[ CAS No. 1224606-06-7 ] {[proInfo.proName]}

Name: 1224606-06-7|(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate|98%
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Quality Control of [ 1224606-06-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1224606-06-7 ]

Product Details of [ 1224606-06-7 ]

CAS No. :	1224606-06-7	MDL No. :	MFCD31657426
Formula :	C₄₃H₇₉NO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NRLNQCOGCKAESA-KWXKLSQISA-N
M.W :	642.09	Pubchem ID :	49785164
Synonyms :	MC3	Chemical Name :	(6Z,9Z,28Z,31Z)-Heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate

Calculated chemistry of [ 1224606-06-7 ]

Physicochemical Properties

Num. heavy atoms :	46
Num. arom. heavy atoms :	0
Fraction Csp3 :	0.79
Num. rotatable bonds :	36
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	211.1
TPSA :	29.54 Å²

Pharmacokinetics

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	1.16 cm/s

Lipophilicity

Log Po/w (iLOGP) :	10.3
Log Po/w (XLOGP3) :	16.02
Log Po/w (WLOGP) :	13.65
Log Po/w (MLOGP) :	8.25
Log Po/w (SILICOS-IT) :	15.24
Consensus Log Po/w :	12.69

Druglikeness

Lipinski :	2.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	3.0
Bioavailability Score :	0.17

Water Solubility

Log S (ESOL) :	-11.54
Solubility :	0.0000000019 mg/ml ; 0.0 mol/l
Class :	Insoluble
Log S (Ali) :	-16.8
Solubility :	0.0 mg/ml ; 1.6e-17 mol/l
Class :	Insoluble
Log S (SILICOS-IT) :	-12.24
Solubility :	0.0000000004 mg/ml ; 0.0 mol/l
Class :	Insoluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	3.0
Synthetic accessibility :	6.43

Safety of [ 1224606-06-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P301+P312-P302+P352-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1224606-06-7 ]

* 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 [ 1224606-06-7 ]

[ 1224606-06-7 ] Synthesis Path-Downstream 1~9

1
[ 75-11-6 ]
[ 1224606-06-7 ]
[ 1347052-30-5 ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)butanoate With dimethyl zinc(II) In hexane; dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: diiodomethane In hexane; dichloromethane at 20℃;	13 To a solution of MC3 (2.1 g, 3.27mmol) in anhydrous C¾C12 (60mL) at 0°C under nitrogen was added 2.5 equivalents diethyl zinc (1M solution in hexanes) (31mL, 3 lmmol). The solution was stirred for 1 hour and then 2.5 equivalents diiodomethane (2.5mL, 3 lmmol) added. The reaction was stirred overnight at room temp. The white suspension was poured into ice (50mL) and diluted to 200mL using ethyl acetate (white solid dissolved). 5% HC1 (lOOmL) was added to wash. The aqueous (acidic) layer was removed and extracted with ethyl acetate (2 x 125mL). The organic (top) layer was washed again with 5% HC1, then saturated NaHC03, water, and brine (150mL each), dried on MgS04, filtered, and concentrated to yield a cloudy pale yellow oil. The procedure above was repeated once to ensure 100% cyclopropylati on. Product was a pale yellow oil. The oil was purified by column chromatography eluting with CHC13 to afford a pale yellow oil. Final yield 1.11 g, 51%.
51%	Stage #1: (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)butanoate With diethylzinc In hexane; dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: diiodomethane In hexane; dichloromethane at 20℃;	30; 32 Synthesis of CP-MC3 Example 30 Synthesis of CP-MC3 CP-MC3 (Compound 45) having the structure shown below was synthesized as described in Scheme 32 below. To a solution of MC3 (2.1 g, 3.27 mmol) in anhydrous CH2Cl2 (60 mL) at 0° C. under nitrogen was added 2.5 equivalents diethyl zinc (1M solution in hexanes) (31 mL, 31 mmol). The solution was stirred for 1 hour and then 2.5 equivalents diiodomethane (2.5 mL, 31 mmol) added. The reaction was stirred overnight at room temp. The white suspension was poured into ice (50 mL) and diluted to 200 mL using ethyl acetate (white solid dissolved). 5% HCl (100 mL) was added to wash. The aqueous (acidic) layer was removed and extracted with ethyl acetate (2*125 mL). The organic (top) layer was washed again with 5% HCl, then saturated NaHCO3, water, and brine (150 mL each), dried on MgSO4, filtered, and concentrated to yield a cloudy pale yellow oil. The procedure above was repeated once to ensure 100% cyclopropylation. Product was a pale yellow oil. The oil was purified by column chromatography eluting with CHCl3 to afford a pale yellow oil. Final yield 1.11 g, 51%.

Reference： [1]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - WO2011/141704, 2011, A1 Location in patent: Page/Page column 109-110
[2]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - US2013/123339, 2013, A1 Location in patent: Paragraph 0726; 0727

2
[ 1169768-28-8 ]
[ 69954-66-1 ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane;Inert atmosphere;	Dilinoleylmethanol (7.8 g, 14.9 mmol), dimethylaminobutyric acid hydrochloride (2.99 g, 17.8 mmol) and a stir bar were added to 500 mL RBF. The flask was flushed with nitrogen and anh. DCM (120 mL) added, followed by EDCI (3.6 g, 18.8 mmol), DIPEA (6.3 mL, 36.3 mmol) and DMAP (450 mg, 3.69 mmol). The reaction was stirred overnight. The reaction was diluted with DCM (300 mL) and washed with sat. NaHC03 (200 mL), water (300 mL) and sat. NaCL (200 mL). Each aq. wash was extracted once with DCM (50 mL). Organics were combined, dried (MgS04) and concentrated to yield a yellow oil with some crystalline matter. This was purified by chromatography (0-2% MeOH in CHC13) to yield Lin-MC3 as a pale yellow oil (9.0 g, 14.1 mmol, 95%).
95%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane;Inert atmosphere;	General procedure: Step 3: Dilinoleylmethanol (7.8 g, 14.9 mmol), dimethylaminobutyric acid hydrochloride (2.99 g, 17.8 mmol) and a stir bar were added to 500 mL RBF. The flask was flushed with nitrogen and anh. DCM (120 mL) added, followed by EDCI (3.6 g, 18.8 mmol), DIPEA (6.3 mL, 36.3 mmol) and DMAP (450 mg, 3.69 mmol). The reaction was stirred overnight. The reaction was diluted with DCM (300 mL) and washed with sat. NaHCO3 (200 mL), water (300 mL) and sat. NaCL (200 mL) Each aq. wash was extracted once with DCM (50 mL). Organics were combined, dried (MgSO4) and concentrated to yield a yellow oil with some crystalline matter. This was purified by chromatography (0-2% MeOH in CHCl3) to yield Lin-MC3 as a pale yellow oil (9.0 g, 14.1 mmol, 95%).
95%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane;Inert atmosphere;	10554] STEP 3: Dilinoleylmethanol (7.8 g, 14.9 mmol), dimethylaminobutyric acid hydrochloride (2.99 g, 17.8 mmol) and a stir bar were added to 500 mE REF. The flask was flushed with nitrogen and anh. DCM (120 mE) added, followed by EDCI (3.6 g, 18.8 mmol), DIPEA(6.3 mE, 36.3 mmol) and DMAP (450 mg, 3.69 mmol). The reaction was stirred overnight. The reaction was diluted with DCM (300 mE) and washed with sat. NaHCO3 (200 mE), water (300 mE) and sat. NaCE (200 mE). Each aq. wash was extracted once with DCM (50 mE). Organics were combined, dried (MgSO4) and concentrated to yield a yellow oil with some crystalline matter. This was purified by chromatography (0-2% MeOR in CHC13) to yield Ein-MC3 as a pale yellow oil (9.0 g, 14.1 mmol, 95%).

91%		Example 5 Synthesis of heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)-butanoate (CL01), according to the following reaction formula Into a 100 mL glass reactor, product 6a (5 g, 9.5 mmol) was added and dissolved in 40 mL of DCM, following by addition of material 9 (4-(dimethylamino) butyric acid hydrochloride salt) (1.9 g, 11.4 mmol), diisopropylethylamine (2.5 mL), and DMAP (0.14 g, 1.4 mmol). After stirred the reaction mixture for 5 min at room temperature, EDC.HCl (2.78 g, 14.5 mmol) was added, then the reaction mixture was stirred overnight at room temperature. After the completion of reaction, the mixture was diluted with 20 mL of DCM, washed with saturated NaHCO3 (16 mL), water (16 mL) and brine solution (16 mL), dried over anhydrous Na2SO4, and filtered. The organic phase was concentrated, to obtain a crude product of about 6.25 g. The crude product was purified with a Flash column (packed the column with 90 g of silica gel, and 210 mL of 0.1% TEA in DCM; mobile phases were: 140 mL of 0.1% TEA solution in DCM; 560 mL solution comprising 2% of methanol and 98% of 0.1% TEA solution in DCM; 140 mL solution comprising of 2.5% of methanol and 97.5% of 0.1% TEA solution in DCM; 420 mL solution comprising 3% methanol and 97% of 0.1% TEA solution in DCM), to obtained pure product 10 (CL01, 5.5 g, 91%) as a colorless oil. 1H-NMR (CDCl3, 400 MHz), delta=5.47-5.24 (m, 8H), 4.93-4.77 (m, 1H), 2.85-2.66 (m, 4H), 2.37-2.22 (m, 4H), 2.12-1.91 (m, 9H), 1.85-1.69 (m, 2H), 1.49 (d, J=5.4, 4H), 1.39-1.17 (m, 39H), 0.90-0.80 (m, 6H).
91%		The dilinoleyl methanol 6 (144 g, 272 mmol) was dissolved in 1 L of dichloromethane and to it the hydrochloride salt of dimethylaminobutyric acid 7 (55 g, 328 mmol) was added followed by diisopropylethylamine (70 mL) and DMAP (4 g). After stirring for 5 min. at ambient temperature, MC1 (80 g, 417 mmol) was added and the reaction mixture was stirred at room temperature overnight after which the TLC (silica gel, 5% MeOH in CH2Cl2) analysis showed complete disappearance of the starting alcohol. The reaction mixture was diluted with CH2Cl2 (500 mL) and washed with saturated NaHCO3 (400 mL), water (400 mL) and brine (500 mL). The combined organic layers were dried over anhyd. Na2SO4 and solvents were removed in vacuo. The crude product (180 g) thus obtained was purified by Flash column chromatography [2.5 Kg silica gel, Using the following eluents i) column packed with 6 L of 0.1% NEt3 in DCM; after loading ii) 4 L of 0.1% NEt3 in DCM; iii) 16 L of 2% MeOH-98% of 0.1% NEt3 in DCM; iv) 4 L of 2.5% MeOH-97.5% of 0.1% NEt3 in DCM; v) 12 L of 3% MeOH-97% of 0.1% NEt3 in DCM] to isolate the pure product 8 (MC3, 159 g, 91%) as a colorless oil. 1H NMR (400 MHz, CDCl3): delta 5.46-5.23 (m, 8H), 4.93-4.77 (m, 1H), 2.83-2.66 (m, 4H), 2.37-2.22 (m, 4H), 2.20 (s, 6H), 2.10-1.96 (m, 9H), 1.85-1.69 (m, 2H), 1.49 (d, J=5.4, 4H), 1.39-1.15 (m, 39H), 0.95-0.75 (m, 6H). 13C NMR (101 MHz, CDCl3): delta 173.56, 130.38, 130.33, 128.17, 128.14, 7754, 77.22, 76.90, 74.44, 59.17, 45.64, 34.36, 32.69, 31.73, 29.87, 29.76, 29.74, 29.70, 29.56, 29.50, 27.44, 27.41, 25.84, 25.55, 23.38, 22.78, 14.27. EI-MS (+ve): MW calc. for C43H79NO2 (M+H)+: 642.6. found: 642.6.
91%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 0.0833333h;	Dilinoleyl methanol 6 (144 g, 272 mmol) was dissolved in 1 L of dichloromethane to which was added the hydrochloride salt of dimethylaminobutyric acid 7 (55 g, 328 mmol) followed by the addition of diisopropylethylamine (70 mL) and DMAP (4 g) . After stirring at ambient temperature for 5 minutes, EDCI (80 g, 417 mmol) was added and the reaction mixture was stirred overnight at room temperature before analysis by TLC (silica gel, 5% MeOH in CH 2 Cl 2) analysis indicated complete disappearance of the starting alcohol It was shown. The reaction mixture was diluted with CH 2 Cl 2 (500 mL) and washed with saturated NaHCO 3 (400 mL), water (400 mL) and brine (500 mL). The combined organic layers were dried over anhydrous Na 2 SO 4 and the solvent was removed in vacuo. The crude product thus obtained (180 g) was purified by flash column chromatography [2.5 Kg silica gel using the following eluent, i) a column packed with 6 L DCM containing 0.1% NEt 3; Ii) DCM 4 L containing 0.1% NEt 3; iii) DCM 16 L containing 2% MeOH and 98% 0.1% NEt 3; iv) 2. DCM 4 L containing 5% MeOH and 97.5% 0.1% NEt 3; v) DCM 12 L with 3% MeOH and 97% 0.1% NEt 3] to give pure product 8 MC 3, 159 g, 91%) was isolated as a colorless oil.
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	A solution of (6Z,9Z,28Z,31Z)- heptatriaconta-6,9,28 ,3 1 -tetraen- 1 9-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1 -ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Synthesis of MC3 (0238) Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. (0679) Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Synthesis of MC3 (0267) Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl-4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Synthesis of MC3 (0265) Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Synthesis of MC3 Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31- tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)- heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61g) and l-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Preparation of DLin-M-C3-DMA {i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31- tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)- heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61g) and l-ethyl-3-(3- dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,3 1Z)-heptatriaconta-6,9,28,3 1- tetraen-19-yl 4-(dimethylamino)hutanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,3 1-tetraen-1 9-ol (0.53 g), 4-N,N-dimethyiaminohutyric acid hydrochloride (0.51 g), 4-N,N-dirnethylaminopyridine (0.61 g) and I -ethyl-3-(3 - dimethylaminopropyl)carhodiiinide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrousmagnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;	A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,Ndimethylaminobutyricacid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. Thesolution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractionswere dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passeddown a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purifiedproduct were combined and the solvent removed, yielding a colorless oil (0.54 g).

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[15]Patent: WO2016/205323,2016,A1 .Location in patent: Page/Page column 82
[16]Patent: WO2017/48843,2017,A1 .Location in patent: Page/Page column 146
[17]Patent: EP3412774,2018,A1 .Location in patent: Paragraph 0391

3
[ 4102-60-7 ]
[ 1224606-06-7 ]

Reference： [1]Patent: WO2011/141704,2011,A1
[2]Angewandte Chemie - International Edition,2012,vol. 51,p. 8529 - 8533
[3]Patent: US2015/272886,2015,A1
[4]Patent: US9394234,2016,B2
[5]Patent: JP5819291,2015,B2
[6]Patent: US2013/123339,2013,A1
[7]Patent: US2016/32320,2016,A1

4
[ 51154-39-3 ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: magnesiumbromide etherate / diethyl ether / Inert atmosphere 2.1: magnesium / tetrahydrofuran / 4 h / 45 °C / Inert atmosphere 2.2: 20 °C 2.3: 1.5 h / 20 °C 3.1: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: magnesium bromide ethyl etherate / diethyl ether / 26 h / Inert atmosphere; Reflux 2.1: iodine; magnesium / diethyl ether / 1 h / 35 °C / Inert atmosphere 2.2: 1 h / 20 °C / Inert atmosphere 2.3: 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C
	Multi-step reaction with 3 steps 1.1: lithium bromide / N,N-dimethyl-formamide / -10 - 45 °C / Inert atmosphere 2.1: magnesium; 1,1-dibromomethane / diethyl ether / 1 h / 40 °C / Inert atmosphere; Reflux 2.2: 1 h / 10 - 20 °C 3.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.08 h / 20 °C 3.2: 20 °C

	Multi-step reaction with 3 steps 1.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 2.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 2.2: 10 - 20 °C / Large scale 2.3: 18 h / 65 °C / Large scale 3.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 3.2: 20 °C
	Multi-step reaction with 3 steps 1.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 2.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 2.2: 10 - 20 °C / Large scale 3.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 3.2: 20 °C
	Multi-step reaction with 3 steps 1.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 2.1: magnesium / diethyl ether / 3.5 h / 40 °C / Inert atmosphere; Large scale 2.2: 3.5 h / 20 °C / Inert atmosphere; Large scale 2.3: 18 h / 65 °C / Inert atmosphere; Large scale 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0.08 h / 20 °C
	Multi-step reaction with 3 steps 1.1: magnesium bromide ethyl etherate / diethyl ether / Inert atmosphere; Sealed tube 2.1: magnesium / tetrahydrofuran / 4.25 h / 45 °C / Inert atmosphere 2.2: 0 - 20 °C 2.3: 1.5 h / 20 °C 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: magnesium bromide diethyl etherate / diethyl ether / Sealed tube; Inert atmosphere 2.1: magnesium / tetrahydrofuran / 4 h / 45 °C / Inert atmosphere 2.2: 20 °C / Inert atmosphere 3.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: magnesium bromide ethyl etherate / diethyl ether / 26 h / Inert atmosphere; Reflux 2.1: iodine; magnesium / diethyl ether / 1 h / 35 °C 2.2: 20 °C 3.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.08 h / 20 °C 3.2: 20 °C

Reference： [1]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - WO2011/141704, 2011, A1
[2]Jayaraman, Muthusamy; Ansell, Steven M.; Mui, Barbara L.; Tam, Ying K.; Chen, Jianxin; Du, Xinyao; Butler, David; Eltepu, Laxman; Matsuda, Shigeo; Narayanannair, Jayaprakash K.; Rajeev, Kallanthottathil G.; Hafez, Ismail M.; Akinc, Akin; Maier, Martin A.; Tracy, Mark A.; Cullis, Pieter R.; Madden, Thomas D.; Manoharan, Muthiah; Hope, Michael J. [Angewandte Chemie - International Edition, 2012, vol. 51, # 34, p. 8529 - 8533]
[3]Current Patent Assignee: BIOMICS BIOTECHNOLOGIES - US2015/272886, 2015, A1
[4]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[5]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[6]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - JP5819291, 2015, B2
[7]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - US2013/123339, 2013, A1
[8]Current Patent Assignee: ARBUTUS BIOPHARMA CORP - US2016/32320, 2016, A1
[9]Current Patent Assignee: GENERATION BIO - KR2020/51708, 2020, A

5
[ 506-43-4 ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 20 °C / Cooling with ice 2.1: magnesium bromide ethyl etherate / diethyl ether / 26 h / Inert atmosphere; Reflux 3.1: iodine; magnesium / diethyl ether / 1 h / 35 °C / Inert atmosphere 3.2: 1 h / 20 °C / Inert atmosphere 3.3: 20 °C 4.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C
	Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 2 h / -10 - 0 °C / Inert atmosphere 2.1: lithium bromide / N,N-dimethyl-formamide / -10 - 45 °C / Inert atmosphere 3.1: magnesium; 1,1-dibromomethane / diethyl ether / 1 h / 40 °C / Inert atmosphere; Reflux 3.2: 1 h / 10 - 20 °C 4.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.08 h / 20 °C 4.2: 20 °C
	Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 4 h / -10 - 0 °C / Inert atmosphere; Large scale 2.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 3.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 3.2: 10 - 20 °C / Large scale 3.3: 18 h / 65 °C / Large scale 4.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 4.2: 20 °C

	Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 4 h / -10 - 0 °C / Inert atmosphere; Large scale 2.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 3.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 3.2: 10 - 20 °C / Large scale 4.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 4.2: 20 °C
	Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 20 °C / Cooling with ice 2.1: magnesium bromide ethyl etherate / diethyl ether / 26 h / Inert atmosphere; Reflux 3.1: iodine; magnesium / diethyl ether / 1 h / 35 °C 3.2: 20 °C 4.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.08 h / 20 °C 4.2: 20 °C

Reference： [1]Jayaraman, Muthusamy; Ansell, Steven M.; Mui, Barbara L.; Tam, Ying K.; Chen, Jianxin; Du, Xinyao; Butler, David; Eltepu, Laxman; Matsuda, Shigeo; Narayanannair, Jayaprakash K.; Rajeev, Kallanthottathil G.; Hafez, Ismail M.; Akinc, Akin; Maier, Martin A.; Tracy, Mark A.; Cullis, Pieter R.; Madden, Thomas D.; Manoharan, Muthiah; Hope, Michael J. [Angewandte Chemie - International Edition, 2012, vol. 51, # 34, p. 8529 - 8533]
[2]Current Patent Assignee: BIOMICS BIOTECHNOLOGIES - US2015/272886, 2015, A1
[3]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[4]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[5]Current Patent Assignee: GENERATION BIO - KR2020/51708, 2020, A

6
[ 1169768-28-8 ]
[ 693-11-8 ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 10h;	A. Lipid Synthesis DLin-MC3-DMA and precursors were synthesized according to procedures described in WO 2010054401 herein incorporated by reference in its entirety. A mixture of dilinoleyl methanol (1.5 g, 2.8 mmol, 1 eq), N,N-dimethylaminobutyric acid (1.5 g, 2.8 mmol, 1 eq), DIPEA (0.73 mL, 4.2 mmol, 1.5 eq) and TBTU(1.35 g, 4.2 mmol, 1.5 eq) in 10 mL of DMF was stirred for 10 h at room temperature. Then the reaction mixture was diluted in ether and washed with water. The organic layer was dried over anhydrous sodium sulfate, filtrated and concentrated under reduced pressure. The crude product was purified by silica gel chromatography using a gradient DCM to DCM:MeOH 98:2. Subsequently the target compound was subjected to an additional RP-HPLC purification which was done using a YMC-Pack C4 column to afford the target compound.
	With O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 10h;
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	Synthesis of MC3 Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,31-tetraen-19-ol (0.53 g), 4-N,N-dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g) in dichloromethane (5 mL) was stirred at room temperature overnight. The solution was washed with dilute hydrochloric acid followed by dilute aqueous sodium bicarbonate. The organic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. The residue was passed down a silica gel column (20 g) using a 1-5% methanol/dichloromethane elution gradient. Fractions containing the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).

Reference： [1]Current Patent Assignee: MODERNA THERAPEUTICS INC - US2013/156849, 2013, A1 Location in patent: Paragraph 0947
[2]Current Patent Assignee: MODERNA THERAPEUTICS INC - US2016/38612, 2016, A1 Location in patent: Paragraph 1412
[3]Current Patent Assignee: ALNYLAM PHARMACEUTICALS INC - US2018/135057, 2018, A1 Location in patent: Paragraph 0354

7
[ 1169768-28-8 ]
4-(dimethylamino) butanoic acid hydrochloride [ No CAS ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
0.54 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃;	Synthesis of MC3 Preparation of DLin-M-C3-DMA (i.e., (6Z,9Z,28Z,3 1Z)-heptatriaconta-6,9,28,3 1 -tetraen-i 9-yl 4-(dimethylamino)butanoate) was as follows. A solution of (6Z,9Z,28Z,31Z)-heptatriaconta-6,9,28,3 1 -tetraen-i 9-ol (0.53 g), 4-N,N-25 dimethylaminobutyric acid hydrochloride (0.51 g), 4-N,N-dimethylaminopyridine (0.61 g) and 1 -ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.53 g)in dichloromethane (5 mL) was stirred at room temperature30 overnight. The solution was washed with dilute hydrochloricacid followed by dilute aqueous sodium bicarbonate. Theorganic fractions were dried over anhydrous magnesium sulphate, filtered and the solvent removed on a rotovap. Theresidue was passed down a silica gel colunm (20 g) using a1-5% methanol/dichloromethane elution gradient. Fractionscontaining the purified product were combined and the solvent removed, yielding a colorless oil (0.54 g).

Reference： [1]Current Patent Assignee: SANOFI - US9127274, 2015, B2 Location in patent: Page/Page column 78

8
[ 60-33-3 ]
[ 1224606-06-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium bis(2-methoxyethoxy)aluminium dihydride / tetrahydrofuran; toluene / 0 - 20 °C / Inert atmosphere 2.1: dmap; triethylamine / dichloromethane / 2 h / -10 - 0 °C / Inert atmosphere 3.1: lithium bromide / N,N-dimethyl-formamide / -10 - 45 °C / Inert atmosphere 4.1: magnesium; 1,1-dibromomethane / diethyl ether / 1 h / 40 °C / Inert atmosphere; Reflux 4.2: 1 h / 10 - 20 °C 5.1: N-ethyl-N,N-diisopropylamine; dmap / dichloromethane / 0.08 h / 20 °C 5.2: 20 °C
	Multi-step reaction with 5 steps 1.1: vitride / tetrahydrofuran; toluene / 5.75 h / 0 - 20 °C / Inert atmosphere; Large scale 2.1: dmap; triethylamine / dichloromethane / 4 h / -10 - 0 °C / Inert atmosphere; Large scale 3.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 4.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 4.2: 10 - 20 °C / Large scale 4.3: 18 h / 65 °C / Large scale 5.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 5.2: 20 °C
	Multi-step reaction with 5 steps 1.1: vitride / tetrahydrofuran; toluene / 5.75 h / 0 - 20 °C / Inert atmosphere; Large scale 2.1: dmap; triethylamine / dichloromethane / 4 h / -10 - 0 °C / Inert atmosphere; Large scale 3.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 4.1: magnesium / diethyl ether / 40 - 45 °C / Inert atmosphere; Large scale 4.2: 10 - 20 °C / Large scale 5.1: dmap; N-ethyl-N,N-diisopropylamine / dichloromethane / 0.08 h / 20 °C 5.2: 20 °C

Multi-step reaction with 4 steps 1.1: dmap; triethylamine / dichloromethane / 4 h / -10 - 0 °C / Inert atmosphere 2.1: lithium bromide / N,N-dimethyl-formamide / 1.5 h / -10 - 0 °C / Inert atmosphere; Large scale 3.1: magnesium / diethyl ether / 3.5 h / 40 °C / Inert atmosphere; Large scale 3.2: 3.5 h / 20 °C / Inert atmosphere; Large scale 3.3: 18 h / 65 °C / Inert atmosphere; Large scale 4.1: dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0.08 h / 20 °C

Reference： [1]Current Patent Assignee: BIOMICS BIOTECHNOLOGIES - US2015/272886, 2015, A1
[2]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[3]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - US9394234, 2016, B2
[4]Current Patent Assignee: ARBUTUS BIOPHARMA CORP; ALNYLAM PHARMACEUTICALS INC - JP5819291, 2015, B2

9
[ 1224606-06-7 ]
C₄₃H₈₇NO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With palladium 10% on activated carbon; hydrogen In methanol; ethyl acetate at 20℃;	17 Compound 7023: Compound 7023:To a solution of compound 7022 in methanol:ethyalcetate solvent mixture (2:1) was added 10% Pd/C, removed air by vacuum, purged with argon, repeated the cycle (2×), finally purged with H2, and continued the reaction under H2 at room temperature for overnight. After completion of the reaction, filtered through small pad of celite, washed with ethyl acetate, evaporated the solvent and purified by column chromatography using dichloromethane:methanol (5%) as gradients to get pure white solid form of compound 7023 in 64% (0.64 g) yields. 1H NMR (400 MHz, CDCl3) δ 5.37 (s, 0H), 4.85 (p, J=6.2, 1H), 2.29 (dt, J=14.8, 7.5, 4H), 2.21 (s, 6H), 1.84-1.71 (m, 2H), 1.49 (d, J=5.4, 4H), 1.36-1.13 (m, 64H), 0.87 (t, J=6.8, 6H). 13C NMR (101 MHz, cdcl3) δ 173.58, 77.54, 77.22, 76.91, 74.49, 59.17, 45.64, 34.36, 32.83, 32.70, 32.15, 29.92, 29.88, 29.81, 29.78, 29.58, 25.55, 23.36, 22.91, 14.33. Calc. mass for the C43H87NO2: 649.6. found 650.8.

Reference： [1]Current Patent Assignee: ALNYLAM PHARMACEUTICALS INC; ARBUTUS BIOPHARMA CORP - US9186325, 2015, B2 Location in patent: Page/Page column 122; 123

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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
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Code	Phrase
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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.
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P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
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P272	Contaminated work clothing should not be allowed out of the workplace.
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P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
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P284	Wear respiratory protection.
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Response
Code	Phrase
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P304	IF INHALED:
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P320
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P321
P322
P330	Rinse mouth.
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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.
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P370	In case of fire:
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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.
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Storage
Code	Phrase
P401
P402	Store in a dry place.
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P411
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P413
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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.
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{[ 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 -

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. 1224606-06-7 ] {[proInfo.proName]}

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[ 1224606-06-7 ] Synthesis Path-Downstream 1~9

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