Home Cart 0 Sign in  

[ CAS No. 100202-39-9 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 100202-39-9
Chemical Structure| 100202-39-9
Structure of 100202-39-9 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

Quality Control of [ 100202-39-9 ]

Related Doc. of [ 100202-39-9 ]

Alternatived Products of [ 100202-39-9 ]
Product Citations

Product Details of [ 100202-39-9 ]

CAS No. :100202-39-9 MDL No. :MFCD01861758
Formula : C5H10ClNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :UOCWTLBPYROHEF-UHFFFAOYSA-N
M.W : 151.59 Pubchem ID :21100040
Synonyms :
Methyl azetidine-3-carboxylate hydrochloride
Chemical Name :Methyl azetidine-3-carboxylate hydrochloride

Calculated chemistry of [ 100202-39-9 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.8
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 39.0
TPSA : 38.33 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) : -7.06 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.0
Log Po/w (XLOGP3) : 0.23
Log Po/w (WLOGP) : -0.2
Log Po/w (MLOGP) : 0.0
Log Po/w (SILICOS-IT) : 0.36
Consensus Log Po/w : 0.08

Druglikeness

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

Water Solubility

Log S (ESOL) : -0.79
Solubility : 24.4 mg/ml ; 0.161 mol/l
Class : Very soluble
Log S (Ali) : -0.59
Solubility : 38.5 mg/ml ; 0.254 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.55
Solubility : 42.5 mg/ml ; 0.281 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 100202-39-9 ]

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 [ 100202-39-9 ]

* 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 [ 100202-39-9 ]
  • Downstream synthetic route of [ 100202-39-9 ]

[ 100202-39-9 ] Synthesis Path-Upstream   1~5

  • 1
  • [ 100202-39-9 ]
  • [ 501-53-1 ]
  • [ 757239-60-4 ]
YieldReaction ConditionsOperation in experiment
99% With sodium hydroxide In tetrahydrofuran; water at 0 - 20℃; for 18 h; A round bottomed flask containing methyl azetidine-3-carboxylate hydrochloride(3 g, 20 mmol), THF (30 mL) and H20 (30 mL) was added with an aqueous solution ofNaOH (4 M, 5 mL, 20 mmol) at 0 °C, followed by benzyl chloroformate (2.84 mL, 20 mmol). The reaction was vigorously stirred at room temperature for 18 hours. The reaction mixture was concentrated in vacuo and the residue partitioned between Et20 (100 mL) and H20 (30 mL). The aqueous phase was back-extracted withEt20 (3 x 50 mL), the combined organic phases were dried (Na2SO4) and concentrated in vacuo to give the title compound (5 g, 99percent) as a colourless oil, which was used in subsequent steps without further purification.‘H NMR (400 MHz, CDC13): ö 7.43-7.25 (m, 5 H), 5.10 (s, 2 H), 4.23-4.13 (m, 4 H), 3.74 (s, 3 H), 3.38 (q, J = 7.2 Hz, 1 H).
Reference: [1] Patent: WO2016/177849, 2016, A1, . Location in patent: Page/Page column 74; 75
[2] Patent: US2011/183960, 2011, A1, . Location in patent: Page/Page column 27
  • 2
  • [ 100202-39-9 ]
  • [ 24424-99-5 ]
  • [ 610791-05-4 ]
YieldReaction ConditionsOperation in experiment
13.5% With sodium hydrogencarbonate In tetrahydrofuran; water; ethyl acetate at 0 - 20℃; for 23 h; A crude product of methyl azetidine-3-carboxylate hydrochloride (calculated as 1.93 g of pure product) was dissolved in water (26 ml), sodium hydrogencarbonate (3.2 g), then a solution of di-t-butyl dicarbonate (2.91 g) in tetrahydrofuran (13 ml) were added with stirring and cooling in an ice bath, followed by stirring at the same temperature for 0.5 hours. The reaction mixture was stirred at room temperature for 19.5 hours. Tetrahydrofuran in the reaction mixture was distilled off, extraction was performed with ethyl acetate. The organic layer was washed with brine (70 ml) and dried over anhydrous sodium sulfate. The concentrated organic layer and the aqueous layer were combined, and tetrahydrofuran (50 ml) was added thereto. This was stirred with cooling in an ice bath, and sodium hydrogencarbonate (3.2 g), then di-t-butyl dicarbonate (2.91 g) were again added thereto. The reaction mixture was stirred at the same temperature for 0.5 hours, then at room temperature for 2.5 days. The reaction mixture was partitioned, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, and dried over anhydrous sodium sulfate. The solvent was distilled off, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=2:1, 1:1, ethyl acetate, then ethyl acetate:methanol=10:1). The fractions containing the target compound were concentrated to give the title compound (370 mg, 13.5percent) as a colorless oil.1H-NMR Spectrum (CDCl3) δ (ppm): 1.44 (9H, s), 3.35 (1H, m), 3.75 (3H, s), 4.10 (4H, d, J=7.6 Hz).
13.5%
Stage #1: With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃; for 20 h;
Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water; ethyl acetate at 0 - 20℃; for 60.5 h;
(Production Example 86) Methyl 1-tert-butoxycarbonylazetidine-3-carboxylate
A crude product of methyl azetidine-3-carboxylate hydrochloride (assessed as 1.93 g of a pure product) was dissolved in water (26 ml), and sodium hydrogencarbonate (3.2 g) and a solution of di-t-butyl dicarbonate (2.91 g) in tetrahydrofuran (13 ml) were added while stirring and cooling in an ice bath, followed by stirring at the same temperature for 0.5 hr.
The reaction mixture was stirred at room temperature for 19.5 hr.
Tetrahydrofuran in the reaction mixture was removed, and extracted with ethyl acetate.
The organic layer was washed with brine (70 ml), and dried over anhydrous sodium sulfate.
The concentrated organic layer and the aqueous layer were combined, and tetrahydrofuran (50 ml) was added.
This was stirred while cooling in an ice bath, and sodium hydrogencarbonate (3.2 g), and di-t-butyl dicarbonate (2.91 g) were again added thereto.
After stirring at the same temperature for 0.5 hr, stirring was carried out at room temperature for 2.5 days.
The reaction mixture was partitioned, and the aqueous layer was extracted with ethyl acetate.
The organic layer was combined and dried over anhydrous sodium sulfate.
The solvent was removed, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate = 2:1, 1:1, ethyl acetate, then ethyl acetate:methanol = 10:1).
Fractions containing the target compound were concentrated to provide the titled compound as a colorless oil (370 mg, 13.5 percent).
1H-NMR Spectrum (CDCl3) δ (ppm): 1.44(9H, s), 3.35 (1H, m), 3.75 (3H, s), 4.10 (4H, d, J = 7.6 Hz).
582 kg
Stage #1: at 5 - 10℃; for 7 h; Large scale
Stage #2: at 5 - 20℃; Large scale
Triethylamine (TEA, 560 kg, 5544 mol, 2.18 eq) was added dropwise to the crudesolution of 2 at 5-10 °C giving a vigorous exothermic reaction over about 7 hrs. The mixture was cooled to 5-15 °C. More triethylamine was added (210 kg, 2082 mol, 0.82 eq). Di-tertbutyl dicarbonate (boc anhydride, Boc2O, CAS Reg. No. 24424-99-5 (587 kg, 2690 mol, 1.06eq.) dropwise at 5-15 °C, giving a slightly exothermic reaction with gas generated for about 7 hrs. The mixture was stirred at 1 520 °C for 16 hrs. Methanol was removed by evaporation at 50°C over about 5 hrs. Toluene (1360 kg, 5.3 wt) and water (1750 kg, 6.8 wt) were added and stirred for 20 mm. The organic phases were separated. The water phase was extracted with toluene. The combined organic phases were washed with brine and dried over MgSO4 (150 kg, 0.58 wt) for 30 mm, and filtered. The filter cake was washed with toluene. The combined organic phases were evaporated at 50-60 °C under vacuum. (vacuum: about 0.08 Mpa, about 40 hrs) to give 3 (CAS Reg. No. 610791-05-4, 582 kg 90.4 wpercent by qNMR assay)in 96.4percent corrected yield.
Reference: [1] Patent: US2008/214815, 2008, A1, . Location in patent: Page/Page column 15
[2] Patent: EP1889836, 2008, A1, . Location in patent: Page/Page column 80
[3] Patent: WO2018/108954, 2018, A1, . Location in patent: Page/Page column 19; 20
  • 3
  • [ 53871-06-0 ]
  • [ 100202-39-9 ]
YieldReaction ConditionsOperation in experiment
100% With hydrogenchloride; hydrogen In methanol; ethyl acetate at 20℃; for 11 h; (Production Example 85) Methyl azetidine-3-carboxylate hydrochloride
A solution of methyl 1-benzhydrylazetidine-3-carboxylate (3.57 g) in methanol (360 ml) were added a 4N solution of hydrochloric acid in ethyl acetate (12.7 ml) and 20 percent palladium hydroxide (3.57 g), followed by stirring at room temperature under a pressurized hydrogen atmosphere (0.4 MPa) for 11 hr.
The catalyst was removed by filtration and washed with methanol and water.
The filtrate was concentrated to provide a crude product of the target compound as a pale yellow oil.
The reaction was assessed as quantitative and the product obtained was assessed as 1.93 g, which were used for the subsequent reaction.
ESI-MS (m/z): 116 [M+H]+.
Reference: [1] Patent: EP1889836, 2008, A1, . Location in patent: Page/Page column 80
[2] Patent: US2008/214815, 2008, A1, . Location in patent: Page/Page column 14-15
  • 4
  • [ 67-56-1 ]
  • [ 36476-78-5 ]
  • [ 100202-39-9 ]
YieldReaction ConditionsOperation in experiment
100% With thionyl chloride In acetonitrile at 0 - 20℃; for 2.33333 h; To a stirring suspension of 3-azetidine carboxylic acid in MeOH at O0C3 was added SOCl2 dropwise. After 20 minutes, the ice bath was removed, the solution was warmed to rt and was stirred for 2 hours. The solvent was removed in vaccuo to afford the title compound as its HCl salt (1.5g, 100percent). 1H NMR (400 MHz, CD3OD) δ 3.71 - 3.77 (m, 1 H) 3.77 (s, 3 H) 4.18 - 4.31 (m, 4 H).
100% at 0 - 25℃; for 2.25 h; Step 1 : Preparation of C34. A suspension of C33 (1.0 g, 9.89 mmol) in methanol (50 mL) was cooled to 0 °C. Thionyl chloride (1.49 mL, 20.3 mmol) was slowly added dropwise over one minute. The reaction was stirred at 0 °C for 15 minutes. The cooling bath was removed and the reaction was stirred at room temperature for 2 hours. The reaction was concentrated to dryness. The residue was diluted with toluene, and then re-concentrated to dryness. The residue was dried under vacuum to afford the hydrochloride salt of C34 as a sticky yellow solid. Yield: 1.52 g, 10.0 mmol, quantitative. 1H NMR (400 MHz, DMSO-d6) δ 9.56 (br s, 1 H), 9.24 (br s, 1 H), 3.98-4.13 (m, 4H), 3.68 (s, 3H), 3.66-3.76 (m, 1 H).
100% at 5 - 65℃; A stirred suspension of azetidine-3-carboxylic acid (2 g, 19.8 mmol) in MeOH (8 ml) was cooled to 5 0C in an ice-water bath. Thionyl chloride (4.3 ml, 59 mmol) was added dropwise at such a rate as to maintain reaction temperature below 30 0C. A further portion of MeOH (8 ml) was added carefully and the mixture heated at 650C overnight. Evaporation of the solvent and co-evaporation with MeOH (2 x 20 ml) at reduced pressure provided the title compound as viscous brown oil that crystallized on standing (3.17 g, 100percent). The material was used without purification.LCMS data: Calculated MH+ (116); Found 100percent (MH+) m/z 116, Rt = 0.18 min.NMR data: 1H NMR (250 MHz, DMSO) δ ppm 9.60-8.90 (2H, br m), 4.05 (4H, br s), 3.65(3H, s)
90% at 20℃; Cooling with ice Synthesis of 192-A. To a solution of azetidine-3-carboxylic acid (5.00 g, 49.5 mmol) in MeOH (100 mL) was added SOCl2 (11.8 g, 99.0 mmol) dropwise at ice bath. The solution was stirred at room temperature overnight. The reaction mixture concentrated to dryness to give 192-A (6.8 g, 90percent) as a white solid.

Reference: [1] Patent: WO2006/33633, 2006, A1, . Location in patent: Page/Page column 68
[2] Patent: WO2012/73138, 2012, A1, . Location in patent: Page/Page column 55-56
[3] Patent: WO2009/135842, 2009, A1, . Location in patent: Page/Page column 150
[4] European Journal of Medicinal Chemistry, 2010, vol. 45, # 6, p. 2453 - 2466
[5] Journal of Medicinal Chemistry, 2017, vol. 60, # 23, p. 9508 - 9530
[6] Patent: WO2017/7756, 2017, A1, . Location in patent: Paragraph 466
[7] Patent: WO2006/64757, 2006, A1, . Location in patent: Page/Page column 126
[8] Patent: WO2009/16084, 2009, A1, . Location in patent: Page/Page column 50
[9] Patent: WO2005/103001, 2005, A1, . Location in patent: Page/Page column 35-36
[10] Patent: WO2010/85584, 2010, A1, . Location in patent: Page/Page column 43-44
[11] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 144 - 148
[12] Patent: WO2018/108954, 2018, A1, . Location in patent: Page/Page column 19
  • 5
  • [ 36476-78-5 ]
  • [ 100202-39-9 ]
YieldReaction ConditionsOperation in experiment
100% With chloro-trimethyl-silane In methanol Preparation 41
Azetidine-3-carboxylic acid methyl ester hydrochloride .
A mixture of azetidine-3-carboxylic acid (1.26 g) and chlorotrimethylsilane (7.1 mL) in methanol (10 mL) was heated at reflux for 5 h and concentrated leaving a solid (1.88 g, 100percent).
1H NMR (300 mHz, D2O) d 4.31 (m, 4H), 3.81 (m, 1H), 3.78 (s, 3H).
Reference: [1] Patent: EP978279, 2000, A1,
[2] Patent: US4534787, 1985, A,
Recommend Products
Same Skeleton Products
Historical Records

Similar Product of
[ 100202-39-9 ]

Chemical Structure| 343238-58-4

A671971[ 343238-58-4 ]

Methyl azetidine-3-carboxylate

Reason: Free-salt

Related Functional Groups of
[ 100202-39-9 ]

Esters

Chemical Structure| 405090-31-5

[ 405090-31-5 ]

Ethyl azetidine-3-carboxylate hydrochloride

Similarity: 0.94

Chemical Structure| 53871-08-2

[ 53871-08-2 ]

tert-Butyl azetidine-3-carboxylate hydrochloride

Similarity: 0.86

Chemical Structure| 89895-55-6

[ 89895-55-6 ]

Methyl piperidine-3-carboxylate hydrochloride

Similarity: 0.78

Chemical Structure| 164323-84-6

[ 164323-84-6 ]

(S)-Methyl piperidine-3-carboxylate hydrochloride

Similarity: 0.78

Chemical Structure| 1229705-59-2

[ 1229705-59-2 ]

Methyl 2-(azetidin-3-yl)acetate hydrochloride

Similarity: 0.76

Related Parent Nucleus of
[ 100202-39-9 ]

Aliphatic Heterocycles

Chemical Structure| 405090-31-5

[ 405090-31-5 ]

Ethyl azetidine-3-carboxylate hydrochloride

Similarity: 0.94

Chemical Structure| 53871-08-2

[ 53871-08-2 ]

tert-Butyl azetidine-3-carboxylate hydrochloride

Similarity: 0.86

Chemical Structure| 89895-55-6

[ 89895-55-6 ]

Methyl piperidine-3-carboxylate hydrochloride

Similarity: 0.78

Chemical Structure| 164323-84-6

[ 164323-84-6 ]

(S)-Methyl piperidine-3-carboxylate hydrochloride

Similarity: 0.78

Chemical Structure| 875629-26-8

[ 875629-26-8 ]

1-Methylazetidine-3-carboxylic acid

Similarity: 0.76

Azetidines

Chemical Structure| 405090-31-5

[ 405090-31-5 ]

Ethyl azetidine-3-carboxylate hydrochloride

Similarity: 0.94

Chemical Structure| 53871-08-2

[ 53871-08-2 ]

tert-Butyl azetidine-3-carboxylate hydrochloride

Similarity: 0.86

Chemical Structure| 875629-26-8

[ 875629-26-8 ]

1-Methylazetidine-3-carboxylic acid

Similarity: 0.76

Chemical Structure| 1229705-59-2

[ 1229705-59-2 ]

Methyl 2-(azetidin-3-yl)acetate hydrochloride

Similarity: 0.76

Chemical Structure| 959238-28-9

[ 959238-28-9 ]

1-Isopropylazetidine-3-carboxylic acid

Similarity: 0.70