[ CAS No. 1228675-18-0 ]

Name: 1228675-18-0|tert-Butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate|98%
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Quality Control of [ 1228675-18-0 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 1228675-18-0 ]

CAS No. :	1228675-18-0	MDL No. :	MFCD17480504
Formula :	C₁₀H₁₈N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	MALCQJIQWIWGOV-UHFFFAOYSA-N
M.W :	198.26	Pubchem ID :	50986452
Synonyms :

Safety of [ 1228675-18-0 ]

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

Application In Synthesis of [ 1228675-18-0 ]

* 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.

Downstream synthetic route of [ 1228675-18-0 ]

[ 1228675-18-0 ] Synthesis Path-Downstream 1~14

1
[ 1228675-18-0 ]
[ 1403676-74-3 ]
tert-butyl 5-((1s,4s)-4-((2-fluoro-4-(methylsulfonyl)phenoxy)methyl)cyclohexyl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]
tert-butyl 5-((1r,4r)-4-((2-fluoro-4-(methylsulfonyl)phenoxy)methyl)cyclohexyl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 45.3% 2: 37.7%	Stage #1: tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate; 4-((2-fluoro-4-(methylsulfonyl)phenoxy)methyl)cyclohexanone With sodium tris(acetoxy)borohydride; acetic acid In 1,2-dichloro-ethane at 45℃; for 2h; Inert atmosphere; Stage #2: With sodium hydrogencarbonate In water; 1,2-dichloro-ethane	1.83 To a solution of tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (0.11 g, 0.56 mmol) and 4-((2-fluoro-4-(methylsulfonyl)phenoxy)methyl)cyclohexanone (0.18 g, 0.61 mmol) in DCE (5 mL) at room temperature under nitrogen was added acetic acid (63.0 μ, 1.10 mmol) and sodium triacetoxyborohydride (0.29 g, 1.4 mmol). The mixture was heated at 45 °C for 2 h. The reaction was quenched with saturated NaHC03 (aq.). The organic layer was separated and the aqueous layer was extracted once with DCM. The combined organic phases were concentrated under reduced pressure and purified by Biotage column chromatography to afford the more polar title compound as an off-white solid (101.0 mg, 37.7%). Exact mass calculated for C24H35FN2O5S: 482.2, found: LCMS mlz = 483.2 [M+H]+; lU NMR (400 MHz, CDCI3) δ ppm 0.44-0.57 (m, 1H), 0.58-0.82 (m, 1H), 1.10-1.24 (m, 2H), 1.29-1.44 (m, 2H), 1.48 (s, 9H), 1.78-1.95 (m, 1H), 2.01 (d, J = 13.64 Hz, 2H), 2.07-2.22 (m, 2H), 2.35-2.52 (m, 3H), 2.66-2.87 (m, 2H), 2.96-3.16 (m, 1H), 3.03 (s, 3H), 3.44-3.73 (m, 1H), 3.92 (d, J = 6.32 Hz,2H), 7.06 (t, J = 8.21 Hz, 1H), 7.61-7.66 (m, 1H), 7.68 (d, J = 9.35 Hz, 1H). The less polar cis analog was also obtained (121.2 mg, 45.3%).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2012/145361, 2012, A1 Location in patent: Page/Page column 200

2
[ 32315-10-9 ]
[ 1228675-18-0 ]
tert-butyl 5-(chlorocarbonyl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In dichloromethane at 0 - 25℃; Inert atmosphere;

Reference： [1]Zeng, Qingbei; Wang, Jiabing; Cheng, Ziqiang; Chen, Kan; Johnström, Peter; Varnäs, Katarina; Li, David Yunzhi; Yang, Zhen Fan; Zhang, Xiaolin [Journal of Medicinal Chemistry, 2015, vol. 58, # 20, p. 8200 - 8215]

3
[ 1228675-18-0 ]
4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 5-methyl-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: pyridine / dichloromethane / 0 - 25 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 25 °C 3.1: hydrogenchloride / water; ethyl acetate; 1,4-dioxane / 1 h / 25 °C 4.1: triethylamine; acetic acid / methanol / 25 °C 4.2: 24 h / 25 °C 5.1: ammonia / methanol / Resolution of racemate

4
[ 1228675-18-0 ]
2-tert-butyl 5-(4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl) 2,5-diazabicyclo[4.1.0]heptane-2,5-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine / dichloromethane / 0 - 25 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 25 °C

5
[ 1228675-18-0 ]
4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyridine / dichloromethane / 0 - 25 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 25 °C 3: hydrogenchloride / water; ethyl acetate; 1,4-dioxane / 1 h / 25 °C

6
[ 1228675-18-0 ]
4-(3-chloro-2-fluorophenylamino)-7-methoxyquinazolin-6-yl 5-methyl-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: pyridine / dichloromethane / 0 - 25 °C / Inert atmosphere 2.1: potassium carbonate / N,N-dimethyl-formamide / 25 °C 3.1: hydrogenchloride / water; ethyl acetate; 1,4-dioxane / 1 h / 25 °C 4.1: triethylamine; acetic acid / methanol / 25 °C 4.2: 24 h / 25 °C

7
[ 1228675-18-0 ]
(M)-tert-butyl 5-(6-chloro-7-(2-fluorophenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / acetonitrile / 2 h / 60 °C 1.2: 18 h / 0 °C 2.1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 90 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: AMGEN INC - US2019/374542, 2019, A1

8
[ 1228675-18-0 ]
(M)-4-(5-acryloyl-2,5-diazabicyclo[4.1.0]heptan-2-yl)-6-chloro-7-(2-fluorophenyl)-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: N-ethyl-N,N-diisopropylamine; trichlorophosphate / acetonitrile / 2 h / 60 °C 1.2: 18 h / 0 °C 2.1: potassium acetate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / 1,4-dioxane; water / 90 °C / Inert atmosphere 3.1: trifluoroacetic acid / dichloromethane / 0.25 h / 20 °C 3.2: 0.75 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: AMGEN INC - US2019/374542, 2019, A1

9
[ 1228675-18-0 ]
(M)-6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione [ No CAS ]
(M)-tert-butyl 5-(6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: (M)-6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione With N-ethyl-N,N-diisopropylamine; trichlorophosphate In acetonitrile at 60℃; for 2h; Stage #2: tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 18h;	222.1 Step 1: (M)-tert-Butyl 5-(6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate DIPEA (0.19 mL, 1.1 mmol) and POCl3 (0.10 mL, 1.11 mmol) were sequentially added to a room temperature solution of (M)-6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione (Intermediate 73B, 270 mg, 0.74 mmol) in acetonitrile (3.5 mL). The homogenous bright-yellow solution was heated at 60° C. After 2 h, the reaction mixture was concentrated under reduced pressure and azeotropically dried with heptane. The resulting dark-orange residue was dissolved in DCM (2.0 mL) and cooled to 0° C. DIPEA (0.65 mL, 3.7 mmol) was added, followed by a solution of tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (Aurum Pharmatech LLC, Franklin Park, N.J., USA, 250 mg, 1.3 mmol) in DCM (1.5 mL). After 18 h, the reaction was diluted with EtOAc (70 mL) and water (70 mL). The layers were partitioned and the aqueous phase was extracted with EtOAc (2*30 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered, and concentrated to afford an orange oil which was purified by silica gel chromatography (eluent: 0-50% (3:1 EtOAc-EtOH)/heptane) to afford (M)-tert-butyl 5-(6,7-dichloro-1-(2-isopropyl-4-methylpyridin-3-yl)-2-oxo-1,2-dihydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (390 mg, 0.72 mmol, 97% yield) as a bright yellow-orange solid.

Reference： [1]Current Patent Assignee: AMGEN INC - US2019/374542, 2019, A1 Location in patent: Paragraph 0717-0718

10
[ 1295516-68-5 ]
[ 1228675-18-0 ]
5-((R)-5-methyl-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptan-2-carboxylate tert-butyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
400 mg	With 4-dimethylaminopyridine In 1-methyl-pyrrolidin-2-one at 120℃; for 12h; Inert atmosphere;	15.a; 37.f f)5-((R)-5-methyl-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicycl o[4.1.0]heptan-2-carboxylate Under the protection of nitrogen, (R)-4-chloro-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-7(6H)-one (300 mg), tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (455 mg) and 4-dimethylaminopyridine (600 mg) were dissolved in N-methylpyrrolidone (5 mL). The reaction solution was stirred at 120°C for 12 hours, then poured into 50 mL of water, extracted with ethyl acetate (20 mL×2), and washed with 15 mL of saturated sodium chloride solution. The organic phase was dried and desolventized to obtain a crude product. The crude product was separated and purified by silica gel column chromatography (PE:EA=1:1-1:2) to obtain 400 mg of a yellow solid.
0.28 g	With 4-dimethylaminopyridine In 1-methyl-pyrrolidin-2-one at 22 - 140℃; for 3h; Inert atmosphere;	2.a a) 5-((R)-5-methyl-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptan-2-carboxylate tert-butyl ester Under nitrogen protection, (R)-4-chloro-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-7(6H)-one (0.21 g), 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate tert-butyl ester (0.31 g) and 4-dimethylaminopyridine (0.39 g) were dissolved in N-methylpyrrolidone (5 mL) at 22°C,then heated to 140°C,The reaction was carried out for 3 hours.After the reaction is complete,The reaction solution was cooled to 20°C,Pour into 20mL ice water,Ethyl acetate (20mL×2) extraction,Washed with saturated brine (10mL×3),The solvent was evaporated under reduced pressure,Silica gel column chromatography (petroleum ether:ethyl acetate=3:11:1) separated,0.28 g of pale yellow liquid was obtained.
0.28 g	With 4-dimethylaminopyridine In 1-methyl-pyrrolidin-2-one at 22 - 140℃; for 3h; Inert atmosphere;	2.a a) 5-((R)-5-methyl-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidin-4-yl)-2,5-diazabicyclo[4.1.0]heptan-2-carboxylate tert-butyl ester Under nitrogen protection, (R)-4-chloro-5-methyl-5,8-dihydropyrido[2,3-d]pyrimidin-7(6H)-one (0.21 g), 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate tert-butyl ester (0.31 g) and 4-dimethylaminopyridine (0.39 g) were dissolved in N-methylpyrrolidone (5 mL) at 22°C,then heated to 140°C,The reaction was carried out for 3 hours.After the reaction is complete,The reaction solution was cooled to 20°C,Pour into 20mL ice water,Ethyl acetate (20mL×2) extraction,Washed with saturated brine (10mL×3),The solvent was evaporated under reduced pressure,Silica gel column chromatography (petroleum ether:ethyl acetate=3:11:1) separated,0.28 g of pale yellow liquid was obtained.

Reference： [1]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3919491, 2021, A1 Location in patent: Paragraph 0187-0289; 0347; 0352
[2]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - WO2022/17448, 2022, A1 Location in patent: Page/Page column 10-11
[3]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - WO2022/17449, 2022, A1 Location in patent: Page/Page column 8

11
[ 1228675-18-0 ]
C₁₇H₂₃N₅O₄*ClH [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 95 °C / Inert atmosphere; Sealed tube 2: hydrogenchloride / isopropyl alcohol / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3919491, 2021, A1

12
[ 1228675-18-0 ]
C₂₉H₃₇ClN₆O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 95 °C / Inert atmosphere; Sealed tube 2: hydrogenchloride / isopropyl alcohol / 2 h / 20 °C 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 12 h / 20 °C

Reference： [1]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3919491, 2021, A1

13
[ 1228675-18-0 ]
C₂₄H₂₉ClN₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: N-ethyl-N,N-diisopropylamine / acetonitrile / 6 h / 95 °C / Inert atmosphere; Sealed tube 2: hydrogenchloride / isopropyl alcohol / 2 h / 20 °C 3: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 12 h / 20 °C 4: hydrogenchloride / methanol; 1,4-dioxane / 2 h / 20 °C

Reference： [1]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3919491, 2021, A1

14
[ 1228675-18-0 ]
(S)-5-chloro-4-methyl-1,4-dihydro-2H-pyrimidino[4,5-d][1,3]oxaazin-2-one [ No CAS ]
C₁₇H₂₃N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
3.2 g	With N-ethyl-N,N-diisopropylamine In acetonitrile at 95℃; for 6h; Inert atmosphere; Sealed tube;	34.e e) tert-butyl 5-((S)-4-methyl-2-oxo-1,4-dihydro-2H-pyrimidin[4,5-d][1,3]oxazin-5-yl)-2,5-diazabicy clo[4.1.0]heptane-2-carboxylate (Compound 34-5a) Compound 34-4a (2g) and tert-butyl 2,5-diazabicyclo[4.1.0]heptane-2-carboxylate (3.58 g) were dissolved in anhydrous MeCN (20 mL), and DIEA (3.89g) was added, and the reaction solution was purged with nitrogen, and the tube was sealed and stirred at 95°C for 6 hours. After the reaction was completed, the reaction solution was concentrated to obtain the crude product of the target product. The crude product was dissolved in DCM, washed with water and concentrated to obtain the crude product, which was separated and purified by column chromatography (EA: PE=1:1) to obtain 3.2 g of a pale brown solid.

Reference： [1]Current Patent Assignee: SINO BIOPHARMACEUTICAL LIMITED - EP3919491, 2021, A1 Location in patent: Paragraph 0302; 0308-0309

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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

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) ]}	{[ 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 -

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. 1228675-18-0 ]

Quality Control of [ 1228675-18-0 ]

Related Doc. of [ 1228675-18-0 ]

Product Details of [ 1228675-18-0 ]

Safety of [ 1228675-18-0 ]

Application In Synthesis of [ 1228675-18-0 ]

[ 1228675-18-0 ] Synthesis Path-Downstream 1~14

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry