 - 1063
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 9, p. 4114 - 4122
  • 6
  • [ 88744-04-1 ]
  • [ 3105-95-1 ]
  • [ 101555-63-9 ]
Reference: [1] Synthesis, 1986, # 4, p. 303 - 305
  • 7
  • [ 3105-95-1 ]
  • [ 41373-39-1 ]
YieldReaction ConditionsOperation in experiment
80%
Stage #1: With dimethylsulfide borane complex; boron trifluoride diethyl etherate In tetrahydrofuran at 0℃; Reflux
Stage #2: With hydrogenchloride; methanol In water at 0℃; Reflux
Amino alcohol B-12: (S)-Piperidin-2-ylmethanolBH3-DMS (62.0 mmol, 4.0 equiv.) and BF3-Et2O (15.5 mmol, 1.0 equiv.) were added at 0° C. to a solution of (2S)-piperidine-2-carboxylic acid (15.5 mmol, 1.0 equiv.) in THF (50 ml), and the mixture was refluxed for 14 hours. The solvent was concentrated under reduced pressure, and then MeOH (40 ml) was added dropwise at 0° C. Concentrated HCl (5 ml) was added to the reaction mixture, and refluxing was carried out for a further 2 hours. The solvent was concentrated, and the residue was stirred for 15 minutes in 10percent isopropanol in DCM and filtered. The filtrate was concentrated to dryness, and a white solid was obtained. Yield: 80percent.
44% With dimethylsulfide borane complex; boron trifluoride diethyl etherate In tetrahydrofuranReflux (S)-Piperidine-2-carboxylic acid (2 g, 15.5 mmol) was initially introduced into tetrahydrofuran (20 ml) and boron trifluoride etherate (2.1 ml, 117.1 mmol) was added, followed by boron dimethylsulfide in tetrahydrofuran (dropwise, 3 ml, 30.9 mmol). The reaction mixture was then refluxed for 16 h. The mixture was quenched with ice-cooled methanol (10 ml), hydrogen chloride solution (conc. aq., 3 ml) was added dropwise and the mixture was refluxed for 30 min. After cooling, the mixture was rendered alkaline with dilute sodium hydroxide solution (4percent) and extracted with methylene chloride (3.x.50 ml). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude product was employed in the next stage without further purification.
44%
Stage #1: With dimethylsulfide borane complex; boron trifluoride diethyl etherate In tetrahydrofuranReflux
Stage #2: With hydrogenchloride; water In tetrahydrofuranCooling with ice; Reflux
Synthesis of Carboxylic Acid 1 (Acid Structural Unit)(S)-2-((1-(4-Methoxy-2,6-dimethylphenylsulfonyl)piperidin-2-yl)methoxy)acetic acidUsed in the Synthesis of Examples 25, 80 and 81 (i): (S)-Piperidine-2-carboxylic acid (2 g, 15.5 mmol) was placed in tetrahydrofuran (20 ml); boron trifluoride etherate (2.1 ml, 117.1 mmol) was added, followed by boron dimethylsulfide in tetrahydrofuran (dropwise, 3 ml, 30.9 mmol). The reaction mixture was then refluxed for 16 h. Quenching was carried out with ice-cold methanol (10 ml); hydrogen chloride solution (conc. aq., 3 ml) was added dropwise, and refluxing was carried out for 30 min. After cooling, the mixture was rendered alkaline with dilute sodium hydroxide solution (4percent) and extracted with dichloromethane (3.x.50 ml). The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The crude product was used in the next stage without being purified further. Yield: 44percent
Reference: [1] Tetrahedron, 2013, vol. 69, # 51, p. 10876 - 10883
[2] Tetrahedron, 2013, vol. 69, # 30, p. 6129 - 6143
[3] Patent: US2010/173889, 2010, A1, . Location in patent: Page/Page column 34
[4] Patent: US2009/253669, 2009, A1, . Location in patent: Page/Page column 46-47
[5] Patent: US2009/264407, 2009, A1, . Location in patent: Page/Page column 77
[6] Patent: US2009/264400, 2009, A1, . Location in patent: Page/Page column 86-87
[7] Synthesis (Germany), 2018, vol. 50, # 5, p. 1113 - 1122
[8] Patent: US2010/113417, 2010, A1, . Location in patent: Page/Page column 30
[9] Patent: WO2009/124746, 2009, A1, . Location in patent: Page/Page column 100-101
  • 8
  • [ 3105-95-1 ]
  • [ 139004-93-6 ]
Reference: [1] Tetrahedron Letters, 1991, vol. 32, # 49, p. 7183 - 7186
  • 9
  • [ 3105-95-1 ]
  • [ 84057-95-4 ]
Reference: [1] Patent: CN107325041, 2017, A,
  • 10
  • [ 501-53-1 ]
  • [ 3105-95-1 ]
  • [ 28697-11-2 ]
Reference: [1] Tetrahedron Letters, 1994, vol. 35, # 47, p. 8871 - 8872
[2] Patent: CN103554112, 2016, B, . Location in patent: Page/Page column 3
  • 11
  • [ 64-17-5 ]
  • [ 3105-95-1 ]
  • [ 123495-48-7 ]
Reference: [1] Tetrahedron Letters, 2006, vol. 47, # 29, p. 5017 - 5020
[2] Patent: EP931078, 2006, B1, . Location in patent: Page/Page column 33
  • 12
  • [ 3105-95-1 ]
  • [ 136030-04-1 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 20, p. 6386 - 6392
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