[ CAS No. 887266-90-2 ]

Name: 887266-90-2|3-Bromo-5-fluorobenzoyl chloride|98%
Brand: Ambeed
SKU: A444542
Price: 13.0 USD
Availability: InStock
Rating: 90 (26 reviews)

{[proInfo.proName]} ,{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]}

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

DV 2D 3D

3d Animation Molecule Structure of 887266-90-2

Structure of 887266-90-2 * Storage: {[proInfo.prStorage]}

Cart0 Add to My Favorites Bulk Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

For Research Only 100K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 887266-90-2 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 887266-90-2 ]

SDS Specification

Alternatived Products of [ 887266-90-2 ]

Product Details of [ 887266-90-2 ]

CAS No. :	887266-90-2	MDL No. :	MFCD07368699
Formula :	C₇H₃BrClFO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RGMMCYNLNAUIJX-UHFFFAOYSA-N
M.W :	237.45 g/mol	Pubchem ID :	2783345
Synonyms :

Calculated chemistry of [ 887266-90-2 ]

Physicochemical Properties

Num. heavy atoms :	11
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	44.28
TPSA :	17.07 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.46 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.11
Log Po/w (XLOGP3) :	3.22
Log Po/w (WLOGP) :	3.39
Log Po/w (MLOGP) :	3.2
Log Po/w (SILICOS-IT) :	3.44
Consensus Log Po/w :	3.07

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.68
Solubility :	0.0498 mg/ml ; 0.00021 mol/l
Class :	Soluble
Log S (Ali) :	-3.25
Solubility :	0.133 mg/ml ; 0.000561 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-4.1
Solubility :	0.0189 mg/ml ; 0.0000794 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.6

Safety of [ 887266-90-2 ]

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P271-P280-P260-P271-P280	UN#:	3265
Hazard Statements:	H314-H302+H312+H332	Packing Group:	Ⅲ
GHS Pictogram:

Application In Synthesis of [ 887266-90-2 ]

* 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 [ 887266-90-2 ]
Downstream synthetic route of [ 887266-90-2 ]

[ 887266-90-2 ] Synthesis Path-Upstream 1~2

1
[ 887266-90-2 ]
[ 179898-34-1 ]

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 11, p. 3243 - 3247

2
[ 67-56-1 ]
[ 887266-90-2 ]
[ 334792-52-8 ]

Yield	Reaction Conditions	Operation in experiment
1.8 g	at 0 - 20℃; for 2.08333 h;	A mixture of 3-bromo-5-fluorobenzoic acid (2.8 g, 13.0 mmol) and thionyl chloride (10 mL) was heated to 70 °C for 2 h, after cooling to room temperature excess thionyl chloride was evaporated. To the residue at 0 °C was methanol (50 mL) and triethylamine (4.5 mL) added, the reaction was stirred at 0°C for 5 minutes and then at room temperature for 2 h. The mixture was concentrated, diluted with ethyl acetate (100 mL) and washed consecutively with: 1) hydrochloric acid (5percent, 50 mL), 2) saturated sodium bicarbonate (50 mL), the organic phase was dried over magnesium sulfate and evaporated. Purification by flash chromatography using heptane:ethyl acetate 9:1 as the eluent gave the title compound (1.8 g, 60percent). H NMR (400 MHz, CDCl₃) d ppm 3.89 (s, 3 H), 7.38 (dtd, 1 H), 7.58 - 7.63 (m, 1 H), 7.90 - 7.93 (m, 1 H); ¹³C NMR (101 MHz, CDCl₃) d 52.9, 115.6, 115.8, 122.8, 122.9, 123.5, 123.7, 128.8, 128.8, 133.6, 133.6, 161.2, 163.7, 164.8, 164.8.

Reference： [1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 22, p. 6974 - 6979,6

[ 887266-90-2 ] Synthesis Path-Downstream 1~57

1
[ 887266-90-2 ]
[ 453565-49-6 ]
[ 453566-33-1 ]
[ 1101110-74-0 ]

Yield	Reaction Conditions	Operation in experiment
	In hexane; dichloromethane; ethyl acetate; N,N-dimethyl-formamide;	3-(5-Cyano-2-pyridyl)-5-(3-bromo-5-fluorophenyl)-1,2,4-oxadiazol Using the general procedure for the preparation of acid chlorides, <strong>[887266-90-2]3-bromo-5-fluorobenzoyl chloride</strong> was prepared from 3-bromo-5-fluorobenzoic acid chloride (554 mg, 2.52 mmol). The acid chloride in dichloromethane (10 mL) was treated with 5-tert-butoxycarbonylpyrid-2-ylamidoxime (601 mg, 2.53 mmol). The mixture was stirred at room temperature for 30 minutes and the solvent was removed in vacuo. The intermediate was dissolved in DMF (15 mL) and heated in sealed tube at 120 C. for 13 hours. After cooling the solvent was removed in vacuo. Silica gel chromatography using a gradient of 5% to 10% ethyl acetate in hexane, afforded 556 mg of crude 3-(5-tert-butoxycarbonyl-2-pyridyl)-5-(3-bromo-5-fluorophenyl)-1,2,4-oxadiazole. A mixture of this crude intermediate in formic acid (98%, 20 mL) was heated at 40 C. for 17 hours. Evaporation of the solvent in vacuo afforded 3-(5-hydroxycarbonylpyrid-2-yl)-5-(3-bromo-5-fluorophenyl)-1,2,4-oxadiazole as a white solid.

Reference： [1]Patent: US2003/55085,2003,A1

2
[ 176548-70-2 ]
[ 887266-90-2 ]

Yield	Reaction Conditions	Operation in experiment
97.1%	With thionyl chloride; at 80℃; for 3h;	10287] Compound 1 (16 g, 73.4 mmol) was dissolved in50C12 (160 mE) and heated to 80 C. for 3 hour. The mixturewas concentrated in vacuo to give compound 2 as brown oil(16.8 g, 97.1%).
	With thionyl chloride;N,N-dimethyl-formamide; In dichlorodimethane; at 0 - 5℃; for 1h;Heating / reflux;	Prepared as described in the general procedure A using 3-bromo, 5-fluoro benzoic acid (4.00 g, 17.5 mmol).Yield g, %, mp 0C; 1HNMR (400 MHz, CDCl3) delta 2.58 (s, 3H), 7.02-7.04 (d, J = 8.0 Hz, IH), 7.45-7.48 (m, IH), 7.73-7.80 (m, 2H), 8.08-8.11 (dt, J = 1.2, 11.2 Hz, IH), 8.31- 8.33 (d, J = 8.0 Hz, IH); 13CNMR (101 MHz, CDCl3) delta 2; IR (Neat, cm"1); GC-MS (EI) m/z 309 (M+); Anal. (C20H18N2O2.HBr.H2O) C, H, N.
	With thionyl chloride; for 2h;Reflux;	General procedure: 3,5-dibromobenzoic acid (5g, 17.8 mmol) was suspended in 25 mL of thionyl chloride, an refluxed for 2h. After cooling to room temperature the excess thionyl chloride was removed under reduce pressure and the residue was cautiously poured into 100 mL of ice cold NH4OH 28%, and stirred at room temperature for 3h. Filtration of the precipitate provide after drying in vacuum the amide intermediate in quantitative yield. The amide was suspended in 25 mL of thionyl chloride, and refluxed for 18h before removing the excess thionyl chloride under reduce pressure. The residue was dissolved in 50 mL of AcOEt, and washed with a saturated solution of NaHCO3 (3 X 50 mL), dry over Na2SO4, and concentrated on a rotary evaporator. Purification of the residue by column chromatography yielded 2.71g (58 %) 9a as a yellow solid.1H NMR (CDCl3), d = 8.07 (t, 1H, J=2.0 Hz, CHAr); 8.40 (t, 1H, J=2.0 Hz, CHAr); 8.52 (t, 1H, J=2.0 Hz, CHAr). 13C NMR (CDCl3), d = 115.7 (1C, Cq); 115.8 (1C, Cq); 124.3 (1C, Cq); 126.2 (1C, CHAr); 131.3 (1C, CHAr); 140.7 (1C, Cq).

	With thionyl chloride; for 2h;Reflux;	A solution of <strong>[176548-70-2]3-bromo-5-fluorobenzoic acid</strong> (commercially available) (10.0 g, 45.7 mmol) in thionyl chloride (80 mL) was heated at reflux for 2 hours. Thionyl chloride was removed under reduced pressure and the residue was added to solution of N,O-dimethylhydroxylamine hydrochloride (5.32 g, 54.8 mmol) and Et3N (10.1 g, 0.1 mol) in DCM (300 mL) dropwise at 0 C. After the reaction mixture was stirred at r.t. overnight, it was washed with water (3*100 mL), brine, dried over anhydrous Na2SO4 and concentrated. The colorless oil was used in next step without further purification (11.0 g, yield: 95%).
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 1.66667h;	Synthesis of 3-Bromo-5-fl uoro-benzoyl chloride lOg of <strong>[176548-70-2]3-bromo-5-fluoro-benzoic acid</strong> are suspended in 1 OOml of DCM, O,5m1 DMF and 4.5m1 oxalyl chloride (1,15 Eq) are added and the resulting mixture is stirred for 100 minutes at RT. The solvent is removed by vacuo and the benzoic acid chloride isisolated by distillation.
	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 1.66667h;	10 g of <strong>[176548-70-2]3-bromo-5-fluoro-benzoic acid</strong> are suspended in 100 ml of DCM, 0.5 ml DMF and 4.5 ml oxalyl chloride (1.15 Eq) are added and the resulting mixture is stirred for 100 minutes at RT. The solvent is removed by vacuo and the benzoic acid chloride is isolated by distillation.
	With oxalyl dichloride; N,N-dimethyl-formamide; In dichloromethane; at 20℃; for 1.66667h;	10g of <strong>[176548-70-2]3-bromo-5-fluoro-benzoic acid</strong> are suspended in 100ml of DCM, 0,5ml DMF and 4.5ml oxalyl chloride (1 ,15 Eq) are added and the resulting mixture is stirred for 100 minutes at RT. The solvent is removed by vacuo and the benzoic acid chloride is isolated by distillation.
	With oxalyl dichloride; In dichloromethane; N,N-dimethyl-formamide; at 20℃; for 1.66667h;	10 g of <strong>[176548-70-2]3-bromo-5-fluoro-benzoic acid</strong> are suspended in 100 ml of DCM, 0.5 ml DMF and 4.5 ml oxalyl chloride (1.15 Eq) are added and the resulting mixture is stirred for 100 minutes at RT. The solvent is removed by vacuo and the benzoic acid chloride is isolated by distillation.
	With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; dichloromethane; at 20℃; for 1.5h;	<strong>[176548-70-2]3-bromo-5-fluorobenzoic acid</strong> (32.0 g, 1 .0 equiv) was stirred in a mixture of DCM (288 mL, 9 vol) and THF (32 mL, 1 vol) until the majority of the solid dissolved. DMF (0.57 mL, 5 mol%) was added, and the flask placed in an ambient temperature water bath. Oxalyl chloride (13.7 mL, 1.10 equiv) was added over 1 h via syringe pump; 30 minute after the end of addition the reaction was complete by HPLC (sample quenched into MeOH to form methyl ester prior to analysis). The resulting thin slurry was aged overnight, concentrated to 100 mL volume, diluted with THF (160 mL, 5 vol) and again concentrated to 100 mL. The resulting thin slurry of acid chloride was diluted to 160 mL total volume with THF. A solution of LiOtBu in THF (20 wt%, 67.3 g, 77 mL, 1.15 equiv) was diluted with THF (243 mL), then this solution was cooled to an internal temperature of - 9 C with an ice/salt bath. To this was added the slurry containing acid chloride over 55 mm, while the internal temperature remained below -3 C . The reaction was complete 15 mm following the end of addition. The solution was aged overnight as it warmed to ambient temperature, diluted with heptane (320 mL, 10 vol), and washed with water (160 mL, 5 vol). The aqueous layer was removed to the insoluble rag at the interlace, then the organic layer was filtered through a pad of solka-floc. The pad was rinsed with heptane (10 mL), then the combined organic layer was washed 2xwith water (2 x 80 mL, 2.5 vol). The resulting organic layer was distilled under reduced pressure to a 100 mL final volume, diluted with heptane (160 mL, 5 vol), and concentrated again to 100 mLtotal volume. The solution of tert-butyl 3-bromo-5-fluorobenzoate was used directly in the next step.NMR 1H (400MHz; CDCI3): 7.89-7.88 (1H, m), 7.60-7.57 (1H, m), 7.40-7.37 (1H, m), 1.57 (9H, 5).

Reference： [1]Patent: US2015/274652,2015,A1 .Location in patent: Paragraph 0286; 0287
[2]Patent: WO2008/92072,2008,A2 .Location in patent: Page/Page column 9-10
[3]Journal of Medicinal Chemistry,2009,vol. 52,p. 3563 - 3575
[4]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247
[5]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6
[6]Patent: US2013/324516,2013,A1 .Location in patent: Paragraph 0411; 0412
[7]Patent: WO2014/154727,2014,A1 .Location in patent: Page/Page column 75; 76
[8]Patent: US2014/296239,2014,A1 .Location in patent: Paragraph 0166; 0167
[9]Patent: WO2014/154726,2014,A1 .Location in patent: Page/Page column 80
[10]Patent: US2014/296296,2014,A1 .Location in patent: Paragraph 0191; 0192
[11]Patent: WO2018/178691,2018,A1 .Location in patent: Page/Page column 246; 247

3
[ 1824-81-3 ]
[ 887266-90-2 ]
[ 1042498-29-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; In dichlorodimethane; at 0 - 5℃;	Prepared as described in the general procedure A using 3-bromo, 5-fluoro benzoic acid (4.00 g, 17.5 mmol).Yield g, %, mp 0C; 1HNMR (400 MHz, CDCl3) δ 2.58 (s, 3H), 7.02-7.04 (d, J = 8.0 Hz, IH), 7.45-7.48 (m, IH), 7.73-7.80 (m, 2H), 8.08-8.11 (dt, J = 1.2, 11.2 Hz, IH), 8.31- 8.33 (d, J = 8.0 Hz, IH); 13CNMR (101 MHz, CDCl3) δ 2; IR (Neat, cm"1); GC-MS (EI) m/z 309 (M+); Anal. (C20H18N2O2.HBr.H2O) C, H, N.

Reference： [1]Patent: WO2008/92072,2008,A2 .Location in patent: Page/Page column 9-10
[2]Journal of Medicinal Chemistry,2009,vol. 52,p. 3563 - 3575

4
[ 887266-90-2 ]
[ 864063-09-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

5
[ 887266-90-2 ]
3-(2-(6-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

6
[ 887266-90-2 ]
3-(2-(5-methylpyridin-2-yl)ethynyl)-5-fluorobenzonitrile hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

7
[ 887266-90-2 ]
[ 1224431-15-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

8
[ 887266-90-2 ]
3-(2-(2-methylthiazol-4-yl)ethynyl)-5-fluorobenzonitrile hydrochloride [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

9
[ 887266-90-2 ]
[ 1312923-99-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

10
[ 887266-90-2 ]
[ 933585-20-7 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; at 20℃;Cooling with ice;	General procedure: 3,5-dibromobenzoic acid (5g, 17.8 mmol) was suspended in 25 mL of thionyl chloride, an refluxed for 2h. After cooling to room temperature the excess thionyl chloride was removed under reduce pressure and the residue was cautiously poured into 100 mL of ice cold NH4OH 28%, and stirred at room temperature for 3h. Filtration of the precipitate provide after drying in vacuum the amide intermediate in quantitative yield. The amide was suspended in 25 mL of thionyl chloride, and refluxed for 18h before removing the excess thionyl chloride under reduce pressure. The residue was dissolved in 50 mL of AcOEt, and washed with a saturated solution of NaHCO3 (3 X 50 mL), dry over Na2SO4, and concentrated on a rotary evaporator. Purification of the residue by column chromatography yielded 2.71g (58 %) 9a as a yellow solid.1H NMR (CDCl3), d = 8.07 (t, 1H, J=2.0 Hz, CHAr); 8.40 (t, 1H, J=2.0 Hz, CHAr); 8.52 (t, 1H, J=2.0 Hz, CHAr). 13C NMR (CDCl3), d = 115.7 (1C, Cq); 115.8 (1C, Cq); 124.3 (1C, Cq); 126.2 (1C, CHAr); 131.3 (1C, CHAr); 140.7 (1C, Cq).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

11
[ 887266-90-2 ]
[ 179898-34-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3243 - 3247

12
[ 179898-34-1 ]
[ 887266-90-2 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

13
[ 1435-51-4 ]
[ 887266-90-2 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

14
[ 887266-90-2 ]
[ 1403612-33-8 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

15
[ 887266-90-2 ]
[ 1403612-35-0 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

16
[ 887266-90-2 ]
[ 1403612-36-1 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

17
[ 887266-90-2 ]
methyl 3-cyano-5-fluorobenzoate [ No CAS ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

18
[ 887266-90-2 ]
[ 1403612-34-9 ]

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

19
[ 67-56-1 ]
[ 887266-90-2 ]
[ 334792-52-8 ]

Yield	Reaction Conditions	Operation in experiment
1.8 g	With triethylamine; at 0 - 20℃; for 2.08333h;	A mixture of 3-bromo-5-fluorobenzoic acid (2.8 g, 13.0 mmol) and thionyl chloride (10 mL) was heated to 70 C for 2 h, after cooling to room temperature excess thionyl chloride was evaporated. To the residue at 0 C was methanol (50 mL) and triethylamine (4.5 mL) added, the reaction was stirred at 0C for 5 minutes and then at room temperature for 2 h. The mixture was concentrated, diluted with ethyl acetate (100 mL) and washed consecutively with: 1) hydrochloric acid (5%, 50 mL), 2) saturated sodium bicarbonate (50 mL), the organic phase was dried over magnesium sulfate and evaporated. Purification by flash chromatography using heptane:ethyl acetate 9:1 as the eluent gave the title compound (1.8 g, 60%). H NMR (400 MHz, CDCl3) d ppm 3.89 (s, 3 H), 7.38 (dtd, 1 H), 7.58 - 7.63 (m, 1 H), 7.90 - 7.93 (m, 1 H); 13C NMR (101 MHz, CDCl3) d 52.9, 115.6, 115.8, 122.8, 122.9, 123.5, 123.7, 128.8, 128.8, 133.6, 133.6, 161.2, 163.7, 164.8, 164.8.

Reference： [1]Bioorganic and medicinal chemistry letters,2012,vol. 22,p. 6974 - 6979,6

20
[ 887266-90-2 ]
tert-butyl (1-(benzyloxy)-1H-indazol-5-yl)(cyanomethyl)carbamate [ No CAS ]
N-(1-(benzyloxy)-1H-indazol-5-yl)-3-bromo-N-(cyanomethyl)-5-fluorobenzamide [ No CAS ]

Reference： [1]Patent: WO2013/120045,2013,A1 .Location in patent: Paragraph 00320

21
[ 887266-90-2 ]
(E)-1-(3-bromo-5-fluorophenyl)-3-(dimethylamino)-2-methylprop-2-en-1-one [ No CAS ]

Reference： [1]Patent: US2013/324516,2013,A1

22
[ 887266-90-2 ]
6-(3-fluoro-5-(4-methyl-1H-pyrazol-3-yl)phenyl)pyrido[3,2-d]pyrimidin-4-amine [ No CAS ]

Reference： [1]Patent: US2013/324516,2013,A1

23
[ 887266-90-2 ]
1-(3-bromo-5-fluorophenyl)propane-1-one [ No CAS ]

Reference： [1]Patent: US2013/324516,2013,A1

24
[ 887266-90-2 ]
3-(3-bromo-5-fluorophenyl)-4-methyl-1H-pyrazole [ No CAS ]

Reference： [1]Patent: US2013/324516,2013,A1

25
[ 887266-90-2 ]
3-(3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-4-methyl-1H-pyrazole [ No CAS ]

Reference： [1]Patent: US2013/324516,2013,A1

26
[ 887266-90-2 ]
[ 6638-79-5 ]
3-bromo-5-fluoro-N-methoxy-N-methylbenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
11.0 g	With triethylamine; In dichloromethane; at 0 - 20℃;	A solution of 3-bromo-5-fluorobenzoic acid (commercially available) (10.0 g, 45.7 mmol) in thionyl chloride (80 mL) was heated at reflux for 2 hours. Thionyl chloride was removed under reduced pressure and the residue was added to solution of N,O-dimethylhydroxylamine hydrochloride (5.32 g, 54.8 mmol) and Et3N (10.1 g, 0.1 mol) in DCM (300 mL) dropwise at 0 C. After the reaction mixture was stirred at r.t. overnight, it was washed with water (3*100 mL), brine, dried over anhydrous Na2SO4 and concentrated. The colorless oil was used in next step without further purification (11.0 g, yield: 95%).

Reference： [1]Patent: US2013/324516,2013,A1 .Location in patent: Paragraph 0411; 0412

27
[ 887266-90-2 ]
(Z)-3-(3-bromo-5-fluoro-phenyl)-3-oxazol-2-yl-acrylic acid ethyl ester [ No CAS ]

Reference： [1]Patent: WO2014/154727,2014,A1
[2]Patent: US2014/296239,2014,A1
[3]Patent: WO2014/154726,2014,A1

28
[ 887266-90-2 ]
3-(3-bromo-5-fluoro-phenyl)-3-oxazol-2-yl-propionic acid ethyl ester [ No CAS ]

Reference： [1]Patent: WO2014/154727,2014,A1
[2]Patent: US2014/296239,2014,A1
[3]Patent: WO2014/154726,2014,A1
[4]Patent: US2014/296296,2014,A1

29
[ 887266-90-2 ]
3-(3-bromo-5-fluoro-phenyl)-3-oxazol-2-yl-propionic acid [ No CAS ]

Reference： [1]Patent: WO2014/154727,2014,A1
[2]Patent: US2014/296239,2014,A1
[3]Patent: WO2014/154726,2014,A1
[4]Patent: US2014/296296,2014,A1

30
[ 288-42-6 ]
[ 887266-90-2 ]
(3-bromo-5-fluoro-phenyl)-oxazol-2-yl-methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Synthesis of (3-Bromo-5-fluoro-phenyl)-oxazol-2-yl-methanone To a stirring mixture of 1 ,3-oxazole (3,46 g, 5Ommol) in dry THE (5OmL) was addedn-BuLi (1,1 Eq, 20,01 ml solution in hexanes) drop wise over 10 minutes at -78Cunder nitrogen atmosphere. After stirring for 30 minutes at -78C zinc chloride (0,1 mmol, 2,2Eq) as a 2M solution in 5-methyl-tetrahydrofurane was added within 30 minutes and the mixture was allowed to reach -20C during the addition. Then the mixture was stirred at 0C for 40 minutes, Cul (8,66g, 45,Smmol) was added andstirring continued for additional 10 minutes. 3-Bromo-5-fluoro-benzoyl chloride (45,Smmol, 8,66g) was dissolved in 50m1 of THE and added to the metallated 1,3- oxazole. Stirring was continued until complete conversion was observed by LCMS and 50m1 water and 50 ml of a 0,5 M citric acid solution were added. The solid material from the reaction mixture was filtered off and washed with 5-methyl-thf. Theorganic phase was separated, washed with brine and dried over Mg504. 10,8g of crude material (yield = 88%) were obtained and used directly in the next step.
		To a stirring mixture of 1,3-oxazole (3.46 g, 50 mmol) in dry THF (50 mL) was added n-BuLi (1.1 Eq, 20.01 ml solution in hexanes) drop wise over 10 minutes at -78 C. under nitrogen atmosphere. After stirring for 30 minutes at -78 C. zinc chloride (0.1 mmol, 2.2Eq) as a 2M solution in 5-methyl-tetrahydrofurane was added within 30 minutes and the mixture was allowed to reach -20 C. during the addition. Then the mixture was stirred at 0 C. for 40 minutes, CuI (8.66 g, 45.5 mmol) was added and stirring continued for additional 10 minutes. 3-Bromo-5-fluoro-benzoyl chloride (45.5 mmol, 8.66 g) was dissolved in 50 ml of THF and added to the metallated 1,3-oxazole. Stirring was continued until complete conversion was observed by LCMS and 50 ml water and 50 ml of a 0.5 M citric acid solution were added. The solid material from the reaction mixture was filtered off and washed with 5-methyl-thf. The organic phase was separated, washed with brine and dried over MgSO4. 10.8 g of crude material (yield=88%) were obtained and used directly in the next step. The mixture was stirred between -78 C. and -60 C. for 30 minutes and then cooled to -78 C. A solution of 3-Bromo-5-chloro-benzoic acid methyl ester (11.0 g, 44.1 mmol) in THF (20 mL) was added drop wise over 10 minutes. The resulting mixture was stirred at -78 C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0 C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N) and extracted with EtOAc (100 mL*3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc mixtures to afford (3-Bromo-5-chloro-phenyl)-(5-methyl-thiazol-2-yl)-methanone (14 g, yield=100%) as a solid.
		To a stirring mixture of 1 ,3-oxazole (3,46 g, 50mmol) in dry THF (50ml_) was added n-BuLi (1 ,1 Eq, 20,01 ml solution in hexanes) drop wise over 10 minutes at -78 C under nitrogen atmosphere. After stirring for 30 minutes at -78C zinc chloride (0,1 mmol, 2,2Eq) as a 2M solution in 5-methyl-tetrahydrofurane was added within 30 minutes and the mixture was allowed to reach -20C during the addition. Then the mixture was stirred at 0C for 40 minutes, Cul (8,66g, 45,5mmol) was added and stirring continued for additional 10 minutes. 3-Bromo-5-fluoro-benzoyl chloride (45,5mmol, 8,66g) was dissolved in 50ml of THF and added to the metallated 1 ,3- oxazole. Stirring was continued until complete conversion was observed by LCMS and 50ml water and 50 ml of a 0,5 M citric acid solution were added. The solid material from the reaction mixture was filtered off and washed with 5-methyl-thf. The organic phase was separated, washed with brine and dried over MgSO4. 10, 8g of crude material (yield = 88%) were obtained and used directly in the next step.

To a stirring mixture of 1,3-oxazole (3.46 g, 50 mmol) in dry THF (50 mL) was added n-BuLi (1.1 Eq, 20.01 ml solution in hexanes) drop wise over 10 minutes at -78 C. under nitrogen atmosphere. After stirring for 30 minutes at -78 C. zinc chloride (0.1 mmol, 2.2Eq) as a 2M solution in 5-methyl-tetrahydrofurane was added within 30 minutes and the mixture was allowed to reach -20 C. during the addition. Then the mixture was stirred at 0 C. for 40 minutes, CuI (8.66 g, 45.5 mmol) was added and stirring continued for additional 10 minutes. 3-Bromo-5-fluoro-benzoyl chloride (45.5 mmol, 8.66 g) was dissolved in 50 ml of THF and added to the metallated 1,3-oxazole. Stirring was continued until complete conversion was observed by LCMS and 50 ml water and 50 ml of a 0.5 M citric acid solution were added. The solid material from the reaction mixture was filtered off and washed with 5-methyl-thf. The organic phase was separated, washed with brine and dried over MgSO4. 10.8 g of crude material (yield=88%) were obtained and used directly in the next step. The mixture was stirred between -78 C. and -60 C. for 30 minutes and then cooled to -78 C. A solution of 3-Bromo-5-chloro-benzoic acid methyl ester (11.0 g, 44.1 mmol) in THF (20 mL) was added drop wise over 10 minutes. The resulting mixture was stirred at -78 C. for 30 minutes and warmed to room temperature with stirring overnight. The mixture was cooled to 0 C. and treated with water (50 mL). The resulting mixture was adjusted to pH around 6 with HCl (1N) and extracted with EtOAc (100 mL*3). The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with petroleum ether/EtOAc mixtures to afford (3-Bromo-5-chloro-phenyl)-(5-methyl-thiazol-2-yl)-methanone (14 g, yield=100%) as a solid.

Reference： [1]Patent: WO2014/154727,2014,A1 .Location in patent: Page/Page column 76; 77
[2]Patent: US2014/296239,2014,A1 .Location in patent: Paragraph 0168; 0169
[3]Patent: WO2014/154726,2014,A1 .Location in patent: Page/Page column 80-81
[4]Patent: US2014/296296,2014,A1 .Location in patent: Paragraph 0193; 0194

31
[ 887266-90-2 ]
C₂₁H₁₅F₄NO₂S [ No CAS ]

Reference： [1]Patent: US2015/274652,2015,A1

32
[ 887266-90-2 ]
C₁₃H₆ClF₄NO₃S [ No CAS ]

Reference： [1]Patent: US2015/274652,2015,A1

33
[ 887266-90-2 ]
C₁₈H₁₄F₆N₂O₄S [ No CAS ]

Reference： [1]Patent: US2015/274652,2015,A1

34
[ 887266-90-2 ]
[ 163733-96-8 ]
C₁₃H₆BrF₄NO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In acetonitrile; at 16℃; for 2h;	10289] To a solution of compound 3 (5.2 g, 35.7 mmol) inMeCN (130 mE) added TEA (7.2 g, 171.4 mmol) followed bycompound 2 (8.4 g, 35.7 mmol). The mixture was stirred at16 C. for 2 hour. Filtrated, the white solid was collected togive the desired product. ECMS: 348/350 [M+1].

Reference： [1]Patent: US2015/274652,2015,A1 .Location in patent: Paragraph 0288; 0289

35
[ 887266-90-2 ]
phenyl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxyl(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

36
[ 887266-90-2 ]
tert-butyl 3-fluoro-5-[1-hydroxy-1-(oxan-4-yl)propyl]benzoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2021/130682,2021,A2
[3]Patent: WO2022/43930,2022,A2

37
[ 887266-90-2 ]
3-fluoro-5-[1-hydroxy-1-(oxan-4-yl)propyl]benzoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2021/130682,2021,A2
[3]Patent: WO2022/43930,2022,A2

38
[ 887266-90-2 ]
3-fluoro-5-[1-(oxan-4-yl)-1-[(trimethylsilyl)oxy]propyl]benzoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2021/130682,2021,A2
[3]Patent: WO2022/43930,2022,A2

39
[ 887266-90-2 ]
2-(4-chlorobenzoyl)-3-fluoro-5-[1-hydroxy-1-(oxan-4-yl)propyl]benzoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

40
[ 887266-90-2 ]
2-(4-chlorobenzoyl)-3-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]benzoic acid bis[(1S)-1-phenylethyl]amine salt [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

41
[ 887266-90-2 ]
2-(trimethylsilyl)ethyl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-1-hydroxy-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

42
[ 887266-90-2 ]
(2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid tris(hydroxymethyl)aminomethane salt [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

43
[ 887266-90-2 ]
2-(4-chlorobenzoyl)-3-fluoro-5-[1-(oxan-4-yl)-1-[(trimethylsilyl)oxy]propyl]benzoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

44
[ 887266-90-2 ]
methyl (S)-2-(4-chlorobenzoyl)-3-fluoro-5-(1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)propyl)benzoate [ No CAS ]
methyl (R)-2-(4-chlorobenzoyl)-3-fluoro-5-(1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)propyl)benzoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

45
[ 887266-90-2 ]
C₂₃H₂₄ClFO₅ [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

46
[ 887266-90-2 ]
(S)-2-(4-chlorobenzoyl)-3-fluoro-5-(1-hydroxy-1-(tetrahydro-2H-pyran-4-yl)propyl)benzoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

47
[ 887266-90-2 ]
prop-2-en-1-yl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-1-hydroxy5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

48
[ 887266-90-2 ]
prop-2-en-1-yl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

49
[ 887266-90-2 ]
(2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

50
[ 887266-90-2 ]
2-(trimethylsilyl)ethyl (2S,3S)-3-(4-chlorophenyl)-3-[1-(4-chlorophenyl)-7-fluoro-1-hydroxy-5-[1-hydroxy-1-(oxan-4-yl)propyl]-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

51
[ 887266-90-2 ]
2-(trimethylsilyl)ethyl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1
[4]Patent: WO2021/130682,2021,A2
[5]Patent: WO2022/43930,2022,A2

52
[ 887266-90-2 ]
2-(trimethylsilyl)ethyl (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-1-methoxy-5-[(1S)-1-(oxan-4-yl)-1-[(trimethylsilyl)oxy]propyl]-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

53
[ 887266-90-2 ]
phenyl (2S,3S)-3-(4-chlorophenyl)-3-[1-(4-chlorophenyl)-7-fluoro-1-hydroxy-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoate [ No CAS ]

Reference： [1]Patent: WO2018/178691,2018,A1
[2]Patent: WO2018/178691,2018,A1
[3]Patent: WO2018/178691,2018,A1

54
[ 887266-90-2 ]
[ 1907-33-1 ]
tert-butyl 3-bromo-5-fluorobenzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran;	3-bromo-5-fluorobenzoic acid (32.0 g, 1 .0 equiv) was stirred in a mixture of DCM (288 mL, 9 vol) and THF (32 mL, 1 vol) until the majority of the solid dissolved. DMF (0.57 mL, 5 mol%) was added, and the flask placed in an ambient temperature water bath. Oxalyl chloride (13.7 mL, 1.10 equiv) was added over 1 h via syringe pump; 30 minute after the end of addition the reaction was complete by HPLC (sample quenched into MeOH to form methyl ester prior to analysis). The resulting thin slurry was aged overnight, concentrated to 100 mL volume, diluted with THF (160 mL, 5 vol) and again concentrated to 100 mL. The resulting thin slurry of acid chloride was diluted to 160 mL total volume with THF. A solution of LiOtBu in THF (20 wt%, 67.3 g, 77 mL, 1.15 equiv) was diluted with THF (243 mL), then this solution was cooled to an internal temperature of - 9 C with an ice/salt bath. To this was added the slurry containing acid chloride over 55 mm, while the internal temperature remained below -3 C . The reaction was complete 15 mm following the end of addition. The solution was aged overnight as it warmed to ambient temperature, diluted with heptane (320 mL, 10 vol), and washed with water (160 mL, 5 vol). The aqueous layer was removed to the insoluble rag at the interlace, then the organic layer was filtered through a pad of solka-floc. The pad was rinsed with heptane (10 mL), then the combined organic layer was washed 2xwith water (2 x 80 mL, 2.5 vol). The resulting organic layer was distilled under reduced pressure to a 100 mL final volume, diluted with heptane (160 mL, 5 vol), and concentrated again to 100 mLtotal volume. The solution of tert-butyl 3-bromo-5-fluorobenzoate was used directly in the next step.NMR 1H (400MHz; CDCI3): 7.89-7.88 (1H, m), 7.60-7.57 (1H, m), 7.40-7.37 (1H, m), 1.57 (9H, 5).
	In tetrahydrofuran; at -9 - -3℃;	3-bromo-5-fluorobenzoic acid (32.0 g, 1.0 equiv) was stirredin a mixture of DCM (288 mL, 9 vol) and THF (32 mL, 1 vol) until the majority of the solid dissolved. DMF (0.57 mL, 5 mol%) was added, and the flask placedin an ambient temperature water bath. Oxalyl chloride (13.7 mL, 1.10 equiv) was added over 1H via syringe pump; 30 minute after the end of addition the reaction was complete by HPLC (sample quenchedinto MeOH to form methyl ester prior to analysis). The resulting thin slurry was aged overnight, concentrated to 100 mL volume, diluted with THF (160 mL, 5 vol) and again concentrated to 100 mL. The resulting thin slurry of acid chloride was diluted to 160 mL total volume with THF. A solution of LiOtBu in THF (20 wt%, 67.3 g, 77 mL, 1 .15 equiv) was diluted with THF (243 mL), then this solution was cooled to an internal temperature of - 9 C with an ice/salt bath. To this was added the slurry containing acid chloride over 55 min, while the internal temperature remained below -3 C . The reaction was complete 15 min following the end of addition. The solution was aged overnight as it warmed to ambient temperature, diluted with heptane (320 mL, 10 vol), and washed with water (160 mL, 5 vol). The aqueous layer was removed to the insoluble rag at the interface, then the organic layer was filtered through a pad of solka-floc. The pad was rinsed with heptane (10 mL), then the combined organic layer was washed 2x with water (2 x 80 mL, 2.5 vol). The resulting organic layer was distilled under reduced pressure to a 100 mL final volume, diluted with heptane (160 mL, 5 vol), and concentrated again to 100 mL total volume. The solution of tert-butyl 3-bromo-5-fluorobenzoate was used directly in the next step. NMR 1H (400MHz; CDCI3): 7.89-7.88 (1H, m), 7.60-7.57 (1H, m), 7.40-7.37 (1H, m), 1 .57 (9H, s).
	With oxalyl dichloride; N,N-dimethyl-formamide; In tetrahydrofuran; at -9 - -3℃; for 1.16667h;	3-bromo-5-fluorobenzoic acid (32.0 g, 1.0 equiv) was stirred in a mixture of DCM (288 mL, 9 vol) and THF (32 mL, 1 vol) until the majority of the solid dissolved. DMF (0.57 mL, 5 mol%) was added, and the flask placed in an ambient temperature water bath. Oxalyl chloride (13.7 mL, 1.10 equiv) was added over 1 h via syringe pump; 30 minute after the end of addition the reaction was complete by HPLC (sample quenched into MeOH to form methyl ester prior to analysis). The resulting thin slurry was aged overnight, concentrated to 100 mL volume, diluted with THF (160 mL, 5 vol) and again concentrated to 100 mL. The resulting thin slurry of acid chloride was diluted to 160 mL total volume with THF. A solution of LiOtBu in THF (20 wt%, 67.3 g, 77 mL, 1.15 equiv) was diluted with THF (243 mL), then this solution was cooled to an internal temperature of - 9 C with an ice/salt bath. To this was added the slurry containing acid chloride over 55 min, while the internal temperature remained below -3 C . The reaction was complete 15 min following the end of addition. The solution was aged overnight as it warmed to ambient temperature, diluted with heptane (320 mL, 10 vol), and washed with water (160 mL, 5 vol). The aqueous layer was removed to the insoluble rag at the interface, then the organic layer was filtered through a pad of solka-floc. The pad was rinsed with heptane (10 mL), then the combined organic layer was washed 2x with water (2 x 80 mL, 2.5 vol). The resulting organic layer was distilled under reduced pressure to a 100 mL final volume, diluted with heptane (160 mL, 5 vol), and concentrated again to 100 mL total volume. The solution of tert-butyl 3-bromo-5-fluorobenzoate was used directly in the next step. NMR 1H (400MHz; CDCl3): 7.89-7.88 (1H, m), 7.60-7.57 (1H, m), 7.40-7.37 (1H, m), 1.57 (9H, s).

Reference： [1]Patent: WO2018/178691,2018,A1 .Location in patent: Page/Page column 246; 247
[2]Patent: WO2021/130682,2021,A2 .Location in patent: Page/Page column 155-156
[3]Patent: WO2022/43930,2022,A2 .Location in patent: Page/Page column 143-144

55
[ 887266-90-2 ]
(2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid tris(hydroxymethyl)aminomethane salt [ No CAS ]

Reference： [1]Patent: WO2021/130682,2021,A2
[2]Patent: WO2022/43930,2022,A2

56
[ 887266-90-2 ]
[ 1016979-31-9 ]

Reference： [1]Journal of Structural Chemistry,2021,vol. 62,p. 845 - 852
Zh. Strukt. Kim.,2021,vol. 62,p. 913 - 920

57
[ 887266-90-2 ]
C₁₆H₁₉N*C₂₂H₂₂ClFO₅ [ No CAS ]

Reference： [1]Patent: WO2022/43930,2022,A2

Related Products

Historical Records

Ghs Precautionary Statements

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

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

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

[ CAS No. 887266-90-2 ]

Quality Control of [ 887266-90-2 ]

Related Doc. of [ 887266-90-2 ]

Product Details of [ 887266-90-2 ]

Calculated chemistry of [ 887266-90-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 887266-90-2 ]

Application In Synthesis of [ 887266-90-2 ]

[ 887266-90-2 ] Synthesis Path-Upstream 1~2

[ 887266-90-2 ] Synthesis Path-Downstream 1~57

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry