146426-40-6|2-(2-Chlorophenyl)-5,7-dihydroxy-8-((3S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one| Ambeed

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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1
[ 146426-40-6 ]
[ 144-49-0 ]
[ 2226731-30-0 ]

Yield	Reaction Conditions	Operation in experiment
63%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	24 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1-methylpiperidin-3-yl 2-fluoroacetate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) and 2- fluoroacetic acid (0.068 g, 0.755 mmol, 1.1 eq) in dimethylformamide (10 mL) at 0°C, triethylamine (0.32 mL, 2.05 1 mmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) wereadded. The reaction mixture was stirred for 16 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford TFA salt of (3 S, 4R)-4-(2-(2- chlorophenyl)-5, 7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl 2- fluoroacetate as a yellow solid (0.21g, 63 %). LC/MS m/z: 462.2 [M+H] HPLC Purity:94.03%; 1HNMR(400MHz, DMSO-d6) : 12.99 (s, 1H), 11.39 (s, 1H), 9.52 (s, 1H),7.57-7.80 (m, 4H), 6.57 (s, 1H), 6.36 (s, 1H), 5.23 (s, 1H), 4.79 (d, J = 50.92 Hz, 2H),3.03-3.19 (m, 7H), 2.75 (d, J = 3.44 Hz, 3H), 1.97 (d, J = 12.84 Hz, 1H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 73

2
[ 146426-40-6 ]
[ 149577-05-9 ]
(3S,4R)-4-(2-(2-chlorophenyl)-5-hydroxy-7-((3-(2-methoxyethoxy)propanoyl)oxy)-4-oxo-4H-chromen-8-yl)-1-methylpiperidin-3-yl 3-(2-methoxyethoxy)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine; In N,N-dimethyl-formamide; at 0 - 20℃; for 12h;	To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, leq) and <strong>[149577-05-9]3-(2-methoxyethoxy)propanoic acid</strong> (0.074 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5 mL) at 0 C, Triethylamine (0.28 mL, 2.05 lmmol, 3.Oeq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) were added. The reaction mixture was stirred for 12 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (50 mL) and extracted with dichloromethane. The organic layer was dried oversodium sulphate and solvent was evaporated under vacuum to afford crude of (3 S, 4R)-4- (2-(2-chlorophenyl)-5 -hydroxy-7-((3 -(2-methoxyethoxy)propanoyl)oxy)-4-oxo-4H- chromen-8-yl)- 1 -methylpiperidin-3 -yl 3 -(2-methoxyethoxy) propanoate (0.3 g, 70%). LC/MS m/z: 662.3 [M+H].

Reference： [1]Patent: WO2018/94275,2018,A1 .Location in patent: Page/Page column 59; 60

3
[ 146426-40-6 ]
[ 149577-05-9 ]
(3S,4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)-1-methylpiperidin-3-yl 3-(2-methoxyethoxy)propanoate [ No CAS ]

Reference： [1]Patent: WO2018/94275,2018,A1

4
[ 146426-40-6 ]
[ 541-41-3 ]
[ 2226731-53-7 ]

Yield	Reaction Conditions	Operation in experiment
0.45 g	In 1-methyl-pyrrolidin-2-one at 20℃; for 6h;	5 2-(2-chlorophenyl)-8-((3S, 4R)-3-((ethoxycarbonyl)oxy)- 1-methylpiperidin-4-yl)-5-hydroxy-4-oxo-4H-chromen-7-yl ethyl carbonate To a stirred solution of2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (1 g, 2.28 mmol, 1.0 eq) in NIVIP (10mL) at 0 °C, diisopropylamine (1.2 mL, 6.86 mmol, 3.0 eq) and ethylchloroformate (0.19mL, 2.28 mmol, 1.0 eq) were added dropwise. The reaction mixture was stirred for 6hours at room temperature. After confirming the reaction by TLC, the reaction mixturewas quenched with ice cold water (20 mL). The solid precipitated was filtered. Crude solid obtained was lyophilized to afford 2-(2-chlorophenyl)-8-((3 S,4R)-3-((ethoxycarbonyl)oxy)- 1 -methylpiperidin-4-yl)-5 -hydroxy-4-oxo-4H-chromen-7-yl ethyl carbonate as a yellow solid (0.45 g). LC/MS m/z: 546.2 [M+H]+.

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 49; 50

5
[ 146426-40-6 ]
[ CAS Unavailable ]
[ 2226731-54-8 ]

Yield	Reaction Conditions	Operation in experiment
1 g	In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 6h;	6 2-(2-chlorophenyl)-5-hydroxy-8-((3S, 4R)-3-((methoxycarbonyl)oxy)-1- methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl methyl carbonate To a stirred solution of2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (1 g, 2.28 mmol, 1.0 eq) in NIVIP (10 mL) at 0 °C, diisopropylamine (1.2 mL, 6.86 mmol, 3.0 eq) and methylchloroformate(0.16 mL, 2.28 mmol, 1.0 eq) were added dropwise. The reaction mixture was stirred for6 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (20 mL). The solid precipitate was filtered. Crude solid obtained was lyophilized to afford 2-(2-chlorophenyl)-5 -hydroxy-8-((3 S, 4R)-3 - ((methoxycarbonyl)oxy)- 1 -methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl methyl carbonate as a yellow solid (1 g). LC/MS m/z: 518.2 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 50; 51

6
[ 146426-40-6 ]
[ 41891-13-8 ]
[ 2226731-13-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 6h;	7 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl ethylcarbamate To a stirred solution of2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (1 g, 2.28 mmol, 1.0 eq) in NIVIP (10mL) at 0 °C, diisopropylamine (1.2 mL, 6.86 mmol, 3.0 eq) and ethylcarbamic chloride (0.25 g, 2.28 mmol, 1.0 eq) were added dropwise. The reaction mixture was stirred for 6 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (20 mL). The solid precipitated was filtered. The solid obtained was lyophilized to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5 , 7-dihydroxy-4-oxo- 4H-chromen-8-yl)-1-methylpiperidin-3-yl ethylcarbamate as a yellow solid (0.69 g, 69 %).LC/MS m/z: 471.0 [M+H] HPLC Purity: 98.32%; 1H NMR (400 MHz, DMSO-d6)’5:12.97 (s, 1H), 10.67 (s, 1H), 7.56-7.79 (m, 4H), 6.50 (s, 1H), 6.33 (s, 1H), 6.11 (s, 1H),4.92 (s, 1H), 3.28-3.32 (m, 1H), 2.77-3.06 (m, 5H), 2.15 (d, J = 5.84 Hz, 4H), 1.96 (t, J =11.48 Hz, 1H), 1.66 (d, J = 11.28 Hz, 1H), 0.85 (t, J = 7.04 Hz, 3H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 51; 52

7
[ 146426-40-6 ]
[ 6452-47-7 ]
[ 2226731-44-6 ]
[ 2226731-14-0 ]

Yield	Reaction Conditions	Operation in experiment
	In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 2h;	8 2-(2-chlorophenyl)-5-hydroxy-8-((3S, 4R)- 1-methyl-3-((methylcarbamoyl)oxy)piperidin-4-yl)-4-oxo-4H-chromen-7-yl methylcarbamate To a stirred solution of2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (1 g, 2.28 mmol, 1.0 eq) in NIVIP (10v mL) at 0 °C, diisopropylamine (1.2 mL, 6.86 mmol, 3.0 eq) and methylcarbamic chloride (0.21 mL, 2.28 mmol, 1.0 eq) were added dropwise. The reaction mixture was stirred for 2 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (20 mL). The solid precipitated was filtered. Crude solidobtained was lyophilized to afford mixture of 2-(2-chlorophenyl)-5-hydroxy-8-((3 S, 4R)-3 -hydroxy- 1 -methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl methylcarbamate and (3 S, 4R)-4-(2-(2-chlorophenyl)-5 , 7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 - yl methylcarbamate as a yellow solid (1 g). LC/MS m/z: 459.0 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 52; 53

8
[ 146426-40-6 ]
[ 79-03-8 ]
[ 2226731-15-1 ]

Yield	Reaction Conditions	Operation in experiment
22%	In 1-methyl-pyrrolidin-2-one at 0 - 20℃; for 6h;	9 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl propionate To a stirred solution of2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (1 g, 2.28 mmol, 1.0 eq) in NIVIP (5mL) at 0 °C, diisopropylamine (1.2 mL, 6.36 mmol, 3.0 eq) and propionyl chloride (0.19 mL, 1.14 mmol, 1.0 eq) were added dropwise. The reaction mixture was stirred for 6 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (20 mL). The solid precipitated was filtered. The crude residue obtained was purified by preparative HPLC to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5 , 7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl propionate as a yellow solid (0.15 g, 22%). LC/MS m/z: 458.4 [M+H] HPLC Purity: 92.17%; 1H NMR (400 IVIHz, DMSO-d6) : 12.95 (s, 1H), 11.02 (s, 1H), 7.58-7.81 (m, 4H), 6.57 (s, 1H), 6.34 (s, 1H), 4.98 (s, 1H), 3.30-3.33 (m, 2H), 2.85-2.92 (m, 3H), 1.94-2.13 (m, 7H),1.67 (d, J = 12.00 Hz, 1H), 0.76-0.80 (m, 3H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 53; 54

9
[ 146426-40-6 ]
[ 107-92-6 ]
[ 2226731-16-2 ]

Yield	Reaction Conditions	Operation in experiment
12%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	10 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl butyrate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy- 1 -methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) and butyric acid (0.06 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5 mL) at 0 °C, Triethylamine (0.32 mL, 2.05 lmmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) were added. The reaction mixture was stirred for 16 hours at room temperature. After confirming thereaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl butyrate as an off white solid (0.03 g, 12 %). LC/MS m/z: 472.1 [M+H] HPLC Purity: 97.04%; 1H NMR (400 MHz, DMSO-d6) : 12.97 (s, 1H), 11.43 (s, 1H), 9.83 (s, 1H), 7.64-7.85 (m, 4H), 6.61 (s, 1H), 5.10 (s, 1H), 3.51-3.52 (m, 1H), 3.05-3.10 (m, 6H), 2.09-2.20 (m, 4H), 1.18-1.35 (m, 3H), 0.59-0.61(m, 3H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 54; 55

10
[ 146426-40-6 ]
[ 79-31-2 ]
[ 2226731-17-3 ]

Yield	Reaction Conditions	Operation in experiment
11%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	11 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1-methylpiperidin-3-yl isobutyrate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy- 1 -methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) and butyric acid (0.06 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5mL) at 0 °C, Triethylamine (0.32 mL, 2.05 lmmol, 3.Oeq) and T3P (0.43mL, 1.37mmol, 2.Oeq) were added. Thereaction mixture was stirred for 16 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4- oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl i sobutyrate as an off white solid (0. 025g, 11 %). LC/MS m/z: 471.1 [M+H] HPLC Purity: 98.38; 1H NMR (400 MHz, DMSO20 d6) : 12.96 (s, 1H), 11.07 (s, 1H), 7.60-7.78 (m, 4H), 6.56 (s, 1H), 6.33 (s, 1H), 4.93 (s,1H), 3.28-3.39 (m, 2H), 2.84-2.91 (m, 3H), 1.71-2.11 (m, 4H), 1.24 (s, 2H), 1.06 (d, J=7.08 Hz, 1H), 0.85 (d, J = 6.88 Hz, 3H), 0.76 (d, J = 6.92 Hz, 3H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 55

11
[ 146426-40-6 ]
[ 18162-48-6 ]
[ 2226731-50-4 ]

Yield	Reaction Conditions	Operation in experiment
69%	With 1H-imidazole In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	29; 30 8-((3S, 4R)-3-((tert-butyldimethylsilyl)oxy)- 1-methylpiperidin-4-yl)-2-(2-chlorophenyl)-5,7-dihydroxy-4H-chromen-4-one To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (2 g, 4.57 mmol, 1.0 eq) and imidazole (0.70 g, 8.72 mmol, 2 eq) in dimithylformamide (20 mL) at 0 °C, tertButyldimethylsilyl chloride (0.74 g, 2.28 mmol, 1.0 eq) was added. The reaction mixturewas stirred for 16 hours at room temperature. After confirming the reaction by TLC, the solvent was evaporated under vacuum. The crude residue obtained was purified by preparative HPLC to afford 8-((3 S, 4R)-3 -((tert-butyldimethyl silyl)oxy)- 1- methylpiperidin-4-yl)-2-(2-chlorophenyl)-5 , 7-dihydroxy-4H-chromen-4-one as a yellow solid (1.6 g, 69 %). LC/MS m/z: 514.0 [M-Hf; HPLC Purity: 99.38%.

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 80; 81; 82

12
[ 146426-40-6 ]
[ 120821-20-7 ]
[ 2226731-55-9 ]

Yield	Reaction Conditions	Operation in experiment
15%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	12 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl 3-((tert-butyldimethylsilyl)oxy)propanoate To a stirred solution 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.5 g, 1.14 mmol, 1 eq) and 3-((tert-butyldimethylsilyl)oxy)propanoic acid (0.35 g, 1.75 mmol, 1.5 eq) in dimethylformamide(5 mL) at 0 °C, Triethylamine (0.48 mL, 3.43 mmol, 3.0 eq) and T3P (0.72mL, 2.28mmol,2.0 eq) were added. The reaction mixture was stirred for 12 hours at room temperature.After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (50 mL) and extracted with dichloromethane. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum. The crude residue obtained was purified by flash column chromatography to afford (3 S, 4R)-4-(2-(2-chlorophenyl)- 5, 7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl 3 -((tert20 butyldimethylsilyl)oxy)propanoate as a gummy solid (0.06 g, 15 %). LC/MS m/z: 588.1[M+H] HPLC Purity: 76.01.

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 56; 57

13
[ 146426-40-6 ]
[ CAS Unavailable ]
[ 2226731-56-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	13 (3S, 4R)-4-(2-(2-chlorophenyl)-5-hydroxy-7-((3-methoxypropanoyl)oxy)-4-oxo-4H- chromen-8-yl)- 1-methylpiperidin-3-yl 3-methoxypropanoate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1.0 eq) and 3-methoxypropanoic acid (0.07 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5 mL) at 0°C, Triethylamine (0.32 mL, 2.05 1 mmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) were added. The reaction mixture was stirred for 12 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water(50 mL) and extracted with dichloromethane. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum to afford crude of (3 S, 4R)-4-(2-(2- chlorophenyl)-5 -hydroxy-7-((3 -methoxypropanoyl)oxy)-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl 3-methoxypropanoate (0.3 g, 70%). LC/MS m/z: 574.2 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 58

14
[ 146426-40-6 ]
[ 129919-88-6 ]
[ 2226731-58-2 ]

Yield	Reaction Conditions	Operation in experiment
15%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 12h;	15 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl (S)-2-((tert-butyldimethylsilyl)oxy)propanoate To a stirred solution 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.7 g, 1.60 mmol, 1 eq) and (S)-2- ((tert-butyldimethylsilyl)oxy)propanoic acid (0.4 g, 1.92 mmol, 1.2 eq) in dimethylformamide (5 mL) at 0 °C, Triethylamine (0.67 mL, 4.8 mmol, 3.0 eq) and T3P (0.9 mL, 3.2 mmol, 2.0 eq) were added. The reaction mixture was stirred for 12 hours atroom temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (30 mL) and extracted with dichloromethane. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum. The crude residue obtained was purified by flash column chromatography to afford (3 S, 4R)-4- (2-(2-chlorophenyl)-5 ,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl(S)-2-((tertbutyldimethylsilyl) oxy)propanoate as a gummy solid (0.06g, 15 %). LC/MS m/z:588.3 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 61; 62

15
[ 146426-40-6 ]
[ 15761-38-3 ]
[ 2226731-59-3 ]

Yield	Reaction Conditions	Operation in experiment
52%	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; triethylamine In dichloromethane at 0 - 20℃; for 12h;	16 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1-methylpiperidin-3-yl (tert-butoxycarbonyl)-L-alaninate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) in dichloromethane (5 mL) at 0 °C, Triethylamine (0.28 mL, 2.05 1 mmol, 3.0 eq) and (tertbutoxycarbonyl)-L-alanine (0.41 g, 0.75 mmol, 1.1 eq) were added followed by HOBT(0.12 g, 0.89 mmol, 1.3 eq) and PyBOP (0.57 g, 0.82 mmol, 1.2 eq). The reaction mixture was stirred for 12 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (50 mL) and extracted with dichloromethane, washed with water and brine solution. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum to afford crude of (3 S, 4R)-4-(2-(2-chlorophenyl)-5 ,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl (tertbutoxycarbonyl)-L-alaninate (0.2 g, 52%). LC/MS m/z: 573.2 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 63

16
[ 146426-40-6 ]
[ 4530-20-5 ]
[ 2226731-60-6 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; triethylamine In dichloromethane at 0 - 20℃; for 12h;	17 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl (tert-butoxycarbony1)1ycinate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) indichloromethane (6 mL) at 0 °C, Triethylamine (0.28 mL, 2.05 1 mmol, 3.0 eq) and (tertbutoxycarbonyl) glycine (0.14 g, 0.75 mmol, 1.1 eq) were added followed by HOBT (0.12 g. 0.89 mmol, 1.3 eq) and PyBOP (0.57g, 0.82mmol, 1.2 eq). The reaction mixture was stirred for 12 hours at room temperature. After confirming the reaction by TLC, thereaction mixture was quenched with ice cold water (50 mL) and extracted with dichloromethane, washed with water and brine solution. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum to afford crude of ((3 S, 4R)-4- (2-(2-chlorophenyl)-5 ,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 - yl(tertbutoxycarbonyl)glycinate (0.2 g, 78%). LC/MS m/z: 559.3 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 64; 65

17
[ 146426-40-6 ]
[ 90181-25-2 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
22%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	18 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl N-(tert-butoxycarbonyl)-O-(tert-butyldimethylsilyl)-L-serinate To a stirred solution of N-(tert-butoxycarbonyl)-O-(tertbutyldimethylsilyl)-L-serine (0.7 g, 2.19 mmol, 1 eq) and 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3 S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.76 g,19.Slmmol, 2eq) in dimethylformamide (10 mL) at 0 °C, Triethylamine (0.78 mL, 5.2 mmol, 3 eq) and T3P (1.1 mL, 3.4 mmol, 2 eq) were added. The reaction mixture was stirred for 16 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (50 mL) and extracted withdichloromethane. The organic layer was washed with 10% NaHCO3 solution (50 mL), water (50 mL) and brine solution (50 mL). The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum. The crude residue obtained was purified by preparative HPLC to afford 3 S,4R)-4-(2-(2-chlorophenyl)-5 , 7-dihydroxy-4- oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl N-(tert-butoxycarbonyl)-O-(tert25 butyldimethylsilyl)-L-serinate as a light yellow solid (0.29 g, 22%). LC/MS m/z: 589.2(Cleavage of silyl group mass) [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 65; 66

18
[ 146426-40-6 ]
[ 13734-41-3 ]
[ 2226731-62-8 ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate; benzotriazol-1-ol; triethylamine In dichloromethane at 0 - 20℃; for 12h;	19 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl (tert-butoxycarbonyl)-L-valinate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) in dichloromethane (6 mL) at 0 °C, Triethylamine (0.28 mL, 2.05 1 mmol, 3.0 eq) and (Tertbutoxycarbonyl)-L-valine (0.16 g, 0.75 mmol, 1.1 eq) were added followed by HOBT (0.12 g. 0.89 mmol, 1.3 eq) and PyBOP (0.57 g, 0.82 mmol, 1.2 eq). The reaction mixture was stirred for 12 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was quenched with ice cold water (50 mL) and extracted with dichloromethane, washed with water and brine solution. The organic layer was dried over sodium sulphate and solvent was evaporated under vacuum to afford crude of (3 S, 4R)-4- (2-(2-chlorophenyl)-5 ,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl (tertbutoxycarbonyl)-L-valinate (0.2 g, 72%). LC/MS m/z: 602.1 [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 67; 68

19
[ 146426-40-6 ]
[ 111-14-8 ]
[ 2226731-26-4 ]

Yield	Reaction Conditions	Operation in experiment
11%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	20 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl heptanoate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) andheptanoic acid (0.089 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5 mL) at 0 °C, Triethylamine (0.32 mL, 2.05 mmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) were added. The reaction mixture was stirred for 16 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5,7- dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl heptanoate as a off white5 solid (0.024 g, 11 %). LC/MS m/z: 514.2 [M+H] HPLC Purity: 98.23%; 1H NMR(400MHz, DMSO-d6) : 2.97 (s, 1H), 11.13 (s, 1H), 7.57-7.79 (m, 4H), 6.56 (s, 1H), 6.33(s, 1H), 4.95 (s, 1H), 3.28-3.32 (m, 1H), 2.87-3.27 (m, 3H), 2.51 (d, J = 12.00 Hz, 1H),2.33 (s, 3H), 2.15-2.25 (m, 3H), 1.92 (d, J = 16.00 Hz, 1H), 1.62 (s, 1H), 1.31-1.42 (m,3H), 1.10-1.22 (m, 4H), 0.83-1.04 (m, 4H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 68; 69

20
[ 146426-40-6 ]
[ 109-52-4 ]
[ 2226731-27-5 ]

Yield	Reaction Conditions	Operation in experiment
11%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	21 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1- methylpiperidin-3-yl pentanoate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.3 g, 0.686 mmol, 1 eq) and Valeric acid (0.08 g, 0.686 mmol, 1.0 eq) in dimethylformamide (5 mL) at 0 °C, Triethylamine (0.32 mL, 2.05 mmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) were added. The reaction mixture was stirred for 16 hours at room temperature. Afterconfirming the reaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford (3 S, 4R)-4-(2-(2-chlorophenyl)-5,7- dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl pentanoate as an off white solid (0.024g, 11 %). LC/MS m/z: 486.2 [M+H] HPLC Purity: 96.85%; 1H NMR (400 IVIHz, DMSO-d6) : 2.96 (s, 1H), 11.13 (s, 1H), 7.57-7.79 (m, 4H), 6.56 (s, 1H), 6.32 (s,1H), 4.95 (s, 1H), 2.84 (d, J = 13.60 Hz, 3H), 2.12-2.20 (m, 5H), 1.90-1.96 (m, 3H), 1.60-1.70 (m, 1H), 1.45-1.48 (m, 1H), 1.19-1.28 (m, 3H), 0.96 (d, J = 2.60 Hz, 2H), 0.84-0.94 (m, 1H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 69; 70

21
[ 146426-40-6 ]
[ 229625-50-7 ]
di-tert-butyl (((2-(2-chlorophenyl)-5-hydroxy-8-((3S, 4R)-3-hydroxy-1-methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl)oxy)methyl) phosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%	With caesium carbonate; potassium iodide In N,N-dimethyl-formamide at 0 - 90℃; for 16h;	22 Di-tert-butyl (((2-(2-chlorophenyl)-5-hydroxy-8-((3S, 4R)-3-hydroxy- 1- methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl)oxy)methyl) phosphate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3 S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one (0.48 g, 1.09 mmol, leq), Cesium carbonate (lOg, 3.29mmol, 3eq) and potassium iodide (0.218g, 1.3lmmol, 1.2eq) in dimethylformamide (10 mL) at 0°C, di-tert-butyl (chloromethyl) phosphate (0.34 g, 1.31 mmol, 1.2 eq) was added. The reaction mixture was stirred for 16 hours at 90 °C. After confirming the reaction by TLC, the reaction mixture was filtered through celite and thefiltrate was evaporated under high vacuum. The crude residue obtained was purified bypreparative HPLC to afford di-tert-butyl (((2-(2-chlorophenyl)-5 -hydroxy-8-((3 S, 4R)-3 -hydroxy- 1 -methylpiperidin-4-yl)-4-oxo-4H-chromen-7-yl) oxy) methyl) phosphate as alight yellow solid (0.25 g, 3 8%). LC/MS m/z: 568.2 (t-butyl cleavage mass) [M+H].

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2018/94275, 2018, A1 Location in patent: Page/Page column 70; 71

22
[ 146426-40-6 ]
[ 445-29-4 ]
[ 2226731-29-7 ]

Yield	Reaction Conditions	Operation in experiment
11%	With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; triethylamine In N,N-dimethyl-formamide at 0 - 20℃; for 16h;	23 (3S, 4R)-4-(2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1-methylpiperidin-3-yl 2-fluorobenzoate To a stirred solution of 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S, 4R)-3- hydroxy- 1 -methylpiperidin-4-yl)-4H-chromen-4-one(0. 3g, 0.686mmo1, 1 eq) and 2- fluorobenzoic acid (0.116 g, 0.755 mmol, 1.leq) in dimethylformamide (10 mL) at 0°C, Triethylamine (0.32 mL, 2.05 1 mmol, 3.0 eq) and T3P (0.43 mL, 1.37 mmol, 2.0 eq) wereadded. The reaction mixture was stirred for 16 hours at room temperature. After confirming the reaction by TLC, the reaction mixture was concentrated. The crude residue obtained was purified by preparative HPLC to afford TFA salt of (3 S, 4R)-4-(2-(2- chlorophenyl)-5, 7-dihydroxy-4-oxo-4H-chromen-8-yl)- 1 -methylpiperidin-3 -yl 2- fluorobenzoate as a light yellow solid (0.03g, 11 %). LC/MS m/z: 524.2 [M+H] HPLCPurity: 99.59%; 1HNMR(400MHz, DMSO-d6): 12.95 (s, 1H), 11.34 (s, 1H), 9.24 (s,1H), 7.26-7.89 (m, 7H), 6.55 (s, 1H), 6.54 (s, 1H), 5.47 (s, 1H), 3.49-3.89 (m, 7H), 3.14-3.25 (m, 2H), 2.66-2.79 (m, 2H), 2.16 (d, J = 13.20 Hz, 1H).

Reference： [1]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Chemical (w/o Dongwoo Fine-Chem) - WO2018/94275, 2018, A1 Location in patent: Page/Page column 72

23
[ 358739-92-1 ]
[ 146426-40-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With BBr₃ In chlorobenzene at 80 - 103℃; for 15h;	10.1.1 Step 1.1: To a clean and dry, three-necked, round-bottomed flask (RBF) (3 L) was added A-1 (90 g, 0.192 mol) and chlorobenzene (774 ml) at room temperature. To the reaction flask was slowly added BBr3 (391.5 g) at room temperature. After completion of BBr3 addition, the temperature of the reaction mixture was slowly raised to 80-83 °C, and the reaction mixture was stirred at the same temperature for 10 hours. The reaction mixture temperature was further raised to 100-103 °C, and the reaction mixture was maintained at 100-103 °C for 5 hours. The reaction progress was monitored by TLC and HPLC. After completion of the reaction, HBr and methyl bromide was removed at room temperature by nitrogen bubbling into the reaction mixture, while maintaining the vigorous stirring. The reaction mixture was slowly quenched with a mixture of methanol (180ml)/water (90ml) (270 ml), followed by methanol (180 ml). The solvent was removed under atmospheric distillation at 25-50 °C to reach the target reaction mass volume of 12 volumes (vol). Then, the reaction mixture pH was adjusted to 3.0 ± 1 using sodium hydroxide solution (48.8 g dissolved in 135 ml of DM water) at 50-55 °C. Again, the solvent was removed under (0568) atmospheric distillation at 50-100 °C to reach the target reaction volume of 12 vol. Then, the pH of the reaction mixture was adjusted to pH 8.1 ± 0.2 using sodium hydroxide solution (8.5 g dissolved in 87 ml of DM water) at 50 °C followed by slow addition of water with constant stirring at 50 °C for 1 hour. The reaction mixture was slowly allowed to come to room temperature and maintained at room temperature for 3 hours. The resulting solid was filtered and washed with a mixture of methanol (315 ml)/water (135 ml) (3 x 450 ml) followed by water (5 x 450 ml). The solid was dried in a vacuum oven at 50-55 °C for 48 hours to obtain A-2 as a yellow solid (70 g, 90%). HPLC Purity: 99.72%.
90%	With BBr₃ In chlorobenzene at 80 - 103℃; for 15h;	13.1.1 Step 1.1: To a clean and dry, three-necked, round-bottomed flask (RBF) (3 L) was added A-1 (90 g, 0.192 mol) and chlorobenzene (774 ml) at room (0502) temperature. To the reaction flask was slowly added BBn (391.5 g) at room (0503) temperature. After completion of BBn addition, the temperature of the reaction mixture was slowly raised to 80-83 °C, and the reaction mixture was stirred at the same temperature for 10 hours. The reaction mixture temperature was further raised to 100- 103 °C, and the reaction mixture was maintained at 100-103 °C for 5 hours. The reaction progress was monitored by TLC and HPLC. After completion of the reaction, HBr and methyl bromide was removed at room temperature by nitrogen bubbling into the reaction mixture, while maintaining the vigorous stirring. The reaction mixture was slowly quenched with a mixture of methanol (180ml)/water (90ml) (270 ml), followed by methanol (180 ml). The solvent was removed under atmospheric distillation at 25-50 °C to reach the target reaction mass volume of 12 volumes (vol). Then, the reaction mixture pH was adjusted to 3.0 ± 1 using sodium hydroxide solution (48.8 g dissolved in 135 ml of DM water) at 50-55 °C. Again, the solvent was removed under atmospheric distillation at 50-100 °C to reach the target reaction volume of 12 vol. (0504) Then, the pH of the reaction mixture was adjusted to pH 8.1 ± 0.2 using sodium hydroxide solution (8.5 g dissolved in 87 ml of DM water) at 50 °C followed by slow addition of water with constant stirring at 50 °C for 1 hour. The reaction mixture was slowly allowed to come to room temperature and maintained at room temperature for 3 hours. The resulting solid was filtered and washed with a mixture of methanol (315 ml)/water (135 ml) (3 x 450 ml) followed by water (5 x 450 ml). The solid was dried in a vacuum oven at 50-55 °C for 48 hours to obtain A-2 as a yellow solid (70 g, 90%). HPLC Purity: 99.72%.
79.9%	With BBr₃ Large scale;	Step 1: A-1 was treated with boron tribromide in chlorobenzene. Removal of byproducts by distillation and crystallization from chlorobenzene-methanol-water resulted in A-2 as free base.

Stage #1: cis-(-)-flavodimethoxol hydrochloride With BBr₃ In methanol; lithium hydroxide monohydrate; chlorobenzene at 25 - 75℃; for 7h; Inert atmosphere; Stage #2: With lithium hydroxide monohydrate; sodium hydroxide In chlorobenzene at 20 - 79℃; Inert atmosphere;

5 Reference Example 5: Manufacturing Method of Crude Alvocidib Free Form Under a nitrogen atmosphere, cis-(-)-flavodimethoxol hydrochloride (40 g) was dissolved in chlorobenzene (354 g) and the mixture was warmed to 75° C. Boron tribromide (177 g) was added dropwise over 4 hours while maintaining the internal temperature at 75° C. A dropping funnel was washed with chlorobenzene (4 g) and added. The mixture was warmed to 80° C. and incubated for 6 hours. The mixture was cooled to room temperature and stirred overnight. The mixture was warmed to 100° C., and incubated and stirred for 2 hours and 30 minutes. The mixture was cooled to 20° C., and a mixture of water (40 g) and methanol (63 g) was added dropwise over 3 hours while maintaining the internal temperature at 25° C. The mixture was incubated and stirred for 15 minutes at 25° C., and then methanol (63 g) was added dropwise while maintaining the internal temperature at 25° C. The mixture was stirred overnight at 25° C. The mixture was warmed to an internal temperature of 72 to 79° C. and concentrated by atmospheric distillation (distillation volume of 79 g). The mixture was concentrated by atmospheric distillation while adding a mixture of water (18 g), methanol (527 g), and chlorobenzene (239 g) dropwise (distillation volume of 799 g). The mixture thereof was cooled to 50° C., and 26.5% sodium hydroxide water (25 g) was added dropwise. The mixture was warmed to an internal temperature of 72 to 79° C. and continuously concentrated by atmospheric distillation while adding a mixture of water (6 g), methanol (176 g), and chlorobenzene (80 g) dropwise (distillation volume of 263 g). After cooling the mixture thereof to 40° C., the mixture was warmed again to 72° C. and concentrated under atmospheric pressure. The mixture was cooled to 50° C. Methanol (112 g) and chlorobenzene (127 g) were added, and an aqueous 26.5% sodium hydroxide solution (14 g) was added dropwise. The mixture was incubated for 1 hour at 50° C. After adding water (160 g) dropwise, the mixture was cooled to 20° C. The mixture was incubated for 1 hour at 20° C. The precipitate was filtered out and washed with a mixture of water (140 g) and methanol (48 g). The precipitate was suspended in water (140 g) and methanol (48 g). The washing solution was added and the mixture was incubated. A crystal was filtered out, washed with a mixture of water (140 g) and methanol (48 g), washed four times with water (200 g), and then dried to obtain a crude alvocidib free form (29.7 g, yield; 86.1%).1H-NMR (400 MHz, MeOH-d4) δ: 1.59 (d, J=11.6 Hz, 1H), 2.75 (s, 3H), 2.97 (ddd, J=12.4 Hz, 12.4 Hz, 2.9 Hz, 1H), 3.04-3.14 (m, 2H), 3.30-3.32 (m, 1H), 3.41 (d, J=12.0 Hz, 1H), 3.57-3.61 (m, 1H), 4.17 (s, 1H), 6.03 (s, 1H), 6.30 (s, 1H), 7.49 (ddd, J=7.4 Hz, 7.4 Hz, 1.6 Hz, 1H), 7.54 (ddd, J=7.6 Hz, 7.6 Hz, 1.7 Hz, 1H), 7.60 (dd, J=8.4 Hz, 1.2 Hz, 1H), 7.68 (dd, J=7.4 Hz, 1.8 Hz, 1H)

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2020/117988, 2020, A1 Location in patent: Paragraph 00346; 00369; 00370
[2]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - WO2020/118252, 2020, A1 Location in patent: Page/Page column 86-87
[3]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2021/113688, 2021, A1 Location in patent: Paragraph 00626-00627; 00631
[4]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Pharma (in: Sumitomo Chemical); Sumitomo Chemical (w/o Dongwoo Fine-Chem) - US2022/220072, 2022, A1 Location in patent: Paragraph 0149-0148

24
[ 146426-40-6 ]
[ 749824-98-4 ]
[ 2434592-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	With dmap In tetrachloromethane; N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere;	10.2.1A Step 2.1A: To a clean and dry, three-necked RBF (3 L) was added A-2 (35.0 g, 0.087 mol) and DMF (245 ml), at room temperature, under nitrogen atmosphere. Then, DMAP (1.06 g, 0.0086 mol) followed by CCl4 (66.5 g 0.434mol) were added to the reaction mixture at room temperature. To the reaction mixture di-tertiary butyl phosphite (25.5g, 0.131 mol) was added at room temperature. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 24 hours. The reaction progress was monitored by HPLC. The reaction mixture was cooled to 0-5 °C, and was quenched with slow addition of DM water (1950 ml) for 30 minutes at 0-5 °C. Then, chloroform (1627.5 ml) was added to the reaction mixture, and the reaction mixture was stirred at 0-5 °C for 10 minutes. The organic layer was separated and dried over sodium sulfate. The solvent was removed under reduced pressure, while maintaining the bath temperature below 45 °C. The resulting residue was co-distilled with toluene (4 × 175 ml). The residue was kept under high vacuum for 45 minutes to obtain A-10 as a pale yellow residue. (51.0 g, 98.5%). HPLC Purity: 91.48%.
	With dmap In tetrachloromethane; N,N-dimethyl-formamide at 20℃; for 24h; Inert atmosphere;	13.2.1A Step 2.1A: To a clean and dry, three-necked RBF (3 L) was added A-2 (35.0 g, 0.087 mol) and DMF (245 ml), at room temperature, under nitrogen atmosphere. Then, DMAP (1.06 g, 0.0086 mol) followed by CCl4 (66.5 g 0.434mol) were added to the reaction mixture at room temperature. To the reaction mixture di- tertiary butyl phosphite (25.5g, 0.131 mol) was added at room temperature. The reaction mixture was stirred at room temperature under nitrogen atmosphere for 24 hours. The reaction progress was monitored by HPLC. The reaction mixture was cooled to 0-5 °C, and was quenched with slow addition of DM water (1950 ml) for 30 minutes at 0-5 °C. Then, chloroform (1627.5 ml) was added to the reaction mixture, and the reaction mixture was stirred at 0-5 °C for 10 minutes. The organic layer was separated and dried over sodium sulfate. The solvent was removed under reduced pressure, while maintaining the bath temperature below 45 °C. The resulting residue was co-distilled with toluene (4 x 175 ml). The residue was kept under high vacuum for 45 minutes to obtain A-10 as a pale yellow residue. (51.0 g, 98.5%). HPLC Purity: 91.48%.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2020/117988, 2020, A1 Location in patent: Paragraph 00369; 00371
[2]Current Patent Assignee: Sumitomo Pharma (in: Sumitomo Chemical); Sumitomo Chemical (w/o Dongwoo Fine-Chem); SUMITOMO CHEMICAL COMPANY LIMITED - WO2020/118252, 2020, A1 Location in patent: Page/Page column 86; 87-88

25
[ 146426-40-6 ]
[ 24424-99-5 ]
[ 2304716-53-6 ]

Yield	Reaction Conditions	Operation in experiment
1.2 g	Stage #1: flavopiridol; di-<i>tert</i>-butyl dicarbonate With triethylamine In dichloromethane at 20℃; for 1h; Inert atmosphere; Stage #2: With potassium carbonate In dichloromethane at 0 - 20℃; for 1h; Inert atmosphere;	14 tert-Butyl (3S,4R)-4-[2-(2-chlorophenyl)-5,7-dihydroxy-4-oxo-4H-chromen-8-yl]-1-methylpiperidin-3-yl carbonate A methylene chloride (10.0 mL) solution of alvocidib (1.00 g), di-tert-butyl-dicarbonate (1.36 g), and triethylamine (1.74 mL) was stirred for 1 hour at room temperature under a nitrogen atmosphere. The mixture was then cooled to 0° C., and potassium carbonate (2.00 g) was added. The reaction mixture was stirred for 1 hour at room temperature. Ethyl acetate and aqueous saturated ammonium chloride solution were then added to the reaction solution. The resulting mixture was filtered through celite, and then the filtrate was partitioned between an organic layer and an aqueous layer. The aqueous layer was extracted twice with ethyl acetate. The resulting organic layer was washed once with water, and dried over anhydrous sodium sulfate, which was then filtered off, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=9:1 to 1:1) to give Reference Example 14 (1.20 g). (LC-MS: [M+H]+/Rt(min))=502/0.754 measurement condition A

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - US2020/207782, 2020, A1 Location in patent: Paragraph 0703-0705

26
[ 146426-40-6 ]
[ 814-49-3 ]
[ 2044686-45-3 ]

Yield	Reaction Conditions	Operation in experiment
67.1%	With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one	1.2 Step 2: A-2 (in free base form) was treated with diethyl chlorophosphate and diisopropylethylamine in N-methylpyrrolidone. Water was added to stop the reaction and precipitate the product. The resulting slurry was filtered, washed with water, and dried under vacuum to produce the compound A-3.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2020/117988, 2020, A1 Location in patent: Paragraph 00346; 00348; 00356

27
[ 146426-40-6 ]
[ 683-08-9 ]
[ 2044686-45-3 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In 1-methyl-pyrrolidin-2-one Large scale;	Step 2: A-2 (in free base form) was treated with diethyl chlorophosphate and diisopropylethylamine in N-methylpyrrolidone. Water was added to stop the reaction and precipitate the product. The resulting slurry was filtered, washed with water, and dried under vacuum to produce the compound A-3.

Reference： [1]Current Patent Assignee: Sumitomo Chemical (w/o Dongwoo Fine-Chem); Sumitomo Pharma (in: Sumitomo Chemical); SUMITOMO CHEMICAL COMPANY LIMITED - WO2021/113688, 2021, A1 Location in patent: Paragraph 00626; 00628; 00631

28
[ 146426-40-6 ]
[ 131740-09-5 ]

Yield	Reaction Conditions	Operation in experiment
22.4 g	Stage #1: 2-(2-chlorophenyl)-5,7-dihydroxy-8-((3S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one With hydrogenchloride In ethanol at 35 - 74℃; Inert atmosphere; Stage #2: In butanone at 80℃; for 4h; Inert atmosphere;	6 Reference Example 6: Manufacturing Method of Alvocidib Hydrochloride Ethanolate Under a nitrogen atmosphere, a crude alvocidib free form (20 g) was dissolved in ethanol (228 g). The mixture was warmed to 35° C. Concentrated hydrochloric acid (10.4 g) was added dropwise while maintaining an internal temperature of 35° C., and a dropping funnel was washed with ethanol (4.6 g). The mixture was warmed to 74° C. and hot-filtered. The filtration paper was washed with ethanol (23 g). The filtrate and washing solution were combined and concentrated under atmospheric pressure (distillation volume of 190 g). The mixture was cooled to 25° C. and incubated overnight. The mixture was cooled to -10° C. and incubated for 2 hours. The precipitate was filtered out, washed with cold ethanol (94 g), and dried to obtain alvocidib hydrochloride ethanolate (22.4 g, yield: 93%).1H-NMR (400 MHz, MeOH-d4) δ: 1.17 (t, J=7.2 Hz, 3H), 1.83-1.91 (m, 1H), 2.86 (s, 3H), 3.09-3.21 (m, 2H), 3.32-3.35 (m, 1H), 3.45 (ddd, J=12.6 Hz, 2.4 Hz, 2.4 Hz, 1H), 3.50-3.53 (m, 1H), 3.60 (q, J=7.1 Hz, 2H), 3.69-3.74 (m, 1H), 4.26 (s, 1H), 6.34 (s, 1H), 6.48 (s, 1H), 7.52 (ddd, J=7.3 Hz, 7.3 Hz, 1.3 Hz, 1H), 7.58 (ddd, J=7.6 Hz, 7.6 Hz, 1.9 Hz, 1H), 7.62 (dd, J=7.8 Hz, 1.4 Hz, 1H), 7.76 (dd, J=7.6 Hz, 1.6 Hz, 1H) Reference Example 7: Manufacturing Method of Alvocidib Hydrochloride Under a nitrogen atmosphere, alvocidib hydrochloride ethanolate (20 g) was dissolved in methyl ethyl ketone (297 g). The mixture was warmed to 80° C. and incubated for 4 hours. The mixture was cooled to 22° C. and incubated for 1 hour. The precipitate was filtered out, washed with methyl ethyl ketone (69 g), and dried to obtain alvocidib hydrochloride (17.7 g, yield: 98%, HPLC purity: 99.6 area %, optical purity: >99.9% ee).1H-NMR (400 MHz, MeOH-d4) δ: 1.83-1.91 (m, 1H), 2.85 (s, 3H), 3.10-3.22 (m, 2H), 3.34 (s, 1H), 3.42-3.46 (m, 1H), 3.49-3.53 (m, 1H), 3.69-3.73 (m, 1H), 4.26 (s, 1H), 6.34 (s, 1H), 6.48 (s, 1H), 7.52 (ddd, J=7.4 Hz, 7.4 Hz, 1.5 Hz, 1H), 7.58 (ddd, J=7.8 Hz, 7.8 Hz, 2.0 Hz, 1H), 7.63 (dd, J=7.8 Hz, 1.4 Hz, 1H), 7.75 (dd, J=7.4 Hz, 1.4 Hz, 1H)

Reference： [1]Current Patent Assignee: SUMITOMO CHEMICAL COMPANY LIMITED; Sumitomo Pharma (in: Sumitomo Chemical); Sumitomo Chemical (w/o Dongwoo Fine-Chem) - US2022/220072, 2022, A1 Location in patent: Paragraph 0152-0157

CAS No. :	146426-40-6	MDL No. :	MFCD20501884
Formula :	C₂₁H₂₀ClNO₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BIIVYFLTOXDAOV-YVEFUNNKSA-N
M.W :	401.84	Pubchem ID :	5287969
Synonyms :	L86-8275;Alvocidib;HL 275;NSC 649890;HMR-1275	Chemical Name :	2-(2-Chlorophenyl)-5,7-dihydroxy-8-((3S,4R)-3-hydroxy-1-methylpiperidin-4-yl)-4H-chromen-4-one

Num. heavy atoms :	28
Num. arom. heavy atoms :	16
Fraction Csp3 :	0.29
Num. rotatable bonds :	2
Num. H-bond acceptors :	6.0
Num. H-bond donors :	3.0
Molar Refractivity :	111.84
TPSA :	94.14 Å²

GI absorption :	High
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.44 cm/s

Log Po/w (iLOGP) :	3.03
Log Po/w (XLOGP3) :	3.25
Log Po/w (WLOGP) :	2.92
Log Po/w (MLOGP) :	1.34
Log Po/w (SILICOS-IT) :	3.37
Consensus Log Po/w :	2.78

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

[ CAS No. 146426-40-6 ] {[proInfo.proName]}

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[ 146426-40-6 ] Synthesis Path-Downstream 1~28

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[ 146426-40-6 ]

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log S (ESOL) :	-4.67
Solubility :	0.0086 mg/ml ; 0.0000214 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.9
Solubility :	0.00505 mg/ml ; 0.0000126 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.59
Solubility :	0.00103 mg/ml ; 0.00000257 mol/l
Class :	Moderately soluble

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	4.22

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

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