[ CAS No. 1378390-29-4 ] {[proInfo.proName]}

Name: 1378390-29-4|3-(2-Bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one|97%
Brand: Ambeed
SKU: A114554
Price: 14.0 USD
Availability: InStock
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Cat. No.: {[proInfo.prAm]}

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Quality Control of [ 1378390-29-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 1378390-29-4 ]

CAS No. :	1378390-29-4	MDL No. :	MFCD30187855
Formula :	C₁₉H₁₅BrO₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	NEADWTKOYDYIHL-UHFFFAOYSA-N
M.W :	371.22	Pubchem ID :	86688342
Synonyms :		Chemical Name :	3-(2-Bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one

Calculated chemistry of [ 1378390-29-4 ] Expand+

Physicochemical Properties

Num. heavy atoms :	23
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.26
Num. rotatable bonds :	2
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	92.33
TPSA :	43.37 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-5.96 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.77
Log Po/w (XLOGP3) :	3.67
Log Po/w (WLOGP) :	4.19
Log Po/w (MLOGP) :	2.81
Log Po/w (SILICOS-IT) :	5.53
Consensus Log Po/w :	3.8

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.71
Solubility :	0.00728 mg/ml ; 0.0000196 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.27
Solubility :	0.0199 mg/ml ; 0.0000537 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-7.08
Solubility :	0.0000312 mg/ml ; 0.0000000841 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	3.06

Safety of [ 1378390-29-4 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P501-P260-P234-P264-P280-P390-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338-P310-P406-P405	UN#:	3261
Hazard Statements:	H314-H290	Packing Group:	Ⅱ
GHS Pictogram:

Application In Synthesis of [ 1378390-29-4 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 1378390-29-4 ]
Downstream synthetic route of [ 1378390-29-4 ]

[ 1378390-29-4 ] Synthesis Path-Upstream 1~6

1
[ 1378391-36-6 ]
[ 1378390-29-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	Stage #1: With N-Bromosuccinimide In tetrahydrofuran; water; dimethyl sulfoxide at 20℃; for 0.55 h; Stage #2: With manganese(IV) oxide In dichloromethane at 20℃; for 15 h;	3-(2-Bromoacetyl)-l 0,1 l-dihydro-5H-dibenzo [c,g] chromen-8(9H)-one 3-Vinyl-10,l l -dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (9.98 g, 36.1 mmol) was dissolved in a stirred solution of THF (70 mL), DMSO (70 mL) and H₂0 (35 mL). NBS (6.75 g, 37.9 mmol) was added in a single portion and the reaction mixture was stirred at RT for 33 min. Upon completion, the reaction medium was diluted with EtOAc and washed twice with H₂0 and once with brine. The organic phase was dried over MgS0₄, filtered and concentrated under reduced pressure. The resulting crude bromohydrin was suspended in DCM (200 mL) and treated with activated Mn0₂ (62.7 g, 722 mmol). After stirring for 15 h at RT, the reaction mixture was filtered over celite and the filter cake was rinsed several times with DCM. The combined filtrate (-400 mL) was treated with MeOH (-100 mL) and the mixture was gradually concentrated under reduced pressure, causing solid material to precipitate from solution. When the liquid volume reached -200 mL, the solid was filtered off and rinsed with MeOH. The concentration/precipitation/filtration/rinsing sequence was performed 2x more, resulting in the collection of 3 crops of powdered 3-(2-bromoacetyl)-10,l l-dihydro-5H- dibenzo[c,g]chromen-8(9H)-one (7.49 g, 56percent over 2 steps).
7.49 g	Stage #1: With N-Bromosuccinimide In tetrahydrofuran; water; dimethyl sulfoxide at 20℃; for 0.55 h; Stage #2: With manganese(IV) oxide In dichloromethane at 20℃; for 15 h;	3-Vinyl-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (9.98 g, 36.1 mmol) was dissolved in a stirred solution of THF (70 mL), DMSO (70 mL) and H₂O (35 mL). NBS (6.75 g, 37.9 mmol) was added in a single portion and the reaction mixture was stirred at RT for 33 min. Upon completion, the reaction medium was diluted with EtOAc and washed twice with H₂O and once with brine. The organic phase was dried over MgSO₄, filtered and concentrated under reduced pressure. The resulting crude bromohydrin was suspended in DCM (200 mL) and treated with activated MnO₂(62.7 g, 722 mmol). After stirring for 15 h at RT, the reaction mixture was filtered over celite and the filter cake was rinsed several times with DCM. The combined filtrate (400 mL) was treated with MeOH (100 mL) and the mixture was gradually concentrated under reduced pressure, causing solid material to precipitate from solution. When the liquid volume reached 200 mL, the solid was filtered off and rinsed with MeOH. The concentration/precipitation/filtration/rinsing sequence was performed 2× more, resulting in the collection of 3 crops of powdered 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (7.49 g, 56percent over 2 steps).

Reference： [1] Patent: WO2013/75029, 2013, A1, . Location in patent: Page/Page column 140; 141; 142
[2] Patent: US2013/309196, 2013, A1, . Location in patent: Paragraph 0366
[3] Patent: US2014/178336, 2014, A1,
[4] Patent: US2015/361073, 2015, A1,

2
[ 1378391-38-8 ]
[ 1378390-29-4 ]

Yield	Reaction Conditions	Operation in experiment
7.49 g	With manganese(IV) oxide In dichloromethane at 20℃; for 15 h;	3-Vinyl-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (9.98 g, 36.1 mmol) was dissolved in a stirred solution of THF (70 mL), DMSO (70 mL) and H₂O (35 mL). NBS (6.75 g, 37.9 mmol) was added in a single portion and the reaction mixture was stirred at RT for 33 min. Upon completion, the reaction medium was diluted with EtOAc and washed twice with H₂O and once with brine. The organic phase was dried over MgSO₄, filtered and concentrated under reduced pressure. The resulting crude bromohydrin was suspended in DCM (200 mL) and treated with activated MnO₂(62.7 g, 722 mmol). After stirring for 15 h at RT, the reaction mixture was filtered over celite and the filter cake was rinsed several times with DCM. The combined filtrate (400 mL) was treated with MeOH (100 mL) and the mixture was gradually concentrated under reduced pressure, causing solid material to precipitate from solution. When the liquid volume reached 200 mL, the solid was filtered off and rinsed with MeOH. The concentration/precipitation/filtration/rinsing sequence was performed 2× more, resulting in the collection of 3 crops of powdered 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (7.49 g, 56percent over 2 steps).

Reference： [1] Patent: US2014/178336, 2014, A1, . Location in patent: Paragraph 0237
[2] Patent: US2015/361073, 2015, A1, . Location in patent: Paragraph 0473

3
[ 1378388-19-2 ]
[ 1378390-29-4 ]

Reference： [1] Patent: WO2013/75029, 2013, A1,
[2] Patent: US2013/309196, 2013, A1,
[3] Patent: US2014/178336, 2014, A1,
[4] Patent: US2015/361073, 2015, A1,

4
[ 22009-38-7 ]
[ 1378390-29-4 ]

Reference： [1] Patent: WO2013/75029, 2013, A1,
[2] Patent: US2013/309196, 2013, A1,
[3] Patent: US2014/178336, 2014, A1,
[4] Patent: US2015/361073, 2015, A1,

5
[ 66192-24-3 ]
[ 1378390-29-4 ]

Reference： [1] Patent: WO2013/75029, 2013, A1,
[2] Patent: US2013/309196, 2013, A1,
[3] Patent: US2014/178336, 2014, A1,
[4] Patent: US2015/361073, 2015, A1,

6
[ 1378388-20-5 ]
[ 1378390-29-4 ]

Reference： [1] Patent: WO2013/75029, 2013, A1,
[2] Patent: US2013/309196, 2013, A1,
[3] Patent: US2014/178336, 2014, A1,
[4] Patent: US2015/361073, 2015, A1,

[ 1378390-29-4 ] Synthesis Path-Downstream 1~7

1
[ 364750-81-2 ]
[ 1378390-29-4 ]
[ 1378390-66-9 ]

Yield	Reaction Conditions	Operation in experiment
69%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 60℃; for 3h;	2S,4S)-l-teri-butyl 2-(2-oxo-2-(8-oxo-8,9,l 0,11 -tetrahydro-5H-dibenzo [c,g] chromen-3-yl)ethyl) 4-methylpyrrolidine-l,2-dicarboxylate To a solution of 3-(2-bromoacetyl)-10,l l-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (647 mg, 1.74 mmol) in MeCN (20 mL) was added ((2S,4S)-l -(tert-butoxycarbonyl)-4-methylpyrrolidine- 2-carboxylic acid (559 mg, 2.44 mmol) and DIPEA (0.36 mL, 2.09 mmol) and the solution was heated to 60 °C. After stirring for 3 h, the solution was cooled to rt, and diluted with EtOAc and washed successively with saturated aqueous NaHCC>3 and brine. The organics were dried over MgS04, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (20percent to 50percent EtOAc/hexanes) to afford (2S,4S)-1 -tert-butyl 2-(2-oxo-2-(8- oxo-8,9, 10,11 -tetrahydro-5H-dibenzo [c,g]chromen-3-yl)ethyl) 4-methylpyrrolidine- 1 ,2-dicarboxylate (621 mg, 69percent).
69%	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 60℃; for 3h;	To a solution of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (647 mg, 1.74 mmol) in MeCN (20 mL) was added ( <strong>[364750-81-2](2S,4S)-1-(tert-butoxycarbonyl)-4-methylpyrrolidine-2-carboxylic acid</strong> (559 mg, 2.44 mmol) and DIPEA (0.36 mL, 2.09 mmol) and the solution was heated to 60° C. After stirring for 3 h, the solution was cooled to rt, and diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (20percent to 50percent EtOAc/hexanes) to afford (2S,4S)-1-tert-butyl 2-(2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl) 4-methylpyrrolidine-1,2-dicarboxylate (621 mg, 69percent).

Reference： [1]Patent: WO2013/75029,2013,A1 .Location in patent: Page/Page column 121; 122; 123
[2]Patent: US2013/309196,2013,A1 .Location in patent: Paragraph 0326

2
[ 1378390-29-4 ]
[ 1438383-89-1 ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridinium hydrobromide perbromide In methanol; dichloromethane at 20℃; for 3h;	PY-2 Example PY-2 3-(2-bromoacetyl)-10,11- 9-bromo-3-(2- dihydro-5H- bromoacetyl)-10,11 - dibenzo[c,g]chromen- dihydro-5H- 8(9H)-one dibenzo[c,g]chromen- 8(9H)-one 9-bromo-3-(2-bromoacetyl)-10,ll-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one A mixture of 3-(2-bromoacetyl)-10,l l-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.58 g, 6.95 mmol), pyridinium tribromide (2.56 g, 8.0 mmol), dichloromethane (22mL) and methanol (2.5mL) was stirred at about 20°C for 3 hours to obtain a slurry. The precipitated product was filtered , washed with dichloromethane (lOmL) and dried in a vacuum oven at 40°C to give 9-bromo- 3-(2-bromoacetyl)-10,l l-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.62 g, 84% yield). 400 MHz lH NMR (CDCI3) δ 8.03-8.01 (m, 1H), 7.85 (d, J= 8.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 7.67 (s, 1H), 5.19 (s, 2H), 4.74 (dd, J= 4.1, 4.1 Hz, 1H), 4.45 (s, 2H), 3.37-3.29 (m, 1H), 2.99-2.92 (m,lH), 2.59-2.46 (m, 2H).
84%	With pyridinium hydrobromide perbromide In dichloromethane at 20℃; for 3h;	DV A mixture of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.58 g, 6.95 mmol), pyridinium tribromide (2.56 g, 8.0 mmol), dichloromethane (22 mL) and methanol (2.5 mL) was stirred at about 20° C. for 3 hours to obtain a slurry. The precipitated product was filtered, washed with dichloromethane (10 mL) and dried in a vacuum oven at 40° C. to give 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.62 g, 84% yield). 400 MHz 1H NMR (CDCl3) δ 8.03-8.01 (m, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 7.67 (s, 1H), 5.19 (s, 2H), 4.74 (dd, J=4.1, 4.1 Hz, 1H), 4.45 (s, 2H), 3.37-3.29 (m, 1H), 2.99-2.92 (m, 1H), 2.59-2.46 (m, 2H)
84%	With pyridinium hydrobromide perbromide In methanol; dichloromethane at 20℃; for 3h;	9-Bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one 9-Bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one A mixture of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.58 g, 6.95 mmol), pyridinium tribromide (2.56 g, 8.0 mmol), dichloromethane (22 mL) and methanol (2.5 mL) was stirred at about 20° C. for 3 hours to obtain a slurry. The precipitated product was filtered, washed with dichloromethane (10 mL) and dried in a vacuum oven at 40° C. to give 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.62 g, 84% yield). 400 MHz 1H NMR (CDCl3) δ 8.03-8.01 (m, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 7.67 (s, 1H), 5.19 (s, 2H), 4.74 (dd, J=4.1, 4.1 Hz, 1H), 4.45 (s, 2H), 3.37-3.29 (m, 1H), 2.99-2.92 (m, 1H), 2.59-2.46 (m, 2H).

With pyridinium hydrobromide perbromide In methanol; dichloromethane at 20℃; for 3h;

6 Reaction of Compound (6) to Compound (I-a) A mixture of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (2.58 g) (Compound (6)), pyridinium tribromide (2.56 g), dichloromethane (22 mL) and methanol (2.5 mL) was stirred at ambient temperature for 3 hours. The mixture was filtered, the filter cake washed with dichloromethane (10 mL) and then dried under reduced pressure at 40° C. to give 9-bromo-3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (Compound (I-a)). HRMS (ESI+ MS/MS) Calculated for Chemical Formula: C19H15Br2O3 m/z (M+H): 448.9388 and 450.9367. Found: 448.9396, and 450.9380. 1H NMR (400 MHz, CDCl3) δ 8.03-8.01 (m, 1H), 7.85 (d, J=8.2 Hz, 1H), 7.82 (s, 1H), 7.71 (s, 1H), 7.67 (s, 1H), 5.19 (s, 2H), 4.74 (dd, J=4.1, 4.1 Hz, 1H), 4.45 (s, 2H), 3.37-3.29 (m, 1H), 2.99-2.92 (m, 1H), 2.59-2.46 (m, 2H)

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2013/75029, 2013, A1 Location in patent: Page/Page column 209
[2]Current Patent Assignee: GILEAD SCIENCES INC - US2013/309196, 2013, A1 Location in patent: Paragraph 0523
[3]Current Patent Assignee: GILEAD SCIENCES INC - US2014/178336, 2014, A1 Location in patent: Paragraph 0239
[4]Current Patent Assignee: GILEAD SCIENCES INC - US2015/361073, 2015, A1 Location in patent: Paragraph 0480

3
[ 334769-80-1 ]
[ 1378390-29-4 ]
[ 1378390-26-1 ]

Yield	Reaction Conditions	Operation in experiment
65%	With triethylamine; In acetonitrile; at 50℃; for 15h;	To a solution of 3-(2-bromoacetyl)-10,l l -dihydro-5H-dibenzo[c,g]chromen-8(9H)-one in MeCN (30 mL) was added (2S,5S)-l -(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid (1.2 g, 3.23 mmol) and triethyl amine (0.48 mL, 3.55 mmol) and the solution was heated to 50 °C. After stirring for 15 h, the solution was cooled to rt, and diluted with EtOAc and washed successively with saturated aqueous NaHCC>3 and brine. The organics were dried over MgSO i, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (20percent to 50percent> EtOAc/hexanes) to afford (2S,5S)-1 -tert-butyl 2-(2-oxo-2-(8-oxo- 8,9,10, 11 -tetrahydro-5H-dibenzo[c,g] chromen-3 -yl)ethyl) 5-methylpyrrolidine-l ,2-dicarboxylate (1.09 g, 65percent).
65%	With triethylamine; In acetonitrile; at 50℃; for 15h;	To a solution of 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one in MeCN (30 mL) was added <strong>[334769-80-1](2S,5S)-1-(tert-butoxycarbonyl)-5-methylpyrrolidine-2-carboxylic acid</strong> (1.2 g, 3.23 mmol) and triethyl amine (0.48 mL, 3.55 mmol) and the solution was heated to 50° C. After stirring for 15 h, the solution was cooled to rt, and diluted with EtOAc and washed successively with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (20percent to 50percent EtOAc/hexanes) to afford (2S,5S)-1-tert-butyl 2-(2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl) 5-methylpyrrolidine-1,2-dicarboxylate (1.09 g, 65percent).

Reference： [1]Patent: WO2013/75029,2013,A1 .Location in patent: Page/Page column 113; 114
[2]Patent: US2013/309196,2013,A1 .Location in patent: Paragraph 0312

4
[ 1378388-16-9 ]
[ 1378390-29-4 ]
[ 1378391-39-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 3.0h;Inert atmosphere; Industrial scale;	Compound 25 (1.96 kg, 5.29 mol, 1.0 eq)And Compound 24 (1.37 kg, 1.05 eq) were dissolved in N, N-dimethylformamide (DMF)Potassium carbonate (730.8 g, 1.05 eq) was added, the mixture was replaced with nitrogen three times in vacuo,Heat to 20-40 C for 3 hours.TLC showed complete reaction of compound 25.The mixture was cooled to 5-10 C, dropped into water, stirred at 5-10 C for 2-3 hours, filtered, washed with water and dried to give 2.85 kg of compound 14 in 98.0% yield. The HPLC purity was 98.56%.
70%	With caesium carbonate; at 20℃; for 4.0h;	(4S)-l-teri-Butyl 2-(2-oxo-2-(8-oxo-8,9,10,ll-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl) 4- (methoxymethyl)pyrrolidine-l,2-dicarboxylate 3-(2-Bromoacetyl)-10,l l-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (7.47 g, 20.1 mmol) and (2S,4S)-l-(tert-butoxycarbonyl)-4-(methoxymethyl)pyrrolidine-2-carboxylic acid (5.22 g, 20.1 mmol) were suspended in 2-Me-THF (75 mL) and treated with Cs2C03 (3.27 g, 10.1 mmol). After stirring 4 h at RT, the reaction mixture was diluted with diluted with DCM. The organic layer was washed with H20. The aqueous layer was then back extracted 2x with DCM. The combined organics were dried over MgS04, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (10% to 50% EtOAc/DCM) to afford (4S)-l-tert-butyl 2- (2-oxo-2-(8-oxo-8,9,10,l l-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl) 4- (methoxymethyl)pyrrolidine-l,2-dicarboxylate (7.73 g, 70%>).
70%	With caesium carbonate; In 2-methyltetrahydrofuran; at 20℃; for 4.0h;	3-(2-Bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (7.47 g, 20.1 mmol) and <strong>[1378388-16-9](2S,4S)-1-(tert-butoxycarbonyl)-4-(methoxymethyl)pyrrolidine-2-carboxylic acid</strong> (5.22 g, 20.1 mmol) were suspended in 2-Me-THF (75 mL) and treated with Cs2CO3 (3.27 g, 10.1 mmol). After stirring 4 h at RT, the reaction mixture was diluted with diluted with DCM. The organic layer was washed with H2O. The aqueous layer was then back extracted 2× with DCM. The combined organics were dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (10% to 50% EtOAc/DCM) to afford (4S)-1-tert-butyl 2-(2-oxo-2-(8-oxo-8,9,10,11-tetrahydro-5H-dibenzo[c,g]chromen-3-yl)ethyl) 4-(methoxymethyl)pyrrolidine-1,2-dicarboxylate (7.73 g, 70%).

Reference： [1]Patent: CN107573355,2018,A .Location in patent: Paragraph 0223-0225
[2]Patent: WO2013/75029,2013,A1 .Location in patent: Page/Page column 140; 142
[3]Patent: US2013/309196,2013,A1 .Location in patent: Paragraph 0367

5
[ 1378388-20-5 ]
[ 1378390-29-4 ]

Reference： [1]Patent: WO2013/75029,2013,A1
[2]Patent: US2013/309196,2013,A1
[3]Patent: US2014/178336,2014,A1
[4]Patent: US2015/361073,2015,A1

6
[ 1378391-38-8 ]
[ 1378390-29-4 ]

Yield	Reaction Conditions	Operation in experiment
7.49 g	With manganese(IV) oxide; In dichloromethane; at 20.0℃; for 15.0h;	3-Vinyl-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (9.98 g, 36.1 mmol) was dissolved in a stirred solution of THF (70 mL), DMSO (70 mL) and H2O (35 mL). NBS (6.75 g, 37.9 mmol) was added in a single portion and the reaction mixture was stirred at RT for 33 min. Upon completion, the reaction medium was diluted with EtOAc and washed twice with H2O and once with brine. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude bromohydrin was suspended in DCM (200 mL) and treated with activated MnO2 (62.7 g, 722 mmol). After stirring for 15 h at RT, the reaction mixture was filtered over celite and the filter cake was rinsed several times with DCM. The combined filtrate (400 mL) was treated with MeOH (100 mL) and the mixture was gradually concentrated under reduced pressure, causing solid material to precipitate from solution. When the liquid volume reached 200 mL, the solid was filtered off and rinsed with MeOH. The concentration/precipitation/filtration/rinsing sequence was performed 2× more, resulting in the collection of 3 crops of powdered 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (7.49 g, 56% over 2 steps).
	With sodium hypochlorite; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; sodium hydrogencarbonate; sodium bromide; In dichloromethane; water; at 0.2℃;	To a 1 L reactor was charged <strong>[1378391-38-8]3-(2-bromo-1-hydroxyethyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one</strong> (25 g), (Compound (5-4))dichloromethane (370 mL), and TEMPO (0.2 g). The mixture was cooled to about 2 C. A solution of sodium bicarbonate (7.4 g), sodium bromide (7.4 g) and water (130 mL) was charged and the mixture agitated. The mixture was combined with an aqueous solution of sodium hypochlorite (11.9% wt., 80 mL). After completion of the reaction, 2-propanol (40 mL) was charged and the mixture warmed to about 25 C. A volume of about two-thirds of dichloromethane was removed under reduced pressure, the mixture cooled to about 5 C. and then filtered through a fritted funnel. The filter cake was washed twice with water (75 mL) and with dichloromethane (30 mL) and then dried at about 40 C. under reduced pressure to provide 3-(2-bromoacetyl)-10,11-dihydro-5H-dibenzo[c,g]chromen-8(9H)-one (Compound (6)). 1H NMR (400 MHz, CDCl3) δ 8.01 (d, J=8.1 Hz, 1H), 8.01 (d, J=8.1 Hz, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.84 (d, J=8.2 Hz, 1H), 7.81 (s, 1H), 7.81 (s, 1H), 7.65 (s, 2H), 7.65 (s, 2H), 5.18 (s, 2H), 4.45 (s, 2H), 3.08-2.91 (m, 2H), 2.75-2.59 (m, 2H), 2.26-2.07 (m, 2H)

Reference： [1]Patent: US2014/178336,2014,A1 .Location in patent: Paragraph 0237
[2]Patent: US2015/361073,2015,A1 .Location in patent: Paragraph 0473

7
[ 1378388-16-9 ]
[ 1378390-29-4 ]
C₃₁H₃₅NO₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; In dichloromethane; at 30 - 35℃; for 16.0h;	100 ml reaction flask,3.7 g of compound 7 was added,2.85 g of compound 6a,2.76 g of potassium carbonate,And 55.5 ml of dichloromethane,Heated to 30-35 C,Stirring for 16 hours,LC monitoring reaction material 7 disappeared,Add water to quench the reaction.The reaction mixture was washed with water,Sodium sulfate,Concentration gave compound 5a (5.68 g, purity 96.58%, yield 100%).

Reference： [1]Patent: CN106831737,2017,A .Location in patent: Paragraph 0127; 0128; 0129

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

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[ CAS No. 1378390-29-4 ] {[proInfo.proName]}

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[ 1378390-29-4 ] Synthesis Path-Upstream 1~6

[ 1378390-29-4 ] Synthesis Path-Downstream 1~7

Related Functional Groups of [ 1378390-29-4 ]

Bromides

Ketones

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Other Aromatic Heterocycles

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[ 1378390-29-4 ]

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