953410-86-1|5-Bromo-7-iodo-1H-indazole| Ambeed

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 953410-86-1 ] Purity: 95% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 953410-86-1 ]

CAS No. :	953410-86-1
Formula :	C₇H₄BrIN₂
M.W :	322.93
SMILES Code :	BrC1=CC(I)=C2NN=CC2=C1
MDL No. :	MFCD13177018
InChI Key :	GEPPVMLPAUPZTA-UHFFFAOYSA-N
Pubchem ID :	59024218

Safety of [ 953410-86-1 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302
Precautionary Statements:	P280-P305+P351+P338

Computational Chemistry of [ 953410-86-1 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	9
Fraction Csp3	0.0
Num. rotatable bonds	0
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	56.51
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	28.68 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.74
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	2.89
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.93
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	2.76
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	3.67
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.8

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-4.27
Solubility	0.0174 mg/ml ; 0.0000539 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-3.15
Solubility	0.227 mg/ml ; 0.000704 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-4.69
Solubility	0.00659 mg/ml ; 0.0000204 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	Yes
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.22 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	0.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<0.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	2.21

Application In Synthesis of [ 953410-86-1 ]

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

Downstream synthetic route of [ 953410-86-1 ]

[ 953410-86-1 ] Synthesis Path-Downstream 1~35

1
[ 953410-86-1 ]
[ 98437-23-1 ]
7-benzo[b]thiophen-2-yl-5-bromo-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 90℃; for 15h;	A mixture of 5-bromo-7-iodo-/H-indazole (Preparation No.22a, 30.0 g, 92.9 mmol) and thianapthene-2-boronc acid (21.5 g, 120.7 mmol), DME (480 mL), water (48 mL), Na2CO3 (29.5 g, 279 mmol) and tetrakis triphenylphosphine palladium (0) (8.6 g, 7.43 mmol) was heated at about 90 0C in an oil bath under an atmosphere of nitrogen for about 15 hours. The solvent was removed under reduced pressure and the residue was suspended in a mixture of ethyl acetate (600 mL) and water (300 mL). The mixture was stirred for about 30 minutes and the resulting solid was collected by filtration and dried to yield 7-Benzo[b]ihiophen-2-yl-5-bromo-lH-indazole (21.4 g, 70%); (DMSO-^6, 400 MHz) δ 13.63 (s, IH), 8.24 (s, IH), 8.05-8.09 (m, 3H), 7.92 (d, IH), 7.65 (s, IH), 7.16 (m, 2H); RP-HPLC (Table 1, Method e) Rt = 2.69 min; m/v. (M-H)' 328.4.

References: [1]Patent: WO2007/117465,2007,A2 .Location in patent: Example 13a.
[2]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 334 - 337.

2
[ 922170-67-0 ]
[ 953410-86-1 ]

Yield	Reaction Conditions	Operation in experiment
69%	With acetic acid; sodium nitrite; In water; at 20℃; for 1h;	Compound 4-bromo-2-iodo-6-methylaniline 20b (3.5 g, 11.2 mmol), acetic acid (45 mL), and water (2.1 mL) were mixed at room temperature, and then sodium nitrite (851 mg, 12.3 mmol) was added. The mixture was stirred at room temperature for another 1 hr, and then water (200 mL) was added. The mixture was adjusted to pH = 9 by using a saturated solution of sodium bicarbonate, and extracted with ethyl acetate (200 mL*2). The organic phases were combined, and concentrated to remove solvent under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate= 5/1) to give a target product 5-bromo-7-iodo-1H-indazole 20c (2.5 g, brown solid), yield: 69%. MS m/z (ESI):323, 325[M+1]
57.1%		To a solution of compound 220-S2 (6.31g, 20.29 mmol) and potassium acetate (2.3 86 g, 24.35 mmol) in CHC13 (100 mL) was added aceticanhydride (6.209 g, 60.87 mmol) dropwise at 0 C under N2 atmosphere and the mixture was stirred at room temperature for 1 hour. The reaction mixture was heated to 60 C and tert-butyl nitrite (10.3 g, 0.1 mol) was added and the reaction was stirred at 60 C overnight. The mixture was diluted with water and extracted with DCM (2x). The combined organic layers were washedwith brine, dried over anhydrous Na2SO4, and concentrated. The residue was dissolved in MeOH and 6 N HC1 (v/v 1:1), and the mixture was stirred at room temperature for 5 hours. The mixture was basified with 10 N aqueous NaOH solution and extracted with DCM twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated. Theresidue was purified by column chromatography on silica gel eluted with petroleum ether/EtOAc (100: ito 8: 1)to afford compound 220-S3 (3.73 g, 57.1 %) as alight yellow solid. LC/IVIS (ESI) m/z: 323 (M+H)t

References: [1]Bioorganic and Medicinal Chemistry Letters,2010,vol. 20,p. 334 - 337.
[2]Journal of Medicinal Chemistry,2020,vol. 63,p. 8276 - 8295.
[3]Patent: EP3409672,2018,A1 .Location in patent: Paragraph 0117; 0119.
[4]Patent: WO2018/160889,2018,A1 .Location in patent: Page/Page column 638; 639; 640.

3
[ 953410-86-1 ]
[ 388578-39-0 ]
(2R,3S,4R,5S,6R)-2-(hydroxymethyl)-6-[2-[7-[2-[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]ethynyl]-1H-indazol-5-yl]ethynyl]tetrahydropyran-3,4,5-triol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With copper(l) iodide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 80℃;Inert atmosphere;	Preparation of Compound 212 (Method D) (2R,3S,4R,5S,6R)-2-(hydroxymethyl)-6-[2-[7-[2-[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6- (hydroxymethyl)tetrahydropyran-2-yl]ethynyl]-lH-indazol-5-yl]ethynyl]tetrahydropyran- -triol To a reaction tube charged with 5-bromo-7-iodo-lH-indazole (45.0 mg, 0.139 mmol) prepared following the procedure described in PCT Int. Appl, 2007117465, Pd(dppf)Cl2. CH2CI2 (6.0 mg, 0.0082 mmol) and Cul (6.0 mg, 0.032 mmol), capped and degassed (vacuum then nitrogen flush, 2x) is added Intermediate M (500 of 0.53 M, 0.265 mmol) as a solution in DMF and DIPEA (400 μ). The reaction tube is degassed again, transferred to a preheated (80C) oil bath and stirred overnight. After cooling down to RT, the reaction mixture is passed through a 200 mg Si-DMT cartridge, rinsed with portions of MeOH and purified by reverse phase HPLC. The fractions are combined and freeze-dried, providing the title compound (18.2 mg, 27% yield) as a fluffy white solid. XH NMR (400 MHz, CD30D) δ 8.14 (s, 1H), 7.97 (d, J = 1.3 Hz, 1H), 7.60 (d, J = 1.2 Hz, 1H), 5.01 (d, J = 2.1 Hz, 1H), 4.93 - 4.78 (m, 1H), 4.16 - 4.09 (m, 1H), 4.06 - 4.01 (m, 1H), 4.01 - 3.81 (m, 6H), 3.80 - 3.70 (m, 2H), 3.69 - 3.58 (m, 2H). ESI-MS m/z: 491.44 (M+l)+

References: [1]Patent: WO2014/100158,2014,A1 .Location in patent: Page/Page column 210-211.

4
[ 953410-86-1 ]
(2R,3S,4R,5S,6R)-2-[2-[5-(6-ethoxy-4-methyl-3-pyridyl)-1H-indazol-7-yl]ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .
[2]Patent: WO2016/199105,2016,A1 .

5
[ 953410-86-1 ]
(2R,3S,4R,5S,6R)-2-[2-[5-(6-benzyloxy-4-methyl-3-pyridyl)-1H-indazol-7-yl]ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .
[2]Patent: WO2016/199105,2016,A1 .

6
[ 953410-86-1 ]
4-methyl-5-[7-[2-[(2R,3S,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]ethynyl]-1H-indazol-5-yl]-1H-pyridin-2-one [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .
[2]Patent: WO2016/199105,2016,A1 .

7
[ 953410-86-1 ]
(2R,3S,4R,5S,6R)-2-(hydroxymethyl)-6-[2-(5-phenyl-1H-indazol-7-yl)ethynyl]tetrahydropyran-3,4,5-triol [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .
[2]Patent: WO2016/199105,2016,A1 .

8
[ 953410-86-1 ]
(2R,3S,4R,5S,6R)-2-[2-[5-(2-cyclopropylethynyl)-1H-indazol-7-yl]ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .
[2]Patent: WO2016/199105,2016,A1 .

9
[ 953410-86-1 ]
[ 824-94-2 ]
5-bromo-7-iodo-2-(4-methoxybenzyl)-2H-indazole [ No CAS ]
5-bromo-7-iodo-1-(4-methoxybenzyl)-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%; 66%		To a cold (0C) solution of Intermediate B8 (992 mg, 3.07 mmol) in DMF (5 mL) was added KOtBu (417 mg, 3.72 mmol). The reaction mixture was stined for 40 mm at 0C. 1- (chloromethyl)-4-methoxy-benzene (500 jiL, 3.69 mmol) was added and the reaction mixture was stined overnight at RT, then quenched with aqueous saturated NH4C1 solution (25 mL) andextracted with EtOAc (3 x 25 mL). The combined organic extracts were washed with brine (25 mL), dried over Na2SO4, filtered and concentrated. The crude mixture was purified by flash chromatography on a Biotage snap 50g silica cartridge, using a gradient of EtOAc (0-30%) in Hex as eluent. The two regioisomers were separated, providing 5-bromo-7-iodo-1-(4-methoxybenzyl)-1H-indazole (B9, 328 mg, 24% yield) and 5-bromo-7-iodo-2-(4- methoxybenzyl)-2H-indazole (B 10, 905 mg, 66% yield). Intermediate B9: ‘H NMR (400 MHz, CDC13) ö 7.98 - 7.94 (m, 2H), 7.86 (d, J = 1.7 Hz, 1H), 7.05 (d, J = 8.4 Hz, 2H), 6.84 - 6.76 (m, 2H), 5.98 (s, 2H), 3.76 (s, 3H). Intermediate B10: ‘H NMR (400 MHz, CDC13) ö 7.83 (s, 1H),7.82 (d, J = 1.6 Hz, 1H), 7.71 (d, J = 1.6 Hz, 1H), 7.31 - 7.25 (m, 2H), 6.95 - 6.87 (m, 2H), 5.57(s, 2H), 3.82 (s, 3H).

References: [1]Patent: WO2016/199105,2016,A1 .Location in patent: Paragraph 000187.

10
[ 953410-86-1 ]
[ 824-94-2 ]
(2R,3S,4R,5S,6R)-2-[2-[5-bromo-2-[(4-methoxyphenyl)methyl]indazol-7-yl]ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

References: [1]Patent: WO2016/199105,2016,A1 .

11
[ 953410-86-1 ]
[ 388578-39-0 ]
(2R,3S,4R,5S,6R)-2-[2-(5-bromo-1 H-indazol-7-yl)ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With copper(l) iodide; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 20 - 50℃; for 48h;Inert atmosphere;	Intermediate B3 (78 mg, 0.290 mmol), Cul (10 mg, 0.053 mmol) and Pd(dppf)C12.DCM (10 mg, 0.0 14 mmol) were loaded in a pressure vial, capped and degassed (vacuum then nitrogen flush, 3x). A solution of Intermediate Ml (500 jiL of 0.53 M, 0.265 mmol) in DMF was added, followed by DIPEA (0.4 mL). The vial was degassed again andtransferred to a preheated (80C) oil bath and stined overnight (20h). The crude reaction mixture was passed through a 200 mg Si-DMT cartridge, and rinsed with portions of DMSO to produce a 1 mL sample, which was purified by reverse phase HPLC. The fractions were combined and freeze-dried to provide the title compound (32 mg, 51% yield).; The title compound was prepared following the procedure used for Compound 15,using Intermediate B8 as starting material. The reaction mixture was stined at RT for 24 h thenat 50C for 24h. After purification by reverse-phase flash chromatography on a BiotageTM 30 gC18 silica cartridge using a gradient of MeCN in H20 (10 to 90%) as eluent and freeze-drying ofthe combined fractions, the title compound (47 mg, 14% yield) was obtained. ‘H NMR (400MHz, CD3OD) ö 8.08 (s, 1H), 8.00 (s, 1H), 7.63 (s, 1H), 5.01 (d, J = 2.1 Hz, 1H), 4.14 - 4.09 (m,1H), 3.97 (dd, J = 9.4, 3.3 Hz, 1H), 3.93 (dd, J = 11.5, 2.1 Hz, 1H), 3.91 - 3.85 (m, 1H), 3.75(dd, J = 11.5, 6.2 Hz, 1H), 3.64 (t, J = 9.5 Hz, 1H). ESI-MS mlz calc. 382.0 1645, found 383.26(M+1).

References: [1]Patent: WO2016/199105,2016,A1 .Location in patent: Paragraph 000195; 000196.

12
[ 953410-86-1 ]
[ 108-24-7 ]
[ 388578-39-0 ]
(2R,3S,4R,5S,6R)-2-[2-(5-bromo-1 H-indazol-7-yl)ethynyl]-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%		In a pressure vessel charged with Intermediate B8 (2.33 g, 7.22 mmol), Cul (273 mg,1.43 mmol) and Pd(dppf)C12.DCM (266 mg, 0.364 mmol), capped and degassed (placed under vacuum and flushed with N2, 3x) was added Intermediate Ml (15 mL of 0.53 M, 7.95 mmol) solution in DMF followed by DIPEA (12 mL). The pressure vessel was degassed again, sealed and transfened to a preheated (50C) oil bath and stined overnight. After cooling down to RT,pyridine (15 mL, 186 mmol) was added, followed by acetic anhydride (15 mL, 159 mmol) and the resulting mixture was stirred overnight, then passed through a silica pad and rinsed with 200 mL EtOAc. The filtrate was transfened to a separatory funnel and washed with H20 (2 x 100 mL) and aqueous saturated NH4C1 solution (2 x 100 mL), dried over Na2SO4, filtered and concentrated, then co-evaporated with heptane (2x). The crude residue was purified by flashchromatography on a BiotageTM snap lOOg silica cartridge, using a gradient of EtOAc (10-60%) in Hex, as eluent. The fractions were combined and concentrated to provide the title compounds (as a mixture of regioisomers which were not separated) (3.03 g, 71% yield).; [000198] To a stined suspension of the regioisomers from Step 1(3.00 g, 5.06 mmol) in MeOH(20 mL) was added a solution of NaOMe (20.0 mL of 0.5 M, 10.1 mmol) in MeOH. Afterstifling for 30 mm, the reaction mixture was diluted with MeOH (25 mL) and treated with a minimal amount of prewashed Dowex 50WX4-400 resin (until pH is slightly acidic), diluted with THF (20 mL), filtered and washed with portions of MeOH/THF (1:1, 4x10 mL). The combined filtrates were concentrated to provide the title compound (1.85 g, 96% yield).

References: [1]Patent: WO2016/199105,2016,A1 .Location in patent: Paragraph 000197; 000198.

13
[ 953410-86-1 ]
[ 108-24-7 ]
[ 388578-39-0 ]
[(2R,3R,4R,5R,6R)-3,4,5-triacetoxy-6-[2-(1-acetyl-5-bromo-indazol-7-yl)ethynyl]tetrahydropyran-2-yl]methyl acetate [ No CAS ]
(2R,3R,4R,5R, 6R)-2-(acetoxymethyl)-6-((2-acetyl-5-bromo-2H-indazol-7-yl)ethynyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		In a pressure vessel charged with Intermediate B8 (2.33 g, 7.22 mmol), Cul (273 mg,1.43 mmol) and Pd(dppf)C12.DCM (266 mg, 0.364 mmol), capped and degassed (placed under vacuum and flushed with N2, 3x) was added Intermediate Ml (15 mL of 0.53 M, 7.95 mmol) solution in DMF followed by DIPEA (12 mL). The pressure vessel was degassed again, sealed and transfened to a preheated (50C) oil bath and stined overnight. After cooling down to RT,pyridine (15 mL, 186 mmol) was added, followed by acetic anhydride (15 mL, 159 mmol) and the resulting mixture was stirred overnight, then passed through a silica pad and rinsed with 200 mL EtOAc. The filtrate was transfened to a separatory funnel and washed with H20 (2 x 100 mL) and aqueous saturated NH4C1 solution (2 x 100 mL), dried over Na2SO4, filtered and concentrated, then co-evaporated with heptane (2x). The crude residue was purified by flashchromatography on a BiotageTM snap lOOg silica cartridge, using a gradient of EtOAc (10-60%) in Hex, as eluent. The fractions were combined and concentrated to provide the title compounds (as a mixture of regioisomers which were not separated) (3.03 g, 71% yield).

References: [1]Patent: WO2016/199105,2016,A1 .Location in patent: Paragraph 000197.

14
[ 583-75-5 ]
[ 953410-86-1 ]

References: [1]Patent: WO2018/160889,2018,A1 .
[2]Patent: EP3409672,2018,A1 .
[3]Journal of Medicinal Chemistry,2020,vol. 63,p. 8276 - 8295.

15
[ 953410-86-1 ]
potassium vinyltrifluoroborate [ No CAS ]
5-bromo-7-vinyl-1H-indazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59.4%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In 1,2-dimethoxyethane; water; at 85℃;Inert atmosphere;	To a solution of compound 220-S3 (1.9 g, 5.92 mmol) in DME/H20 (40 mL, v/v3/i) was added potassium trifluoro(vinyl)borate (0.793g, 5.92 mmol), K2C03 (0.980 g, 7.10 mmol) and Pd(PPh3)4 (0.684 g, 0.59 mmol). The mixture was degassed under N2 atmosphere three times and stirred at 85 C under N2 atmosphere overnight. The mixture was diluted with EtOAc and washed with water and brine, dried over anhydrous Na2SO4, and concentrated. The residue was purified by column chromatography on silica gel eluted with petroleum ether/EtOAc (100: 1 to 8: 1) to afford compound 220-S4 (0.78 g, 59.4 %)as a light yellow solid. LC/IVIS (ESI) m/z: 223 (M+H) .

References: [1]Patent: WO2018/160889,2018,A1 .Location in patent: Page/Page column 638; 640.

16
[ 953410-86-1 ]
1-(5-bromo-1H-indazol-7-yl)ethanol [ No CAS ]