Home Cart 0 Sign in  
X

[ CAS No. 398489-26-4 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type HazMat fee for 500 gram (Estimated)
Excepted Quantity USD 0.00
Limited Quantity USD 15-60
Inaccessible (Haz class 6.1), Domestic USD 80+
Inaccessible (Haz class 6.1), International USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic USD 100+
Accessible (Haz class 3, 4, 5 or 8), International USD 200+
3d Animation Molecule Structure of 398489-26-4
Chemical Structure| 398489-26-4
Chemical Structure| 398489-26-4
Structure of 398489-26-4 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 398489-26-4 ]

Related Doc. of [ 398489-26-4 ]

Alternatived Products of [ 398489-26-4 ]

Product Details of [ 398489-26-4 ]

CAS No. :398489-26-4 MDL No. :MFCD01861741
Formula : C8H13NO3 Boiling Point : -
Linear Structure Formula :- InChI Key :VMKIXWAFFVLJCK-UHFFFAOYSA-N
M.W : 171.19 Pubchem ID :1519404
Synonyms :
N-Boc-3-azetidinone

Calculated chemistry of [ 398489-26-4 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 0
Fraction Csp3 : 0.75
Num. rotatable bonds : 3
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 47.18
TPSA : 46.61 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) : -6.8 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.95
Log Po/w (XLOGP3) : 0.76
Log Po/w (WLOGP) : 0.43
Log Po/w (MLOGP) : 0.13
Log Po/w (SILICOS-IT) : 0.58
Consensus Log Po/w : 0.77

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.18
Solubility : 11.3 mg/ml ; 0.0657 mol/l
Class : Very soluble
Log S (Ali) : -1.32
Solubility : 8.22 mg/ml ; 0.048 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -0.83
Solubility : 25.3 mg/ml ; 0.148 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.84

Safety of [ 398489-26-4 ]

Signal Word:Danger Class:9
Precautionary Statements:P280-P301+P312+P330-P302+P352-P305+P351+P338+P310 UN#:3335
Hazard Statements:H302-H315-H318-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 398489-26-4 ]

* 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 [ 398489-26-4 ]
  • Downstream synthetic route of [ 398489-26-4 ]

[ 398489-26-4 ] Synthesis Path-Upstream   1~24

  • 1
  • [ 398489-26-4 ]
  • [ 183062-96-6 ]
Reference: [1] Patent: JP2016/56133, 2016, A,
[2] Patent: WO2018/2760, 2018, A1,
  • 2
  • [ 398489-26-4 ]
  • [ 141699-55-0 ]
YieldReaction ConditionsOperation in experiment
99% for 2 h; Sodium borohydride (1.01 g, 26.7 mmol) was added slowly to a solution of 1-Boc-3-azetidinone (2.28 g, 13.3 mmol) in ethanol (30 mL), stirred for 2 hours, the mixture was then concentrated under reduced pressure. The residue was treated with water (50 mL), extracted with ethyl acetate (50 mL×3). The organic layers were combined, dried over anhydrous sodium sulfate, then filtrated, the filtrate was concentrated under reduced pressure to give compound 54-d (2.28 g, yield: 99percent), which was used directly for the next step without purification. LC-MS (ESI): m/z=175 [M+H]+.
Reference: [1] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0353; 0354
  • 3
  • [ 398489-26-4 ]
  • [ 142253-56-3 ]
Reference: [1] Patent: CN103709085, 2016, B,
  • 4
  • [ 141699-55-0 ]
  • [ 398489-26-4 ]
YieldReaction ConditionsOperation in experiment
95% With pyridine-SO3 complex; triethylamine In dimethyl sulfoxide at 10 - 20℃; Inert atmosphere A 5 L-3-neck flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen inlet was charged with Py-SO3 (277 g, 1.74 mol) and DMSO (900 mL) and cooled to 10° C. in ice-bath. TEA (177 g/244 mL, 1.74 mol) was added. A solution of tert-butyl-3 hydroxyazetidine-1-carboxylate (Preparation 1, 100.8 g, 0.58 mol) in DMSO (500 mL) was added slowly via addition funnel at 10° C. The reaction was stirred at ambient temperature overnight. GC/MS analysis of the reaction mixture reveals that the reaction was completed. The reaction was quenched with brine (1 L). Solids were filtered and the aqueous was extracted with ethyl acetate (3×1 L). The combined organics were washed with saturated aqueous NaHCO3 (1.5 L), brine (1.5 L), dried over sodium sulfate, filtered, and concentrated to give the desired   product (94 g, 95percent yield). 1H NMR (CDCl3) δ 4.6 (s, 4H), 1.4 (s, 9H).
95% With sulfur trioxide pyridine complex; triethylamine In dimethyl sulfoxide at 10℃; for 20 h; Inert atmosphere A 5L-3-neck flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen inlet was charged with Py-S03 (277 g, 1.74 mol) and DMSO (900 mL) and cooled to 10°C in ice-bath. TEA (177 g/244 mL, 1 .74 mol) was added. A solution of tert-butyl-3 hydroxyazetidine-1-carboxylate (Preparation 1 a, 100.8 g, 0.58 mol) in DMSO (500 mL) was added slowly via addition funnel at 10°C. The reaction was stirred at ambient temperature overnight. GC/MS analysis of the reaction mixture reveals that the reaction was completed. The reaction was quenched with brine (1 L). Solids were filtered and the aqueous was extracted with ethyl acetate (3 x 1 L). The combined organics were washed with saturated aqueous NaHC03 (1 .5 L), brine (1.5 L), dried over sodium sulfate, filtered, and concentrated to give the desired product (94 g, 95percent yield). 1H NMR (CDCI3) δ 4.6 (s, 4 H), 1 .4 (s, 9 H).
95% With sulfur trioxide pyridine complex; triethylamine In dimethyl sulfoxide at 10 - 20℃; Inert atmosphere; Cooling with ice Preparation 2a: tert-butyl 3-oxoazetidine-1 -carboxylate; (3-oxoazetidine-1 - carboxylic acid tert-butyl ester) A 5L-3-neck flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen inlet was charged with Py-S03 (277 g, 1.74 mol) and DMSO (900 ml.) and cooled to 10°C in ice-bath. TEA (177 g/244 ml_, 1 .74 mol) was added. A solution of tert-butyl-3 hydroxyazetidine-1 -carboxylate (Preparation 1 a, 100.8 g, 0.58 mol) in DMSO (500 ml.) was added slowly via addition funnel at 10°C. The reaction was stirred at ambient temperature overnight. GC/MS analysis of the reaction mixture reveals that the reaction was completed. The reaction was quenched with brine (1 L). Solids were filtered and the aqueous was extracted with ethyl acetate (3 x 1 L). The combined organics were washed with saturated aqueous NaHC03 (1 .5 L), brine (1.5 L), dried over sodium sulfate, filtered, and concentrated to give the desired product (94 g, 95percent yield). H NMR (CDCI3) δ 4.6 (s, 4 H), 1 .4 (s, 9 H).
91.1%
Stage #1: With oxalyl dichloride In dichloromethane at -78℃;
Stage #2: With triethylamine In dichloromethane at 20℃;
To a -78 0C solution of 2M oxalyl chloride (31.8 mL, 63.5 mmol) in 200 mL DCM was added DMSO (9.01 mL, 127 mmol), followed by the slow addition by addition funnel of a solution of tert- butyl 3-hydroxyazetidine-l-carboxylate (10.0 g, 57.7 mmol) in 200 mL DCM. The cloudy reaction mixture was stirred at -78 0C for 15 minutes, then a solution triethylamine (32.2 mL, 231 mmol) in 40 mL DCM was added slowly by addition funnel. The reaction mixture was stirred another 15 minutes, the bath was removed, and the reaction was allowed to warm to ambient temperature and stirred for 15 hours. Water and brine were added, and the mixture was extracted with DCM. The combined extracts were dried (Na2SO4), filtered and concentrated. The crude was purified on silica gel (3-20percent ethyl acetate in hexanes gradient) to give the desired product (9.0 g, 91.1 percent yield) as a white solid.
90% With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 15 h; A solution of oxalyl chloride (545 μL, 6.36 mmol) in dichloromethane (25 mL) was cooled to -78 0C. While maintaining an internal temperature of -78 0C, the dropwise addition of DMSO (903 μL, 12.7 mmol) followed by 1,1-dimethylethyl 3-hydroxyazetidine- EPO <DP n="176"/>1-carboxylate (1 g, 5.78 mmol in 30 niL of dichloromethane) and finally triethylamine (3.25 mL, 23.1 mmol in 20 mL of dichloromethane) was performed. The mixture was allowed to warm to room temperature and was stirred for 15 hours. The reaction mixture was diluted with water and partitioned and the organic portion was washed twice with water. The combined aqueous portion was extracted once with dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by column chromatography. Eluting with 30percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 893 mg, 5.20 mmol (90percent) of 1,1-dimethylethyl 3-oxoazetidine- 1-carboxylate as a colorless oil, which solidified upon standing. 1H NMR (400 MHz, DMSO): 4.67 (s, 4H), 1.42 (s, 9H). GC/MS for C8H13NO3: 171.
90% With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 15 h; A solution of oxalyl chloride (545 μL, 6.36 mmol) in dichloromethane (25 mL) was cooled to -78 °C. While maintaining an internal temperature of -78 °C, the dropwise addition of DMSO (903 μL, 12.7 mmol) followed by 1,1-dimethylethyl 3 -hydroxy azetidine-1-carboxylate (1 g, 5.78 mmol in 30 mL of dichloromethane) and finally triethylamine (3.25 mL, 23.1 mmol in 20 mL of dichloromethane) was performed. The mixture was allowed to warm to room temperature and was stirred for 15 hours. The reaction mixture was diluted with water and partitioned and the organic portion was washed twice with water. The combined aqueous portion was extracted once with dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by column chromatography. Eluting with 30percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 893 mg, 5.20 mmol (90percent) of 1,1-dimethylethyl 3-oxoazetidine-l-carboxylate as a colorless oil, which solidified upon standing. 1H NMR (400 MHz, DMSO): 4.67 (s, 4H), 1.42 (s, 9H). GC/MS for C8Hi3NO3: 171.
90% With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 20℃; for 15 h; A solution of oxalyl chloride (545 μL, 6.36 mmol) in dichloromethane (25 mL) was cooled to -78 0C. While maintaining an internal temperature of -78 °C, the dropwise addition of DMSO (903 μL, 12.7 mmol) followed by 1,1-dimethylethyl 3 -hydroxyazetidine- 1-carboxylate (1 g, 5.78 mmol in 30 mL of dichloromethane) and finally triethylamine (3.25 mL, 23.1 mmol in 20 mL of dichloromethane) was performed. The mixture was allowed to warm to room temperature and was stirred for 15 hours. The reaction mixture was diluted with water and partitioned and the organic portion was washed twice with water. The combined aqueous portion was extracted once with dichloromethane. The combined organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by column chromatography. Eluting with 30percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 893 mg, 5.20 mmol (90percent) of 1,1-dimethylethyl 3-oxoazetidine-l-carboxylate as a colorless oil, which solidified upon standing. 1H NMR (400 MHz, DMSO): 4.67 (s, 4H), 1.42 (s, 9H). GC/MS for C8Hi3NO3: 171.
90% With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -78 - 20℃; for 15 h; A solution of oxalyl chloride (6.36 mmol) in DCM (25 ml) was cooled to -78C and DMSO (12.7 mmol), intermediate 664602 (1 g, 5.78 mmol), TEA (3.25 ml) were added sequentially. The organic phase was separated, washed twice with water, extracted with methylene chloride once, and the organic phase was concentrated.The crude product was purified by column chromatography (PE: EA = 4: 1) and the organic phase was concentrated to dryness, 1) to give intermediate 664603 (0.89 g, 90percent).
81% With oxalyl dichloride; triethylamine In dichloromethane; dimethyl sulfoxide at -78 - 20℃; A mixture of oxalyl chloride (2.78 ml, 31.8 mmol) in (( (80 ml) in a 500 ml round-bottomed flask was cooled to -78°C, and DMSO (4.51 ml, 63.5 mmol) was added dropwise to the mixture over 15 min. The reaction mixture was then stirred at the same temperature for 15 min. A solution of tert-butyl 3- hydroxyazetidine-l-carboxylate (5 g, 28.9 mmol) in CH2CI2 (50 ml) followed by a solution triethylamine (16.09 ml, 1 15 mmol) in CH2CI2 (70 ml) were added dropwise to the reaction mixture. The reaction mixture was warmed to room temperature, and then stirred overnight. The reaction mixture was washed with brine, and the aqueous layer back extracted with CH2CI2 (200 ml). The combined organic layers were washed with water, dried over Na2S04, filtered and concentrated in vacuum to provide a crude mixture. The crude product was then purified by column chromatography (15 percent EtOAc in Hexane) to afford tert-butyl 3-oxoazetidine-l-carboxylate Yield: 4 g (81 percent). XH NMR (400 MHz, CDC13): δ 4.69 (s, 4H), 1.49 (s, 9H).
81% With pyridine-SO3 complex; triethylamine In dichloromethane; dimethyl sulfoxide at 10 - 20℃; for 1.5 h; 3-Oxo-azetidine- l-carboxylic acid tert-butyl ester:To a solution of l-Z?
52% With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃; for 3 h; To a mixture of tert-butyl 3-hydroxyazetidine-1-carboxylate (10.0 g, 57.7 mmol), dimethyl sulfoxide (24.0 mL, 338 mmol), triethylamine (40 mL, 300 mmol) and methylene chloride (2.0 mL) was added sulfur trioxide-pyridine complex (40 g, 200 mmol) portionwise at 0° C. The mixture was stirred for 3 hours, quenched with brine, and extracted with methylene chloride. The combined extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column (0-6percent ethyl acetate (EtOAc) in hexanes) to give tert-butyl 3-oxoazetidine-1-carboxylate (5.1 g, 52percent yield).
52% With sulfur trioxide pyridine complex; dimethyl sulfoxide; triethylamine In dichloromethane at 0℃; Step A:
tert-Butyl 3-Oxoazetidine-1-carboxylate
To a mixture of tert-butyl 3-hydroxyazetidine-1-carboxylate (10.0 g, 57.7 mmol), dimethyl sulfoxide (24.0 mL, 338 mmol), triethylamine (40 mL, 300 mmol) and methylene chloride (2.0 mL) was added sulfur trioxide-pyridine complex (40 g, 200 mmol) portionwise at 0° C.
The mixture was stirred for 3 hours, quenched with brine, and extracted with methylene chloride.
The combined extracts were dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by silica gel column (0-6percent ethyl acetate (EtOAc) in hexanes) to give tert-butyl 3-oxoazetidine-1-carboxylate (5.1 g, 52percent yield).
650 mg With pyridinium chlorochromate In dichloromethane at 20 - 35℃; PCC (4.94 g, 22.8 mmol) was added portion wise to a stirred solution of tert-butyl-3-hydroxyazetidine-1-carboxylate (3.3 g, 19 mmol) in DCM (50 mL) at 20-35° C. and the reaction mixture was stirred continuously at the same temperature for 12-16 h. The reaction mixture was filtered and the filtrate was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (using 60-120 silica gel and 10percent EtOAc in Hexane as eluent) to afford 650 mg of the title compound. 1H NMR (400 MHz, DMSO) δ ppm 4.66 (4H, s), 1.4 (9H, s).
650 mg With pyridinium chlorochromate In dichloromethane at 20 - 35℃; PCC (4.94 g, 22.8 mmol) was added portion wise to a stirred solution of tert-butyl-3-hydroxyazetidine-1-carboxylate (3.3 g, 19 mmol) in DCM (50 mL) at 20-35° C. and the reaction mixture was stirred continuously at the same temperature for 12-16 h. The reaction mixture was filtered and the filtrate was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the crude product, which was purified by column chromatography (using 60-120 silica gel and 10percent EtOAc in Hexane as eluent) to afford 650 mg of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 4.66 (4H, s), 1.4 (9H, s) ppm.

Reference: [1] ACS Medicinal Chemistry Letters, 2014, vol. 5, # 5, p. 550 - 555
[2] Journal of the American Chemical Society, 2013, vol. 135, # 42, p. 15742 - 15745
[3] Patent: US2012/35122, 2012, A1, . Location in patent: Paragraph 0622; 0623
[4] Patent: WO2013/116236, 2013, A1, . Location in patent: Page/Page column 28
[5] Patent: WO2013/169622, 2013, A1, . Location in patent: Page/Page column 53; 54
[6] Organic Process Research and Development, 2015, vol. 19, # 11, p. 1548 - 1553
[7] Patent: WO2010/22076, 2010, A1, . Location in patent: Page/Page column 127
[8] Patent: WO2007/44515, 2007, A1, . Location in patent: Page/Page column 174-175
[9] Patent: WO2008/76415, 2008, A1, . Location in patent: Page/Page column 339
[10] Patent: WO2008/124085, 2008, A2, . Location in patent: Page/Page column 189
[11] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 5, p. 416 - 421
[12] Patent: CN103709085, 2016, B, . Location in patent: Paragraph 0290-0292
[13] Patent: WO2013/148620, 2013, A1, . Location in patent: Page/Page column 23; 24
[14] Patent: WO2009/120655, 2009, A1, . Location in patent: Page/Page column 35-36
[15] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 4, p. 1084 - 1088
[16] Marine Drugs, 2016, vol. 14, # 5,
[17] Patent: US2011/224190, 2011, A1, . Location in patent: Page/Page column 36
[18] Patent: US2015/246046, 2015, A1, . Location in patent: Paragraph 0130
[19] Patent: US2009/233903, 2009, A1, . Location in patent: Page/Page column 62-63
[20] Patent: US2003/229226, 2003, A1, . Location in patent: Page 22-23
[21] Patent: WO2009/54941, 2009, A1, . Location in patent: Page/Page column 63
[22] Patent: US2010/261701, 2010, A1, . Location in patent: Page/Page column 145; 146
[23] Patent: EP2287173, 2011, A1, . Location in patent: Page/Page column 52
[24] Patent: WO2013/36611, 2013, A1, . Location in patent: Page/Page column 27; 28
[25] ACS Catalysis, 2013, vol. 3, # 11, p. 2612 - 2616
[26] Patent: US2014/256941, 2014, A1, . Location in patent: Paragraph 0156
[27] Patent: US2015/5280, 2015, A1, . Location in patent: Paragraph 0634 - 0636
[28] Patent: US2015/368238, 2015, A1, . Location in patent: Paragraph 0626; 0627
[29] Patent: WO2007/143823, 2007, A1, . Location in patent: Page/Page column 49
  • 5
  • [ 24424-99-5 ]
  • [ 398489-26-4 ]
Reference: [1] Patent: EP2287173, 2011, A1,
[2] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 5, p. 416 - 421
[3] Patent: US2012/35122, 2012, A1,
[4] Patent: WO2013/116236, 2013, A1,
[5] Patent: WO2013/169622, 2013, A1,
[6] Patent: US2015/5280, 2015, A1,
[7] Patent: US2015/368238, 2015, A1,
[8] Patent: CN103709085, 2016, B,
[9] Patent: WO2007/143823, 2007, A1,
  • 6
  • [ 398489-26-4 ]
  • [ 74-88-4 ]
  • [ 429669-07-8 ]
Reference: [1] Organic Letters, 2018,
  • 7
  • [ 398489-26-4 ]
  • [ 158602-35-8 ]
Reference: [1] Patent: WO2018/2760, 2018, A1,
  • 8
  • [ 398489-26-4 ]
  • [ 1779-49-3 ]
  • [ 934664-41-2 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: at 20℃; for 1 h;
Stage #2: at 35℃; for 2 h;
A mixture of potassium /e/t-butoxide (15.5 g, 137 mmol) and methyltriphenylphosphine bromide (49 g, 137 mmol) in diethyl ether (300 mL) was stirred at room temperature for 1 hour, followed by the addition of 1,1-dimethylethyl 3-oxoazetidine- 1 -carboxylate (10 g, 58 mmol in 100 mL diethyl ether). The mixture was stirred at 35 °C for 2 hours and then allowed to cool to room temperature. The mixture was filtered through a pad of celite, washing with diethyl ether. The filtrate was partitioned with water and washed twice with water, brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an orange oil which was purified by column chromatography. Eluting with 10percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 9.80 g, 58 mmol (100percent) of 1,1-dimethylethyl 3 -methylideneazetidine- 1-carboxylate as a colorless oil. 1H NMR (400 MHz, DMSO): 5.05-4.85 (m, 2H)3 4.95-4.63 (m, 4H), 1.45 (s, 9H). GC-MS for C9H15NO2: 169.
100%
Stage #1: With potassium <i>tert</i>-butylate In diethyl ether at 20℃; for 1 h;
Stage #2: at 35℃; for 2 h;
A mixture of potassium ter/-butoxide (15.5 g, 137 mmol) and methyltriphenylphosphine bromide (49 g, 137 mmol) in diethyl ether (300 mL) was stirred at room temperature for 1 hour, followed by the addition of 1,1-dimethylethyl 3-oxoazetidine-l-carboxylate (10 g, 58 mmol in 100 mL diethyl ether). The mixture was stirred at 35 0C for 2 hours and then allowed to cool to room temperature. The mixture was filtered through a pad of celite, washing with diethyl ether. The filtrate was partitioned with water and washed twice with water, brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an orange oil which was purified by column chromatography. Eluting with 10percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 9.80 g, 58 mmol (100percent) of 1,1-dimethylethyl <n="341"/>3-methylideneazetidine-l-carboxylate as a colorless oil. 1H NMR (400 MHz, DMSO): 5.05-4.85 (m, 2H), 4.95-4.63 (m, 4H), 1.45 (s, 9H). GC-MS for C9H15NO2: 169.
100%
Stage #1: With potassium <i>tert</i>-butylate In diethyl ether at 20℃; for 1 h;
Stage #2: at 35℃; for 2 h;
A mixture of potassium tert-butoxide (15.5 g, 137 mmol) and methyltriphenylphosphine bromide (49 g, 137 mmol) in diethyl ether (300 mL) was stirred at room temperature for 1 hour, followed by the addition of 1,1 -dimethyl ethyl 3-oxoazetidine- 1-carboxylate (10 g, 58 mmol in 100 mL diethyl ether). The mixture was stirred at 35 °C for 2 hours and then allowed to cool to room temperature. The mixture was filtered through a pad of celite, washing with diethyl ether. The filtrate was partitioned with water and washed twice with water, brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an orange oil which was purified by column chromatography. Eluting with 10percent ethyl acetate in hexanes, isolated product was concentrated in vacuo to afford 9.80 g, 58 mmol (100percent) of 1,1-dimethylethyl 3-methylideneazetidine-l-carboxylate as a colorless oil. 1H NMR (400 MHz, DMSO): 5.05-4.85 (m, 2H), 4.95-4.63 (m, 4H), 1.45 (s, 9H). GC-MS for C9H15NO2: 169.
82.6%
Stage #1: With potassium <i>tert</i>-butylate In diethyl ether at 0 - 20℃; for 1.5 h;
Stage #2: Cooling with ice
3-(3-Chlorophenyl-ethynyl)-7-(6-methyl-3-nitro-2-pyridyl)-l-oxa-2.7-diazaspiro[4.31oct-2-ene l-(t.butoxycarbonyl)-3-methylene-azetidine (Compund 28a)To a suspension of methyltriphenylphosponium bromide (1.56 g, 4.37 mmol) in 30 ml of Et20 stirred at 0°C was added potassium tert-butylate (0.459 g, 4.09 mmol). After 0.5h the cold bath was removed and the mixture was stirred for lh at r.t. Afterrwards, it was cooled off in water- ice bath, and l-(t.butoxycarbonyl)-3-azetidinone (500 mg, 2.92 mmol) was added. The cold bath was removed. After overnight resting, the reaction mixture was quenched with a saturated solution of NH4C1 in water, extracted with Et20, dried on a2S04, evaporated to dryness in vacuo, dissolvent. The residual crude was purified by automated flash chromatography (SP1.(R).TM - Biotage; gradient Petroleum Ether - Acetone from 10 : 0 to 7 : 3) to give the title compound ( 426 mg) as a dense colourless oil. Yield: 86.2percent. MS: [M+H]+ = 170.45
81%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at 20℃; for 1 h;
Stage #2: at 35℃; for 2 h;
A mixture of methyltriphenylphosphonium bromide (49 g, 137 mmol), potassium 2-methylpropan- 2-olate (15.5 g, 138 mmol) in tetrahydrofuran (400 mL) was stirred for 1 h at room temperature. This was followed by the addition of a solution of fert-butyl 3-oxoazetidine-l-carboxylate (10 g, 58.4 mmol) in tetrahydrofuran (100 mL) drop wise with stirring. Then the reaction system was stirred for additional 2 h while the temperature was maintained at 35 °C. The solution was diluted with water, extracted with ethyl acetate, washed with brine and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (solvent gradient: 0-10percent ethyl acetate in petroleum ether) to afford the title compound (8.0 g, 81percent) as a yellow oil. LCMS (ESI): [M+H]+ = 170.
80%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at 70℃; for 4 h;
Stage #2: at 50 - 70℃; for 15 h;
Step 1: Preparation of tert-butyl 3-methyleneazetidine-l-carboxylate [0217] Potassium tert-butoxide (4.27 g, 37.96 mmol) was added to a suspension of methyltriphenylphosphonium bromide (13.56 g, 37.96 mmol) in tetrahydrofuran (80 mL) and the reaction mixture was heated at 70 °C for 4 h. Then the reaction mixture was cooled to 50 °C and added a solution of tert-butyl 3-oxoazetidine-l-carboxylate (5 g, 29.2 mmol) in tetrahydrofuran (20 mL) and heated at 70 °C for 15 h. The reaction mixture was cooled to room temperature and evaporated to dryness. The crude material was purified by combiflash purifier using 4percent ethyl acetate in hexane to afford the title compound tert-butyl 3- methyleneazetidine-l-carboxylate (4 g, 80percent yield) as a colorless liquid. 1H NMR (400 MHz, CDC13) δ 4.98 (s, 2H), 4.47 (s, 4H), 1.45 (s, 9H).
78.7%
Stage #1: With potassium <i>tert</i>-butylate In diethyl ether at 0 - 20℃;
Stage #2: for 2 h; Reflux
To a 00C mixture of KOtBu (5.90 g, 52.6 mmol) in 95 mL ether was added methyltriphenylphosphonium bromide (18.8 g, 52.6 mmol). The reaction mixture was warmed to ambient temperature and stirred 1.5 hours. A solution of tert-bvXyl 3- oxoazetidine-1-carboxylate (4.50 g, 26.3 mmol) in 10 mL ether was added. The reaction mixture was heated to reflux for 2 hours, then cooled to ambient temperature. Solids were removed by vacuum filtration through compressed Celite and rinsed with ether, and the filtrate was concentrated. The resulting residue was suspended in 1 :1 hexanes: ethyl acetate, and the solids were removed by vacuum filtration through GF/F paper and rinsed with 1 : 1 hexanes: ethyl acetate. The filtrate was concentrated, and the resulting oil was purified on silica gel (5-20percent ethyl acetate in hexanes gradient) to give the desired product (3.50 g, 78.7 percent yield) as a clear colorless oil.
10.9 g
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at 0℃; for 1 h;
Stage #2: at 50℃; for 2 h;
[0379] After potassium tert-butoxide (13.3 g) was added to a mixture of methyl(triphenyl)phosphonium bromide (38.7 g) and THF (150 mL) at 0°C, the resultant was stirred for 1 hour. A solution of tert-butyl 3-oxoazetidine-l-carboxylate (16.9 g) in THF (50 mL) was added to the reaction mixture, and the resultant was stirred for 2 hours at 50°C. After water was added to the reaction rnixture, extraction thereof was performed using ethyl acetate. The obtained organic layer was sequentially washed with water and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was dissolved into a solution in which ethyl acetate and hexane is mixed at a ratio of 1:3, the resultant was filtered using celite, and then the filtrate was concentrated under reduced pressure. The obtained residue was purified by a silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the title compound (10.9g). NMR (300 MHz, DMSO-ds) δ 1.45 (9H, s), 4.46-4.51 (4H, m), 4.96-5.02 (2H, m).

Reference: [1] Patent: WO2007/44515, 2007, A1, . Location in patent: Page/Page column 175
[2] Patent: WO2008/76415, 2008, A1, . Location in patent: Page/Page column 339-340
[3] Patent: WO2008/124085, 2008, A2, . Location in patent: Page/Page column 190
[4] ACS Medicinal Chemistry Letters, 2012, vol. 3, # 5, p. 416 - 421
[5] Patent: WO2012/4400, 2012, A1, . Location in patent: Page/Page column 47-48
[6] Patent: WO2014/210354, 2014, A1, . Location in patent: Page/Page column 138
[7] Patent: WO2015/48507, 2015, A1, . Location in patent: Paragraph 0217
[8] Patent: WO2010/22076, 2010, A1, . Location in patent: Page/Page column 127; 128
[9] Organic Letters, 2009, vol. 11, # 16, p. 3523 - 3525
[10] Patent: WO2013/152065, 2013, A2, . Location in patent: Page/Page column 30
[11] Patent: WO2013/152063, 2013, A1, . Location in patent: Page/Page column 26
[12] Patent: WO2014/142363, 2014, A1, . Location in patent: Paragraph 0379; 1353; 1535
  • 9
  • [ 398489-26-4 ]
  • [ 934664-41-2 ]
YieldReaction ConditionsOperation in experiment
99% With potassium <i>tert</i>-butylate; methyl-triphenylphosphonium iodide In diethyl ether at 35℃; for 2 h; Was added t-BuOK in 300ml diethyl ether (15.5g, 0.14mol) and methyl triphenylphosphonium bromide (49g, 0.14mol) at room temperature the reaction mixture was stirred1hour, then intermediate 664603 (10g, 58mmol). The reaction mixture was after thereaction was stirred for 35 2h, cooled to room temperature. Filtered, the filter cakewashed with diethyl ether. The filtrate was washed with water and brine, dried over anhydrous Na 2SO 4Dried, filtered and concentrated to give an oil product groups, columnchromatography give Intermediate 664604 (9.80g, 99percent).
Reference: [1] Patent: CN103709085, 2016, B, . Location in patent: Paragraph 0293-0295
  • 10
  • [ 398489-26-4 ]
  • [ 934664-41-2 ]
Reference: [1] MedChemComm, 2013, vol. 4, # 1, p. 244 - 251
  • 11
  • [ 398489-26-4 ]
  • [ 7677-24-9 ]
  • [ 24424-99-5 ]
  • [ 1035351-06-4 ]
YieldReaction ConditionsOperation in experiment
7%
Stage #1: at 20℃; for 18 h; Inert atmosphere
Stage #2: With hydrogenchloride In water; acetic acid for 3 h; Reflux
To a solution of ieri-butyl 3-oxoazetidine-l-carboxylate LII (2.0 g, 11.7 mmol) in THF (50 mL) under an argon atmosphere was added Znl2 (0.11 mg, cat) followed by TMSCN (1.62 g, 16.4 mmol). The mixture was stirred at room temperature for 18 h, and was concentrated to dryness under reduced pressure. The residue was dissolved in EtOAc (100 mL), washed with aqueous NaHC03 and water and then concentrated to dryness. The residue was dissolved in HOAc (25 mL) and treated with concentrated aqueous HCI (25 mL). The mixture was heated at reflux for 3 h and was concentrated to dryness. The residue was dissolved in iPrOH (20 mL) and 2 M aqueous NaOH (20 mL) followed by Boc20 (1.66 g, 8.0 mmol) were added. The iPrOH was removed with a rotary evaporator, water (30 mL) was then added to the residue and the mixture was extracted with Et20 (2 x 30 mL). The aqueous phase was acidified with 1 N aqueous HCI to pH=2 and extracted with EtOAc (3 x 30 mL). The organic phase was dried over Na2S04, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100percent EtOAc-->l:l EtOAc:MeOH) affording l-(feri-butoxycarbonyl)-3-hydroxyazetidine-3-carboxylic acid LIII (0.17 g, 0.79 mmol, 7percent). ESMS found for C9H15N05 m/z 216 (M-H)".
Reference: [1] Patent: WO2011/143497, 2011, A1, . Location in patent: Page/Page column 49; 50
  • 12
  • [ 398489-26-4 ]
  • [ 1035351-06-4 ]
Reference: [1] Patent: WO2008/124821, 2008, A1,
  • 13
  • [ 398489-26-4 ]
  • [ 1314987-79-5 ]
Reference: [1] Patent: US2015/336982, 2015, A1,
  • 14
  • [ 398489-26-4 ]
  • [ 1029413-51-1 ]
Reference: [1] Patent: US2015/336982, 2015, A1,
  • 15
  • [ 398489-26-4 ]
  • [ 50586-62-4 ]
  • [ 1153949-11-1 ]
YieldReaction ConditionsOperation in experiment
91%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at -15 - -5℃; for 3 h; Inert atmosphere
Stage #2: for 18 h; Inert atmosphere
24.8 g of diethyl cyanomethyl phosphate and 300 ml of anhydrous tetrahydrofuran were added to a 1000 ml four-necked flask under nitrogen.Slowly cool down to -15 ~ -10 ° C, under the protection of nitrogen, slowly add 128.5 ml of 1.0N potassium t-butoxide potassium tetrahydrofuran solution,At the same time, the temperature is controlled below -5 ° C, after the end of the addition,The reaction temperature was continued to be stirred at -10 to -5 ° C for 3 hours;The temperature of the control was below -5 ° C, and a solution of the intermediate 6 in tetrahydrofuran (20.0 g of the intermediate 6 dissolved in 67 ml of tetrahydrofuran) was slowly added dropwise.After the completion of the dropwise addition, the temperature was controlled to continue stirring at -10 to -5 ° C for 2 hours;The reaction solution was slowly warmed to 25 to -30 ° C and stirred at this temperature for 16 hours.After the reaction was completed, 300 ml of a 12.5percent aqueous sodium chloride solution was slowly added, and the layers were separated.The aqueous phase was extracted with 300 mL of ethyl acetate.The organic phases were combined and washed with brine (200 mL)A product of 20.65 white solid was obtained in a yield of 91percent.
61%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at -14 - 5℃; for 3 h;
Stage #2: at -10 - 20℃;
Step 4. tert-Butyl 3-(cyanomethylene)azetidine-l-carboxylate (13) Diethyl cyanomethyl phosphate (12, 745 g, 4.20 mol, 1.20 equiv) and anhydrous tetrahydrofuran (THF, 9 L) was added to a four-neck flask equipped with a thermowell, an addition funnel and the nitrogen protection tube at room temperature. The solution was copied with an ice-methanol bath to - 14 °C and a l .O M solution of potassium teri-butoxide (f-BuO ) in anhydrous tetrahydrofuran (THF, 3.85 L, 3.85 mol, 1.1 equiv) was added over 20 minutes keeping the reaction temperature below - 5 °C. The resulting reaction mixture was stirred for 3 hours at - 10 °C and a solution of l -/er/-butoxycarbonyl-3-azetidinone (11, 600 g, 3.50 mol) in anhydrous tetrahydrofuran (THF, 2 L) was added over 2 h keeping the internal temperature below - 5 °C. The reaction mixture was stirred at - 5 to - 10 °C over 1 hour and then slowly warmed up to room temperature and stirred at room temperature for overnight. The reaction mixture was then diluted with water (4.5 L) and saturated aqueous sodium chloride solution (NaCl, 4.5 L) and extracted with ethyl acetate (EtOAc, 2 x 9 L). The combined organic layers were washed with brine (6 L) and dried over anhydrous sodium sulfate (Na2S04). The organic solvent was removed under reduced pressure and the residue was diluted with dichloromethane (CH2CI2, 4 L) before being absorbed onto silica gel (S1O2, 1.5 Kg). The crude product, which was absorbed on silica gel, was purified by flash column chromatography (Si02, 3.5 Kg, 0 - 25percent EtOAc/hexanes gradient elution) to afford terf-butyl 3-(cyanomethylene)azetidine-l - carboxylate (13, 414.7 g, 679.8 g theoretical, 61 percent yield) as white solid. For 13: NMR (CDC , 300MHz), 6 5.40 (m, 1H), 4.70 (m, 2H), 4.61 (m, 2H), 1.46 (s, 9H) ppm; C,oH, N202 (MW, 194.23), LCMS (EI) mle 217 (M+ + Na).
4.3 g With potassium <i>tert</i>-butylate In tetrahydrofuran at -7 - 20℃; Inert atmosphere Dissolving cyanomethyl diethyl phosphate in THF (75 mE), cooling to —7-—5° C. under the protection of nitrogen, dropwise adding potassium tert-butoxide/THF (3.6 g is dissolved in 35 mE of THF), keeping for 3 h after addition, dropwise adding 1 -l3oc-3-azetidinone/THF solution (5 g is dissolved in 15 mE of THF), keeping for 1 hand then stirring overnight at room temperature, using EAH20 for extraction afier adding water for quenching, spinning it dry to obtain 8 g of crude product, and putting the product into the column to obtain 4.3 g of white solid productCF0726Y.
Reference: [1] Patent: CN108752254, 2018, A, . Location in patent: Paragraph 0097-0099
[2] Patent: WO2013/36611, 2013, A1, . Location in patent: Page/Page column 28; 29
[3] Patent: US2016/333015, 2016, A1, . Location in patent: Paragraph 0055; 0056; 0081; 0082; 0105; 0106; 0134; 0135
  • 16
  • [ 398489-26-4 ]
  • [ 2537-48-6 ]
  • [ 1153949-11-1 ]
YieldReaction ConditionsOperation in experiment
99%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃;
To a suspension of sodium hydride (60percent dispersion in mineral oil, 0.257 g, 6.42 mmol) in tetrahydrofuran (32 mL) at 0° C. under a nitrogen atmosphere was added diethyl cyanomethylphosphonate (1.19 g, 6.72 mmol) (purchased from Aldrich).
The reaction was then stirred for 45 minutes at room temperature.
A solution of tert-butyl 3-oxoazetidine-1-carboxylate (1.00 g, 5.84 mmol) (purchased from Alfa Aesar) in tetrahydrofuran (8.8 mL) was introduced dropwise and the mixture was stirred for 16 hours.
Brine and ethyl acetate were added and the layers separated.
The aqueous layer was extracted with three portions of ethyl acetate.
The combined extracts were dried over sodium sulfate, filtered and concentrated to afford product, used without further purification in Step 2 (1.12 g, 99percent).
1H NMR (300 MHz, CDCl3): δ 5.38 (p, 1H), 4.73-4.68 (m, 2H), 4.64-4.59 (m, 2), 1.46 (s, 9H).
98%
Stage #1: With sodium hydride In tetrahydrofuran at 0 - 20℃;
Stage #2: at 0℃;
Stage #3: With water In tetrahydrofuran
Step A: Preparation of tert-butyl 3-(cyanomethylene)azetidine-l -carboxylate:In a 5L flask, a suspension of NaH (24.531 g, 613.34 mmol) in 500 mL of THF was cooled in an ice bath. A solution of diethyl cyanomethylphosphonate (104.08 mL, 648.39 mmol) in THF (200 mL) was added dropwise. After addition, another 120 mL of THF was added to aid stirring. The reaction was warmed to ambient temperature for 1 hour then cooled back to 0 °C for 1 hour to give a milky yellow solution. Then a solution of tert-butyl 3-oxoazetidine- 1-carboxylate (100.00 g, 584.13 mmol) in THF (400 mL) was added dropwise over an hour. The resultant reaction mixture was stirred for 15 hours, then quenched with water and concentrated to remove THF. The resultant aqueous solution was extracted with EtOAc. The combined organic layers were washed with brine and dried with MgS04. The filtrate was concentrated down to a yellow oil, which precipitated out a yellow solid after sitting overnight. This solid was diluted in cold EtOAc, sonicated, filtered and washed with cold EtOAc and hexanes to afford 82.09 g of a cream colored solid (80percent). Additional product was isolated by concentrating the filtrate in vacuo and purifying by silica chromatography using a gradient of 20-30percent EtOAc/Hexanes to afford an additional 18.6 g (18percent>) of tert-butyl 3-(cyanomethylene)azetidine-l-carboxylate. lH NMR (CDC13) δ 5.38 (m, 1H), 4.69-4.72 (m, 2H), 4.60-4.63 (m, 2H), 1.46 (s, 9H).
95%
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 30℃;
Stage #2: at 0 - 30℃;
To a solution of 1.0 M of potassium tert-butoxide in tetrahydrofuran (30.7 mL) at 0 0C was added dropwise a solution of diethyl cyanomethylphosphonate (5.20 mL, 0.0322 mol) in tetrahydrofuran (39.12 mL). The reaction was warmed to room temperature and then cooled to 0 0C again. To the reaction mixture was added a solution of tert-butyl 3-oxoazetidine-l-carboxylate (5.0 g, 0.029 mol) in tetrahydrofuran (7.82 mL). The reaction was allowed to warm up to room temperature and stirred at room temperature overnight. After being quenched with water, the mixture was extracted with EtOAc. The combined organic layers were washed with brine, dried and evaporated to dryness. The crude mixture was purified on silica gel, eluting with 0 to 70percent EtOAc in hexanes, to give the desired product (5.40 g, 95percent). LCMS (M+Na) 217.1.
95% With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; Step 2: tert-butyl 3-(cyanomethylene)azetidine-l-carboxylateTo a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (30.7 mL, 0.0307 mol) at 0 °C was added dropwise a solution of diethylcyanomethylphosphonate (5.20 mL, 0.0322 mol) in tetrahydrofuran (39.12 mL). The reaction was warmed to room temperature and then cooled at 0 °C again. To the reaction mixture was added a solution of tert-butyl 3-oxoazetidine-l-carboxylate (5.0 g, 0.029 mol, Aldrich: Cat.No.696315) in tetrahydrofuran (7.82 mL). The reaction was allowed to warm to room temperature and stirred overnight. After quenched with water, the mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over MgS04 and evaporated under reduced pressure. The crude mixture was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0 - 70percent) to give the desired product (5.40 g, 95percent). LCMS (M+Na)+: m/z = 217.1.
95% With potassium <i>tert</i>-butylate In tetrahydrofuran at 0 - 20℃; To a solution of 1.0 M potassium tert-butoxide in tetrahydrofuran (30.7 mL, 30.7 mmol) at 0° C. was added dropwise a solution of diethyl cyanomethylphosphonate (5.20 mL, 32.2 mmol) in tetrahydrofuran (39 mL). The reaction was warmed to room temperature and then cooled at 0° C. again. To the reaction mixture was added a solution of tert-butyl 3-oxoazetidine-1-carboxylate (5.0 g, 0.029 mol, from Aldrich) in tetrahydrofuran (8 mL). The reaction was allowed to warm to room temperature and stirred overnight. After quenched with water, the mixture was extracted with ethyl acetate (EtOAc). The combined organic layers were washed with brine, dried over MgSO4, and evaporated under reduced pressure. The crude mixture was purified by flash chromatography on a silica gel column eluting with ethyl acetate in hexanes (0-70percent) to give the desired product (5.40 g, 95percent). LCMS cacld. for C10H14N2O2Na (M+Na)+: m/z=217.1. Found: 217.1
84%
Stage #1: With sodium hydride In tetrahydrofuran at 0 - 20℃; for 2 h;
Stage #2: at 0℃;
A suspension of NaH (260 mg, 11 mmol) in 25 mL of THF was cooled in a 100 mL flask in an ice bath. A solution of diethyl cyanomethylphosphonate (1.1 mL, 6.72 mmol, 1.15 equiv.) in THF (20 mL) was added dropwise. The reaction was warmed to room temperature for 1 h then cooled back to 0 °C for 1 h to give a milky yellow solution. Then a solution of tert-butyl 3-oxoazetidine-1-carboxylate (1) (1.0 g, 5.84 mmol) in THF (10 mL) was added drop-wise over 1 h. The resulting reaction mixture was stirred overnight, then quenched with water and concentrated to remove THF. The resulting aqueous solution was extracted with EtOAc. The combined organic layers were washed with brine and dried with MgSO4. The filtrate was concentrated down to a yellow oil which was purified by silica chromatography using a gradient of 20–30percent EtOAc/hexanes to afford compound 2: Yield 939 mg (84percent); m.p. 75–77 °C; IR (KBr): 2987, 2222,1684, 1406, 1162 cm–1. Anal. calcd for C10H14N2O2: C, 61.84; H, 7.27; N, 14.42; found: C, 61.95; H, 7.46; N, 14.38percent. MS (m/z): 217 [M + Na]+; 1H NMR (300 MHz, CDCl3): δ 1.46 (s, 9H), 4.62 (t, J = 1.9 Hz, 2H),4.70 (t, J = 3.2 Hz, 2H), 5.38 (t, J = 2.3 Hz, 1H); 13C NMR (75 MHz, DMSO-d6): δ 27.9, 39.5, 79.4, 92.8, 115.2, 155.6, 158.4.
83%
Stage #1: With sodium hydride In tetrahydrofuran at 0 - 25℃; for 2 h; Inert atmosphere
Stage #2: at 0 - 25℃;
Sodium hydride (0.260 g, 0.011 mol) was dissolved in a tetrahydrofuran solvent in a nitrogen-sealed three-necked flask, Cooled to 0 ° C, and compound 7 (1100 ml, 6.72 mmol, 1.15 equiv) was dissolved in tetrahydrofuran solvent,Slowly added to the preceding solution. The mixture was allowed to warm to room temperature (25 ° C) for 1 hour,The reaction was further cooled to 0 ° C and reacted for 1 hour.Compound 1 (1.0 g, 5.84 mmol)Dissolved in tetrahydrofuran solvent,The above mixed solution was slowly added,And the mixture was stirred for 1 hour. To room temperature (25 & lt; 0 & gt; C)The reaction was run overnight (12 h).Cold water quenching, rotary steam solvent in addition to tetrahydrofuran. Extracted with ethyl acetate, the aqueous layer was separated and the organic layer was washed with brine. Dried over anhydrous magnesium sulphate, filtered, concentrated and purified by column chromatography to give 0.939 g of a white solid in 83percent yield.
73%
Stage #1: With sodium hydride In tetrahydrofuran at 4℃; for 0.75 h; Inert atmosphere
Stage #2: at 20℃; for 16 h;
0.81 g sodiumhydride (55percent purity, 18.6 mmol, 1.1 eq.) was suspended in 96 mL THE under argon atmosphere. At 4 C bath temperature 3. 45 g diethyl (cyanomethyl)phosphonate (19.5 mmol, 1.15 eq.) was added drop wise. After 45 minutes at room temperature 2.90 g of the commercial available starting material tert-butyl 3-oxoazetidine-1-carboxylate (16.9 mmol, 1.0 eq.), dissolved in 15 mL THE, were added drop wise. It was stirred at room temperature for 16 hours. The reaction mixture was poured into half concentrated sodium chloride solution and extracted three times with EE, dried over sodium sulfate and was concentrated under reduced pressure. The crude product was purified by flash chromatography to provide 2.40 g of the target compound:12.36 mmol, 73percent.1H NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.34-1.43 (m, 9 H) 4.57 (br. s., 2 H) 4.64 (br. s.,2 H) 5.79 - 5.86 (m, 1 H).
66.1%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 3 - 18.2℃; for 1.58333 h; Inert atmosphere
Stage #2: for 24 h;
An oven-dried 1 L 4-neck round bottom flask fitted with stir bar, septa, nitrogen inlet, 250 ml addition funnel and thermocouple was charged with sodium hydride (5.6 g, 0.14 mol) and tetrahydrofuran (THF) (140 mL) under a nitrogen atmosphere. The mixture was chilled to 3° C., and then charged with diethyl cyanomethylphosphonate (22.4 mL, 0.138 mol) dropwise via a syringe over 20 minutes. The solution became a light yellow slurry. The reaction was then stirred for 75 minutes while warming to 18.2° C. A solution of tert-butyl 3-oxoazetidine-1-carboxylate (20 g, 0.1 mol) in tetrahydrofuran (280 mL) was prepared in an oven-dried round bottom, charged to the addition funnel via canula, then added to the reaction mixture dropwise over 25 minutes. The reaction solution became red in color. The reaction was allowed to stir overnight. The reaction was checked after 24 hours by TLC (70percent hexane/EtOAc) and found to be complete. The reaction was diluted with 200 mL of 20percent brine and 250 mL of EtOAc. The solution was partitioned and the aqueous phase was extracted with 250 mL of EtOAc. The combined organic phase was dried over MgSO4 and filtered, evaporated under reduced pressure, and purified by flash chromatography (0percent to 20percent EtOAc/hexanes, 150 g flash column) to give the desired product, tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (15 g, 66.1percent yield).
66.1%
Stage #1: With sodium hydride In tetrahydrofuran at 3 - 18.2℃; for 1.58333 h; Inert atmosphere
Stage #2: Inert atmosphere
An oven-dried 1 L 4-neck round bottom flask fitted with stir bar, septa, nitrogen inlet, 250 ml addition funnel and thermocouple was charged with sodium hydride (5.6 g, 0.14 mol) and tetrahydrofuran (THF) (140 mL) under a nitrogen atmosphere.
The mixture was chilled to 3° C., and then charged with diethyl cyanomethylphosphonate (22.4 mL, 0.138 mol) dropwise via a syringe over 20 minutes.
The solution became a light yellow slurry.
The reaction was then stirred for 75 minutes while warming to 18.2° C. A solution of tert-butyl 3-oxoazetidine-1-carboxylate (20 g, 0.1 mol) in tetrahydrofuran (280 mL) was prepared in an oven-dried round bottom, charged to the addition funnel via canula, then added to the reaction mixture dropwise over 25 minutes.
The reaction solution became red in color.
The reaction was allowed to stir overnight.
The reaction was checked after 24 hours by TLC (70percent hexane/EtOAc) and found to be complete.
The reaction was diluted with 200 mL of 20percent brine and 250 mL of EtOAc.
The solution was partitioned and the aqueous phase was extracted with 250 mL of EtOAc.
The combined organic phase was dried over MgSO4 and filtered, evaporated under reduced pressure, and purified by flash chromatography (0percent to 20percent EtOAc/hexanes, 150 g flash column) to give the desired product, tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (15 g, 66.1percent yield).
62%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 73 h;
Stage #2: With water In tetrahydrofuran; mineral oil at 20℃;
To a suspension of NaH (60percent in mineral oil) (1.4g 35 mmol) in THF (100 mL) at 0 °C was added dropwise diethyl phosphonate (6.45 mL, 41 mmol) and stirred at room temperature for 1 h. A solution of l-boc-3-one-azetidine (45a) (5g, 29.2 mmol) in THF (45 mL) was added to the anion at room temperature and stirred for 72 h. The reaction was quenched with water (100 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with brine (100 mL), dried, filtered and concentrated in vacuum. The residue obtained was purified by flash column chromatography (silica gel 80 g, eluting with ethylacetate/hexanes, 0-100percent) to furnish tert-butyl 3 -(cyanomethylene)azetidine-l -carboxylate (45b) (3.52 g, 62percent) as a white solid.1H NMR (300 MHz, DMSO) δ 5.84 (s, J= 2.5, IH), 4.74 - 4.51 (m, 4H), 1.53 - 1.30 (s, 9H); MS (ES-) 193.4 (M-l); IR (KBr) 2222 cm"1; Analysis; Calcd for C10H14N2O2: C, 61.84; H, 7.27; N, 14.42; Found C, 61.94; H, 7.28; N, 14.38.
414.7 g
Stage #1: With potassium <i>tert</i>-butylate In tetrahydrofuran at -14 - -5℃; for 3 h; Inert atmosphere
Stage #2: at -5 - 20℃;
tert-Butyl 3-(cyanomethylene)azetidine-1-carboxylate (2) [0157] Diethyl cyanomethyl phosphate (745 g, 4.20 mol, 1.20 equiv) and anhydrous tetrahydrofuran (THF, 9 L) were added to a four-neck flask equipped with a thermowell, an addition funnel and the nitrogen protection tube at room temperature. The solution was cooled with an ice-methanol bath to −14° C. and a 1.0 M solution of potassium tert-butoxide (t-BuOK) in anhydrous tetrahydrofuran (THF, 3.85 L, 3.85 mol, 1.1 equiv) was added over 20 min keeping the reaction temperature below −5° C. The resulting reaction mixture was stirred for 3 h at −10° C. and a solution of 1-tert-butoxycarbonyl-3-azetidinone (600 g, 3.50 mol) in anhydrous tetrahydrofuran (THF, 2 L) was added over 2 h keeping the internal temperature below −5° C. The reaction mixture was stirred at −5 to −10° C. over 1 h and then slowly warmed up to room temperature and stirred at room temperature for overnight. The reaction mixture was then diluted with water (4.5 L) and saturated aqueous sodium chloride solution (NaCl, 4.5 L) and extracted with ethyl acetate (EtOAc, 2×9 L). The combined organic layers were washed with brine (6 L) and dried over anhydrous sodium sulfate (Na2SO4). The solvent was removed under reduced pressure and the residue was diluted with dichloromethane (CH2Cl2, 4 L) before being absorbed onto silica gel (SiO2, 1.5 Kg). The crude product, which was absorbed on silica gel, was purified by flash column chromatography (SiO2, 3.5 Kg, 0-25percent EtOAc/hexanes gradient elution) to afford tert-butyl 3-(cyanomethylene)azetidine-1-carboxylate (2, 414.7 g, 679.8 g theoretical, 61percent yield) as a white solid. For 2: 1H NMR (300 MHz, CDCl3) δ 5.40 (m, 1H), 4.70 (m, 2H), 4.61 (m, 2H), 1.46 (s, 9H) ppm; C10H14N2O2 (MW, 194.23), LCMS (EI) m/e 217 (M++Na).

Reference: [1] Patent: US2009/233903, 2009, A1, . Location in patent: Page/Page column 26-27; 58
[2] Patent: WO2011/130146, 2011, A1, . Location in patent: Page/Page column 84-85
[3] Patent: WO2009/64835, 2009, A1, . Location in patent: Page/Page column 44
[4] Patent: WO2012/177606, 2012, A1, . Location in patent: Page/Page column 57-58
[5] Patent: US2014/343030, 2014, A1, . Location in patent: Paragraph 0420; 0421; 0422
[6] Journal of Chemical Research, 2016, vol. 40, # 4, p. 205 - 208
[7] Patent: CN105541891, 2016, A, . Location in patent: Paragraph 0070; 0071; 0072; 0073; 0074; 0075
[8] Patent: WO2016/41925, 2016, A1, . Location in patent: Page/Page column 255; 256
[9] Patent: US2011/224190, 2011, A1, . Location in patent: Page/Page column 36-37
[10] Patent: US2015/246046, 2015, A1, . Location in patent: Paragraph 0131
[11] Patent: WO2011/31554, 2011, A2, . Location in patent: Page/Page column 154
[12] Patent: WO2013/55645, 2013, A1, . Location in patent: Paragraph 00368
[13] Patent: US2014/256941, 2014, A1, . Location in patent: Paragraph 0157
[14] European Journal of Organic Chemistry, 2017, vol. 2017, # 31, p. 4530 - 4542
[15] Patent: EP3290418, 2018, A1, . Location in patent: Paragraph 0081
  • 17
  • [ 398489-26-4 ]
  • [ 15898-47-2 ]
  • [ 1153949-11-1 ]
YieldReaction ConditionsOperation in experiment
37% With n-butyllithium In tetrahydrofuran; hexane at 0 - 20℃; for 1 h; Inert atmosphere Under nitrogen, a suspension of (cyanomethyl)triphenylphosphanium bromide (13.4 g, 35.09 mmol) in anhydrous THF (100 mL) was cooled to 0° C., a solution of 2.5 M n-BuLi in n-hexane (15.5 mL, 38.59 mmol) was added dropwise. The mixture tert-butyl-3-oxoazetidine-1-carboxylate (6.0 g, 35.09 mmol) was added, and the mixture was warmed to room temperature and stirred for further 1 hour. The reaction was quenched with saturated aqueous ammonium chloride solution (50 mL), extracted with ethyl acetate (150 mL×3). The organic layers were combined, washed with water (100 mL×3) and saturated brine (100 mL) in sequence, dried over anhydrous sodium sulfate. The resultant mixture was filtrated, the filtrate was concentrated in vacuum, and the residue was purified by silica column chromatography (petroleum ether:ethyl acetate=5:1) to give a white solid 5-c (2.5 g, yield: 37percent). LC-MS (ESI): m/z=217 [M+Na]+.
Reference: [1] Patent: US2015/336982, 2015, A1, . Location in patent: Paragraph 0134; 0135
  • 18
  • [ 398489-26-4 ]
  • [ 75-16-1 ]
  • [ 1104083-23-9 ]
YieldReaction ConditionsOperation in experiment
87% at 0 - 20℃; for 3 h; Step a. tert-FJutyl 3-hydroxy-3-methylazetidine-l- carboxylate. Methyl magnesium bromide (3M in diethyl ether; 2.92 mL, 8.76 mmol) was added portionwise into a cold (0 °C) solution of tert-butyl 3-oxoazetidine-l-carboxylate (0.5 g, 2.92 mmol) and anhydrous THF (3 mL). The mixture was allowed to come to room temperature and stirred for 3 hours and carefully quenched with aqueous ammonium chloride. The mixture was extracted with ethyl acetate, washed with brine and dried over anhydrous MgS04. The solvents were removed under vacuum and the residue was purified on silica gel (Biotage; eluting solvents hexanes: EtOAc 1/1 ratio) to afford tert-butyl 3- hydroxy-3-methylazetidine-l-carboxylate as oil (480 mg, 87percent yield): XH NMR (500MHz, CDCk) δ ppm 3.87 (d, J= 9.0 Hz, 2H), 3.82 (d, J= 9.0, 2H), 2.46 (s, 1H), 1.51 (s, 3H), 1.44 (s, 9H).
84%
Stage #1: at 0 - 20℃; for 19.75 h;
Stage #2: With ammonium chloride In diethyl ether; water at 20℃;
Step B: Preparation of 3-hvdroxy-3-methyl-azetidine-1-carboxylic acid tert-butyl ester.; A solution of 1 -Boc-azetidin-3-one (3.5 g, 20 mmol) in 50 ml_ anh Et2O was cooled to 0 0C and 3M MeMgBr in Et2O (10 ml_, 30 mmol) was added dropwise over 1 h. After 45 min, the reaction was allowed to warm to rt and stir an additional for 18h. Then Vi sat'd NH4CI (aq.) was added and the mixture extracted with EtOAc (2x). The combined organic layers were dried and the resulting semisolid was purified by RP HPLC (Agilent) to give the title compound as a white solid (3.2 g, 84percent). 1H NMR (CDCI3): 3.84 (q, J = 9.2 Hz, 4H), 1.97 (bs, 1 H), 1.52 (s, 3H), 1.44 (m, 9H).
78.3% at 0℃; for 1 h; Inert atmosphere In an oven dried flask, tert-butyl 3-oxoazetidine-l-carboxylate (1.01 g,5.900 mmol) was dissolved in diethyl ether (0.2 M) and place under an atmosphere of N2. The reaction mixture was cooled to 0°C and treated dropwise with methylmagnesium bromide (2.07 mL, 6.195 mmol, 3.0 M). The reaction mixture was stirred at 0°C for 1 hour then quenched by pouring onto ice. The mixture was extracted with diethyl ether, washed with water and brine, dried over Na2S04, filtered, and concentrated in vacuo to provide tert- butyl 3-hydroxy-3-methylazetidine-l-carboxylate (865.3 mg, 4.621 mmol, 78.3percent yield).
430 mg at 20 - 35℃; for 1 h; Methyl magnesium bromide (3.0M in Diethyl ether) (1.5 mL, 4.5 mmol) was added to cold (-10° C.) solution of tert-butyl 3-oxoazetidine-1-carboxylate (650 mg, 3.8 mmol) in THF (10 mL) and stirring was continued at 20-35° C. for 1 h. After which the reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with ethylacetate. The organic layer separated was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the residue. The residue was purified by column chromatography (using 60-120 silica gel and 50percent EtOAc in Hexane as eluent) to afford 430 mg of the title compound. 1H NMR (400 MHz, DMSO) δ ppm 5.56 (1H, s), 3.7-3.5 (4H, m), 1.4 (9H, s), 1.3 (3H, s).
430 mg at -10 - 35℃; for 1 h; Methyl magnesium bromide (3.0M in Diethyl ether) (1.5 mL, 4.5 mmol) was added to cold (−10° C.) solution of tert-butyl 3-oxoazetidine-1-carboxylate (650 mg, 3.8 mmol) in THF (10 mL) and stifling was continued at 20-35° C. for 1 h. After which the reaction mixture was quenched with saturated aqueous NH4Cl solution and extracted with ethylacetate. The organic layer separated was washed with water, dried over anhydrous sodium sulphate and concentrated under reduced pressure to afford the residue. The residue was purified by column chromatography (using 60-120 silica gel and 50percent EtOAc in Hexane as eluent) to afford 430 mg of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 5.56 (1H, s), 3.7-3.5 (4H, m), 1.4 (9H, s), 1.3 (3H, s) ppm.

Reference: [1] Patent: WO2015/179190, 2015, A1, . Location in patent: Paragraph 0304
[2] Patent: WO2010/59393, 2010, A1, . Location in patent: Page/Page column 151
[3] Patent: WO2013/55645, 2013, A1, . Location in patent: Paragraph 00397
[4] Patent: WO2011/63502, 2011, A1, . Location in patent: Page/Page column 52
[5] Patent: US2015/5280, 2015, A1, . Location in patent: Paragraph 0637 - 0639
[6] Patent: US2015/368238, 2015, A1, . Location in patent: Paragraph 0628; 0629
[7] Patent: CN105732602, 2016, A, . Location in patent: Paragraph 0386; 0388; 0389; 0390; 0391
  • 19
  • [ 398489-26-4 ]
  • [ 676-58-4 ]
  • [ 1104083-23-9 ]
YieldReaction ConditionsOperation in experiment
99%
Stage #1: at 0℃; for 1 h;
Stage #2: With water; ammonium chloride In tetrahydrofuran
Step 1
In a dry round-bottomed flask, 1-Boc-3-azetidinone (0.70 g, 4.1 mmol) was dissolved in THF (20 mL).
The solution was cooled to 0° C. and methylmagnesium chloride (3.0 M solution in THF, 2.0 mL, 6.0 mmol) was added dropwise.
The reaction mixture was stirred at 0° C. for 1 h.
The reaction mixture was quenched with 10 mL saturated NH4Cl, diluted with 5 mL water and extracted with 100 mL EtOAc (2*).
The combined organic layers were washed with 10 mL water and 10 mL brine then combined, dried over sodium sulfate, filtered and concentrated to afford 757 mg (99percent) of 3-hydroxy-3-methyl-azetidine-1-carboxylic acid tert-butyl ester as an off-white solid.
Reference: [1] Patent: US2011/230462, 2011, A1, . Location in patent: Page/Page column 91
[2] Patent: WO2009/80682, 2009, A1, . Location in patent: Page/Page column 68
  • 20
  • [ 398489-26-4 ]
  • [ 589-87-7 ]
  • [ 1357614-50-6 ]
YieldReaction ConditionsOperation in experiment
28%
Stage #1: With n-butyllithium In tetrahydrofuran; diethyl ether at -78℃; for 0.166667 h; Inert atmosphere
Stage #2: at -78℃; for 1.5 h;
Compound 43.1. tert-Buty\ 3-(4-bromophenyl)-3-hydroxyazetidine-l-carboxylate. Into a 1 -L 3-necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1 -bromo-4-iodobenzene (25.0 g, 88.4 mmol) in tetrahydrofuran/diethyl ether (400/200 mL). The solution was cooled to -78 °C then n-BuLi (2.5 M, 37.1 mL, 92.8 mmol) was added drop-wise over 10 min. To the resulting mixture was added lert-butyl 3-oxoazetidine- l -carboxylate ( 16.6 g, 97.0 mmol) in THF (100 mL) drop- wise at -78 °C. The resulting mixture was stirred for 1.5 h at -78 °C, then carefully quenched with water (300 mL). The aqueous phase was extracted with ethyl acetate (200 mL) and the combined organic layers were washed with brine (2 x 100 mL), dried (Na2S04), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :20-l :5) as the eluent followed by re- crystallized from ethyl acetate:PE in the ratio of 1 : 100 to yield 8.0 g (28percent) of the title compound as a white solid.
28%
Stage #1: With n-butyllithium In tetrahydrofuran; diethyl ether at -78℃; for 0.166667 h; Inert atmosphere
Stage #2: at -78℃; for 1.5 h;
Compound 43.1. teri-Butyl 3-(4-bromophenyl)-3-hydroxyazetidine-l-carboxylate.
Into a 1-L 3 -necked round-bottom flask, purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 1 -bromo-4-iodobenzene (25.0 g, 88.4 mmol) in tetrahydrofuran/diethyl ether (400/200 mL). The solution was cooled to -78 °C then n-BuLi (2.5 M, 37.1 mL, 92.8 mmol) was added drop-wise over 10 min. To the resulting mixture was added /er/-butyl 3-oxoazetidine-l-carboxylate (16.6 g, 97.0 mmol) in THF (100 mL) drop- wise at -78 °C. The resulting mixture was stirred for 1.5 h at -78 °C, then carefully quenched with water (300 mL). The aqueous phase was extracted with ethyl acetate (200 mL) and the combined organic layers were washed with brine (2 x 100 mL), dried ( a2S04), filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with ethyl acetate/petroleum ether (1 :20-1 :5) as the eluent followed by re- crystallized from ethyl acetate:PE in the ratio of 1 : 100 to yield 8.0 g (28percent) of the title compound as a white solid.
Reference: [1] Patent: WO2014/8197, 2014, A1, . Location in patent: Page/Page column 113
[2] Patent: WO2015/95767, 2015, A1, . Location in patent: Page/Page column 128
  • 21
  • [ 398489-26-4 ]
  • [ 106-37-6 ]
  • [ 1357614-50-6 ]
Reference: [1] Patent: WO2015/112441, 2015, A1, . Location in patent: Page/Page column 48
[2] Patent: US2016/333021, 2016, A1, . Location in patent: Paragraph 0317
  • 22
  • [ 398489-26-4 ]
  • [ 1357614-50-6 ]
Reference: [1] Patent: US2012/35122, 2012, A1,
[2] Patent: WO2013/116236, 2013, A1,
[3] Patent: WO2013/169622, 2013, A1,
  • 23
  • [ 398489-26-4 ]
  • [ 142253-58-5 ]
Reference: [1] Patent: WO2016/41925, 2016, A1,
  • 24
  • [ 398489-26-4 ]
  • [ 1453315-68-8 ]
Reference: [1] Organic Letters, 2013, vol. 15, # 18, p. 4766 - 4769
Recommend Products
Same Skeleton Products
Historical Records

Pharmaceutical Intermediates of
[ 398489-26-4 ]

Cobimetinib Related Intermediates

Chemical Structure| 105258-93-3

[ 105258-93-3 ]

Benzyl 3-oxoazetidine-1-carboxylate

Chemical Structure| 61079-72-9

[ 61079-72-9 ]

2,3,4-Trifluorobenzoic acid

Chemical Structure| 75844-69-8

[ 75844-69-8 ]

tert-Butyl piperidine-1-carboxylate

Chemical Structure| 29632-74-4

[ 29632-74-4 ]

2-Fluoro-4-iodoaniline

Chemical Structure| 128117-22-6

[ 128117-22-6 ]

1-Cbz-3-Hydroxyazetidine

Baricitinib Related Intermediates

Chemical Structure| 91-00-9

[ 91-00-9 ]

Diphenylmethanamine

Chemical Structure| 1029716-44-6

[ 1029716-44-6 ]

1-(1-Ethoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Chemical Structure| 141699-55-0

[ 141699-55-0 ]

tert-Butyl 3-hydroxyazetidine-1-carboxylate

Chemical Structure| 18621-17-5

[ 18621-17-5 ]

1-Benzhydrylazetidin-3-ol

Chemical Structure| 3680-69-1

[ 3680-69-1 ]

4-Chloro-7H-pyrrolo[2,3-d]pyrimidine

Related Functional Groups of
[ 398489-26-4 ]

Amides

Chemical Structure| 123387-72-4

[ 123387-72-4 ]

tert-Butyl methyl(2-oxoethyl)carbamate

Similarity: 0.89

Chemical Structure| 147621-21-4

[ 147621-21-4 ]

tert-Butyl azetidine-1-carboxylate

Similarity: 0.89

Chemical Structure| 170384-29-9

[ 170384-29-9 ]

tert-Butyl (2-oxopropyl)carbamate

Similarity: 0.89

Chemical Structure| 315718-06-0

[ 315718-06-0 ]

tert-Butyl ethyl(2-oxoethyl)carbamate

Similarity: 0.87

Chemical Structure| 325775-44-8

[ 325775-44-8 ]

tert-Butyl 3-(aminomethyl)azetidine-1-carboxylate

Similarity: 0.85

Ketones

Chemical Structure| 170384-29-9

[ 170384-29-9 ]

tert-Butyl (2-oxopropyl)carbamate

Similarity: 0.89

Chemical Structure| 101385-93-7

[ 101385-93-7 ]

N-Boc-3-Pyrrolidinone

Similarity: 0.85

Chemical Structure| 98977-36-7

[ 98977-36-7 ]

1-Boc-3-Piperidinone

Similarity: 0.83

Chemical Structure| 396731-40-1

[ 396731-40-1 ]

tert-Butyl 3,5-dioxopiperidine-1-carboxylate

Similarity: 0.81

Chemical Structure| 870089-49-9

[ 870089-49-9 ]

tert-Butyl 3-acetylazetidine-1-carboxylate

Similarity: 0.79

Related Parent Nucleus of
[ 398489-26-4 ]

Aliphatic Heterocycles

Chemical Structure| 147621-21-4

[ 147621-21-4 ]

tert-Butyl azetidine-1-carboxylate

Similarity: 0.89

Chemical Structure| 325775-44-8

[ 325775-44-8 ]

tert-Butyl 3-(aminomethyl)azetidine-1-carboxylate

Similarity: 0.85

Chemical Structure| 177947-96-5

[ 177947-96-5 ]

tert-Butyl 3-formylazetidine-1-carboxylate

Similarity: 0.84

Chemical Structure| 142253-56-3

[ 142253-56-3 ]

1-Boc-Azetidine-3-yl-methanol

Similarity: 0.83

Chemical Structure| 141699-55-0

[ 141699-55-0 ]

tert-Butyl 3-hydroxyazetidine-1-carboxylate

Similarity: 0.83

Azetidines

Chemical Structure| 147621-21-4

[ 147621-21-4 ]

tert-Butyl azetidine-1-carboxylate

Similarity: 0.89

Chemical Structure| 325775-44-8

[ 325775-44-8 ]

tert-Butyl 3-(aminomethyl)azetidine-1-carboxylate

Similarity: 0.85

Chemical Structure| 177947-96-5

[ 177947-96-5 ]

tert-Butyl 3-formylazetidine-1-carboxylate

Similarity: 0.84

Chemical Structure| 142253-56-3

[ 142253-56-3 ]

1-Boc-Azetidine-3-yl-methanol

Similarity: 0.83

Chemical Structure| 141699-55-0

[ 141699-55-0 ]

tert-Butyl 3-hydroxyazetidine-1-carboxylate

Similarity: 0.83