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[ CAS No. 22264-50-2 ] {[proInfo.proName]}

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Chemical Structure| 22264-50-2
Chemical Structure| 22264-50-2
Structure of 22264-50-2 * Storage: {[proInfo.prStorage]}
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Product Details of [ 22264-50-2 ]

CAS No. :22264-50-2 MDL No. :MFCD00661068
Formula : C5H9NO2 Boiling Point : -
Linear Structure Formula :- InChI Key :FVTVMQPGKVHSEY-UHFFFAOYSA-N
M.W : 115.13 Pubchem ID :89643
Synonyms :
1-Aminocyclobutanecarboxylic acid

Calculated chemistry of [ 22264-50-2 ]

Physicochemical Properties

Num. heavy atoms : 8
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 2.0
Molar Refractivity : 28.55
TPSA : 63.32 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) : -9.09 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.31
Log Po/w (XLOGP3) : -2.94
Log Po/w (WLOGP) : -0.05
Log Po/w (MLOGP) : -2.59
Log Po/w (SILICOS-IT) : 0.04
Consensus Log Po/w : -0.85

Druglikeness

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

Water Solubility

Log S (ESOL) : 1.36
Solubility : 2660.0 mg/ml ; 23.1 mol/l
Class : Highly soluble
Log S (Ali) : 2.17
Solubility : 17000.0 mg/ml ; 148.0 mol/l
Class : Highly soluble
Log S (SILICOS-IT) : 0.06
Solubility : 133.0 mg/ml ; 1.16 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.05

Safety of [ 22264-50-2 ]

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 [ 22264-50-2 ]

* 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 [ 22264-50-2 ]
  • Downstream synthetic route of [ 22264-50-2 ]

[ 22264-50-2 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 845621-11-6 ]
  • [ 22264-50-2 ]
YieldReaction ConditionsOperation in experiment
70%
Stage #1: With sodium hydroxide; sodium hypochlorite In water at 5℃; for 1 h;
Stage #2: With hydrogenchloride In water at 15 - 25℃; for 3 h;
Stage #3: With hydrogenchloride In water
EXAMPLE 2; Synthesis of cyclobutaneaminoacid from cyclobutaneamidoacid Aminoacid Zwitterion 14; Amidoacid 12 (1.43g, 10.0 mmol, 1 eq. ) was slowly added to a solution of IN aqueous NAOH (10 ml, 10.0 mmol, 1 eq. ) under N2 at 0°C with a water-ice bath. NAOCI solution (10-13percent solution from Aldrich Chem. Co. , 9.0 ml, ca. 15.0 mmol, 1.5 eq. ) was added slowly, and the resulting mixture was stirred at 5 °C for one hour. 10 N NAOH solution (2.0 ml, 20 mmol, 2 eq. ) was added slowly in order to keep the temperature at below 20 °C, and the mixture was stirred at 15-25 °C for three hours. LC-MS indicated that the reaction was completed. After quenching with a solution OF NA2S203-5 H2O (2.48 g, 10 mmol, 1 eq. ) in H20 (3 ML) at 15°C, the reaction mixture was stirred for 1 h and neutralized to pH = 7.0 with 12N aq. HCI. The volatiles were removed under vacuum by azeotroping with toluene to give ca. 9g of white solid. The solid was extracted with methanol (3 x 30 mL), and 2. 0g crude product was obtained after evaporation of methanol. 1H NMR assay showed this solid contained 0. 81G amino acid 10 (70percent yield) with the remainder being inorganic salts. BOTH H and 13C NMR data were compared and found to be identical with an authentic sample from Sumitomo Chemical, Inc.
Reference: [1] Patent: WO2005/19158, 2005, A1, . Location in patent: Page/Page column 18
  • 2
  • [ 89691-88-3 ]
  • [ 22264-50-2 ]
Reference: [1] Journal of Organic Chemistry, 1995, vol. 60, # 18, p. 5790 - 5794
[2] Journal of Medicinal Chemistry, 1984, vol. 27, # 12, p. 1663 - 1668
[3] Journal of the Chemical Society, 1960, p. 2119 - 2132
[4] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
  • 3
  • [ 117488-20-7 ]
  • [ 22264-50-2 ]
Reference: [1] Organic Preparations and Procedures International, 1995, vol. 27, # 2, p. 185 - 212
  • 4
  • [ 67-56-1 ]
  • [ 22264-50-2 ]
  • [ 215597-35-6 ]
Reference: [1] ACS Combinatorial Science, 2016, vol. 18, # 6, p. 330 - 336
  • 5
  • [ 22264-50-2 ]
  • [ 109-74-0 ]
  • [ 4043-88-3 ]
Reference: [1] European Journal of Inorganic Chemistry, 2014, vol. 2014, # 17, p. 2829 - 2838
  • 6
  • [ 67-56-1 ]
  • [ 22264-50-2 ]
  • [ 92398-47-5 ]
YieldReaction ConditionsOperation in experiment
100% at 0 - 20℃; for 0.12 h; To a stirred solution of 1-aminocyclobutane-l-carboxylic acid (2.7 g, 23.4 mmol) in MeOH (40 ml), was carefully added acetyl chloride (4.2 ml, 58.6 mmol) drop wise at 0 °C. The reaction mixture was then warmed to room temperature and stirred for about 12 hours. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated under reduced pressure to give methyl 1-aminocyclobutane-l -carboxylate hydrochloride (3.02 g, yield: 100 percent) as a white solid.To a stirred solution of methyl 1-aminocyclobutane-l -carboxylate hydrochloride (3.02 g, 23.4 mmol) in THF (40 ml), were added N(Et)3(9.6 ml, 69.6 mmol) and (Boc)20 (6.4 ml, 23.8 mmol) at 0 °C. The reaction mixture was then warmed to room temperature and stirred for about 12 hours. After completion of the reaction (monitored by TLC), saturated NH4C1 solution was added, extracted with EtOAc (2 X 100 mL). The combined organic phases were washed with brine, dried over Na2S04and concentrated under reduced pressure to give the crude product. Purification by flash chromatography with EtOAc-hexane (3: 7) as an eluent to afford the desired product (5.32 g, yield: 100percent) as an oil. 1H NMR (300 MHz, DMSO-d6): δ 7.64 (s, 1H), 3.60 (s, 3H), 2.44-2.38 (m, 2H), 2.14-2.04 (m, 2H), 1.88-1.80 (m, 2H), 1.36 (s, 9H).
78% Cooling with ice; Reflux 1-Aminocyclobutamic acid (250 mg, 2.17 mmol) was dissolved in 10 mL of anhydrous methanol, 0.3 mL of thionyl chloride was added dropwise to the ice bath,Remove the ice bath and heat the reflux overnight.Evaporated to dryness under reduced pressure to give 1-aminocyclopropylcarboxylic acid hydrochloride (280 mg) as a white solid in 78percent yield.
71% at 0 - 20℃; for 20 h; 1-aminocyclobutanecarboxylic acid (100 mg) was dissolved in 10 ml of methanol, and the reaction solution was cooled to 0°C.At 0-5°C, HCl gas was introduced and stopped after 2 hours. The reaction solution was warmed to room temperature and reacted at room temperature for 18 hours. The mixture was concentrated under reduced pressure to give a yellow oil.Add 15 ml of ether to the concentrate and stir for 30 minutes.Filtered to give 10 mg (71percent yield) of the title compound as a white solid.
Reference: [1] Patent: WO2017/17630, 2017, A1, . Location in patent: Page/Page column 80-81
[2] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
[3] Patent: CN104230766, 2017, B, . Location in patent: Paragraph 0382; 0383; 0384
[4] Patent: CN104341351, 2018, B, . Location in patent: Paragraph 0356-0359
[5] Journal of Medicinal Chemistry, 1984, vol. 27, # 12, p. 1663 - 1668
[6] Patent: US2006/183694, 2006, A1, . Location in patent: Page/Page column 23-24
[7] Patent: US2007/10455, 2007, A1, . Location in patent: Page/Page column 24
[8] Patent: US2008/14173, 2008, A1, . Location in patent: Page/Page column 25
[9] Patent: WO2003/99274, 2003, A1, . Location in patent: Page 61
[10] Patent: WO2003/99316, 2003, A1, . Location in patent: Page 80
[11] Patent: US2004/77551, 2004, A1, . Location in patent: Page/Page column 130
[12] Patent: WO2005/46712, 2005, A1, . Location in patent: Page/Page column 67; 68
[13] Patent: WO2005/51410, 2005, A1, . Location in patent: Page/Page column 68
[14] Patent: US2005/143316, 2005, A1, . Location in patent: Page/Page column 29
[15] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 12, p. 3502 - 3506
[16] Patent: US2008/119461, 2008, A1, . Location in patent: Page/Page column 30
  • 7
  • [ 22264-50-2 ]
  • [ 92398-47-5 ]
Reference: [1] Patent: US2004/48802, 2004, A1,
[2] Patent: US2009/274648, 2009, A1,
[3] Patent: US2009/304626, 2009, A1,
  • 8
  • [ 24424-99-5 ]
  • [ 22264-50-2 ]
  • [ 120728-10-1 ]
YieldReaction ConditionsOperation in experiment
75% With sodium hydrogencarbonate In 1,4-dioxane; water at 0 - 20℃; for 12 h; To a stirred solution of 1-aminocyclobutane-1-carboxylic acid (2 g, 17 mmol) in 1,4- dioxane: H2O (20: 20 mL), were added NaHCO3 (4.4 g, 57 mmol) and (Boc)2O (4.5 g, 20.4 mmol) at 0°C and stirred the reaction mixture for about 12 hours at room temperature. After complete conversion of starting material, the reaction mixture was washed with EtOAc (30 mL) to remove the impurities, then aqueous layer was acidified with 1N HCl (PH =2-3) and extracted with CH2Cl2 (2x40 mL). The combined organic extracts were washed with water, brine, dried over Na2S04, filtered and evaporated under reduced pressure. The crude residue was purified by silica gel column chromatography by using 35 percent EtOAc: n-Hexane as an eluent to afford the desired product (2.8 g, yield: 75percent) as an off white solid. 1H MR (300 MHz, CD3OD): δ 2.62-2.53 (m, 2H), 2.25-2.15 (m, 2H), 2.05-1.97 (m, 2H), 1.42 (s, 9H); ES Mass: 238.04 [M+Na]+.
62.41% With sodium hydroxide In 1,4-dioxane at 0 - 20℃; To a stirred solution of 1-aminocyclobutane-l-carboxylic acid (30 g, 139.53 mmol, 1.0 eq) in 1,4-dioxane (300 ml) at 0 °C was added 2N NaOH solution (300 ml) followed by (Boc)20 (45.62 g, 209.30 mmol, 1.5 eq). The reaction mixture was allowed to stir at room temperature for overnight. TLC indicated starting material was consumed and the desired product was observed. The organic phase was evaporated under reduced pressure, the reaction mixture was diluted with water (50 ml), cooled to 0 °C, pH adjusted to 5 with IN HC1 and then extracted with DCM (3x300 ml). The combined organic extracts were washed with water (300 ml), brine (100 ml) solution, dried over Na2S04, filtered and evaporated under reduced pressure. The residue was stirred with n-hexane (300 ml) at room temperature for about 30 minutes, the obtained solid was filtered and dried under vacuum to give the desired product (35.0 g, yield: 62.41percent) as a white solid. 1H NMR (300 MHz, DMSO-d6): δ ppm 12.19 (brs, 1H), 7.70-7.16 (m, 1H), 2.45-2.36 (m, 2H), 2.12-2.03 (m, 2H), 1.86-1.78 (m, 2H), 1.36 (brs, 9H); ESI-MS: m/z 238.13 (M+Na)+.
19% With sodium hydroxide In tetrahydrofuran; water at 20℃; for 24 h; Stage 1. 1 -[(tert-Butoxycarbonyl)am ino]cyclobutanecarboxyl ic acid To a solution of 1-amino-1-cyclobutane carboxylic acid (2.92 g, 25.4 mmol), NaOH (3.04 g, 76.2 mmol), THF (100 mL) and water (100 mL) at RT was added d-tert-buty dcarbonate (8.30 g, 38.1 rnmoD and the reaction was strred for 24 hrs, The reacUon mixture was acdfled to pH5 usng 2M HC and the mixture was extracted w[th EtOAc (2x 200 mL). The cornbned organcs were dried over MgSO4, ifitered and concentrated in vacuo to give the tWe compound as a whfte sod (1.05 g, 19percent). LCMS: m/z 238 [M+Hj.
1.09 g With sodium hydroxide In methanol; water at 0 - 20℃; for 12 h; Intermediate 68 1-([(1,1-dimethylethyl)oxy]carbonyl}amino)cyclobutanecarboxylic acid [0684] [0685] To a solution of 1-aminocyclobutanecarboxylic acid (626 mg, 5.44 mmol) in 5.6 ml of 1 M aqueous sodium hydroxide and 4 ml of methanol was added Boc-anhydride (1.425 g, 6.53 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 12 hours. After most of the methanol was evaporated, the solution was acidified to pH 2 with 1 M HCl and extracted with ethyl acetate. The organic extracts were combined and washed with brine. Evaporation of the solvent afforded the title compound (1.09 g). [0686] 1H NMR (400 MHz, DMSO-d6): δ ppm 12.21 (1H, s), 7.44 (1H, s), 2.29-2.47 (2H, m), 2.09 (2H, q), 1.74-1.94 (2H, m), 1.36 (9H, s); UPLC: 0.56 min, 216 [M+H]+

Reference: [1] Patent: WO2017/21922, 2017, A1, . Location in patent: Page/Page column 26
[2] Journal of the American Chemical Society, 1997, vol. 119, # 49, p. 11807 - 11816
[3] Patent: WO2016/178092, 2016, A2, . Location in patent: Page/Page column 51; 52
[4] Patent: WO2014/1802, 2014, A1, . Location in patent: Page/Page column 59; 60
[5] Patent: WO2011/69951, 2011, A1, . Location in patent: Page/Page column 79
[6] Patent: WO2011/154677, 2011, A1, . Location in patent: Page/Page column 72
[7] Patent: WO2012/76877, 2012, A1, . Location in patent: Page/Page column 93
[8] Patent: US2013/267510, 2013, A1, . Location in patent: Paragraph 0684-0686
  • 9
  • [ 22264-50-2 ]
  • [ 180205-34-9 ]
Reference: [1] ACS Combinatorial Science, 2016, vol. 18, # 6, p. 330 - 336
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