[ CAS No. 897019-59-9 ] {[proInfo.proName]}

Name: 897019-59-9|3-(Benzyloxy)azetidine hydrochloride|97%
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Quality Control of [ 897019-59-9 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 897019-59-9 ]

SDS Specification

Alternatived Products of [ 897019-59-9 ]

Product Details of [ 897019-59-9 ]

CAS No. :	897019-59-9	MDL No. :	MFCD09907646
Formula :	C₁₀H₁₄ClNO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BQTSSUSLZRYTQB-UHFFFAOYSA-N
M.W :	199.68	Pubchem ID :	46737011
Synonyms :

Calculated chemistry of [ 897019-59-9 ]

Physicochemical Properties

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.4
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	58.48
TPSA :	21.26 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.25 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.0
Log Po/w (XLOGP3) :	1.78
Log Po/w (WLOGP) :	1.44
Log Po/w (MLOGP) :	1.46
Log Po/w (SILICOS-IT) :	2.11
Consensus Log Po/w :	1.36

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.34
Solubility :	0.907 mg/ml ; 0.00454 mol/l
Class :	Soluble
Log S (Ali) :	-1.84
Solubility :	2.85 mg/ml ; 0.0143 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.18
Solubility :	0.131 mg/ml ; 0.000655 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.47

Safety of [ 897019-59-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 897019-59-9 ]

* 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 [ 897019-59-9 ]
Downstream synthetic route of [ 897019-59-9 ]

[ 897019-59-9 ] Synthesis Path-Upstream 1~2

1
[ 1027995-71-6 ]
[ 897019-59-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	at 20℃; for 1 h;	Procedure for preparation of 3-(benzyloxy)azetidine hydrochloride 24:; tert-butyl 3-(benzyloxy)azetidine-l-carboxylate 23 (1.0 gm) was taken into a round bottomed flask and was added methanolic-HCl (15 mL, 20percent) and was stirred for lh at room temperature. After completion of the reaction (monitored by TLC), the solvent was removed under vacuum to get a white solid as a crude product. The crude product was washed with ethyl acetate repeatedly and then dried well to obtain compound 24 as a white solid (92percent) and was used further without purification.
92%	With hydrogenchloride In methanol at 20℃; for 1 h;	Procedure for preparation of 3-(benzyloxy)azetidine hydrochloride 24 tert-butyl 3-(benzyloxy)azetidine-1-carboxylate 23 (1.0 μm) was taken into a round bottomed flask and was added methanolic-HCl (15 mL, 20percent) and was stirred for 1 h at room temperature. After completion of the reaction (monitored by TLC), the solvent was removed under vacuum to get a white solid as a crude product. The crude product was washed with ethyl acetate repeatedly and then dried well to obtain compound 24 as a white solid (92percent) and was used further without purification.

Reference： [1] Patent: WO2012/83246, 2012, A1, . Location in patent: Page/Page column 46
[2] Patent: US9388164, 2016, B2, . Location in patent: Page/Page column 74; 75
[3] Organic Letters, 2017, vol. 19, # 9, p. 2270 - 2273
[4] Patent: WO2017/202704, 2017, A1, . Location in patent: Page/Page column 44; 45

2
[ 100-39-0 ]
[ 897019-59-9 ]

Reference： [1] Patent: WO2012/83246, 2012, A1,
[2] Organic Letters, 2017, vol. 19, # 9, p. 2270 - 2273
[3] Patent: WO2017/202704, 2017, A1,
[4] Patent: WO2011/61214, 2011, A1,

[ 897019-59-9 ] Synthesis Path-Downstream 1~22

2
[ 100-39-0 ]
[ 897019-59-9 ]

Reference： [1]Patent: WO2012/83246,2012,A1
[2]Organic Letters,2017,vol. 19,p. 2270 - 2273
[3]Patent: WO2017/202704,2017,A1
[4]Patent: WO2011/61214,2011,A1

3
3-(benzyloxy)-1-(diphenylmethyl)azetidine [ No CAS ]
[ 897019-59-9 ]

Yield	Reaction Conditions	Operation in experiment
92%		Ste 2: 3-(Benzyloxy)azetidine hydrochlorideA 16 mL vial was charged with 3-(benzyloxy)-l-(diphenylmethyl)azetidine (103 mg, 0.31 mmol; which may be prepared as described in Step 1) and 1,2-dichloroethane (1.4 mL). 1-Chloroethyl chloroformate (45 pL, 0.41 mmol) was added and the reaction mixture was stirred at 70 C for 1.5 h . After cooling to room temperature, methanol (1.4 mL) was added and the reaction mixture was stirred at 70 C for 1.5 h. The reaction mixture was cooled and concentrated to dryness. The residue was purified on column chromatography (eluent: Pentane/NH3 7N in MeOH, 98/2) to give the title compound (57 mg, 92%).LCMS (ESI+) m/z 164 (M + H+ (-HQ)) : 100%.*H NMR (DMSO-c/6, 300 MHz) : delta (ppm) : 7.40-7.23 (m, 5H), 4.36 (s, 2H), 4.34-4.21 (m, 1 H), 3.57-3.24 (m, 4H).

Reference： [1]Patent: WO2011/61214,2011,A1 .Location in patent: Page/Page column 62

4
[ 897019-59-9 ]
(E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylic acid hydrochloride [ No CAS ]
6-{(1E)-3-[3-(benzyloxy)azetidin-1-yl]-3-oxoprop-1-en-1-yl}-3 4-dihydro-1,8-naphthyridin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In 1,2-dimethoxyethane; at 20℃;	Step 3: 6-{(lE)-3-[3-(Benzyloxy)azetidin-l-yl]-3-oxoprop-l-en-l-yl}-3,4- dih dro-l,8-naphthyridin-2(lH)-oneA 16 mL vial flask was successively charged with (2E)-3-(7-oxo-5,6,7,8-tetrahydro- l,8-naphthyridin-3-yl)acrylic acid hydrochloride (60 mg, 0.24 mmol), DMF (5.8 mL), <strong>[897019-59-9]3-(benzyloxy)azetidine hydrochloride</strong> (58 mg, 0.29 mmol; which may be prepared as described in Step 2), DIPEA (96 pL, 0.58 mmol), DMAP (2.4 mg, 0.02 mmol) and EDAC (56 mg, 0.29 mmol). The reaction mixture was stirred at room temperature overnight and concentrated to dryness. The residue was purified by precipitation in MeOH/H20 and then triturated in acetone/diethyl ether to give the title compound as a beige solid (33 mg, 38%). LC-MS (ESI+) m/z 364 (M + H)+ : 100%.*H NMR (DMSO-c/e, 300 MHz) : delta (ppm) : 10.66 (br s, 1H), 8.40-8.30 (m, 1H), 8.06- 7.97 (m, 1H), 7.46-7.26 (m, 6H), 6.71 (d, J = 15.6 Hz, 1H), 4.53-4.35 (m, 4H), 4.19-4.04 (m, 2H), 3.82-3.70 (m, 1H), 2.98-2.84 (m, 2H). The CH2 missing is hidden by the DMSO signal.

Reference： [1]Patent: WO2011/61214,2011,A1 .Location in patent: Page/Page column 62-63

5
[ 1027995-71-6 ]
[ 897019-59-9 ]

Yield	Reaction Conditions	Operation in experiment
92%	With hydrogenchloride; methanol; at 20℃; for 1h;	Procedure for preparation of 3-(benzyloxy)azetidine hydrochloride 24:; tert-butyl 3-(benzyloxy)azetidine-l-carboxylate 23 (1.0 gm) was taken into a round bottomed flask and was added methanolic-HCl (15 mL, 20%) and was stirred for lh at room temperature. After completion of the reaction (monitored by TLC), the solvent was removed under vacuum to get a white solid as a crude product. The crude product was washed with ethyl acetate repeatedly and then dried well to obtain compound 24 as a white solid (92%) and was used further without purification.
92%	With hydrogenchloride; In methanol; at 20℃; for 1h;	Procedure for preparation of 3-(benzyloxy)azetidine hydrochloride 24 tert-butyl 3-(benzyloxy)azetidine-1-carboxylate 23 (1.0 mum) was taken into a round bottomed flask and was added methanolic-HCl (15 mL, 20%) and was stirred for 1 h at room temperature. After completion of the reaction (monitored by TLC), the solvent was removed under vacuum to get a white solid as a crude product. The crude product was washed with ethyl acetate repeatedly and then dried well to obtain compound 24 as a white solid (92%) and was used further without purification.
	With hydrogenchloride; In ethyl acetate; at 20℃; for 6h;	Compound llA was treated with 25 mL EA solution of HCl (1 M) and the mixture wasstirred at rt for 6 hrs. The solvent was concentrated in vacuo to give about 410 mg of crude 3-benzyloxyazetidine (Compound llB) as a colorless oil which was used directly in the next step.MS: calc'd 164 (M+Ht, measured 164 (M+Ht.

Reference： [1]Patent: WO2012/83246,2012,A1 .Location in patent: Page/Page column 46
[2]Patent: US9388164,2016,B2 .Location in patent: Page/Page column 74; 75
[3]Organic Letters,2017,vol. 19,p. 2270 - 2273
[4]Patent: WO2017/202704,2017,A1 .Location in patent: Page/Page column 44; 45

6
[ 897019-59-9 ]
[ 116834-64-1 ]
[ 1383372-04-0 ]

Yield	Reaction Conditions	Operation in experiment
		General Procedure for Compound of Formula II wherein R a is hydrogen and Rlb is -O-benzyl:; To a stirred solution of the carboxylic acid 18 (0.61 mmol) (prepared as in Example 2) in DMF at 0 C under nitrogen atmosphere, EDCI (0.129 gm, 0.671 mmol), HOBt (0.91 gm, 0.671 mmol) and DIPEA (0.31 ml, 1.83 mmol) were added and the resultant solution was stirred at room temperature for 30 min. Amine hydrochloride 24 (0.61 mmol) was then added at 0 C and stirred overnight at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was poured into 1.0 M HC1 and extracted with EtOAc. The organic layer was washed with sat. aq. NaHC03, dried over NaS04 and filtered. The solvent was removed by rotary evaporation and the product was isolated by chromatography on silica gel (60-120 silica gel, 2% MeOH-DCM) or preparative HPLC to yield final compound (50-60%) as an off-white solid.Compound 108: N-(4-(3-(benzyloxy)azetidine-l-carbonyl)phenyl)quinoline-8- sulfonamide:1H NMR (400 MHz, DMSOd6) delta: 2.6 (s, 2H), 2.2 (dd, 2H), 4.1-4.2 (dd, 3H), 7.16-7.4 (m, 5H), 7.37-7.57 (m, 3H), 7.79-7.84 (m, 2H), 8.2-8.40 (m, 3H), 9.10 (d, 1H), 10.5 (s, 1H); HPLC purity: 98.9%; MS: m/z 474.1 ( +i)+.
		General Procedure for Compound of Formula II Wherein R1a is Hydrogen and R1b is -O-benzyl (0151) To a stirred solution of the carboxylic acid 18 (0.61 mmol) (prepared as in Example 2) in DMF at 0 C. under nitrogen atmosphere, EDCI (0.129 gm, 0.671 mmol), HOBt (0.91 gm, 0.671 mmol) and DIPEA (0.31 ml, 1.83 mmol) were added and the resultant solution was stirred at room temperature for 30 min. Amine hydrochloride 24 (0.61 mmol) was then added at 0 C. and stirred overnight at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was poured into 1.0 M HCl and extracted with EtOAc. The organic layer was washed with sat. aq. NaHCO3, dried over NaSO4 and filtered. The solvent was removed by rotary evaporation and the product was isolated by chromatography on silica gel (60-120 silica gel, 2% MeOH-DCM) or preparative HPLC to yield final compound (50-60%) as an off-white solid. Compound 108 N-(4-(3-(benzyloxy)azetidine-1-carbonyl)phenyl)quinoline-8-sulfonamide (0152) (0153) 1H NMR (400 MHz, DMSOd6) delta: 2.6 (s, 2H), 2.2 (dd, 2H), 4.1-4.2 (dd, 3H), 7.16-7.4 (m, 5H), 7.37-7.57 (m, 3H), 7.79-7.84 (m, 2H), 8.2-8.40 (m, 3H), 9.10 (d, 1H), 10.5 (s, 1H); HPLC purity: 98.9%; MS: m/z 474.1 (M+1)+.

Reference： [1]Patent: WO2012/83246,2012,A1 .Location in patent: Page/Page column 47
[2]Patent: US9388164,2016,B2 .Location in patent: Page/Page column 74; 75; 76

7
[ 897019-59-9 ]
C₂₃H₃₂N₄O₈S [ No CAS ]