[ CAS No. 151213-40-0 ] {[proInfo.proName]}

Name: 151213-40-0|(4aS,7aS)-Octahydro-1H-pyrrolo[3,4-b]pyridine|97%
Brand: Ambeed
SKU: A101196
Price: 11.0 USD
Availability: InStock
Rating: 90 (35 reviews)

,{[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+

DV 2D 3D

3d Animation Molecule Structure of 151213-40-0

Structure of 151213-40-0 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 110K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 151213-40-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 151213-40-0 ]

SDS Specification

Alternatived Products of [ 151213-40-0 ]

Product Details of [ 151213-40-0 ]

CAS No. :	151213-40-0	MDL No. :	MFCD08458306
Formula :	C₇H₁₄N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KSCPLKVBWDOSAI-NKWVEPMBSA-N
M.W :	126.20	Pubchem ID :	10313138
Synonyms :

Calculated chemistry of [ 151213-40-0 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	0
Fraction Csp3 :	1.0
Num. rotatable bonds :	0
Num. H-bond acceptors :	2.0
Num. H-bond donors :	2.0
Molar Refractivity :	44.97
TPSA :	24.06 Å²

Pharmacokinetics

GI absorption :	Low
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) :	-7.11 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.69
Log Po/w (XLOGP3) :	-0.05
Log Po/w (WLOGP) :	-0.8
Log Po/w (MLOGP) :	0.57
Log Po/w (SILICOS-IT) :	1.08
Consensus Log Po/w :	0.5

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.59
Solubility :	32.4 mg/ml ; 0.256 mol/l
Class :	Very soluble
Log S (Ali) :	0.0
Solubility :	125.0 mg/ml ; 0.99 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.42
Solubility :	4.81 mg/ml ; 0.0381 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.16

Safety of [ 151213-40-0 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P210-P264-P280-P302+P352-P370+P378-P362+P364-P332+P313-P305+P351+P338+P310-P403+P235	UN#:	2735
Hazard Statements:	H315-H318-H227	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 151213-40-0 ]

* 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 [ 151213-40-0 ]
Downstream synthetic route of [ 151213-40-0 ]

[ 151213-40-0 ] Synthesis Path-Upstream 1~12

1
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 151096-09-2 ]

Yield	Reaction Conditions	Operation in experiment
89.7%	at 65 - 70℃; for 6 - 8 h;	Example 1 Preparation of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. (III) Dimethylsulfoxide (600 ml), 50 g of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (IV) and 25.70 ml of [S,S]-2,8-diazabicyclo [4.3.0] nonane (V) were stirred at 65 - 70 °C for 6 - 8 hours. Completion of the reaction was monitored by HPLC. The reaction mass was cooled to 25-30 °C, 100 ml of water was added and stirred for 2 hours. The solid was filtered off with suction, washed with 100 ml water and dried under vacuum at 75°C, affording 61.0 g of the title compound. Yield: 89.7 percent Purity: 98 percent (HPLC) Chiral impurity (R,R isomer content): 3 - 5 percent
66%	With triethylamine In N,N-dimethyl-formamide; acetonitrile at 0 - 78℃; for 11 h; Reflux	1 -cyclopropyl-^-difiuoro-δ-methoxy^-oxo- 1 ,4-dihydro-3-quinolinecarboxylic acid (100g, 0.338 mole) and triethylamine were taken in mixture of acetonitrile (300 ml) and dimethylformamide (80 ml) . To it was added (S,S)-2,8-diazabicyclo [4.3.0] nonane (47g, 0.373 mole) and refluxed at 72- 78°C for 10 hours at reflux. The reaction mixture was cooled to room temperature, and further to 0-5°C maintained for 1 hr, filtered and washed with acetonitrile (50 ml) to get the desired product.Dry wt: 89.7g, Yield: 66percent.

Reference： [1] Patent: EP1992626, 2008, A1, . Location in patent: Page/Page column 10
[2] Patent: WO2009/125425, 2009, A2, . Location in patent: Page/Page column 11
[3] Patent: WO2008/59521, 2008, A2, . Location in patent: Page/Page column 27
[4] Patent: WO2007/10555, 2007, A2, . Location in patent: Page/Page column 12; 14
[5] Patent: EP2551268, 2013, A1, . Location in patent: Paragraph 0051,0052
[6] Patent: US2013/59880, 2013, A1, . Location in patent: Paragraph 0070; 0071; 0072; 0073; 0074; 0075; 0076
[7] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 254 - 258

2
[ 496919-99-4 ]
[ 151213-40-0 ]
[ 151096-09-2 ]

Reference： [1] Patent: WO2008/59223, 2008, A2, . Location in patent: Page/Page column 15-16

3
[ 112811-71-9 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
89.78%	Stage #1: at 90 - 100℃; for 3 h; Stage #2: With triethylamine In acetonitrile at 20℃; for 0.5 h;	In a 2000 mL three-necked round-bottomed flask, 150.00 g of acetic anhydride was added, stirred, heated to 80 °C,boric acid 28. 00g, stirring evenly, slowly warming to 110 °C, stirring reaction 2 hours. Cooled to 60-70 ° C, ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate 100 was added. And the reaction was continued at 90 to 100 °C for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature. 650 mL of acetonitrile and 592 mL of triethylamine were added to the reaction solution, and the mixture was stirred for 30 minutes. To the reaction solution was added 39.39 g of (S, S) -2,8-diazabicyclo [4.3.0] nonane (1.01eq), heating reflux reaction 3 hours, TLC detection reaction is completed, down to room temperature, stirring 30 minutes, ice bath temperature 5 ~ 10 °C 90mL concentrated hydrochloric acid, adjust PH = 1. 2, continue ice bath Stirring and crystallization for 8 hours, filtration, ice-ethanol 50mLX2 washing filter cake, filter cake 50 ~ 60 ° C / _0.095MPa vacuum drying 12 hours to obtain crude moxifloxacin hydrochloride 121. 48g light yellow powder, yield: 89 78percent, HPLC: 99.7percent.

Reference： [1] Patent: CN102731496, 2016, B, . Location in patent: Paragraph 0038; 0039

4
[ 139678-43-6 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
89.1%	Stage #1: With triethylamine In acetonitrile at 15℃; Stage #2: With hydrogenchloride In water	To the other reactor was added 60 g of (S, S) -2,8-diazabicyclo [4.3.0] nonane,40 (^ acetonitrile,4 (^ triethylamine,120 g of the above-prepared moxifloxacin hydrochloride intermediate was added with stirring,The reaction temperature was 15 ° C,The tracking reaction was monitored by TLC,To (S, S) -2,8-diazabicyclo [4.3.0] nonane;After the reaction is complete,The filtrate was added with 50 g of purified water, Keeping the temperature of the reaction solution at about 20 ° C,Concentrated hydrochloric acid,To a pH of 0.5, Stirring crystallization centrifugal filtration, And the resulting solid was dried at 70 ° C for about 7 hours,Moxifloxacin hydrochloride was crude 114g,The crude yield of moxifloxacin hydrochloride was 91.8percent and the purity of HPCL was 99.45percent.

Reference： [1] Patent: CN104031043, 2016, B, . Location in patent: Paragraph 0028; 0029

5
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
76.3%	Stage #1: With triethylamine In acetonitrile at 80 - 90℃; for 5 h; Large scale Stage #2: With hydrogenchloride In methanol at 0 - 20℃; for 3 h; Large scale	(1) The 100L reactor was sequentially charged with 24.49 kg of Im-1 and 60 L of acetonitrile.Further, 8.77 kg of SM2 and 11.71 kg of triethylamine were added, and the mixture was heated to reflux at 80 to 90 ° C with stirring.(2) Reflow reaction for 5 h, TLC monitoring (developing solvent: ethyl acetate).(3) After the reaction is completed, the temperature is lowered to room temperature, and the reaction liquid is transferred to a 500 L reaction vessel.60 L of methanol was added with stirring.(4) Add hydrochloric acid dropwise under stirring to adjust pH ≈0.5, about 18.44L concentrated hydrochloric acid, dark green solid precipitated.(5) After the completion of the dropwise addition, stirring at room temperature for 2 h; cooling to 0 to 5 ° C, stirring for 1 h;(6) Centrifugation, the filter cake is washed with 24 L of methanol cooled to 0-5 ° C.Drying at 50-55 ° C for 20 to 24 hours, to obtain crude product Im-2 19.35kg,Yellow powder solid, yield 76.3percent.

Reference： [1] Patent: CN108276402, 2018, A, . Location in patent: Paragraph 0075; 0083; 0084; 0085; 0086; 0087; 0088; 0089

6
[ 139693-52-0 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
45 g	Stage #1: With triethylamine In ethanol at 70℃; for 4 h; Stage #2: With hydrogenchloride In water at 30℃; for 1 h; Heating	The main ring chelate compound 50g, anhydrous ethanol 200g, (3,3)-2,8-diazabicyclo[4,3,0]nonane 15.7g and triethylamine 12.0g were added to the reaction flask. Temperature 70 °C reaction 4. Oh; the end of the reaction, temperature control 30 ° C to the solution was added dropwise 12mol / L of hydrochloric acid, stirring while stirring, adjust the pH to 1, stirring for 1h, temperature control to 10 °C, Crystal growth 2h; After crystal growth, filtration, washing with 95 percent ethanol twice, each time 50g; Wet powder 60 °C vacuum drying to 2.8percent moisture, to obtain moxifloxacin hydrochloride dry powder 45.0g, a single impurity 0.1percent, The total impurity is 0.2percent; after refining with ethanol and water, the content is 99percent, which meets the quality standards of the European Pharmacopoeia EP-7.0 and the total impurity is less than 0.1percent

Reference： [1] Patent: WO2010/52726, 2010, A1, . Location in patent: Page/Page column 5; 6
[2] Patent: CN103172629, 2016, B, . Location in patent: Paragraph 0037
[3] Patent: CN104230925, 2018, B, . Location in patent: Paragraph 0063; 0064; 0069; 0071; 0073; 0075; 0077; 0079

7
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
3.3 g	Stage #1: With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20 - 85℃; for 36 h; Inert atmosphere Stage #2: With hydrogenchloride In water at 15℃; for 1 h; Inert atmosphere	Under nitrogen protection, 1-cyclopropyl-6, 7-difluoro-1, 4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid 10.0 g (0·0339 mοl) and (S,S) -2,8-diazabicyclo[4,3,0] nonane 5 .13g(0.0406mol)were added to 70 mL acetonitrile, it was stirred at 20 ° C~30 ° C and 1,8-diazabicyclo[5·4·0]undec-7-ene 7.74 g (0.0508 mol) was added, it was stirred at 75 ° C~85 ° C for 36 h. Concentrated in vacuo (temperature 45 ° C ~ 65 ° C, pressure -0 · 08MPa ~ -0.1MPa) to remove most of the solvent, it was then dissolved in chloroform, the mass concentration is 2percent aqueous acetic acid solution (the mass concentration refers to the mass of acetic acid as a percentage of the total mass of the aqueous acetic acid solution), the mass concentration was 10percent saline (the mass concentration refers to the mass of sodium chloride as a percentage of the total mass of brine were sequentially added, respectively, then the mixture was stirred, allowed to stand, and the aqueous layer was separated. The organic layer was concentrated in vacuo (temperature 35 ° C ~ 55 ° C, pressure -0.08MPa ~ -0.1MPa) to remove most of the solvent, ethyl acetate was added, and the mixture was cooled to 10 ° C to 20 ° C and stirred for 2 hours to 3 hours. Centrifugation, rinsed three times with ethyl acetate, dried in vacuo (vacuum degree -0.01MPa~-0.1MPa, temperature 45~55°C) dried for 14 to 18 hours, to obtain 4.01g of moxifloxacin , yield 29.5percent.HPLC purity 93.54percent. Under nitrogen protection, add 4.0 g of moxifloxacin to 2.5 mL of water and 10 mL of methanol.Stir at 170 ° C for 1 hour, filter, and cool to 35 ° C.The pH was adjusted to 1.4 to 1.8 by the addition of 6N hydrochloric acid. Cool to 15 ° C and stir for 1 hour.It was filtered, washed with water, and stirred at 15 ° C for 1 hour in a solution of water 5 mL and concentrated hydrochloric acid.Filtered, washed with water, vacuum dried (vacuum degree - 0.01 MPa ~ -0.1 MPa, temperature 45 ~ 55 ° C) for 16 hours, to obtain 3.3 g of moxifloxacin hydrochloride,Yield 75.6percent (total yield 22.3percent, based on 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid ). The HPLC purity was 99.23percent, and the maximum single impurity was 0.47percent.

Reference： [1] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2014, vol. 121, p. 254 - 258
[2] Patent: CN109096276, 2018, A, . Location in patent: Paragraph 0090-0093

8
[ 496919-99-4 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	Stage #1: at 10 - 100℃; for 3 h; Stage #2: With hydrogenchloride In methanol; butan-1-ol at 25 - 30℃; for 2 h;	1 -cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid- O³,O⁴ bis(propyloxy-O)borate (100.Og) was suspended in n-butanol (500.0 ml) to which (S,S)-2,8-diazabicyclo (4,3,0) nonane (29.0 g) diluted with 100.0 ml n-butanol was added slowly at 10-15°C. The contents were heated to 100°C and maintained for 3 hours. After the completion of reaction it was cooled to 25-3O⁰C. 200.0 ml methanol was added and pH was adjusted 1.0-2.0 using methanolic hydrochloric acid. The contents were stirred at 25-3O⁰C for 2 hours. After completion of reaction the reaction mass was distilled to residue. Purified water 500 ml was added and pH was adjusted to 7.5-9.0 using liquor ammonia. The reaction mass was then extracted with dichloromethane. The organic layer was dried using sodium <n="15"/>sulphate and concentrated to residue. The residue was stripped with 100 ml methanol. 300 ml methanol was charged and pH was adjusted to 1.0-2.0 using methanolic hydrochloric acid, the contents were further cooled to 0-5⁰C and maintained for 1 hour. The solid was filtered and washed with chilled methanol (50.0 ml) and dried under vacuum at 85-9O⁰C to yield 75.0 g (75percent) of moxifloxacin hydrochloride.

Reference： [1] Patent: WO2008/59223, 2008, A2, . Location in patent: Page/Page column 13-14

9
[ 151213-40-0 ]
[ 186826-86-8 ]

Reference： [1] Patent: WO2006/134491, 2006, A2, . Location in patent: Page/Page column 16-17

10
[ 151213-40-0 ]
[ 186826-86-8 ]

Reference： [1] Patent: EP2551268, 2013, A1,
[2] Patent: US2013/59880, 2013, A1,
[3] Patent: CN105566322, 2016, A,

11
[ 1558014-39-3 ]
[ 151213-42-2 ]
[ 151213-40-0 ]

Reference： [1] Asian Journal of Chemistry, 2013, vol. 25, # 15, p. 8701 - 8707

12
[ 1257241-37-4 ]
[ 151213-42-2 ]
[ 151213-40-0 ]

Reference： [1] Asian Journal of Chemistry, 2013, vol. 25, # 15, p. 8701 - 8707

[ 151213-40-0 ] Synthesis Path-Downstream 1~88

Yield	Reaction Conditions	Operation in experiment
	With 1,4-diaza-bicyclo[2.2.2]octane; In DMF (N,N-dimethyl-formamide); acetonitrile; at 20℃; for 16h;	A mixture of 3.07 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1.39 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong>, 2.24 g of 1,4-diazabicyclo[2.2.2]octane (DABCO), 29.5 ml dimethylformamide and 29.5 ml of acetonitrile is stirred at room temperature for 16 hours. The reaction mixture is concentrated at a bath temperature of 60 C. using a rotary evaporator, and the residue is taken up in 10 ml of water. The resulting solution Is adjusted to pH 7 using dilute hydrochloric acid, and the solid is filtered off. The filtrate is extracted three times using 20 ml of dichloromethane each time. The organic phase is dried over sodium sulphate and filtered and the filtrate is concentrated at a bath temperature of 60 C. using a rotary evaporator. This gives 2.4 g of a light-brown solid which has the X-ray powder diffractogram shown in FIG. 4 and is therefore predominantly amorphous. [00039] At a relative atmospheric humidity of 95% (established using a saturated solution of Na2HPO4×12 H2O with sediment in water), the solid obtained according to this procedure absorbs approximately 17% by weight of water within one day.

2
[ 117528-65-1 ]
[ 151213-40-0 ]
[ 195532-12-8 ]

Yield	Reaction Conditions	Operation in experiment
95%	In dichloromethane; at 20℃; for 70h;	At ambient temperature in 100 mL dichloromethane,10.0 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid (compound of formula 3) and6.3 g of <strong>[151213-40-0](4aS,7aS)-octahydro-1H-pyrrolo[3,4-b]pyridine</strong> (compound of formula 2) andTriethylamine was stirred together for 70 hours.All volatile components were removed in vacuo and recrystallized from ethanol.Pressurization with suction, washing with ethanol, vacuum drying at 60 C. to give product 12.5 g, yield 95%, HPLC purity 99.84%, as shown in FIG. 2Show.
90%	With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; ethanol; at 70℃;	EXAMPLE;100 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are reacted with 48 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> at elevated temperature (>70 C.) in a mixture of ethanol and N-methylpyrrolidone (80/20 w/w) with addition of an excess of diisopropylethylamine. After cooling, a yield of 90% of theory is obtained.
		[00040] 1012 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are initially charged in a mixture of 3300 ml of ethanol, 1980 ml of N-methyl-pyrrolidone and 534 g of diisopropylethylamine (Huenig base). The mixture is heated to reflux, and 459 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> are then added dropwise. After the dropwise addition has ended, the mixture is stirred under reflux for another 3 hours and then allowed to cool to room temperature, and the solid is filtered off with suction and washed with a total of 1800 ml of ethanol. [00041] The resulting solid is suspended in a mixture of 4650 ml of ethanol and 41 g of Huenig base, and the reaction mixture is heated under reflux for 3 hours. The reaction mixture is allowed to cool again to room temperature, and the solid is filtered off with suction, washed with a total of 1000 ml of EtOH and dried at from 60 to 70 C. in a vacuum drying cabinet until the weight remains constant. This gives 1130 g of a beige solid which has the X-ray powder diffractogram shown in FIG. 1, the differential thermodiagram shown in FIG. 2 and the IR spectrum shown in FIG. 3. [00042] At a relative atmospheric humidity of 95% (established using a saturated solution of Na2HPO4×12 H2O with sediment in water), the solid obtained according to this procedure absorbs approximately 1% by weight of water within one day.

	With 1-Methylpyrrolidine; 1-ethyl-piperidine; In ethanol; for 3h;Heating / reflux;	[00044] A mixture of 4.6 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of ethanol, 9 ml of N-methyl-pyrrolidine and 2.12 g of N-ethyl-piperidine is heated to reflux. 2.08 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> are added dropwise, and the mixture is then stirred under reflux for 3 hours. At room temperature, the solid is filtered off with suction, washed with a total of 10 ml of ethanol and dried until the weight remains constant. This gives 5.1 g of a beige solid whose differential thermodiagram corresponds to that of the modification B.
	With 1-Methylpyrrolidine; triethylamine; In ethanol; for 3h;Heating / reflux;	[00043] A mixture of 4.6 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 15 ml of ethanol, 9 ml of N-methyl-pyrrolidine and 1.9 g of triethylamine is heated to reflux. 2.08 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> are added dropwise, and the mixture is then stirred under reflux for 3 hours. At room temperature, the solid is filtered off with suction, washed with a total of 10 ml of ethanol and dried until the weight remains constant. This gives 5.23 g of a beige solid whose differential thermodiagram corresponds to that of the modification B.
	With N-ethyl-N,N-diisopropylamine; In sulfolane; ethanol; for 3h;	[00046] A mixture of 9.2 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 30 ml of ethanol, 18 ml of sulpholane and 4.85 g of Huenig base is heated to reflux. 4.17 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> are added dropwise, and the mixture is then stirred under reflux for 3 hours. At room temperature, the solid is filtered off with suction, washed with a total of 20 ml of ethanol and dried until the weight remains constant. This gives 10.8 g of a beige solid whose differential thermodiagram corresponds to that of the modification B.
	With N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); ethanol; for 3h;Heating / reflux;	[00045] A mixture of 9.2 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 30 ml of ethanol, 18 ml of dimethylformamide and 4.85 g of Huenig base is heated to reflux. 4.17 g of (1S,6S)-2,8-diazabicyclo-[4.3.0]nonane are added dropwise, and the mixture is then stirred under reflux for 3 hours. At room temperature, the solid is filtered off with suction, washed with a total of 20 ml of ethanol and dried until the weight remains constant. This gives 11 g of a beige solid whose differential thermodiagram corresponds to that of the modification B.
	With 1,4-diaza-bicyclo[2.2.2]octane; In DMF (N,N-dimethyl-formamide); acetonitrile; at 20℃; for 16h;	A mixture of 3.07 g of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, 1.39 g of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong>, 2.24 g of 1,4-diazabicyclo[2.2.2]octane (DABCO), 29.5 ml dimethylformamide and 29.5 ml of acetonitrile is stirred at room temperature for 16 hours. The reaction mixture is concentrated at a bath temperature of 60 C. using a rotary evaporator, and the residue is taken up in 10 ml of water. The resulting solution is adjusted to pH 7 using dilute hydrochloric acid, and the solid is filtered off. The filtrate is extracted three times using 20 ml of dichloromethane each time. The organic phase is dried over sodium sulphate and filtered and the filtrate is concentrated at a bath temperature of 60 C. using a rotary evaporator. This gives 2.4 g of a light-brown solid which has the X-ray powder diffractogram shown in FIG. 4 and is therefore predominantly amorphous.

Reference： [1]Patent: CN107987074,2018,A .Location in patent: Paragraph 0055; 0056; 0059-0064
[2]Patent: US2009/318700,2009,A1 .Location in patent: Page/Page column 2
[3]Patent: US6664268,2003,B1 .Location in patent: Page column 4
[4]Patent: US6664268,2003,B1 .Location in patent: Page column 5
[5]Patent: US6664268,2003,B1 .Location in patent: Page column 5
[6]Patent: US6664268,2003,B1 .Location in patent: Page column 5
[7]Patent: US6664268,2003,B1 .Location in patent: Page column 5
[8]Patent: US6649762,2003,B1 .Location in patent: Page/Page column 3

3
[ 151213-39-7 ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
91%	With hydrogen;5%-palladium/activated carbon; In methanol; at 90℃; under 67506.8 Torr; for 5h;	28.4 g (0.131 mol) [S, S] -8-Benzyl-2, 8-diazabicyclo [4.3. 0] nonan werden in 190 ml Methanol ueber 5.8 g Palladium auf Aktivkohle (5%) bei [90C] und 90 bar innerhalb von 5 Stunden hydriert. Dann wird der Katalysator abgesaugt, mit Methanol ge- waschen und das Filtrat im Vakuum eingeengt. Der Rueckstand wird ohne zu fraktionieren destilliert. Es werden 15 g (91 % d. Th. ) Produkt erhalten. Siedepunkt : [44-59C/0.] 18 mbar [[] [D24=-2. 29] (unverduennt) ee > 99% (gaschromatographisch nach Derivatisierung mit [MOSHEFS] Reagenz bestimmt)
90.5%	With 5%-palladium/activated carbon; ammonium formate; In methanol; at 70℃; for 4h;Inert atmosphere;	Compound 6b (2.0 g, 9.3 mmol), 5% Pd/C (0.2 g), ammonium formate (2.9 g, 46.3 mmol), methanol (40 mL) were added sequentially to three-necked flask. The mixture was heated to 70 C for 4h in the N2 atmosphere and Pd/C was removed by filtrating. After removing the solvent of the filtrate under vacuum, the residue was dissolved in the water, and extracted with cyclohexane (3×20 mL). The combined cyclohexane phase was washed by water (3×20 mL) and the combined aqueous phase was extracted by chloroform (3×20 mL). Removal of chloroform under vacuum afforded the yellow oil (1.1 g, 90.5% yield, 99.6% purity).
84%	With palladium 10% on activated carbon; hydrogen; In methanol; under 7500.75 Torr; for 24h;Autoclave; Green chemistry;	The above product (Compound 1-1, 10.8 g, 50 mmol) was dissolved in methanol (250 mL).0.5 g of 10% palladium carbon was placed in an autoclave, and hydrogenated at room temperature under a pressure of 1.0 MPa for 24 hours.After the reaction was completed, the palladium carbon was removed by filtration, and the filtrate was adjusted to pH = 10.0 with sodium methoxide/methanol solution, and filtered.The filtrate was concentrated to dryness and then distilled under reduced pressure to give the product (S,S)-2,8-diazabicyclo[4,3,0]decane 5.3 g,The yield was about 84% and the ee value was 98.1%.

	5%-palladium/activated carbon; In methanol; at 55℃; for 4h;Inert atmosphere;	S,S)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane (17.78g, 0.0823 mole) was taken in methanol (53.34ml) and reduced in presence of 5% Pd/C (3.9g) under nitrogen atmosphere. The reaction mass was heated to 55C for 4 hrs , cooled to 250C, filtered and washed with methanol (9.0 ml) . The solvent was distilled off. Methanol is again added and codistilled the solvent under reduced pressure at 50- 550C to get the desired product. Constant weight : 10.3 gm. [alpha]o22: -2, ee>99.5% by gas chromatography; moisture content: 0.3%
	With hydrogen;palladium 10% on activated carbon; In methanol; at 60℃; under 22502.3 Torr; for 9h;	In a 500 mL steel autoclave, 11.2 g raw intermediate (IVc), 90 mL methanol, and 1.2 g of dry 10% Pd/C are loaded. The reaction is heated to 60 0C by hydrogenation at 30 bar for about 9 hours. Once the reaction is complete (followed by GC) , the catalyst is filtered off and concentrated to residue, thus obtaining 8 g oil. The latter is purified by distillation at 9 mbar and 115 0C, thus obtaining the compound (I) .The reaction of the examples 2-7 can be repeated starting from the intermediate (X) , thus obtaining, if desired, the other enantiomer of the compound (I) .
7 g	With palladium 10% on activated carbon; hydrogen; In methanol; at 87 - 93℃; under 3750.38 - 67506.8 Torr; for 2h;Inert atmosphere; Autoclave;	To the above-mentioned (s, s) - 6-benzyl-hexahydro-pyrrolo [3,4. b] pyridine -5,7-dione 13.5g adding methanol 100 ml mixing dissolution, is provided in the high-pressure autoclave, adding 10% Pd/C2 . 5 kg, nitrogen gas pressurized to 5 kg/cm2, to maintain 30 minutes, detection autoclave does not leak, the nitrogen 3 times, hydrogen replacement 3 times, to 200rpm actuated stirring, the hydrogen is pressurized to 20 kg/cm2, off hydrogen gas, the temperature is increased to 90 C, temperature stable replacement hydrogen to 90 kg/cm2, stirring hydrogenation, hydrogen-absorbing so far to makes up the hydrogen, to continue in 87-93 C stirring 2 hours, the hydrogenation finishes, cooling to 20-25C, filtering, 5g a methanol rinse Pd/C, Pd/C recycled, the filtrate water bath heating, evaporating under reduced pressure, the residue is dissolved in water 50 ml, with cyclonexane 50mLx3 extraction, water combined cyclohexane layer 60mLx3 anti-stripping, merged layer, adding NaOH4.5g, chloroform for 60mLx3 extraction, merger chloroform level drying with anhydrous sodium sulfate, after filtration the filtrate to dryness under reduced pressure, to obtain light yellow mucus (s, s) - 6-benzyl-octahydro-pyrrolo [3,4-b] pyridine 7 g.

Reference： [1]Patent: WO2003/106450,2003,A1 .Location in patent: Page column 56,57
[2]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707
[3]Synthetic Communications,2017,vol. 47,p. 238 - 244
[4]Patent: CN104262225,2017,B .Location in patent: Paragraph 0058-0060
[5]Patent: WO2009/125425,2009,A2 .Location in patent: Page/Page column 6; 11
[6]Patent: WO2010/100215,2010,A1 .Location in patent: Page/Page column 36-37
[7]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258
[8]Patent: CN105777750,2016,A .Location in patent: Paragraph 0037; 0038; 0039; 0040

Yield	Reaction Conditions	Operation in experiment
		The aqueous phase is extracted again with 150 ml of tert.-butylmethylether. The combined organic phases are dried over sodium sulfate and concentrated. Distillation proceeds in a vacuum. Yield: 18.5 g of [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane Boiling point: 107-109 C./0.1 mbar. [alpha]D24 =17.3 C. (undiluted).

Yield	Reaction Conditions	Operation in experiment
		Example 5 STR110 Analogously to Example 1, the reaction is carried out with cis-2,8-diazabicyclo[4.3.0]nonane to give 1-cyclopropyl-7-(cis-2,8-diazabicyclo[4.3.0]non-8-yl)-8-ethinyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid of melting point 225-227 C. (with decomposition). 1 H NMR (d6 -DMF): delta4.9 s (--C C--H).

6
[ 280-57-9 ]
[ 119915-47-8 ]
[ 151213-40-0 ]
1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide;	EXAMPLE Z22 STR110 0.56 g (2 mmol) of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid is heated at 120 C. for 2 hours with 0.38 g (3 mmol) of [S,S]-2,8-diazabicyclo[4.3.0]nonane and 0.45 g (4 mmol) of 1,4-diazabicyclo[2.2.2]octane in 3.5 ml of dimethyl sulphoxide. After cooling, the solvent is removed under high vacuum. The residue is taken up with acetonitrile. The solid is separated off, washed with acetonitrile and dried at 60 to 80 C. Yield: 0.5 g (65% of theory) of 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-5-methyl-4-oxo-3-quinolinecarboxylic acid, Melting point: 217-219 C. (with decomposition), [alpha]D: -119 (c=0.5, DMF).

Reference： [1]Patent: US5480879,1996,A

7
[ 280-57-9 ]
[ 82419-35-0 ]
[ 151213-40-0 ]
10-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid [ No CAS ]
UIKRM-1-033 [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; acetonitrile;	EXAMPLE Z18 STR106 1.4 g (5 mmol) of <strong>[82419-35-0]9,10-difluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]-benzoxazine-6-carboxylic acid</strong> are reacted in 15 ml of acetonitrile/7.5 ml of dimethylformamide with 0.85 g (7.7 mmol) of 1,4-diazabicyclo[2.2.2]octane and 0.7 g (5.6 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane in an analogous manner to EXAMPLE Z1A. Yield: 1.24 g (64% of theory) of 10-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid, Melting point: 265-268 C. (with decomposition), [alpha]D: -232.2 (c=0.58, CHCl3). 3S-10-([S,S]-2,8-Diazabicyclo[4.3.0]non-8-yl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid is also obtained in an analogous manner.

Reference： [1]Patent: US5480879,1996,A

8
[ 280-57-9 ]
[ 94242-51-0 ]
[ 151213-40-0 ]
ethyl 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile;	EXAMPLE Z17 STR105 1.52 g (5 mmol) of ethyl 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate are reacted in 30 ml of acetonitrile with 550 mg (5 mmol) of 1,4-diazabicyclo[2.2.2]octane and 760 mg (6 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane at 50 C. for 2 hours and at 60 C. for 2 hours. After cooling, the suspension which is obtained is filtered with suction, and the precipitate is washed with water and dried at 90 C. in vacuo. Yield: 0.99 g (47.5% of theory) of ethyl 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, Melting point: 194-195 C. (from acetonitrile), [alpha]D23: -188.9 (c=0.51, CHCl3).

Reference： [1]Patent: US5480879,1996,A

9
[ 171059-42-0 ]
[ 151213-40-0 ]
1-cyclopropyl-7-(cis-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-5-vinyl-3-quinolinecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1,4-diaza-bicyclo[2.2.2]octane; In N-methyl-acetamide; water; acetonitrile;	STR91 0.93 g of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-5-vinyl-3-quinolinecarboxylic acid, 0.57 g of S,S-2,8-diazabicyclo[4.3.0]nonane and 0.34 g of DABCO are refluxed for 2 hours in a mixture of 6 ml of acetonitrile and 3 ml of dimethylformamide. The reaction mixture is concentrated in vacuo, and the residue is boiled up in 10 ml of water. The product is filtered off with suction while hot, washed with water and dried. 0.76 g of 1-cyclopropyl-7-(S,S-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-5-vinyl-3-quinolinecarboxylic acid is obtained. Melting point: 195-197 C (with decomposition).

Reference： [1]Patent: US5578604,1996,A

10
[ 100491-29-0 ]
[ 151213-40-0 ]
ethyl 7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-diaza-bicyclo[2.2.2]octane; acetonitrile;	A. Ethyl 7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate 1.9 g (5 mmol) of ethyl 7-chloro-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate are stirred with 680 mg (5.4 mmol) of [S,S]-2,8-diazabicyclo[4.3.0]nonane at 10 C. for 3 hours in 20 ml of acetonitrile and in the presence of 560 mg (5 mmol) of 1,4-diazabicyclo[2.2.2]octane. The suspension is filtered with suction, washed with water and dried. 0.35 g of product is obtained. By concentrating the mother liquors, stirring the residue with water, isolating the undissolved product and purifying by chromatography (silica gel, eluent: dichloromethane/methanol/17% strength aqueous ammonia), a further 0.7 g of product is isolated. Total yield: 1.05 g (44% of theory), Melting point: 184-185 C. (with decomposition), [alpha]D23: +6.8 (c=0.46, CHCl3)

Reference： [1]Patent: US5480879,1996,A

11
[ 101987-89-7 ]
[ 151213-40-0 ]
8-chloro-1-cyclopropyl-6-fluoro-7-(octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In 1,4-diaza-bicyclo[2.2.2]octane; N-methyl-acetamide; acetonitrile;	EXAMPLE Z2 STR90 A. 8-Chloro-1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 15 g (50 mmol) of 8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour in a mixture consisting of 150 ml of acetonitrile/75 ml of dimethylformamide in the presence of 8.25 g (75 mmol) of 1,4-diazabicyclo[2.2.2]octane (DABCO) together with 7.0 g (55 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane. The solution is cooled and scratched to induce crystallisation, and the precipitate which has separated out is, after standing overnight, filtered off with suction, washed with acetonitrile and dried at 100 C. in an air-circulation drying oven. Yield: 13.5 g (66.6% of theory), Melting point: 193-196 C. (with decomposition), Rf value (silica gel; methylene chloride/methanol/17% strength aqueous NH3 =30:8:1): 0.4.

Reference： [1]Patent: US5480879,1996,A

12
[ 106890-70-4 ]
[ 151213-40-0 ]
1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With 1-methyl-pyrrolidin-2-one; In 1,4-diaza-bicyclo[2.2.2]octane; acetonitrile;	A. 6 g (20 mmol) of 1-cyclopropyl-5,6,7,8-tetrafluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour in 40 ml of acetonitrile/20 ml of N-methylpyrrolidone in the presence of 2.2 g (20 mmol) of 1,4-diazabicyclo[2.2.2]octane together with 2.7 g (21.4 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane. The resulting suspension is cooled, and the precipitate is filtered off with suction, washed with acetonitrile and dried at 100 C./12 mbar. Yield: 6.7 g (82.3% of theory) of 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-5,6,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid, Melting point: 257-259 C. (with decomposition); after recrystallisation from glycol monomethyl ether: melting point: 260-265 C. (with decomposition).

Reference： [1]Patent: US5480879,1996,A

13
[ 94695-52-0 ]
[ 151213-40-0 ]
1-cyclopropyl-6,8-difluoro-7-((4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.1%		The specific process is: adding 10 mL of methanol to a 25 mL reaction flask.Additional compound 2-1 (0.91 g, 3.2 mmol) was added.Isobutylamine (0.42g),Copper dichloride(0.2g),Ethylene glycol (0.22g),Nitrogen protection, stirring at 50 C for 4 hoursAfter that, 0.4 g of compound 1 ((S,S)-2,8-diazo-bicyclo[4.3.0]nonane) was added, and the mixture was heated under reflux for 5 hours.Filtration, adding 4 mL of aqueous sodium hydroxide solution (2M) to the filtrate, and heating and refluxing for 1 hour.The temperature was lowered to room temperature, and the pH of the reaction mixture was adjusted to 7-8 with 4M hydrochloric acid.The aqueous layer was extracted three times with 100 mL of ethyl acetate.Combine the organic layers, dry,Moxifloxacin impurity A (1.08g) was separated by concentrated silica gel column chromatography.The yield was 87.1%.
	In 1,4-diaza-bicyclo[2.2.2]octane; N-methyl-acetamide; water; acetonitrile;	EXAMPLE Z1 STR89 A. 1-Cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 141.5 g (0.5 mol) of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are heated under reflux for 1 hour in a mixture consisting of 1500 ml of acetonitrile and 750 ml of dimethylformamide in the presence of 55 g (0.5 mol) of 1,4-diazabicyclo[2.2.2]-octane together with 69.25 g (0.55 mol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane (ee 99.5%, GC 99.8% pure). The suspension is cooled and the precipitate is filtered off with suction, washed with water and subsequently stirred with 1 l of water (pH 7). The sediment is filtered off with suction and dried at 60 C. in an air-circulation oven. Yield: 163.4 g (84% of theory), Melting point: 249-251 C. (with decomposition).

Reference： [1]Patent: CN110183445,2019,A .Location in patent: Paragraph 0046-0050
[2]Patent: US5480879,1996,A

14
[ 100361-18-0 ]
[ 151213-40-0 ]
1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride [ No CAS ]
1-cyclopropyl-7-([S,S]-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile;	EXAMPLE Z6 STR94 1.4 g (5 mmol) of <strong>[100361-18-0]7-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid</strong> are stirred in 15 ml of acetonitrile together with 1.3 g (10.3 mmol) of (+)-[S,S]-2,8-diazabicyclo[4.3.0]nonane at room temperature for 1 hour with the exclusion of water. After standing overnight, the mixture is filtered with suction, and the sediment is washed with acetonitrile and, for purification, subjected to chromatography on silica gel (eluent: methylene chloride/methanol/17% strength aqueous ammonia 30:8:1; Rf value: 0.4). The resulting 1-cyclopropyl-7-([S,S]-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid is dissolved in 15 ml of half-concentrated hydrochloric acid and the solution is then evaporated and the residue stirred with ethanol. The precipitate is filtered off with suction, washed with ethanol and dried at 120 C./12 mbar. Yield: 960 mg (47% of theory) of 1-cyclopropyl-7-([S,S]-2,8-diazabicyclo[4.3.0]non-8-yl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid hydrochloride, Melting point: 345-346 C. (with decomposition), [alpha]D30: +5.4 (c=0.5, H2 O).

Reference： [1]Patent: US5480879,1996,A

15
[ 151213-39-7 ]
palladium on active charcoal [ No CAS ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;	2 [S,S]-2,8-Diazabicyclo[4.3.0]nonane 28.4 g (0.131 mol) of [S,S]-8-benzyl-2,8-diazabicyclo[4.3.0]nonane are hydrogenated in 190 ml of methanol over 5.8 g of palladium on active charcoal (5%) at 90 C. and 90 bar within the space of 5 hours. The catalyst is then filtered off with suction and washed with methanol, and the filtrate is concentrated in a rotary evaporator. The residue is distilled without fractionating. Yield: 15.0 g (90.5% of theory) of [S,S]-2,8-diazabicyclo[4.3.0]nonane, boiling point: 44-59 C. 0.18 mbar, [alpha]D22 =-2.29 (undiluted), ee>99% (determined by gas chromatography after derivatisation with Mosher's reagent).

Reference： [1]Patent: US5480879,1996,A

16
[ 159991-20-5 ]
[ 151213-40-0 ]
[ 159877-30-2 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; triethylamine; In water; acetonitrile; trifluoroacetic acid;	EXAMPLE 5 7-[(S,S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6,8-difluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid STR18 A solution of 301 mg of 6,7,8-trifluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (JP-A-5-163244), 463 mg of (S,S)-2,8-diazabicyclo[4.3.0]nonane, 1 ml of triethylamine in 10 ml of acetonitrile was heated under reflux for 15 hours. To the mixture was added 50 ml of water, and the solvent was removed under reduced pressure. The mixture was extracted from three 50 ml portions of chloroform, and the extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure. A residue was dissolved in 10 ml of trifluoroacetic acid, and the solution was stirred at room temperature for 2 hours. Trifluoracetic acid was removed under reduced pressure and to a residue was added 1N sodium hydroxide aqueous solution till a pH became 12. To the solution was added hydrochloric acid till the pH became 7.4. The solution was extracted with six 50 ml portions of chloroform. The extract was dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure and a residue was recrystallized from ethanol to yield 320 mg of the titled compound. Melting point: 271-273 C. [alpha]D25: -130.90 (c=0.99, 1N NaOH) 1 H-NMR (400 MHz, 0.1N NaOD) delta ppm: 1.45-1.80 (6H, m), 2.29-2.39 (1H, m), 2.55-2.65 (1H, m), 2.88-2.95 (1H, m), 3.31-3.38 (1H, m), 3.43-3.60 (2H, m), 3.90-4.04 (3H, m), 4.92-5.14 (1H, m), 7.64 (1H, d, J=14.7Hz), 8.39 (1H, s). Elementary analysis, for C20 H20 F3 N3 O3; Calcd. (%): C 58.97; H 4.95; N 10.31 Found (%): C 58.72; H 4.91; N 10.22

Reference： [1]Patent: US5654318,1997,A

17
[ 181261-66-5 ]
[ 151213-40-0 ]
8Chloro-1-cyclopropyl-1,4-dihydro-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-4-oxo-1,6-naphthyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; acetonitrile;	EXAMPLE 7 STR32 8Chloro-1-cyclopropyl-1,4-dihydro-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-4-oxo-1,6-naphthyridine-3-carboxylic acid 200 mg (0.67 mmol) of 7,8-dichloro-1-cyclopropyl-1,4-dihydro-4-oxo-1,6-naphthyridine-3-carboxylic acid are stirred with 190 mg (1.5 mmol) of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> in a mixture of 1.7 ml of dimethylformamide and 1.7 ml of acetonitrile under argon overnight. The precipitate is isolated and washed with acetonitrile. The crude product is purified on silica gel (eluent: dichloromethane/methanol/aqueous ammonia solution 75:20:25). Yield: 56 mg (21% of theory)

Reference： [1]Patent: US5811433,1998,A

18
7,8-dichloro-1-›(1R,2S)-2-fluorocyclopropyl-1,4-dihydro-5-methyl-4-oxo-1,6-naphthyridine-3-carboxylic acid [ No CAS ]
[ 151213-40-0 ]
8-Chloro-1-›(1R,2S)-2-fluorocyclopropyl-1,4-dihydro-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-5-methyl-4-oxo-1,6-naphthyridine-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; water; acetonitrile;	EXAMPLE 49 STR74 8-Chloro-1-?(1R,2S)-2-fluorocyclopropyl-1,4-dihydro-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-5-methyl-4-oxo-1,6-naphthyridine-3-carboxylic acid 496 mg (1.5 mmol) of 7,8-dichloro-1-?(1R,2S)-2-fluorocyclopropyl-1,4-dihydro-5-methyl-4-oxo-1,6-naphthyridine-3-carboxylic acid are stirred with 420 mg (1.5 mmol) of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> in a mixture of 4.4 ml of dimethylformamide and 4.4 ml of acetonitrile under argon at room temperature for two days. The solvents are removed in vacuo, water is added to the residue, the pH is adjusted to 7 with dilute hydrochloric acid, the precipitate is extracted with dichloromethane, and the extract is dried over sodium sulphate and concentrated on a rotary evaporator. Yield: 550 mg (87% of theory) Melting point: 147-149 C. (with decomposition)

Reference： [1]Patent: US5811433,1998,A

19
[ 280-57-9 ]
[ 117528-65-1 ]
[ 151213-40-0 ]
[ 195532-12-8 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; water; acetonitrile;	EXAMPLE 1 8-Cyano-1-cyclopropyl-7-((1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid 690 mg (2.25 mmol) of 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid are stirred with 312 mg (2.47 mmol) of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> and 504 mg (4.50 mmol) of 1,4-diazabicyclo[2.2.2]-octane (DABCO) in a mixture of 6.6 ml of dimethylformamide and 6.6 ml of acetonitrile at room temperature overnight. All the volatile components are removed in vacuo, the residue is taken up in water and the resulting solution is brought to pH 7 with dilute hydrochloric acid. The precipitate formed is filtered off with suction, the filtrate is extracted with methylene chloride and the combined organic phases are dried with sodium sulfate and concentrated in vacuo. Yield: 650 mg (73%) Melting point: 246-248 C. (decomposition)

Reference： [1]Patent: US6278013,2001,B1

20
[ 280-57-9 ]
methyl 7-chloro-8-cyano-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate [ No CAS ]
[ 151213-40-0 ]
methyl 8-cyano-1-cyclopropyl-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In chloroform; acetonitrile;	EXAMPLE 17 Methyl 8-cyano-1-cyclopropyl-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate 200 mg (0.625 mmol) of methyl 8-cyano-1-cyclopropyl-7-chloro-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 86 mg (0.683 mmol) of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> and 150 mg (1.34 mmol) of 1,4-diazabicyclo[2.2.2]-octane are stirred in 6 ml of acetonitrile at room temperature for 48 hours. Thereafter, the mixture is evaporated and the residue is partitioned between 15 ml of chloroform and 20 ml of saturated sodium carbonate solution. The organic phase is separated off, the aqueous phase is extracted again with chloroform and, after drying with sodium sulfate, the combined extracts are evaporated. For purification, the residue is chromatographed over silica gel with ethyl acetate/ethanol/25% strength aqueous ammonia solution. Yield: 140 mg Melting point: 231C. (with decomposition)

Reference： [1]Patent: US6278013,2001,B1

21
[ 195532-54-8 ]
[ 151213-40-0 ]
ethyl 8-cyano-1-cyclopropyl-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile;	EXAMPLE 18 Ethyl 8-cyano-1-cyclopropyl-7-[(1S,6S)-2,8-diazabicyclo[4.3.0]nonan-8-yl]-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate 14.32 g (45 mmol) of ethyl 8-cyano-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylate, 6.31 g (50 mmol) of <strong>[151213-40-0](1S,6S)-2,8-diazabicyclo[4.3.0]nonane</strong> and 10.22 g (101 mmol) of triethylamine are boiled under reflux in 270 ml of acetonitrile for 4 hours. The reaction mixture is left to stand at room temperature for some hours and the solid which has crystallized out is filtered off with suction, rinsed with acetonitrile and dried. 15.6 g of a beige solid are obtained (82% of theory). Melting point: 209 to 210 C.

Reference： [1]Patent: US6278013,2001,B1

22
(1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-(oxo-κO)-3-quinoline-carboxylato-κO3)difluoro-Boron [ No CAS ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
		Example 4 5Preparation of l-cycIopropyl-6-fluoro-l,4-dihydro-8-methoxy-7-[(4a5>,7a5')- octahydro-6H-pyrroIo[3,4-£]pyridin-6-yl]-4-oxo-3-quinolinecarboxylic acid hydrochloride (Moxifloxacin hydrochloride (Form A))0 l-CyclopiOpyl-6,7-difluoiO-8-methoxy-4-oxo-l,4-dihydroquinoline-3-carboxylic acid boron difluoride chelate (III) (150g, 0.44 moles) was suspended in methanol EPO <DP n="18"/>(750 ml) and (4£uS',7ai9)octahydiO-l//-pynOlo[3,4-6]pyridino (66 g, 0.52 moles) followed by triethylamine (60.9g, 0.60 moles) were added. The reaction mixture was stirred at 3O0C for 10 h. Thereafter triethylamine (220.8 g, 2.19 moles) was added and the suspension was heated to reflux for 22 h. After completion of> reaction the solvent and excess triethylamine were distilled off under reduced pressure at 40-50C. The crude residue was suspended in a mixture of acetonitrile (600 ml) and methanol (600 ml) and concentrated hydrochloric acid was added till a clear solution was formed at pH ~7. Carbon (7.5 g) was added, the reaction mixture was stirred at 20-250C and filtered. The clear filtrate was slowly) acidified with the remaining amount of concentrated hydrochloric acid ( 136 g, 1.3 moles) at 2O0C and the precipitated solid was stirred at 20-250C for 2h followed by another hour at 0-50C. The product was filtered under nitrogen atmosphere, washed with a mixture of acetonitrile-methanol (1 :1, 150 ml) and dried under reduced pressure at 60-700C till moisture content was less than 2 %. The dry i weight of the product was 97 g, with chromatographic purity >99.7 %.

Reference： [1]Patent: WO2006/134491,2006,A2 .Location in patent: Page/Page column 16-17

23
(1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-(oxo-κO)-3-quinoline-carboxylato-κO3)difluoro-Boron [ No CAS ]
[ 151213-40-0 ]
(1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-(oxo-κO3)-3-quinolinecarboxylato-κO3)difluoroboron [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92%	With triethylamine; In acetonitrile; at 30 - 80℃; for 1 - 2h;Product distribution / selectivity;	EXAMPLE 1; Stage I15 Preparation of (l-cycIopropyl-6-fluoro-l,4-dihydro-8-methoxy-7-[(4aiS',7a>S')- octahydro-6H-pyrrolo[3,4-Z>]pyridin-6-yl]-4-(oxo-/r0)-3- quinolinecarboxylato- /rO3)difluoroboron (Moxifloxacin boron difluoride chelate (V)).Boron difluoride chelate derivative (III) (5 g; 0.0146 moles) was suspended in 0 acetonitrile (25 ml) and (4a57a5)octahydro-lH-pyrrolo[3,4-/>]pyridine (2.2 g, 0.0175 moles) followed by triethylamine (3.4 g, 0.0335 moles) were added. The reaction mass was heated to reflux and maintained at 70-800C for 1 h. After completion of reaction, the reaction mass was cooled to 40-450C and solvent was distilled off under reduced pressure to get residue. 5 [ A small portion of the reaction mixture was filtered, washed with acetonitrile and dried and the solid product was analysed]'Eta NMR (DMSO-dr.) delta ppm: 0 8.95 (s, 1 Eta), 7.79 (d, J=14EtaZ, IH), 4.35 (m, IH), 4.07-3.95 (m, 2H), 3.58 (s, 3H), 3.48-3.3 (m. 3H), 2.86 (m, I H), 2.50 (m, IH), 2.28 (m, IH), 1.73-1.63 (m, IH), 1.44 (m, I H), 1.30-1.25 (m, 2H), 1.06-1.01 (m, 2H). EPO <DP n="15"/>m/z 450 I M+H IIR (KBr, cm-l): 3337, 3080, 2958, 2932, 2853, 1903, 1717, 1629, 1567,1522, 1503, 1471 , 1461 , 1436, 1371 , 1336, 1306, 1296, 1284, 1253, 1220, 1 189, 1 150, 1060, 1033, 985, 974.; EXAMPLE 2Stage-IPreparation of (l-cycIopropyl-6-fluoro-l,4-dihydro-8-methoxy-7-[(4aiS',7a5)- octahydro~6H-pyrrolo[3,4-£]pyridin-6-yl]-4~(oxo-AO)-3- quinolinecarboxylato- Lambda6>3)difluoroboron (Moxifloxacin boron difluoride chelate (V))l -CyclopiOpyl-6,7-difluoiO-8-methoxy-4-oxo-l,4-diliydroquinoline-3-carboxylic acid borondifluoride chelate (III) (275 g; 0.80 moles) was suspended in acetonitrile (550 ml) and triethylamine (186.3 g, 1.84 moles) was added. EPO <DP n="16"/>(4a1S'.7a1S')octahydro-l /-/-py?Olo[3,4-/?]pyridine (121.3 g, 0.96 moles) was added dropwise and the reaction mixture was stirred for 2 hrs at 30 to 35C. After completion of reaction, the product obtained was filtered, washed with acetonitrile ( . 38 ml) and dried at 50 to 550C under reduced pressure. (Yield, 331 g (92%))

Reference： [1]Patent: WO2006/134491,2006,A2 .Location in patent: Page/Page column 13-15

24
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 151096-09-2 ]

Yield	Reaction Conditions	Operation in experiment
89.7%	In dimethyl sulfoxide; at 65 - 70℃; for 6 - 8h;	Example 1 Preparation of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid. (III) Dimethylsulfoxide (600 ml), 50 g of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (IV) and 25.70 ml of [S,S]-2,8-diazabicyclo [4.3.0] nonane (V) were stirred at 65 - 70 C for 6 - 8 hours. Completion of the reaction was monitored by HPLC. The reaction mass was cooled to 25-30 C, 100 ml of water was added and stirred for 2 hours. The solid was filtered off with suction, washed with 100 ml water and dried under vacuum at 75C, affording 61.0 g of the title compound. Yield: 89.7 % Purity: 98 % (HPLC) Chiral impurity (R,R isomer content): 3 - 5 %
66%	With triethylamine; In N,N-dimethyl-formamide; acetonitrile; at 0 - 78℃; for 11h;Reflux;	1 -cyclopropyl-^-difiuoro-delta-methoxy^-oxo- 1 ,4-dihydro-3-quinolinecarboxylic acid (100g, 0.338 mole) and triethylamine were taken in mixture of acetonitrile (300 ml) and dimethylformamide (80 ml) . To it was added (S,S)-2,8-diazabicyclo [4.3.0] nonane (47g, 0.373 mole) and refluxed at 72- 78C for 10 hours at reflux. The reaction mixture was cooled to room temperature, and further to 0-5C maintained for 1 hr, filtered and washed with acetonitrile (50 ml) to get the desired product.Dry wt: 89.7g, Yield: 66%.
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 85℃; for 12h;	A mixture of l-Cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-l,4-dihydro-3- quinoline carboxylic acid (100 grams), [S,S]-2,8-diazabicyclo [4,3,0] nonane (52 grams), l,8-Diazabicyclo(5,4,0)undec-7-ene (10 grams) and acetonitrile (300 ml) was heated to 850C. The reaction mixture was stirred for 12 hours at 85C. The solvent was distilled off completely under reduced pressure at below 7O0C. The reaction mixture cooled to 6O0C and water was added. The pH of the reaction mixture was adjusted to 5.8 with hydrochloric acid. The reaction mixture was extracted with methylene chloride. The solvent was distilled off completely under reduced pressure. Acetone (300 ml) was added to the obtained residue. The reaction mixture was stirred for 30 minutes at 25-300C. The obtained solid was filtered, washed with acetone and dried at 600C. The obtained solid was recrystallized by using acetone as a solvent. Yield: 100 grams. Water content: 2.2% Chloride content: 130 ppm.

	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 65 - 75℃;Product distribution / selectivity;	Reference Example: Preparation of Moxifloxacin; A solution of lOOg of 1-Cyclopropyl -6,7difluoro-l,4-dihydro-4-oxo-methoxyquinolone- 3-carboxilic acid), 52gr of (S,S)2,8 diazabicyclo[4,3,0]nonane, lOgr of 1,8- diazabycyclo[5,4,0]undec-7-ene and 300ml of acetonitrile is heated to 65 -70C temperature and stirred till the reaction get completed and evaporated the solvent. Added 5 %aqueous isopropylalcohol to the reaction mass and adjusted the pH to basic with caustic solution and then filtered the reaction mass. Combined the total filtrate and adjusted the pH to 5.0 to 6.0 with aqueous HCl.and isolated the separated solid at a temperature of 10-150C to afford Moxifloxacin.; Example 5: Preparation of novel crystalline form X of anhydrous Moxifloxacin hydrochloride5Og of 1-cyclopropyl -6,7-difluoro -1,4-difluoro-l, 4 - dihydro - 4 - oxo-8-methoxy quinolone-3-carboxilic acid , (S, S) diazabicyclo nonane and 5gr of 1,8-diazabicyclo [5,4,0] undec-7-ene (5g) in 300 ml acetonitrile heated to 65-75C and stirred. Evaporated the solvent completely and added 5 % aqueous isopropyl alcohol. Adjusted the pH to 8.5 with caustic solution, then the reaction mass filtered. Adjusted the pH filtrate to 5 with aqueous hydrochloric acid. Cooled the reaction mixture to 10- 150C. Isolated the separated solid to afford moxifloxacin. This wet Moxifloxacin, suspended in 400 ml Toluene and heated 110-1120C to reflux azeotropically and then reaction mass is cooled to 25-35C. Quenched the reaction mass with 200 ml of isopropyl alcohol and adjusted pH to .98 with hydrochloric acid in Isopropyl alcohol. Isolated the solid by filtration and washed the material with isopropyl alcohol. Dried at 80-90C under vacuum to afford the novel crystalline form -X of anhydrous Moxifloxacin hydrochloride. (Weight: 33.0 grams, M.C by KF method is 0.09%w/w, Purity by HPLC: 99.94%)
		50.0 g of 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinic acid of formula (V) (1.0 mol. equiv.), 15.80 g of Mg(OH)2 (1.6 mol. equiv.) and 300 mL of Acetonitrile were introduced into a 4-neck flask provided with a mechanical stirrer, thermometer, cooler and thermostat. Heating is carried out at 78C for one hour under slow stirring with the aim of forming the Moxifloxacin complex with Magnesium. A solution formed by 34.20 g of (4aS, 7aS)-Octahydro-1H-pyrrole[3,4-b]pyridine of formula (VI) and 150 mL of Acetonitrile is dosed in 1 hour. The reaction mixture is left at reflux for another 4 hours. Upon completing the reaction (conversion exceeding 90%) the mixture is cooled at 50C and the ACN is distilled under vacuum up to obtaining a soft pasty residue. Such residue is cooled at 0C and a cold solution at 0C made up of 150 mL of Acetone and 300 mL of Dichloromethane is then added slowly. Stirring is carried out for 10 minutes at room temperature then 2.5 g of dicalite and 2.5 g of acticarbone are added. Stirring is carried out for 10 minutes then filtration is carried out on a dicalite panel. The filtrate is concentrated to dryness in the rotavapor then recovered using 300 mL of dichloromethane. This organic solution is washed using a solution made up of 100 mL of a saturated NaHCO3 solution and 50 mL of purified water. The underlying organic phase containing the product is separated and the aqueous phase is re-extracted using 100 mL of dichloromethane. The organic phases are mixed again and then dried obtaining 71.0 g of Moxifloxacin base, with HPLC purity equivalent to 90.27% and with formula (VII) impurity equivalent to 1.09%.
		50.0 g of 1-Cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinic acid of formula (V) (1.0 mol. equiv.), 15.80 g of Mg(OH)2 (1.6 mol. equiv.) and 300 mL of Acetonitrile were introduced into a 4-neck flask provided with a mechanical stirrer, thermometer, cooler and thermostat. Heating was carried out at 78C for one hour under slow stirring with the aim of forming the Moxifloxacin complex with Magnesium. A solution formed by 34.20 g of (4aS,7aS)-Octahydro-1H-pyrrole[3,4-b]pyridine of formula (VI) and 150 mL of Acetonitrile was dosed in 1 hour. The reaction mixture was left at reflux for another 4 hours. Upon completing the reaction (conversion exceeding 90%) the mixture was cooled at 50C and the ACN was distilled under vacuum up to obtaining a soft pasty residue. Such residue was cooled at 0C and a cold solution at 0C made up of 150 mL of Acetone and 300 mL of Dichloromethane was then added slowly. Stirring was carried out for 10 minutes at room temperature then 2.5 g of dicalite and 2.5 g of acticarbone were added. Stirring was carried out for 10 minutes then filtration was carried out on a dicalite panel. The filtrate was concentrated to dryness in the rotavapor then recovered using 300 mL of dichloromethane. This organic solution was washed using a solution made up of 100 mL of a saturated NaHCO3 solution and 50 mL of purified water. The underlying organic phase containing the product was separated and the aqueous phase was re-extracted using 100 mL of dichloromethane. The organic phases were mixed again and then dried obtaining 71.0 g of Moxifloxacin base, with HPLC purity equivalent to 90.27% and with formula (VII) impurity equivalent to 1.09%. The solid residue was recovered using 100 mL of purified water and 800 mL of Isopropanol. Heating was carried out at reflux up to complete dissolution. A solution of 26.06 g of paratoluenesulfonic acid (1.1 mol. equiv.) in 100 mL of Isopropanol was dripped at 70C in one hour. It was slowly brought to 35C, then it was left under stirring at 35C for one night. The suspension was paper-filtered at 35C and the solid was washed using 100 mL of Isopropanol. The solid was dried in an oven at 50C for at least 8 hours. 72.5 g equivalent to a 74.6% molar yield of Moxifloxacin Tosylate were obtained as a hazelnut-coloured solid with HPLC purity equivalent to 98.46% and with a formula (VII) impurity content equivalent to 0.54%.1H-NMR (400 MHz, DMSO-d6): delta/ppm=0.84-1.24 (m, 4H), 1.70-1.85 (m, 4H), 2.30 (s, 3H), 2.65-2.2.72 (m, 1H), 2.98-3.03 (m, 1H), 3.24-3.28 (m, 1H), 3.52-3.55 (m, 1H), 3.59 (s, 3H), 3.75-3.92 (m, 3H), 4.09-4.20 (m, 2H), 7.12 (d, 1H, j=7.88 Hz), 7.49 (d, 1H, j=8.04 Hz), 7.71 (d, 1H, j=14.13 Hz), 8.69 (s, 1H). Melting point=273C (determined using DSC).

Reference： [1]Patent: EP1992626,2008,A1 .Location in patent: Page/Page column 10
[2]Patent: WO2009/125425,2009,A2 .Location in patent: Page/Page column 11
[3]Patent: WO2008/59521,2008,A2 .Location in patent: Page/Page column 27
[4]Patent: WO2007/10555,2007,A2 .Location in patent: Page/Page column 12; 14
[5]Patent: EP2551268,2013,A1 .Location in patent: Paragraph 0051,0052
[6]Patent: US2013/59880,2013,A1 .Location in patent: Paragraph 0070; 0071; 0072; 0073; 0074; 0075; 0076
[7]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

25
[ 151213-40-0 ]
(1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-(oxo-κO3)-3-quinolinecarboxylato-κO3)difluoroboron [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 1 Obtaining Moxifloxacin In a four-mouth 500 ml flask with refrigerant, thermometer, mechanical stirring and nitrogen bubbler with the outlet connected to a washing flask with a solution of H2SO4 is placed 50 g (0.1694 moles, 1 eq) of the compound II, and 150 ml of acetonitryl (3 volumes), and it is heated to T = 76-80 C (reflux). Once reflux has been reached, and maintaining T = 76-80 C, a compensated addition funnel is used to add 19.14 g (0.1186 moles, 0.7 eq) of hexamethyldisilazane. Once the addition has been completed, the reaction is maintained with stirring at T = 76-80 C for 1 hour. Once that period has elapsed the reaction mixture is cooled to T = 0-15 C and 28.85 g (0.2033 moles, 1.2 eq) of boron trifluoride etherate is added, maintaining T<15 C. Once the addition has been completed, it is maintained at T = 0-15C until the starting product has disappeared (approximately 2 hours) and it is then adjusted to pH = 8-9 with triethylamine (approximately 30 ml). To the resulting suspension is added a solution of 32.07 g (0.2541 moles, 1.5 eq) of (S,S)-2,8-diazabicyclo[4.3.0]nonane and 25.71 g of triethylamine (0.2541 moles, 1.5 eq) in 150 ml of acetonitryl, maintaining T = 15-25 C. The resulting amber solution is maintained with stirring under those conditions until the starting product has disappeared (approximately 5-6 hours). Once the reaction is completed it is distilled until a stirrable paste is obtained, 250 ml of methanol is added, the resulting solution is brought to T = 63-67 C (reflux) and is maintained under those conditions until the boron compound (VIII) has disappeared (approximately 5-6 hours). The reaction completed, the methanol is distilled at low pressure, and to the resulting concentrate is added 250 ml of water. The resulting suspension is taken to pH = 12.0 with NaOH 30% and, later to pH=8.0-8.2 with HCl 35% and is extracted with methylene chloride (3 x 125 ml). The combined organic extracts are dried over anhydrous MgSO4 and are concentrated to dryness, obtaining 60.72 g of base Moxifloxacin. Yield: 89.3%. Example 2: Obtaining Moxifloxacin In a four-mouth 500 ml flask with refrigerant, thermometer, mechanical stirring and nitrogen bubbler with the outlet connected to a washing flask with a solution of H2SO4 is placed 50 g (0.1694 moles, 1 eq) of the compound II, 150 ml of acetonitryl (3 volumes), and it is heated to T = 76-80 C (reflux). Once reflux has been reached, and maintaining T = 76-80 C, a compensated addition funnel is used to add 19.14 g (0.1186 moles, 0.7 eq) of hexamethyldisilazane. Once addition has been completed, the reaction is maintained with stirring at T = 76-80 C for 1 hour. Once that period has elapsed the reaction mixture is cooled to T = 0-15 C and 28.85 g (0.2033 moles, 1.2 eq) of boron trifluoride etherate is added, maintaining T<15 C. Once the addition has been completed, it is maintained at T = 0-15 C until the starting product has disappeared (approximately 2 hours), and it is then adjusted to pH = 8-9 with triethylamine (approximately 30 ml). To the resulting suspension is added a solution of 32.07 g (0.2541 moles, 1.5 eq) of (S,S)-2,8-diazabicyclo[4.3.0]nonane and 25.71 g of triethylamine (0.2541 moles, 1.5 eq) in 150 ml of acetonitryl and maintaining T at 15-25C. The resulting amber solution is maintained with stirring under those conditions until the starting product has disappeared (approximately 5-6 hours). Once the reaction is completed it is distilled until a stirrable paste is obtained, 250 ml of methanol is added, the resulting solution is brought to T = 63-67 C (reflux) and is maintained under those conditions until the boron complex (compound VIII) has disappeared, (approximately 5-6 hours). The reaction completed, the methanol is distilled at low pressure and to the resulting concentrate is added 340 ml of water. The resulting suspension is taken to pH = 12 with NaOH 30% and then to pH = 8.0-8.2 with HCl 35%. The dark solution obtained is heated to T = 50-60 C and is maintained under those conditions until the product has precipitated. Once the product has precipitated out, it is maintained under those conditions for 2 hours, following which it is cooled to T = 40 C and filtered. The solid obtained is washed with 10 ml of water and dried at 40C, to provide 48.52 g of base Moxifloxacin as a yellow solid. Example 3: Obtaining Moxifloxacin fluorhydrate In a four-mouth 500 ml flask with refrigerant, thermometer, mechanical stirring and nitrogen bubbler with the outlet connected to a washing flask with a solution of H2SO4 is placed 50 g (0.1694 moles, 1 eq) of the compound II, 150 ml of acetonitryl (3 volumes), and it is heated to T = 76-80 C (reflux). Once reflux has been reached, and maintaining T = 76-80 C, a compensated addition funnel is used to add 19.14 g (0.1186 moles, 0.7 eq) of hexamethyldisilazane. Once addition has been completed, the reaction is maintained with stirring at T = 76-80 C for 1 hour. Once that period has elapse...

Reference： [1]Patent: EP1832587,2007,A1 .Location in patent: Page/Page column 5; 5-6; 6

26
[ 496919-99-4 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
75%		1 -cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid- O3,O4 bis(propyloxy-O)borate (100.Og) was suspended in n-butanol (500.0 ml) to which (S,S)-2,8-diazabicyclo (4,3,0) nonane (29.0 g) diluted with 100.0 ml n-butanol was added slowly at 10-15C. The contents were heated to 100C and maintained for 3 hours. After the completion of reaction it was cooled to 25-3O0C. 200.0 ml methanol was added and pH was adjusted 1.0-2.0 using methanolic hydrochloric acid. The contents were stirred at 25-3O0C for 2 hours. After completion of reaction the reaction mass was distilled to residue. Purified water 500 ml was added and pH was adjusted to 7.5-9.0 using liquor ammonia. The reaction mass was then extracted with dichloromethane. The organic layer was dried using sodium <n="15"/>sulphate and concentrated to residue. The residue was stripped with 100 ml methanol. 300 ml methanol was charged and pH was adjusted to 1.0-2.0 using methanolic hydrochloric acid, the contents were further cooled to 0-50C and maintained for 1 hour. The solid was filtered and washed with chilled methanol (50.0 ml) and dried under vacuum at 85-9O0C to yield 75.0 g (75%) of moxifloxacin hydrochloride.

Reference： [1]Patent: WO2008/59223,2008,A2 .Location in patent: Page/Page column 13-14

27
[ 496919-99-4 ]
[ 151213-40-0 ]
[ 151096-09-2 ]

Yield	Reaction Conditions	Operation in experiment
		l-cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid- O3,O4 bis(propyloxy-0)borate (100.Og) was suspended in acetonitrile (445.0 ml). (S, S)-2,8- diazabicyclo (4,3,0) nonane (29.0 g) diluted with 50.0 ml acetonitrile was slowly added at 10-15C followed by triethyl amine (25.0 g). The contents were heated to reflux temperature for2 hours. Cooled to 25-3O0C. Methanol (200.0 ml) was added and pH was adjusted to 1.0-2.0 using hydrochloric acid and stirred at 10-150C for 2 hours. After the completion of reaction, the reaction mass was concentrated to residue. Purified water 500.0 ml was added and pH was adjusted to 7.5-9.0 using liquour ammonia under stirring. The contents were heated to70-750C and ammonia is expelled off by purging Nitrogen gas to the reaction mass. The <n="17"/>reaction mass was cooled to 25-30C and stirred for Ihour. The resulting solid was filtered and washed with purified water and dried under vacuum at 55-600C to obtain 75.0 g moxifloxacin base.

Reference： [1]Patent: WO2008/59223,2008,A2 .Location in patent: Page/Page column 15-16

28
[ 496919-99-4 ]
[ 151213-40-0 ]
(4aS-cis)-1-cyclopropyl-7-(2,8 diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic aid-O₃,O₄-bis(propyloxy-O)borate. [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
93.8%	With triethylamine; In acetonitrile; for 2h;Heating / reflux;	l-cyclopropyl-6, 7-difluoro-8-methoxy-4-oxo-l, 4-dihydro-3-quinoline carboxylic acid- O3,O4 bis(propyloxy-O)borate (100.Og) was suspended in acetonitrile (445.0 ml). (S, S)-2,8- diazabicyclo (4,3,0) nonane (29.0 g) diluted with 50.0 ml acetonitrile. The contents were heated to reflux temperature optionally in presence of triethyl amine and maintained for 2 hours. The reaction mass was distilled under vacuum to residue. Diisopropyl ether (500.0 ml) was added and the contents were cooled to 25-300C. The resulting product was filtered and washed with diisopropyl ether (50.0 ml) and dried at 45-500C under vacuum to yield 120.0 g(93.8 %) of (4aS-Cis)-l-Cyclorhoropyl-7-(2,8 diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8- methoxy-4-oxo-l,4-dihydro-3-quinoline carboxylic aid-O3, O4) bis (propyloxy-O)borate.
93.8%	In acetonitrile;Reflux;Product distribution / selectivity;	1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid-O3,O4 bis(propyloxy-O)borate (100.0 g) was suspended in acetonitrile (445.0 ml). (S,S)-2,8-diazabicyclo(4,3,0)nonane (29.0 g) diluted with 50.0 ml acetonitrile. The contents were heated to reflux temperature optionally in presence of triethyl amine and maintained for 2 hours. The reaction mass was distilled under vacuum to residue. Diisopropyl ether (500.0 ml) was added and the contents were cooled to 25-30 C. The resulting product was filtered and washed with diisopropyl ether (50.0 ml) and dried at 45-50 C. under vacuum to yield 120.0 g (93.8%) of (4aS-Cis)-1-Cyclopropyl-7-(2,8 diazabicyclo[4.3.0]non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic aid-O3,O4) bis(propyloxy-O)borate.

Reference： [1]Patent: WO2008/59223,2008,A2 .Location in patent: Page/Page column 14
[2]Patent: US2010/152229,2010,A1 .Location in patent: Page/Page column 5

29
[ 1028205-74-4 ]
[ 151213-40-0 ]
[ 1028205-69-7 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 32 - 80℃; for 35.75h;Product distribution / selectivity;	A mixture of 20 grams of l-cyclopropyl-NjN-diethyl-jT-difluoro-l^-dihydro-delta- methoxy-4-oxoquinoline-3-carboxamide, 11.8 grams of (S,S)2,8-diazabicyclo (4.3.0) nonane, 100 ml of acetonitrile and 2 grams of l,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was heated to 800C. The reaction mixture was stirred for 35 hours at 8O0C. The reaction mixture was cooled to 320C and stirred for 45 minutes at 32C. The solvent was distilled <n="23"/>off under reduced pressure. Water (100 ml) was added to the obtained residue. The reaction mixture was cooled to 25-350C. The reaction mixture was extracted with ethyl acetate. The solvent was distilled off to get the title compound as a residue. Yield: 12 grams.
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 20 - 85℃; for 35h;Inert atmosphere;	Under nitrogen protection, 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid dimethylamide 20.0 g (0.0571 mol) and (S,S) -2,8-diazabicyclo[4,3,0]nonane11.8 g (0.0935 mol) were added to 100mL of acetonitrile, it was stirred at 20 C ~30 C and1,8-diazabicyclo[5 · 4 · 0] undec-7-ene 12.5g (0.0821mol) was added, It was stirred at 75 C~85 C for 35 h. It was slowly cooled under stirring to 5 C~10 C for 2 hours ~ 3 hours. Filtered, rinsed with acetonitrile and dried. Dried in vacuo (vacuum degree -0.01MPa~-0.1MPa, temperature 45C~55C) for 16 hours, to obtain 7-((S,S) -2,8-diazabicyclo[4,3,0]nonane -2-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8 -methoxy-4-oxo-3-quinolinecarboxylic acid dimethylamide 12.0 g, the yield was 46.0%. The HPLC purity was 94.69%.

Reference： [1]Patent: WO2008/59521,2008,A2 .Location in patent: Page/Page column 20-21
[2]Patent: CN109096276,2018,A .Location in patent: Paragraph 0084; 0085; 0087

30
[ 153361-99-0 ]
[ 151213-40-0 ]
[ 1028205-72-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 1,8-diazabicyclo[5.4.0]undec-7-ene; In acetonitrile; at 25 - 80℃; for 35.75h;	A mixture of 20 grams of l-cyclopropyl-6,7-difluoro-8-methoxy-l,4-dihydro-4- oxoquinoline-3-carboxamide, 2.9 grams of (S,S)-2,8-diazabicyclo (4.3.0) nonane , 100 ml of acetonitrile and 2 grams of diazabicyclo[5.4.0]undec-7-ene (DBU) was heated to 75-80C. The reaction mixture was stirred for 35 hours at 75-80C. The reaction mixture was cooled to 25-350C. The reaction mixture was stirred for 45 minutes at 25-350C. The solid obtained was filtered and washed with acetonitrile. The material was dried at 40-450C to get the title compound. Yield: 12 grams; M.R: 210-2120C.

Reference： [1]Patent: WO2008/59521,2008,A2 .Location in patent: Page/Page column 22

Yield	Reaction Conditions	Operation in experiment
73%	With hydrogenchloride; hydrogen; In methanol;	The product (1-4, 5.3 g, mmol) is dissolved in 100 ml methanol, HCl/methanol solution is added to adjust the pH to be equal to 1.0, 1.0 g activated carbon is added and then stirred for 0.5 h, and the activated carbon is removed by filtration. The filtrate is added with 0.5 g 10% Pd/c, introduced with hydrogen to obtain a pressure of 1.5 MPa and reacted overnight at room temperature, Pd/c is removed by filtration upon complete reaction, and washing is carried out by 5 ml methanol. The filtrates are combined and then the pH is adjusted to be equal to 10.0 by sodium methylate/methanol solution, salts are removed by filtration, and (S,S)-2,8-diazabicyclo[4,3,0]nonane (1.52 g, yield 73%, 95.0% ee) is obtained by distillation under reduced pressure after mother liquor is dried by concentration. 1H NMR (500 MHZ, CDCl3) delta3.08-3.07 (m, 1H), 3.06-2.81 (m, 4H), 2.70-2.67 (m, 1H), 2.52-2.51 (m, 1H), 2.00-1.99 (m, 1H), 1.95-1.87 (br, 2H), 1.63-1.60 (m, 2H), 1.35-1.32 (m, 2H).
57%	With hydrogen; In chloroform;	The product (4-3. 9.0 g) in the previous step, 3.0 g 10% palladium on carbon and 50.0 ml acetic acid are added to an autoclave, hydrogen is introduced to the autoclave to obtain a pressure of 1.0 MPa after three nitrogen displacements, and reaction is carried out for 48 h at room temperature. The reactant is dried by concentration under reduced pressure upon complete reaction, the resultant oily product is added to 50 ml NaOH (10%) solution and heated up for reflux reaction for 24 hours, the reactant is extracted by 100 ml chloroform three times upon complete reaction, and the solvent is dried by concentration and then distilled under reduced pressure to obtain 3.1 g (S,S)-2,8-diazabicyclo[4,3,0]nonane with the total yield of 57%, 94.3% ee.
	With sodium borohydrid; In methanol; water;	Embodiment 2 Preparation of (S,S)-2,8-diazabicyclo[4,3,0]nonane (1-2, 10.0 g, 26.3 mmol), 50.0 ml methanol and 5.8 g sodium borohydride are added to a three-neck falsk, a large amount of bubbles are generated, the temperature rises naturally and reaction is carried out for 3 h. 100.0 ml water is added upon complete spotting plate reaction, and extraction is carried out by 50 ml*2 ethyl acetate. Organic phase is washed with saturated saline solution, dried by anhydrous sodium sulfate and filtered, the filtrate is dried by concentration under reduced pressure to obtain 6.6 g mixture of (2-1) and (1-4), and the product is directly used for the next reaction without classification. A small amount of the mixture is subjected to column chromatography to obtain the product (2-1). 1H NMR (500 MHZ, CDCl3) delta7.34-7.24 (m, 10H), 3.80-3.50 (m, 1H), 3.66-3.65 (m, 2H), 3.57-3.52 (m, 2H), 3.39-3.34 (m, 1H), 2.80-2.76 (m, 2H), 2.30-2.27 (m, 1H), 2.23-2.17 (m, 2H), 1.72-1.64 (m, 2H), 1.52-1.45 (m, 1H), 1.36-1.34 (m, 4H), MS-ESI: m/z: 339 (M 41).

32
[ 151213-40-0 ]
(S,S)-2,8-diazabicyclo[4.3.0]nonane dihydrobromide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen bromide; In ethanol;	Example 1 1; The preparation of (R, R)-2, 8-diazabicyclo [4.3.0]nonane (Formula I-b)Formula XII-b Formula I-bThe title compound (9.12 g) is prepared from mixture system of (R, R)-6-(toluene-4- sulfonyl)-octahydro-pyrrolo[3,4-b]pyridine (24.0 g), hydrobromic acid (48%, 156 ml), propionic acid (72 ml) and phenol (14.6 g) following the same procedure described in example 9. After conventional work up and distillation 3.4 g of oil is obtained (yield: 78.0%).[alpha]D = +2.33 (H2O, C=I); ee > 99% (determined by gas chromatography after derivatisaion with Mosher's reagent).Eta-NMR (CDCb): 1.40 (IH, m), 1.51 (IH, m), 1.62 (2H, m), 2.21 (2H, br), 2.49 (IH, m), 2.57 (IH, td), 2.74 (IH, d), 2.93 (4H, m), 3.13 (IH, t).The free base is converted to di-hydroboromic aicd salt in a solvent mixture of hydrobromic aicd/ethanol. Melting point: 301-305 C; [alpha]D = - 4.38 (H2O, C=I).

Reference： [1]Patent: WO2008/85480,2008,A1 .Location in patent: Page/Page column 13-14

33
[ 87-69-4 ]
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 1082245-30-4 ]

Yield	Reaction Conditions	Operation in experiment
90.32%		Example 8 Preparation of 1-cyclopropyl-7-[(S,S)-2,8-diazabicyclo[4.3.0]non-8-yl]-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid -L-(+)-tartarate (IIa) (Insitu preparation without isolation of Moxifloxacin base) 750 ml of N, N-dimethylformamide, 50 g of 1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (IV) and 25.70 ml of [S,S]-2,8-diazabicyclo [4.3.0] nonane (V) were stirred at 65 - 70 C for 6-8 hours. Completion of the reaction was monitored by HPLC. The reaction mass was cooled to 25-30 C, 50 g of L-(+)-tartaric acid was added, and the reaction mass was stirred at 75 - 80 C for 3-4 hours. The reaction mass was cooled to 25-30C and stirred for 10 12 hours. The solid was filtered off with suction, washed with 150 ml of N, N-dimethylformamide and dried under vacuum at 75C, affording 84.5 g of the title compound. Yield: 90.32 % Purity: 99.80 % (HPLC) Chiral impurity (R,R isomer content): 0.06 %

Reference： [1]Patent: EP1992626,2008,A1 .Location in patent: Page/Page column 12

34
[ 139693-52-0 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
		The mixture of (S,S)2,8-diazabicyclo[4,3,0]nonane (32.8 gm), (1- cyclopropyl-6,7-difluoro-1 ,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid- O3,O4) bis (acyloxy-O)borate (100 gm), 1 ,8-diazabicyclo[5,4,0]undec-7-ene (12.6 gm) and toluene (500 ml) is heated to 75 - 800C for 1 hour 30 minutes. Distilled off the solvent completely under vacuum and methanol (400 ml) and water (100 ml) are added to reaction mass. The pH is adjusted to 1.0 - 2.0 with concentrated hydrochloric acid at 250C and cooled to 50C. The solid obtained is collected by filtration and the solid is dried at 60-650C for 5 hours to obtain 72.5 gm moxifloxacin hydrochloride monohydrate polymorph IV. The product obtained above may further be processed, if required, to obtain moxifloxacin hydrochloride monohydrate polymorph IV in higher chromatographic purity as follows:The product obtained above (50 gm) is suspended in water (600 ml). The pH is adjusted to 7.5 - 8.0 with 50 % aqueous sodium hydroxide solution and extracted moxifloxacin free base with methylene dichloride (500 ml). Distilled off the methylene dichloride layer to get moxifloxacin free base as oily residue. To the oily residue, methanol (360 ml) and water (100 ml) are added and the contents are heated to 600C. The clear solution obtained is subjected to carbon treatment and the reaction mass is filtered through cellite bed and the bed is washed with hot methanol and water mixture (50ml, 4:1 by volume). The filtrate is cooled to 250C. The pH is adjusted to 1.0 - 2.0 with concentrated hydrochloric acid at 250C and cooled to O0C. The solid obtained is collected by filtration and the solid is dried at 60-650C for 5 hours to obtain 46 gm of moxifloxacin hydrochloride monohydrate polymorph IV.
		To a 5 L reactor was charged 215 g of (S, S) -2,8-diazabicyclo [4.3.0] nonane,400 ml of methanol and 300 g of triethylamine,A solution of 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylic acid-O3, O4- diacetate boron Ester of methanol solution,Drop finished,Reflux 6 ~ 10h.Reaction is completed,The solvent was distilled off under reduced pressure,The residue was dissolved by the addition of 500 ml of ethanol,With concentrated hydrochloric acid to adjust the pH to acidic,Cooling crystallization,filter,To give 610 g of a yellow solid,That is, crude moxifloxacin hydrochloride.
45 g		The main ring chelate compound 50g, anhydrous ethanol 200g, (3,3)-2,8-diazabicyclo[4,3,0]nonane 15.7g and triethylamine 12.0g were added to the reaction flask. Temperature 70 C reaction 4. Oh; the end of the reaction, temperature control 30 C to the solution was added dropwise 12mol / L of hydrochloric acid, stirring while stirring, adjust the pH to 1, stirring for 1h, temperature control to 10 C, Crystal growth 2h; After crystal growth, filtration, washing with 95 % ethanol twice, each time 50g; Wet powder 60 C vacuum drying to 2.8% moisture, to obtain moxifloxacin hydrochloride dry powder 45.0g, a single impurity 0.1%, The total impurity is 0.2%; after refining with ethanol and water, the content is 99%, which meets the quality standards of the European Pharmacopoeia EP-7.0 and the total impurity is less than 0.1%

Reference： [1]Patent: WO2010/52726,2010,A1 .Location in patent: Page/Page column 5; 6
[2]Patent: CN103172629,2016,B .Location in patent: Paragraph 0037
[3]Patent: CN104230925,2018,B .Location in patent: Paragraph 0063; 0064; 0069; 0071; 0073; 0075; 0077; 0079

35
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 192927-63-2 ]

Yield	Reaction Conditions	Operation in experiment
		Example 6: One-pot Preparation of Moxifloxacin hydrochloride monohydrate.Added 70gr of l-Cyclopropyl-6,7-difluro-8-methoxy-4-oxo-l,4-dihyro-3-quinoline carboxylic acid to a solution of 14.7 gr of boric acid andl75ml of acetic anhydride ,0.07g of zinc chloride at 25-45C. Heated the reaction mixture to 100-1200C. Stirred for 90 min. Cooled the reaction mixture to 0-50C. Isolated the material by filtration and washed with hexanes. A solution of 7Og of the obtained wet material [(l-cylcopropyl)-6,7- difluoro-8-methoxy,-4-oxo-l ,4-dihydro,quinoline -3-carboxylate-O3, O4)-bis-(acetate-O) boran], 30 g of [S, S]-2,8-diaza bicyclo (4,3,0)nonane, 30 ml of triethylamine and 300ml of acetonitrile is heated to reflux. Stirred at reflux for 90 mins. Distilled the solvent completely under reduced pressure at 85C. Added 316ml of aqueous sodium hydroxide solution at 50-70C. Heated the reaction mixture to 85-95C and stirred for 2 hrs. Adjusted the pH of the reaction mixture to 9 with acetic acid at 25-350C. Extracted the reaction mixture with methylene chloride and separated the organic phase. Distilled the EPO <DP n="16"/>solvent completely under reduced pressure at 60C. Dissolved the residue in 240ml of acetone at 40-50C, stirred for 15 min. Adjusted the pH to 1.0 with hydrochloric acid at 40-500C. Cooled to 10-150C and stirred for 90min. Filtered the precipitated solid and washed with acetone to get l-Cyclopropyl-6-fluoro-l,4-dihydro-8-methoxy-7[(4aS,7aS)- octahydro-6H-pyrrolo [3 ,4-b]pyridine-6-yl]-4-oxo-3 -quinoline carboxylic acid hydrochloride which is further purified using 405ml of methanol and 45 ml of water. Dissolved the compound by adjusting the pH to 7.8 with aqueous sodium hydroxide solution at 50-60C and treated with carbon. Filtered through hiflow and washed with methanol and water. Cooled the filtrate to 10-150C. Adjusted the pH with hydrochloric acid and stirred for 90 min. Filtered the precipitated solid and washed with methanol. Dried the compound at 50-600C until the water content reaches to 3-6%w/w to get Moxifloxacin hydrochloride monohydrate. Yield : 50 gr

Reference： [1]Patent: WO2007/10555,2007,A2 .Location in patent: Page/Page column 14-15

36
[ 1322062-44-1 ]
[ 151213-40-0 ]
C₂₅H₃₂FN₃O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	In N,N-dimethyl-formamide; at 130℃; for 26h;	General procedure: Compound 6a was prepared by stirring 37.8 mg (0.10 mmol) 5a with 44.3 mg (0.5 mmol) piperazine in 2 mL DMF at 130 C for 26 h. Product was purified by semi-preparative HPLC. Compounds 6b-d were prepared similarly.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4585 - 4588

37
[ 1322062-45-2 ]
[ 151213-40-0 ]
C₂₆H₃₄FN₃O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	In N,N-dimethyl-formamide; at 130℃; for 26h;	General procedure: Compound 6a was prepared by stirring 37.8 mg (0.10 mmol) 5a with 44.3 mg (0.5 mmol) piperazine in 2 mL DMF at 130 C for 26 h. Product was purified by semi-preparative HPLC. Compounds 6b-d were prepared similarly.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 4585 - 4588

38
[ 139693-52-0 ]
[ 151213-40-0 ]
1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3-quinolinecarboxylic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		b). Preparation of Moxifloxacin Hydrochloride Monohydrate Polymorph IVThe mixture of (S,S)2,8-diazabicyclo[4,3,0]nonane (32.8 gm), (1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid-O3,O4) bis (acyloxy-O)borate (100 gm), 1,8-diazabicyclo[5,4,0]undec-7-ene (12.6 gm) and toluene (500 ml) is heated to 75 -80 C. for 1 hour 30 minutes. Distilled off the solvent completely under vacuum and methanol (400 ml) and water (100 ml) are added to reaction mass. The pH is adjusted to 1.0-2.0 with concentrated hydrochloric acid at 25 C. and cooled to 5 C. The solid obtained is collected by filtration and the solid is dried at 60-65 C. for 5 hours to obtain 72.5 gm moxifloxacin hydrochloride monohydrate polymorph IV.The product obtained above may further be processed, if required, to obtain moxifloxacin hydrochloride monohydrate polymorph IV in higher chromatographic purity as follows:The product obtained above (50 gm) is suspended in water (600 ml). The pH is adjusted to 7.5-8.0 with 50% aqueous sodium hydroxide solution and extracted moxifloxacin free base with methylene dichloride (500 ml). Distilled off the methylene dichloride layer to get moxifloxacin free base as oily residue. To the oily residue, methanol (360 ml) and water (100 ml) are added and the contents are heated to 60 C. The clear solution obtained is subjected to carbon treatment and the reaction mass is filtered through cellite bed and the bed is washed with hot methanol and water mixture (50 ml, 4:1 by volume). The filtrate is cooled to 25 C. The pH is adjusted to 1.0-2.0 with concentrated hydrochloric acid at 25 C. and cooled to 0 C. The solid obtained is collected by filtration and the solid is dried at 60-65 C. for 5 hours to obtain 46 gm of moxifloxacin hydrochloride monohydrate polymorph IV.

Reference： [1]Patent: US2011/212990,2011,A1 .Location in patent: Page/Page column 2

39
[ 100986-89-8 ]
[ 151213-40-0 ]
UIKRM-1-033 [ No CAS ]

Reference： [1]Antimicrobial Agents and Chemotherapy,2010,vol. 54,p. 5214 - 5221

40
[ 160199-00-8 ]
[ 151213-40-0 ]
[ 1345538-58-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 6577 - 6581

41
[ 1253122-67-6 ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogen;10% palladium hydroxide on charcoal; In isopropyl alcohol; at 70℃; for 13h;	Example 14: Production of (1S,6S)-cis-2,8-diazabicyclo[4.3.0]nonane The solution consisting of (1S,6S)-cis-8-((S)-1-phenylethyl)-2,8-diazabicyclo[4.3.0]nonane produced in Example 12 (488 mg, 1.2 mmol), isopropanol (4.9 ml) and 10wt% palladium hydroxide (II) - carbon (49 mg) was stirred under hydrogen atmosphere at 70C for 13 hours. After the catalyst was removed by filtration under reduced pressure, the filtrate was concentrated under reduced pressure. Water (2 ml) was added to the concentrate. The aqueous layer was washed with toluene (4 ml) twice. The aqueous layer was concentrated under reduced pressure and the concentrate was dried in vacuo, to obtain the target compound as a pale brown oil (146 mg, yield: 65%, purity: 66.8wt%, diastereomer purity: 92.5%de). The target compound: 1H-NMR (CDCl3): delta(ppm) 1.44(m, 1H), 1.55(m, 1H), 1. 70 (m, 2H), 1.88(br, 2H), 2.09(m, 1H), 2.61(dt, 1H), 2.78(d, 1H), 2.90-3.04(m, 4H), 3.17(m, 1H)

Reference： [1]Patent: EP2423211,2012,A1 .Location in patent: Page/Page column 18

42
[ 151213-40-0 ]
[ 721970-37-2 ]

Reference： [1]Patent: EP2551268,2013,A1
[2]Patent: US2013/59880,2013,A1

43
[ 151213-40-0 ]
[ 186826-86-8 ]

Reference： [1]Patent: EP2551268,2013,A1
[2]Patent: US2013/59880,2013,A1
[3]Patent: CN105566322,2016,A
[4]Patent: CN110194767,2019,A

44
[ 151213-40-0 ]
[ 1420107-30-7 ]

Reference： [1]Patent: EP2551268,2013,A1
[2]Patent: US2013/59880,2013,A1

45
[ 766-11-0 ]
[ 151213-40-0 ]
[ 1427172-49-3 ]

Yield	Reaction Conditions	Operation in experiment
83%	In 1-methyl-pyrrolidin-2-one; at 150℃;	Step 1: Synthesis of (4aS,7aS)-6-(5-bromopyridin-2-yl)octahydro-1H-pyrrolo [3,4-b]pyridine (23a) Compound 2-fluoro-5-bromopyridine (1 g, 5.7 mmol) was dissolved in NMP (10 mL), and 23a' (2.15 g, 17.1 mmol) was added. The mixture was heated to 150 C for reacting overnight. TLC (petroleum ether/ ethyl acetate = 50/1) was employed to monitor the reaction. After the reation completed, the mixture was diluted with water, and extracted with ethyl acetate. The organic phase was combined, washed with saturated sodium chloride solution, and dried over anhydrous sodium sulfate. Column chromatography (dichloromethane/methanol = 50/1) afforded 1.34 g of white solid (compound 23a), yield 83%. m.p.: 100-101 C. 1H NMR (400 MHz, CDCl3) delta 8.13 (s, 1H), 7.46 (d, J = 9.0 Hz, 1H), 6.23 (d, J = 9.0 Hz, 1H), 3.54 - 3.46 (m, 2H), 3.46 - 3.41 (m, 2H), 3.41 - 3.33 (m, 1H), 3.00 (dt, J = 11.9, 3.2 Hz, 1H), 2.70 - 2.62 (m, 1H), 2.42 - 2.32 (m, 1H), 1.83 - 1.71 (m, 2H), 1.70 - 1.57 (m, 1H), 1.54-1.43 (m, 2H). MS(EI) m/z: 281(M+).

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650
[2]Patent: EP2940024,2015,A1 .Location in patent: Paragraph 0075; 0076

46
[ 151213-40-0 ]
[ 1427172-09-5 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650
[2]Patent: EP2940024,2015,A1

47
[ 151213-40-0 ]
[ 1427172-50-6 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650
[2]Patent: EP2940024,2015,A1

48
[ 151213-40-0 ]
[ 1427172-10-8 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650

49
[ 151213-40-0 ]
[ 1427172-11-9 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650

50
[ 151213-40-0 ]
[ 1427172-51-7 ]

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 2642 - 2650
[2]Patent: EP2940024,2015,A1

51
[ 1427038-03-6 ]
[ 151213-40-0 ]

Reference： [1]Science China Chemistry,2013,vol. 56,p. 307 - 311

52
[ 1009051-59-5 ]
[ 151213-40-0 ]

Reference： [1]Science China Chemistry,2013,vol. 56,p. 307 - 311

53
C₂₂H₂₈N₂O [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Science China Chemistry,2013,vol. 56,p. 307 - 311

54
[ 1427038-01-4 ]
[ 151213-40-0 ]

Reference： [1]Science China Chemistry,2013,vol. 56,p. 307 - 311

55
[ 1427038-02-5 ]
[ 151213-40-0 ]

Reference： [1]Science China Chemistry,2013,vol. 56,p. 307 - 311

56
[ 151213-40-0 ]
(1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid-O³,O⁴)bis(acyloxy-O)borate [ No CAS ]
1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridine-6-yl]-4-oxo-3-quinolinecarboxylic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43 g		Preparation of moxifloxacin hydrochloride non-hygroscopic anhydrous Form HI The mixture of <strong>[151213-40-0](S,S)-2,8-diazabicyclo[4,3,0]nonane</strong> (18.5 gm), (1-cyclopropyl- 6,7-difluoro- l,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid-03,04) bis (acyloxy-O)borate (56 gm), l,8-diazabicyclo[5,4,0]undec-7-ene (7 gm), methylene chloride (280 ml) and water (1 15 ml) were heated to reflux. The reaction mass was maintained for 2 hour 30 minutes at reflux and then cooled to room temperature. To the reaction mass was added methanol (225 ml) and sulfuric acid (20.5 gm) slowly for 1 hour and then maintained for 1 hour 30 minutes at room temperature. The pH of the reaction mass was adjusted to 7.5 to 8.0 with ammonia and then the layers were separated. The aqueous layer was extracted with methylene chloride. Combined organic layer were then concentrated to obtain a residual solid. To the residual solid was added water (50 ml) and methanol (210 ml). The pH of the reaction mass was adjusted to 1.0 to 2.0 with hydrochloric acid and maintained for 1 hour 30 minutes at room temperature. The reaction mass was then cooled to 0 to 5C and then added n-butanol (250 ml). The reaction mass was then heated to reflux and maintained for 4 hours. The solution was then cooled to room temperature and stirred for 1 hour. The separated solid was filtered and then dried at 90 to 95C under vacuum for 5 hours to obtain 43 gm of moxifloxacin hydrochloride non-hygroscopic anhydrous Form HI .

Reference： [1]Patent: WO2013/153558,2013,A1 .Location in patent: Page/Page column 6-7

57
1-benzyl-4-(3-ethoxycarbonyl propyl)-3-pyrrolidone [ No CAS ]
[ 64-04-0 ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
61.0%	In ethanol; water; toluene;	Embodiment 3 Preparation of (S,S)-2,8-diazabicyclo[4,3,0]nonane 20 ml toluene, 1-benzyl-4-(3-ethoxycarbonyl propyl)-3-pyrrolidone (2.0 g, 5.92 mmol) and (R)-1-phenethylamine (1.0 g, 8.89 mmol) are added to a three-neck flash equipped with a water separator and then subjected to refluxing water separation for 20 hours under the protection of nitrogen, the solvent is dried by spinning in vacuum, the resultant oily product is dissolved in 20 ml ethanol and added to an autoclave, and 0.2 g RaneyNi is added to the autoclave for the purpose of hydrogenation reaction for 24 hours at room temperature under 10 kg pressure. At the end of reaction, the reactant is filtered by a Buchner funnel with diatomite as cushion, and the filtrate is dried by spinning to obtain oily crude product, which is then subjected to column chromatographic separation to obtain oily product (3-2, 3.61 mmol, yield 61.0%). 1H NMR (400 MHz, CDCl3) delta 8.06 (d, J=7.6 Hz, 2H), 7.55 (t, J=7.3 Hz, 1H), 7.44 (t, J=7.5 Hz, 2H), 7.20 (m, 10H), 4.36 (t, J=6.0 Hz, 2H), 3.73 (d, J=6.5 Hz, 1H), 3.55 (q, J=12.9 Hz, 2H), 3.24 (d, J=6.3 Hz, 1H), 2.84 (s, 1H), 2.79-2.68 (m, 1H), 2.22 (m, 3H), 1.85-1.69 (m, 3H), 1.44 (m, 1H), 1.28 (m, 4H).

Reference： [1]Patent: US2014/66626,2014,A1 .Location in patent: Page/Page column

58
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
3.3 g		Under nitrogen protection, 1-cyclopropyl-6, 7-difluoro-1, 4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid 10.0 g (0·0339 momicronl) and (S,S) -2,8-diazabicyclo[4,3,0] nonane 5 .13g(0.0406mol)were added to 70 mL acetonitrile, it was stirred at 20 C~30 C and 1,8-diazabicyclo[5·4·0]undec-7-ene 7.74 g (0.0508 mol) was added, it was stirred at 75 C~85 C for 36 h. Concentrated in vacuo (temperature 45 C ~ 65 C, pressure -0 · 08MPa ~ -0.1MPa) to remove most of the solvent, it was then dissolved in chloroform, the mass concentration is 2% aqueous acetic acid solution (the mass concentration refers to the mass of acetic acid as a percentage of the total mass of the aqueous acetic acid solution), the mass concentration was 10% saline (the mass concentration refers to the mass of sodium chloride as a percentage of the total mass of brine were sequentially added, respectively, then the mixture was stirred, allowed to stand, and the aqueous layer was separated. The organic layer was concentrated in vacuo (temperature 35 C ~ 55 C, pressure -0.08MPa ~ -0.1MPa) to remove most of the solvent, ethyl acetate was added, and the mixture was cooled to 10 C to 20 C and stirred for 2 hours to 3 hours. Centrifugation, rinsed three times with ethyl acetate, dried in vacuo (vacuum degree -0.01MPa~-0.1MPa, temperature 45~55C) dried for 14 to 18 hours, to obtain 4.01g of moxifloxacin , yield 29.5%.HPLC purity 93.54%. Under nitrogen protection, add 4.0 g of moxifloxacin to 2.5 mL of water and 10 mL of methanol.Stir at 170 C for 1 hour, filter, and cool to 35 C.The pH was adjusted to 1.4 to 1.8 by the addition of 6N hydrochloric acid. Cool to 15 C and stir for 1 hour.It was filtered, washed with water, and stirred at 15 C for 1 hour in a solution of water 5 mL and concentrated hydrochloric acid.Filtered, washed with water, vacuum dried (vacuum degree - 0.01 MPa ~ -0.1 MPa, temperature 45 ~ 55 C) for 16 hours, to obtain 3.3 g of moxifloxacin hydrochloride,Yield 75.6% (total yield 22.3%, based on <strong>[112811-72-0]1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid</strong> ). The HPLC purity was 99.23%, and the maximum single impurity was 0.47%.

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258
[2]Patent: CN109096276,2018,A .Location in patent: Paragraph 0090-0093

59
cis-6-benzyltetrahydro-1H-pyrrolo[3,4-b]pyridine-5,7(6H,7aH)-dione [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

60
[ 151213-40-0 ]
[ 151213-39-7 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

61
[ 147-71-7 ]
[ 151213-40-0 ]
[ 151636-46-3 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

62
8-benzyl-2,8-diazabicyclo[4.3.0]nonane [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy,2014,vol. 121,p. 254 - 258

63
[ 1430075-11-8 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1
[2]Patent: EP2679588,2014,A1
[3]Patent: EP2679588,2014,A1
[4]Patent: EP2679588,2014,A1

64
1-benzyl-4-(3-benzoyloxypropyl)-3-pyrrolidone [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1

65
[ 1430075-01-6 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1
[2]Patent: EP2679588,2014,A1
[3]Patent: EP2679588,2014,A1
[4]Patent: EP2679588,2014,A1

66
[ 1430075-04-9 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1

67
[ 1430075-02-7 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1
[2]Patent: CN107793414,2018,A
[3]Patent: CN107793414,2018,A

68
[ 1430075-03-8 ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
97%	With 5%-palladium/activated carbon; hydrogen; In methanol; at 20℃; under 3750.38 Torr; for 15h;	Compound (5S,6S)-2-(R-1-phenyl-ethyl)-8-benzyl-2,8-diazabicyclo[4.3.0]nonane (6.41 g, 20 mmol, Examples 5-2 or 6-1) Palladium carbon (0.20 g, 5% Pd/C, 50% aqueous) and methanol (30 mL) are mixed, hydrogen is passed to 0.5 MPa, and the reaction is carried out at room temperature for 15 hours. The TLC test material disappears. Filter, concentrate,The target compound (S,S)-2,8-diazabicyclo[4.3.0]nonane 2.45 g was obtained in a yield of 97%.
73%		The product (1-4, 5.3g, mmol) is dissolved in 100ml methanol, HCl/methanol solution is added to adjust the pH to be equal to 1.0, 1.0g activated carbon is added and then stirred for 0.5h, and the activated carbon is removed by filtration. The filtrate is added with 0.5g 10%Pd/c, introduced with hydrogen to obtain a pressure of 1.5MPa and reacted overnight at room temperature, Pd/c is removed by filtration upon complete reaction, and washing is carried out by 5ml methanol. The filtrates are combined and then the pH is adjusted to be equal to 10.0 by sodium methylate/methanol solution, salts are removed by filtration, and (S,S)-2,8-diazabicyclo[4,3,0]nonane (1.52g, yield 73%, 95.0% ee) is obtained by distillation under reduced pressure after mother liquor is dried by concentration. 1H NMR(500MHZ,CDCl3)delta3.08-3.07(m,1H), 3.06-2.81(m,4H), 2.70-2.67(m,1H), 2.52-2.51 (m,1H), 2.00-1.99 (m,1H), 1.95-1.87 (br,2H), 1.63-1.60 (m,2H), 1.35-1.32 (m,2H).

Reference： [1]Patent: CN107793414,2018,A .Location in patent: Paragraph 0175-0177; 0185
[2]Patent: EP2679588,2014,A1 .Location in patent: Paragraph 0038; 0042

69
[ 1430075-05-0 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1

70
[ 1430075-08-3 ]
[ 151213-40-0 ]

Yield	Reaction Conditions	Operation in experiment
3.1 g		The product (4-3. 9.0g) in the previous step, 3.0g 10% palladium on carbon and 50.0 ml acetic acid are added to an autoclave, hydrogen is introduced to the autoclave to obtain a pressure of 1.0MPa after three nitrogen displacements, and reaction is carried out for 48h at room temperature. The reactant is dried by concentration under reduced pressure upon complete reaction, the resultant oily product is added to 50ml NaOH (10%) solution and heated up for reflux reaction for 24 hours, the reactant is extracted by 100ml chloroform three times upon complete reaction, and the solvent is dried by concentration and then distilled under reduced pressure to obtain 3.1g (S,S)-2,8-diazabicyclo[4,3,0]nonane with the total yield of 57%, 94.3% ee.

Reference： [1]Patent: EP2679588,2014,A1 .Location in patent: Paragraph 0052; 0054

71
C₂₄H₃₀N₂O₂ [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1
[2]Patent: EP2679588,2014,A1
[3]Patent: EP2679588,2014,A1
[4]Patent: EP2679588,2014,A1

72
C₂₉H₃₂N₂O₂ [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1

73
[ 1430075-09-4 ]
[ 151213-40-0 ]

Reference： [1]Patent: EP2679588,2014,A1
[2]Patent: EP2679588,2014,A1
[3]Patent: EP2679588,2014,A1
[4]Patent: EP2679588,2014,A1

74
[ 89-00-9 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707
[2]Patent: CN105566319,2016,A
[3]Patent: CN105777750,2016,A
[4]Synthetic Communications,2017,vol. 47,p. 238 - 244

75
6,7-dihydro-5H-pyrrolo[3,4-b]pyridine hydrochloride salt [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

76
6,7-dihydro-5H-pyrrolo[3,4-b]pyridine hydrochloride salt [ No CAS ]
[ 151213-42-2 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

77
[ 1558014-39-3 ]
[ 151213-42-2 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

78
[ 1558014-41-7 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

79
[ 1558014-42-8 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

80
[ 1558079-66-5 ]
[ 23981-80-8 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

81
[ 18184-75-3 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707
[2]Patent: CN105777750,2016,A
[3]Synthetic Communications,2017,vol. 47,p. 238 - 244

82
[ 1257241-37-4 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

83
[ 1257241-37-4 ]
[ 151213-42-2 ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707

84
cis-8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]-nonane [ No CAS ]
[ 151213-40-0 ]

Reference： [1]Asian Journal of Chemistry,2013,vol. 25,p. 8701 - 8707
[2]Patent: CN105777750,2016,A
[3]Synthetic Communications,2017,vol. 47,p. 238 - 244

85
[ 112811-71-9 ]
[ 151213-40-0 ]
[ 1403836-23-6 ]

Yield	Reaction Conditions	Operation in experiment
		Under nitrogen protection,A solution of 1.1 g (40 mmol) of CuCl,(110 mmol) of ethylene glycol,Isobutylamine (12.4 g, 170 mmol)And 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate 32.3g (100mmol)Was charged into a reaction vessel equipped with 320 mL of methanol,The reaction was carried out at 50 C for 3 hours,The temperature was then raised to 68 C,(S, S) -2,8-diazabicyclo [4.3.0] nonane 13.9 g (110 mmol)The reaction was continued for 4 hours,The insoluble matter was filtered off by hot filtration (temperature: 58 C)Concentrated hydrochloric acid was added dropwise at room temperature,Adjust the pH to 2,Stirring for 2 hours after cooling to -5 crystallization,Filtration,Cold ethanol washing,Vacuum drying,Moxifloxacin hydrochloride as a white solid (40.7 g)The yield was 93.0%Purity 99.82% (HPLC area normalization method).
	With aluminum (III) chloride; 1,8-diazabicyclo[5.4.0]undec-7-ene; In N,N-dimethyl-formamide; at 60℃; for 3h;	In a 2L four-necked flask, the addition of a cyclohexyl ester100g (0.309mol),(S,S)-2,8-diazabicyclo[4,3,0]decane 40.5g (0.321mol),1000ml of acetonitrile, stirred, and charged with triethylamine 32.5 g (0.321 mol), AlCl3 2.05 g (0.015 mol),The temperature is raised to 60 C, and the heat preservation reaction is about 3 h.The system is basically clarified, sampled, TLC (developing agent is methanol:acetone:Ammonia = 15:5:3) Detection of traces of substantially unreacted starting material (additional cycloester),Cool to room temperature, filter, and continue to warm the filtrate to 50 C.Adding L-(+)-tartaric acid to 27.84 g (0.185 mol),Stirring for about 2 hours,The system is largely precipitated, cooled to 0-5 C, filtered,The filter cake was washed with acetonitrile and the filter cake was collected.Dry at 50-80 C under vacuum to constant weight, collect powder,Obtained 142g of moxifloxacin ethyl ester tartrate.The molar yield is 91.0% (calculated as the ratio of moxifloxacin ethyl ester to tartaric acid of 2:1),The substance has a purity of 99.82% and an optical isomer content of 0.08%.

Reference： [1]Patent: CN105524060,2016,A .Location in patent: Paragraph 0020; 0026
[2]Patent: CN110194767,2019,A .Location in patent: Paragraph 0044-0049

86
[ 112811-71-9 ]
[ 151213-40-0 ]
[ 186826-86-8 ]

Yield	Reaction Conditions	Operation in experiment
89.78%		In a 2000 mL three-necked round-bottomed flask, 150.00 g of acetic anhydride was added, stirred, heated to 80 C,boric acid 28. 00g, stirring evenly, slowly warming to 110 C, stirring reaction 2 hours. Cooled to 60-70 C, ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate 100 was added. And the reaction was continued at 90 to 100 C for 3 hours. After completion of the reaction, the reaction mixture was cooled to room temperature. 650 mL of acetonitrile and 592 mL of triethylamine were added to the reaction solution, and the mixture was stirred for 30 minutes. To the reaction solution was added 39.39 g of (S, S) -2,8-diazabicyclo [4.3.0] nonane (1.01eq), heating reflux reaction 3 hours, TLC detection reaction is completed, down to room temperature, stirring 30 minutes, ice bath temperature 5 ~ 10 C 90mL concentrated hydrochloric acid, adjust PH = 1. 2, continue ice bath Stirring and crystallization for 8 hours, filtration, ice-ethanol 50mLX2 washing filter cake, filter cake 50 ~ 60 C / _0.095MPa vacuum drying 12 hours to obtain crude moxifloxacin hydrochloride 121. 48g light yellow powder, yield: 89 78%, HPLC: 99.7%.

Reference： [1]Patent: CN102731496,2016,B .Location in patent: Paragraph 0038; 0039

87
[ 112811-72-0 ]
[ 151213-40-0 ]
1-cyclopropyl-6-(S,S-2,8-diazabicyclo[4.3.0]nonane-8-yl)-7-fluoro-8-methoxy-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
16.47%	With triethylamine; In 1,4-dioxane; at 85℃; for 5h;	Reaction: In a 100 mL round-bottomed flask, 5 g of the compound of Formula 3, 50 mL of 1,4-dioxane are added, and the mixture is stirred and mixed, and then 4.27 g of the compound of Formula 4 is added to the system at a time, and then added at one time. 7mL of triethylamine; after the addition was complete, the system was warmed to 85[deg.]C and the reaction was stirred for 5h at this temperature.Post-treatment: After the reaction was completed, the system was cooled to 70 C., and the reaction solution was concentrated to dryness under reduced pressure to obtain a crude product of the compound represented by Formula 1 as a dark brown oil.Purification and separation: The prepared crude product of the formula 1 was purified by column chromatography (eluent; ethyl acetate:methanol=5:1), and the compound of the formula 1 was concentrated to dryness under reduced pressure. Obtained 1.12g brown solid compound of the formula 1, the yield of 16.47%.

Reference： [1]Patent: CN107778308,2018,A .Location in patent: Paragraph 0082; 0083; 0084; 0085

88
[ 112811-72-0 ]
[ 151213-40-0 ]
[ 721970-36-1 ]

Yield	Reaction Conditions	Operation in experiment
72.1%		The specific process is: adding 10 mL of methanol to a 25 mL reaction flask.Additional compound 2-4 (0.91 g, 3.2 mmol), ethylene glycol (0.22 g), isobutylamine (0.42 g),Copper dichloride (0.2g),Nitrogen protection, stirring at 50 C for 4 hoursAfter adding 0.4 g of compound 1 ((S,S)-2,8-diazo-bicyclo[4.3.0] decane),After heating for 5 hours,Filter and add 4 mL of aqueous sodium hydroxide solution (2M).Continue to heat and reflux for 1 hour.At room temperature, the reaction solution was adjusted to pH 7-8 with 4M hydrochloric acid.Add 50 mL of ethyl acetate to separate layers.The aqueous layer was extracted three times with 100 mL of ethyl acetate.The organic layers were combined, dried and concentrated on silica gel column chromatography.The obtained moxifloxacin 1.1 g was dissolved in 5 mL of dry DMF.Then add 0.5g of trimethylsilyl iodide, 45mg of sodium iodide,The reaction was completed by refluxing at 70 C for 8 hours under a nitrogen atmosphere.After cooling to room temperature, it was diluted with 10 mL of dichloromethane, and slowly added to a sodium hydrogencarbonate solution (10 mL) at 0 C, stirring was continued for 20 minutes, and the pH was adjusted to 7 with glacial acetic acid.Layered, concentrated in organic solvent layer,Drying by silica gel column separationCompound E (0.89g),The yield was 72.1%.

Reference： [1]Patent: CN110183445,2019,A .Location in patent: Paragraph 0059-0062

Same Skeleton Products

Related Products

Historical Records

Related Parent Nucleus of
[ 151213-40-0 ]

Aliphatic Heterocycles

[ 913812-09-6 ]

(R)-1-(Pyrrolidin-3-yl)piperidine

Similarity: 0.82

[ 531-67-9 ]

2-(Piperidin-2-yl)piperidine

Similarity: 0.81

[ 119904-90-4 ]

(S)-Quinuclidin-3-amine dihydrochloride

Similarity: 0.79

[ 123536-14-1 ]

(R)-3-Aminoquinuclidine dihydrochloride

Similarity: 0.79

[ 6530-09-2 ]

3-Aminoquinuclidine dihydrochloride

Similarity: 0.79

Other Aliphatic Heterocycles

[ 2051-28-7 ]

Decahydroquinoline

Similarity: 0.78

[ 90673-35-1 ]

3,8-Diazabicyclo[3.2.1]octane dihydrochloride

Similarity: 0.75

[ 283-38-5 ]

1,4-Diazabicyclo[3.2.2]nonane

Similarity: 0.75

[ 125224-62-6 ]

(1S,4S)-2-Methyl-2,5-diazabicyclo[2.2.1]heptane dihydrobromide

Similarity: 0.73

[ 114086-15-6 ]

2-Methyl-2,5-diazabicyclo[2.2.1]heptane dihydrobromide

Similarity: 0.73

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 151213-40-0 ] {[proInfo.proName]}

Quality Control of [ 151213-40-0 ]

Related Doc. of [ 151213-40-0 ]

Product Details of [ 151213-40-0 ]

Calculated chemistry of [ 151213-40-0 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 151213-40-0 ]

Application In Synthesis of [ 151213-40-0 ]

[ 151213-40-0 ] Synthesis Path-Upstream 1~12

[ 151213-40-0 ] Synthesis Path-Downstream 1~88

Related Parent Nucleus of [ 151213-40-0 ]

Aliphatic Heterocycles

Other Aliphatic Heterocycles

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Parent Nucleus of
[ 151213-40-0 ]