[ CAS No. 1093418-75-7 ]

Name: 1093418-75-7|Methyl 4-bromo-2-iodobenzoate|99%
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Product Details of [ 1093418-75-7 ]

CAS No. :	1093418-75-7	MDL No. :	MFCD16877107
Formula :	C₈H₆BrIO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VAYKANWZAJRNOM-UHFFFAOYSA-N
M.W :	340.94	Pubchem ID :	58484707
Synonyms :

Safety of [ 1093418-75-7 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P264-P270-P271-P280-P301+P312-P302+P352-P304+P340-P305+P351+P338-P330-P332+P313-P337+P313-P362-P403+P233-P405-P501	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1093418-75-7 ]

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

Upstream synthesis route of [ 1093418-75-7 ]
Downstream synthetic route of [ 1093418-75-7 ]

[ 1093418-75-7 ] Synthesis Path-Upstream 1~3

1
[ 1093418-75-7 ]
[ 1261470-87-4 ]

Reference： [1] Organic Letters, 2018, vol. 20, # 17, p. 5190 - 5193

2
[ 1093418-75-7 ]
[ 1190360-23-6 ]

Reference： [1] Patent: KR2018/14985, 2018, A,

3
[ 1093418-75-7 ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	at 60℃; for 2 h;	Into a 250-mE round-bottom flask, was placed methyl 4-bromo-2-iodobenzoate (5.8 g, 17.01 mmol, 1.00 equiv), NMP (60 mE), CuCN (1.82 g, 20.45 mmol, 1.20 equiv). The resulting solution was stirred for 2 hours at 60° C. in an oil bath. The resulting solution was extracted with ethyl acetate (50 mEx2) and the organic layers combined. The resulting mixture was washed with Fe504 (aq.) (50 mEx2). The mixture was dried over anhydrous sodium sulfate. The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1/3). This resulted in 3.68 g (90percent) of methyl 4-bromo-2-cyanobenzoate as a white solid.
2.39 g	at 60℃; for 1 h;	[0363] Preparation Example 75: Preparation of methyl 4-bromo-2-cyanobenzoate[0364][0365] To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and coppercyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60°C for 1 hr. The reactionmixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) wasadded, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturatedaqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution,and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the titlecompound (2.39 g).MS (ESI) m/z:240(M+H)+.

Reference： [1] Patent: US2018/215731, 2018, A1, . Location in patent: Paragraph 1118; 1120
[2] Patent: EP2565182, 2013, A1, . Location in patent: Paragraph 0363; 0364; 0365

[ 1093418-75-7 ] Synthesis Path-Downstream 1~51

1
[ 619-42-1 ]
[ 1093418-75-7 ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 4-methoxycarbonylphenyl bromide With cadmium(II) chloride-N,N,N',N'-tetramethylethylenediamine; 2,2,6,6-tetramethylpiperidinyl-lithium In tetrahydrofuran; hexane at 20℃; for 2h; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran; hexane Inert atmosphere; regioselective reaction;
60%	Stage #1: 4-methoxycarbonylphenyl bromide With 2,2,6,6-tetramethyl-piperidine; n-butyllithium; cadmium(II) chloride-N,N,N',N'-tetramethylethylenediamine In tetrahydrofuran; hexane at 0 - 20℃; Inert atmosphere; Stage #2: With iodine In tetrahydrofuran; hexane Inert atmosphere; chemoselective reaction;

Reference： [1]L'Helgoual'ch, Jean-Martial; Bentabed-Ababsa, Ghenia; Chevallier, Floris; Yonehara, Mitsuhiro; Uchiyama, Masanobu; Derdour, Aicha; Mongin, Florence [Chemical Communications, 2008, # 42, p. 5375 - 5377]
[2]Location in patent: experimental part Snegaroff, Katia; L'Helgoual'ch, Jean-Martial; Bentabed-Ababsa, Ghenia; Nguyen, Tan Tai; Chevallier, Floris; Yonehara, Mitsuhiro; Uchiyama, Masanobu; Derdour, Aicha; Mongin, Florence [Chemistry - A European Journal, 2009, vol. 15, # 39, p. 10280 - 10290]

2
[ 1093418-75-7 ]
[ 86-74-8 ]
[ 1198843-15-0 ]

Yield	Reaction Conditions	Operation in experiment
45%	With 18-crown-6 ether; copper; potassium carbonate In 1,2-dichloro-benzene for 24h; Inert atmosphere; Reflux;

Reference： [1]Location in patent: experimental part Jiang, Zuoquan; Xu, Xichen; Zhang, Zhiqiang; Yang, Chuluo; Liu, Zhongyin; Tao, Youtian; Qin, Jingui; Ma, Dongge [Journal of Materials Chemistry, 2009, vol. 19, # 41, p. 7661 - 7665]

3
[ 917-92-0 ]
[ 1093418-75-7 ]
[ 1257834-06-2 ]
[ 1257834-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran at 20℃; Inert atmosphere;	34.1 Example 34; N-{4-[3-tert-Butyl-1-(6-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-isoquinolin-6-yl]-phenyl}-methanesulfonamide (I-48); step 1-; To a solution 150a (5.93 g, 17.4 mmol), Pd(PPh3)2Cl2 (610 mg, 870 mmol), CuI (0.331 g, 1.74 mmol) and THF (178 mL) was added TEA (14.1 g, 19.4 mL, 139 mmol). The reaction mixture was degassed with Ar and then 3,3-dimethylbut-1-yne was added to the mixture. The mixture was stirred at RT overnight then diluted with ether and washed with H2O. The organic extract was washed with 2N HCl and sat. AQ. NaHCO3, dried (Na2SO4), filtered and concentrated. The crude material was purified by SiO2 chromatography eluting with an EtOAc/hexane (0 to 10% EtOAc) to afford 150b. NMR indicated the product contained 10% of starting material.

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - US2010/311760, 2010, A1 Location in patent: Page/Page column 53-54

4
[ 135484-83-2 ]
[ 1093418-75-7 ]

Yield	Reaction Conditions	Operation in experiment
94%		Methyl 2-amino-4-brombenzoate (10 g, 43.47 mmol) is suspended in sulphuric acid 20% (200 mL) and obtained solution is cooled down to 0 C. Sodium nitrite (3.60 g, 52.16 mmol), dissolved in water (40 mL), is added dropwise between 0 C.-5 C. and the reaction mixture is stirred for further 40 minutes at this temperature. Afterwards a cooled solution (ca. 0 C.) of potassium iodide (14.43 g, 86.93 mmol) in water (40 mL) is added dropwise and the reaction mixture is stirred for 1 h at 5 C. The reaction mixture is poured onto ice-water and extracted with ethyl acetate. The organic layer is washed with water, 10% aq. sodium thiosulfate solution, brine, dried over Na2SO4 and concentrated in vacuo. Yield 94%.
81%		Into a 1000-mE 3-necked round-bottom flask, was placed <strong>[135484-83-2]methyl 2-amino-4-bromobenzoate</strong> (5.0 g, 21.73 mmol, 1.00 equiv), a solution of sulfuric acid (20%) (20 mE) in water (100 mE). This was followed by the addition of a solution of NaNO2 (1.8 g, 26.09 mmol, 1.20 equiv) in water (20 mE) dropwise with stirring at 00 C., after stirred 1 hour at 00 C. To this was added a solution of iodopotassium (7.21 g, 43.43 mmol, 2.00 equiv) in water (30 mE) dropwise with stirring at 00 C. The resulting solution was stirred for 1 hour at 00 C. in a water/ice bath. The reaction was then quenched by the addition of 200 mE of water/ice. The resulting solution was extracted with ethyl acetate (100 mEx3) and the organic layers combined. The resulting mixture was washed with brine (100 mExl). The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1/5). This resulted in 5.97 g (81%) of methyl 4-bromo-2-iodobenzoate as light yellow oil.
7.05 g		[0360] Preparation Example 74: Preparation of methyl 4-bromo-2-iodobenzoate[0361][0362] To <strong>[135484-83-2]methyl 2-amino-4-bromobenzoate</strong> (5.75 g) was added cooled 20% sulfuric acid (75 mL), sodium nitrite (2.07g) was added by small portions under ice-cooling, and the mixture was stirred at the same temperature for 40 min. ToEP 2 565 182 A142510152025303540455055this reaction mixture was added dropwise a solution of potassium iodide (8.3 g) in water (25 mL) under cooling to 5C,20% sulfuric acid (30 mL) was added, and the mixture was stirred at 5C for 2 hr. This reaction mixture was neutralizedwith 4N aqueous sodium hydroxide solution under ice-cooling, 10% aqueous sodium sulfite solution (45 mL) and sodiumchloride were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with 10% aqueoussodium sulfite solution added saturated brine and saturated brine, dried over sodium sulfate, and the solvent wasevaporated. The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound(7.05 g).

Reference： [1]Patent: US2016/75704,2016,A1 .Location in patent: Paragraph 0227-0228
[2]Patent: US2018/215731,2018,A1 .Location in patent: Paragraph 1118; 1119
[3]Patent: EP2565182,2013,A1 .Location in patent: Paragraph 0360; 0361; 0362
[4]Organic Letters,2018,vol. 20,p. 5190 - 5193

5
[ 1093418-75-7 ]
copper(l) cyanide [ No CAS ]
[ 1223434-15-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	In 1-methyl-pyrrolidin-2-one; at 60℃; for 2h;	Into a 250-mE round-bottom flask, was placed methyl 4-bromo-2-iodobenzoate (5.8 g, 17.01 mmol, 1.00 equiv), NMP (60 mE), CuCN (1.82 g, 20.45 mmol, 1.20 equiv). The resulting solution was stirred for 2 hours at 60 C. in an oil bath. The resulting solution was extracted with ethyl acetate (50 mEx2) and the organic layers combined. The resulting mixture was washed with Fe504 (aq.) (50 mEx2). The mixture was dried over anhydrous sodium sulfate. The residue was applied onto a silica gel colunm with ethyl acetate/petroleum ether (1/3). This resulted in 3.68 g (90%) of methyl 4-bromo-2-cyanobenzoate as a white solid.
2.39 g	In 1-methyl-pyrrolidin-2-one; at 60℃; for 1h;	[0363] Preparation Example 75: Preparation of methyl 4-bromo-2-cyanobenzoate[0364][0365] To a mixture of methyl 4-bromo-2-iodobenzoate (3.52 g) described in Preparation Example 74 and coppercyanide (1.16 g) was added N-methylpyrrolidone (21 mL), and the mixture was stirred at 60C for 1 hr. The reactionmixture was cooled, a solution of saturated aqueous ammonium chloride solution and aqueous ammonia (1:1) wasadded, and the mixture was extracted with ethyl acetate. The organic layer was washed with a solution of saturatedaqueous ammonium chloride solution and aqueous ammonia (1:1), saturated aqueous ammonium chloride solution,and saturated brine. The organic layer was dried over sodium sulfate, and the solvent was evaporated to give the titlecompound (2.39 g).MS (ESI) m/z:240(M+H)+.

Reference： [1]Patent: US2018/215731,2018,A1 .Location in patent: Paragraph 1118; 1120
[2]Patent: EP2565182,2013,A1 .Location in patent: Paragraph 0363; 0364; 0365

6
[ 1093418-75-7 ]
[ 65094-22-6 ]
[ 1369842-52-3 ]

Yield	Reaction Conditions	Operation in experiment
73%	Stage #1: diethyl (bromodifluoromethyl)phosphonate With zinc In 1,4-dioxane at 60℃; for 3h; Inert atmosphere; Stage #2: With copper(l) iodide; 1,10-Phenanthroline In 1,4-dioxane at 20℃; for 0.5h; Inert atmosphere; Stage #3: methyl 4-bromo-2-iodobenzoate In 1,4-dioxane at 60℃; for 48h; Inert atmosphere;

Reference： [1]Feng, Zhang; Chen, Fei; Zhang, Xingang [Organic Letters, 2012, vol. 14, # 7, p. 1938 - 1941]

7
[ 1093418-75-7 ]
C₃₆H₄₃FN₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 5 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.5 h / 80 °C / Inert atmosphere
	Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation

Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.5 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[3]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[4]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

8
[ 1093418-75-7 ]
C₃₇H₄₅FN₄O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.17 h / 80 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.17 h / 80 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

9
[ 1093418-75-7 ]
N-[(1S)-1-cyano-2-[2-fluoro-4-[1'-(oxetan-3-yl)spiro[1H-isobenzofuran-3,4'-piperidine]-5-yl]phenyl]ethyl]-3-azabicyclo[2.2.2]octane-4-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.17 h / 80 °C / Inert atmosphere; Microwave irradiation 6: toluene-4-sulfonic acid / water; acetonitrile / 72 h / 20 °C
	Multi-step reaction with 7 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: sodium carbonate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) / water; acetone / 1.17 h / 80 °C / Inert atmosphere; Microwave irradiation 7: toluene-4-sulfonic acid / water; acetonitrile / 72 h / 20 °C
	Multi-step reaction with 8 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 6: Burgess Reagent / dichloromethane / 0.67 h / 29 °C 7: toluene-4-sulfonic acid / water; acetonitrile / 20 °C 8: 4-methyl-morpholine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / N,N-dimethyl-formamide / 2.5 h / 20 °C

Multi-step reaction with 9 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 7: Burgess Reagent / dichloromethane / 0.67 h / 29 °C 8: toluene-4-sulfonic acid / water; acetonitrile / 20 °C 9: 4-methyl-morpholine; 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide / N,N-dimethyl-formamide / 2.5 h / 20 °C

10
[ 1093418-75-7 ]
C₂₉H₃₆FN₃O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation
	Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

11
[ 1093418-75-7 ]
C₂₄H₂₆FN₃O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 6: Burgess Reagent / dichloromethane / 0.67 h / 29 °C 7: toluene-4-sulfonic acid / water; acetonitrile / 20 °C
	Multi-step reaction with 8 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 7: Burgess Reagent / dichloromethane / 0.67 h / 29 °C 8: toluene-4-sulfonic acid / water; acetonitrile / 20 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

12
[ 1093418-75-7 ]
C₁₂H₁₄BrNO [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C
	Multi-step reaction with 4 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

13
[ 1093418-75-7 ]
C₂₉H₃₄FN₃O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 5: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 6: Burgess Reagent / dichloromethane / 0.67 h / 29 °C
	Multi-step reaction with 7 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C 6: dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); potassium carbonate / water; acetone / 0.75 h / 80 °C / Inert atmosphere; Microwave irradiation 7: Burgess Reagent / dichloromethane / 0.67 h / 29 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

14
[ 1093418-75-7 ]
5-bromo-1'-(oxetan-3-yl)spiro[1H-isobenzofuran-3,4'-piperidine] [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: hydrogenchloride / tetrahydrofuran; water / 30 h / 90 °C 4: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C
	Multi-step reaction with 5 steps 1: isopropylmagnesium chloride/lithium chloride complex / tetrahydrofuran / 1.08 h / -70 - 20 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triethylamine; p-toluenesulfonylanhydride / tetrahydrofuran / 0 - 20 °C 4: trifluoroacetic acid / dichloromethane / 1.17 h / 20 °C 5: acetic acid; sodium tris(acetoxy)borohydride / tetrahydrofuran / 0.92 h / 20 °C

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1
[2]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1

15
[ 1093418-75-7 ]
[ 79099-07-3 ]
C₁₇H₂₀BrNO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With isopropylmagnesium chloride/lithium chloride complex In tetrahydrofuran at -70 - 20℃; for 1.08333h;	2 Step 2: Synthesis of Intermediate I-7.2 I-7.1 (9.42 g, 27.63 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (6.24 g, 30.40 mmol) in dry THF (200 mL) is cooled down to -70° C. Isopropylmagnesium chloride-lithium chloride complex (1.3 mol/L in THF, 23.38 mL, 30.40 mmol) is added dropwise and reaction mixture is stirred for further 20 minutes at this temperature, is allowed to come to r.t. and stirred for 45 minutes. The reaction mixture is quenched with water and extracted with ethyl acetate. The organic layer is washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude residue is purified by flash column chromatography (petroleum ether:EtOAc=95:5 to 40:60) to provide I-7.2. Yield 74%, m/z 326,328 [M+H-tert-Bu]+, rt 1.09 min, LC-MS Method Z011_S03.

Reference： [1]Current Patent Assignee: C.H. Boehringer Sohn AG & Co. KG - US2016/75704, 2016, A1 Location in patent: Paragraph 0229-0230

16
[ 67-56-1 ]
[ 1133123-02-0 ]
[ 1093418-75-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sulfuric acid; In water; at 80℃; for 1.5h;	To <strong>[1133123-02-0]4-bromo-2-iodobenzoic acid</strong> (9.0 g, 27.53 mmol) in methanol (50 mL) is added concentrated sulphuric acid (10 mL) and the reaction mixture is stirred for 90 minutes at 80 C. The reaction mixture is poured onto ice water, sodium hydrogen carbonate is added until a pH value of 7 is reached and the reaction mixture is extracted with ethyl acetate. The organic layer is washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Yield 95%.

Reference： [1]Patent: US2016/75704,2016,A1 .Location in patent: Paragraph 0232-0233
[2]Organic and Biomolecular Chemistry,2017,vol. 15,p. 9680 - 9684

17
[ 1093418-75-7 ]
[ 191162-39-7 ]
C₁₇H₁₂BrNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In ethanol; water; toluene at 80℃;	8 Preparation of Compound 105-3 Compound 21-4 5g (28.90mmol), methyl 4-bromo-2-iodo-benzoate (methyl 4-bromo-2-iodobenzoate) 10.84g (31.79mmol), Pd (pph3) 43.34g (2.89mmol), Insert the K2CO3 11.98g (86.71mmol) into toluene, H2O, by ethanol 60mL, 12mL, 12mL wasrefluxed at 80 ° C. Ethyl acetate (Ethyl acetate) and was extracted with distilled water,to remove water and to give the title compound 105-3 8.11g (82%) was purified by column chromatography.

Reference： [1]Current Patent Assignee: LT SAMBO CO LTD - KR2016/52399, 2016, A Location in patent: Paragraph 0197-0200

18
[ 1093418-75-7 ]
(1-phenyl-1H-indol-3-yl)boronic acid [ No CAS ]
C₂₂H₁₆BrNO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane Reflux;	1 [Synthesis of 1-1`] Round bottom flask was charged with (1-phenyl-1H-indol-3-yl) boronic acid 83.70 g, methyl 4-bromo-2-iodobenzoate 100 g of 1,4-Dioxane was dissolved in 1200 ml K2CO3 (2M) and 450 ml Pd (PPh3) 4 was put 10.2 g was stirred under reflux. Check the reaction by TLC and the reaction was terminated after addition of water. After purification the organic layer was extracted with EA and filtered under reduced pressure to give the intermediate column 1-1` 93.2 g (yield: 78%).

Reference： [1]Current Patent Assignee: DONGJIN SEMICHEM CO.,LTD. - KR2015/132020, 2015, A Location in patent: Paragraph 0069-0072

19
[ 1093418-75-7 ]
[ 1365647-82-0 ]
C₂₂H₁₄BrNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
67%	With tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tri-tert-butyl phosphine; sodium t-butanolate In toluene Reflux;	Synthesis of A1-3 6.5 g of intermediate A1-2, methyl 4-bromo-2-iodobenzoate 11.7 g,4.5 g of t-BuONa, 1.2 g of Pd2(dba) 3, (t-Bu)3P 1.5 ml were dissolved in 150 ml of toluene, and the mixture was stirred under reflux. After completion of the reaction was confirmed by TLC, the organic layer was extracted with MC,After pressure filtration, the column was purified to obtain 8.83 g (yield 67%) of Intermediate A1-3

Reference： [1]Current Patent Assignee: DONGJIN SEMICHEM CO.,LTD. - KR2015/124924, 2015, A Location in patent: Paragraph 0077; 0082; 0083

20
[ 1093418-75-7 ]
C₁₉H₁₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: copper(l) iodide; caesium carbonate / toluene / 16 h / 130 °C / Inert atmosphere 2: water; sodium hydroxide / methanol / 12 h / Reflux