Name: 1609393-90-9|2-MEthoxy-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)aniline|95%
Brand: Ambeed
SKU: A986099
Rating: 90 (30 reviews)

1
[ 13073-25-1 ]
[ 1609393-90-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0.5 h 2: zinc; ammonium chloride / water; ethanol / 1 h 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 15 h / 100 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 20 °C 2: zinc; ammonium chloride / water; ethanol / 20 °C 3: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 100 °C
	Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h 1.2: 20 °C 2.1: zinc; ammonium chloride / water / 20 °C 3.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 100 °C

Multi-step reaction with 3 steps 1.1: potassium carbonate / N,N-dimethyl-formamide / 0.25 h 1.2: 20 °C 2.1: water; zinc; ammonium chloride / ethanol / 20 °C 3.1: potassium acetate; palladium bis[bis(diphenylphosphino)ferrocene] dichloride / 1,4-dioxane / 4.5 h / 100 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; BIOCON LIMITED - WO2014/74661, 2014, A1
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2015/69310, 2015, A1
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - TWI582077, 2017, B
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/92196, 2020, A1

2
[ 98775-19-0 ]
[ 1609393-90-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: zinc; ammonium chloride / water; ethanol / 1 h 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 15 h / 100 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: zinc; ammonium chloride / water; ethanol / 20 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 100 °C
	Multi-step reaction with 2 steps 1: zinc; ammonium chloride / water / 20 °C 2: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 100 °C

Multi-step reaction with 2 steps 1: water; zinc; ammonium chloride / ethanol / 20 °C 2: potassium acetate; palladium bis[bis(diphenylphosphino)ferrocene] dichloride / 1,4-dioxane / 4.5 h / 100 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO; BIOCON LIMITED - WO2014/74661, 2014, A1
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2015/69310, 2015, A1
[3]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - TWI582077, 2017, B
[4]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/92196, 2020, A1

3
[ 116557-46-1 ]
[ 73183-34-3 ]
[ 1609393-90-9 ]

Yield	Reaction Conditions	Operation in experiment
81%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃; for 15h;Inert atmosphere;	Step 3[00174j IntlO (2.0 g, 9.9 mmol) was dissolved in dioxane (40 mL) and the vessel purged with nitrogen for 5 minutes. Next bis(pinacolato)diborone (3.77 g, 14.85 mmol), [1,1 ?-bis(diphenylphosphino)ferrocene] dichloropalladium (II) complex with dichloromethane (404 mg, 0.49 mmol) and potassium acetate (2.91 g, 29.7 mmol) were added. The flask was evacuated and backfilled with nitrogen, and then heated to 100 Cfor 15 hours. Water was added to quench the reaction and the product was then extracted with EtOAc. The combined organic layers were washed with brine (x3), dried over sodium sulfate, filtered, concentrated and purified using automated chromatography (elutes at 40% ethyl acetate) to provide Intl 1 (2.0 g, 8 1%). ?H NMR (400MHz, chloroform-d) oe 7.12 (dd,J=7.3, 1.8 Hz, 1H), 6.96-6.89 (m, 1H), 6.88-6.83 (m, 1H),3.82 (s, 3H), 1.37 (s, 12H). LC retention time 0.65 [J]. m/z: 250 (MHj.
60.2%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃;	Step 3 A solution of <strong>[116557-46-1]3-bromo-2-methoxyaniline</strong> from Step 2 (1.94 g, 9.60 mmol), 4,4,445,5,55'-octamethyl-2,2'-bi(l,3,2-dioxaborolane) (3.66 g, 14.40 mmol), PdCl2(dppf)-CH2Cl2 complex (0.392 g, 0.480 mmol) and potassium acetate (2.83 g, 28.8 mmol) in dioxane (32 mL) in a flask was heated to reflux (-100 C) overnight then cooled to room temperature, concentrated in vacuo on CELITE. This crude product was purified by flash chromatography using a 120g silica gel column (solid loading) eluting with 0-50% ethyl acetate/hexanes. Appropriate fractions (eluted near 25% EtOAc/hexanes) were collected and concentrated in vacuo to give 2-methoxy-3-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)aniline (1.47 g, 5.78 mmol, 60.2% yield) as a crystalline off-white solid. LCMS MH+ 250.1.
60.2%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; at 100℃;	In the flask will come from step 2<strong>[116557-46-1]3-bromo-2-methoxyaniline</strong> (1.94 g, 9.60 mmol)4,4,4 ', 4', 5,5,5 ', 5'-octamethyl-2,2'-bis(1,3,2-dioxaborolane)(3.66 g, 14.40 mmol),PdCl2 (dppf) -CH2Cl2 (0.392 g, 0.480 mmol) and potassium acetate (2.83 g, 28.8 mmol) in dioxane (32 mL)The solution was heated to reflux (about 100 & lt; 0 & gt; C) overnight,Then cooled to room temperature,Concentrated on diatomaceous earth in a vacuum.The crude product was purified by flash chromatography using 120 g of a silica gel column (solid loading) with 0-50% ethyl acetate / hexane. The appropriate fractions were collected (eluted with nearly 25% EtOAc / hexanes) and concentrated in vacuo,To give 2-methoxy-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline in an off-white crystalline solid form (1.47 g , 5.78 mmol, 60.2% yield).

58%		A suspension of <strong>[116557-46-1]3-bromo-2-methoxyaniline</strong> (500 mg, 2.47 mmol), bis(pinacolato)diboron (755 mg, 2.97 mmol) and potassium acetate (729 mg, 7.42 mmol) in 1,4-dioxane (8 mL) was sparged with nitrogen for 5 min. Pd(dppf)Cl2·DCM (173 mg, 0.21 mmol) was added and the mixture was heated under reflux for 2.5 h then cooled to room temperature. The reaction was diluted with DCM (35 mL) and washed with water (35 mL). The organic phase was concentrated under reduced pressure then purified by flash column chromatography, eluting with 0-100% EtOAc in isohexane, to return 49h (358 mg, 58%) an off-white solid. 1H NMR (300 MHz, DMSO-d6) delta 6.72-6.83 (m, 3H), 4.80 (s, 2H), 3.64 (s, 3H), 1.28 (s, 12H).
47%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate; In 1,4-dioxane; at 100℃;Inert atmosphere;	A 500 ml round-bottomed flask was charged with SI (6.61 g, 32.7 mmol), S2 (12.46 g, 49.1 mmol), Pd(dppfkCl2(l.05 g, 1.1 mmol), KOAc (9.62 g, 98.2 mmol) and l,4-dioxane (200 ml), degassed and refilled with N2. The resulting solution was heated to l00C under an N2 atmosphere and then stirred overnight. After cooled to room temperature, the solution was quenched with water (10 ml) and diluted with ethyl acetate (150 ml). The resulting mixture was washed with brine (3x100 ml), dried with Na2S04. After the solvent was removed in vacuo, the residue was subjected to flash column over silica gel eluting with ethyl acetate/hexane (1:3, v/v) to obtain compound S3 (3.83 g, 47%) as off-white solid. 1 H NMR (400 MHz, CDCb, ppm): d 7.11 (d, J = 7.1 Hz, 1H, ArH), 6.93 (t, J = 6.9 Hz, 1H, ArH), 6.86 (d, J = 6.9 Hz, 1H, ArH), 3.82 (br? 2H, NH2), 3.81 (s, 3H, OMe), 1.36 (s, 12H, Me); 13C NMR (lOOMHz, CDCb, ppm): d 152.7, 139.6, 126.1, 124.3, 119.1, 83.6, 24.9. The carbon directly attached to the boron atom was not detected, likely due to quadrapolar relaxation; HRMS (ESI) m/z 250.1614 [M + H]+calcd for C13H21BNO3, found 250.1609.
358 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium acetate; In 1,4-dioxane; for 2.5h;Inert atmosphere; Reflux;	[00239] 3-Bromo-2-methoxyaniline (500 mg, 2.47 mmol), bis(pinacolato)diboron (755 mg,2.97 mmol) and potassium acetate (728 mg, 7.42 mmol) were mixed in 1,4-dioxane (8 mL) and nitrogen gas was blown through for 5 minutes. 1,1-Bis(diphenyl-phosphino)ferrocene- palladium(ll)dichloride DCM adduct (173 mg, 0.21 mmol) was added and nitrogen blown through again. The mixture was heated under reflux conditions for 2.5 hours then allowed to cool (black mixture). Dl water and DCM were added (35mls of each) and the mixture wasstirred vigourously for 30 minutes then passed through a hydrophobic frit. The DCM phase was concentrated down to remove excess Dioxane then redissolved in minimum DCM and was purified by flash chromatography eluting with 0-100% ethyl acetate/isohexane over 40 minutes. Product containing fractions were concentrated down to give 2-methoxy-3-(4,4,5,5-tetramethyl- 1 ,3,2-dioxaborolan-2-yl)aniline as an off-white solid 358mg. [00240] 1H NMR (DMSO-d6): O 6.88 (m, 3H), 4.80 (bs, 2H), 3.64 (5, 3H), 1.29 (5, 12H).

Reference： [1]Patent: WO2014/74661,2014,A1 .Location in patent: Paragraph 00174
[2]Patent: WO2015/69310,2015,A1 .Location in patent: Paragraph 00186
[3]Patent: TWI582077,2017,B .Location in patent: Page/Page column 87; 88
[4]European Journal of Medicinal Chemistry,2016,vol. 112,p. 20 - 32
[5]Angewandte Chemie - International Edition,2018,vol. 57,p. 11924 - 11928
Angew. Chem.,2018,vol. 130,p. 12100 - 12104,5
[6]Patent: WO2019/226863,2019,A1 .Location in patent: Paragraph 39; 40; 41
[7]Patent: WO2015/79251,2015,A1 .Location in patent: Paragraph 00239; 00240

4
[ 7238-61-1 ]
[ 1609393-90-9 ]
[ 1609393-91-0 ]

Yield	Reaction Conditions	Operation in experiment
83%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere;	[00175j A stirred mixture of <strong>[7238-61-1]<strong>[7238-61-1]2-bromo-4-methylthiazol</strong>e</strong> (201 mg, 1.13 mmol), Intll (309 mg, 1.24 mmol) and 1,1 ?-bis(di-tert-butylphosphino)ferrocene palladium dichloride (36.8 mg in dioxane (8 mL) was degassed by bubbling nitrogen through the mixture for 5 minutes. Subsequently tribasic potassium phosphate (2M in water, 1.69 mL, 3.39 mmol)was added and the reaction mixture heated at 100 C for one hour. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and then dried over sodium sulfate, filtered, concentrated and purified by automated chromatography providing Intl2 (218 mg, 83%). ?H NMR (400MHz, chloroform-d) oe 7.63 (dd, J7.9, 1.6 Hz, 1H), 7.02 (t, J=7.8 Hz, 1H), 6.96 (d, J=1.0 Hz, 1H), 6.80 (dd, J7.8, 1.5 Hz, 1H),3.88 (br. s., 2H), 3.80 (s, 3H), 2.53 (d, J1.0 Hz, 3H). LC retention time 0.65 [J]. m/z:221 (MHj.

Reference： [1]Patent: WO2014/74661,2014,A1 .Location in patent: Paragraph 00175

5
[ 1609393-90-9 ]
[ 298694-30-1 ]
2-methoxy-3-(2-methylthiazol-4-yl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With dipotassium hydrogenphosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II); In 1,4-dioxane; water; at 100℃; for 1h;Inert atmosphere;	Step 4 A stirred mixture of <strong>[298694-30-1]4-bromo-2-methylthiazole</strong> (128 mg, 0.719 mmol), 2- methoxy-3-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)aniline from Step 3 (197 mg, 0.791 mmol) and l, -bis(di-tert-butylphosphino)ferrocene palladium dichloride (14.06 mg, 0.022 mmol) in dioxane (4 mL) was degassed by bubbling nitrogen through the mixture for 5 minutes. 2M sq potassium phosphate dibasic solution (1.078 mL, 2.157 mmol) was quickly added and the reaction mixture heated at 100 C for one hour. LC-MS showed complete conversion to the desired product mass. The reaction mixture was cooled to room temperature, then diluted with EtOAc (75mL). This solution was then dried over sodium sulfate, filtered, concentrated and purified by flash chromatography, eluting with 0-100% EtOAc in hexanes. Afforded 2-methoxy-3-(2-methylthiazol-4- yl)aniline (Preparation 12, 122 mg, 0.543 mmol, 75% yield) as a yellow oil. LCMS MH+ 221.1.
75%		By bubbling nitrogen through <strong>[298694-30-1]4-bromo-2-methylthiazole</strong> (128 mg, 0.719 mmol)2-methoxy-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) aniline from Step 3 (197 mg, 0.791 mmol )And 1,1'-bis (di-t-butylphosphino)Ferrocene palladium dichloride (14.06 mg, 0.022 mmol)Stored in dioxane (4 mL)The mixture was stirred for 5 minutes and the mixture was degassed.Quickly add 2MDipotassium phosphateAqueous solution(1.078 mL, 2.157 mmol) and the reaction mixture was heated at 100 & lt; 0 & gt; C for 1 hour.LC-MS showed complete conversion to the desired product. The reaction mixture was cooled to room temperature and then diluted with EtOAc (75 mL). The solution was then dried over sodium sulfate, filtered, concentrated and purified by flash chromatography eluting with 0 to 100% EtOAc in hexanes. A solution of 2-methoxy-3- (2-methylthiazol-4-yl) aniline (prepared 12,122 mg, 0.543 mmol, 75% yield) as a yellow oil.

Reference： [1]Patent: WO2015/69310,2015,A1 .Location in patent: Paragraph 00187
[2]Patent: TWI582077,2017,B .Location in patent: Page/Page column 88; 89

6
[ 28165-50-6 ]
[ 1609393-90-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 1 h / 20 °C 2: dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium acetate / 1,4-dioxane / 100 °C
	Multi-step reaction with 2 steps 1.1: triphenylphosphine / tetrahydrofuran / 20 °C 1.2: 1 h / 20 °C 2.1: potassium acetate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / 1,4-dioxane / 100 °C

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2015/69310, 2015, A1
[2]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - TWI582077, 2017, B

7
[ 1609393-90-9 ]
[ 125708-66-9 ]

Yield	Reaction Conditions	Operation in experiment
57%	With sodium perborate; water In tetrahydrofuran at 20℃;	5.1.2.8 3-Amino-2-methoxyphenol (46h) To a solution of 49h (358 mg, 1.44 mmol) in THF (10 mL) was added water (5 mL) and sodium perborate (569 mg, 3.7 mmol). The mixture was stirred at ambient temperature overnight. Excess THF was removed under reduced pressure. The residue was stirred with sat. NH4Cl solution (10 mL) and DCM (50 mL) for 1 h, then separated. The organics were concentrated under reduced pressure and purified by flash column chromatography, eluting with 0-60% EtOAc in isohexane, to return 46h (120 mg, 57%) as an off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.80 (s, 1H), 6.55 (t, J = 7.84 Hz, 1H), 6.12 (d, J = 7.95 Hz, 1H), 6.05 (d, J = 7.77 Hz, 1H), 4.71 (s, 2H), 3.62 (s, 3H).

Reference： [1]Newton, Rebecca; Bowler, Katherine A.; Burns, Emily M.; Chapman, Philip J.; Fairweather, Emma E.; Fritzl, Samantha J.R.; Goldberg, Kristin M.; Hamilton, Niall M.; Holt, Sarah V.; Hopkins, Gemma V.; Jones, Stuart D.; Jordan, Allan M.; Lyons, Amanda J.; Nikki March; McDonald, Neil Q.; Maguire, Laura A.; Mould, Daniel P.; Purkiss, Andrew G.; Small, Helen F.; Stowell, Alexandra I.J.; Thomson, Graeme J.; Waddell, Ian D.; Waszkowycz, Bohdan; Watson, Amanda J.; Ogilvie, Donald J. [European Journal of Medicinal Chemistry, 2016, vol. 112, p. 20 - 32]

8
sodium perborate [ No CAS ]
[ 1609393-90-9 ]
[ 7732-18-5 ]
[ 125708-66-9 ]

Yield	Reaction Conditions	Operation in experiment
125 mg	In tetrahydrofuran at 20℃;	[00241] 2-Methoxy-3-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2-yl)aniline (358 mg, 1 .44mmol) was completely dissolved in THF (10 mL). Water (5 mL) was added followed by sodiumperborate (569 mg, 3.7 mmol). The mixture was stirred at ambient temperature overnight. Excess THF was removed under vacuo - some solid. Saturated ammonium chloride (10mls) and DCM (50mls) were added and the mixture stirred vigourously for one hour before passing through a hydrophobic frit. The DCM was concentrated down and purified by flashchromatography eluting with 0-60% ethyl acetate/isohexane over 40 minutes. Product containing fractions were concentrated to give 3-amino-2-methoxyphenol as an off white crystalline solid, l2Smgs. [00242] 1H NMR (DMSO-d6): O 8.80 (5, 1H), 6.55 (t, J= 8.1 Hz, 1H), 6.04 (dd, J= 1.3 and 8.1 Hz, 1H), 4.71 (bs, 2H), 3.62 (5, 3H).

Reference： [1]Current Patent Assignee: CANCER RESEARCH UK - WO2015/79251, 2015, A1 Location in patent: Paragraph 00241; 00242

9
[ 1609393-90-9 ]
3-((6,7-dimethoxyquinazolin-4-yl)amino)-2-methoxyphenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium perborate; water / tetrahydrofuran / 20 °C 2: hydrogenchloride / isopropyl alcohol / 0.5 h / 100 °C / Microwave irradiation

Reference： [1]Newton, Rebecca; Bowler, Katherine A.; Burns, Emily M.; Chapman, Philip J.; Fairweather, Emma E.; Fritzl, Samantha J.R.; Goldberg, Kristin M.; Hamilton, Niall M.; Holt, Sarah V.; Hopkins, Gemma V.; Jones, Stuart D.; Jordan, Allan M.; Lyons, Amanda J.; Nikki March; McDonald, Neil Q.; Maguire, Laura A.; Mould, Daniel P.; Purkiss, Andrew G.; Small, Helen F.; Stowell, Alexandra I.J.; Thomson, Graeme J.; Waddell, Ian D.; Waszkowycz, Bohdan; Watson, Amanda J.; Ogilvie, Donald J. [European Journal of Medicinal Chemistry, 2016, vol. 112, p. 20 - 32]

10
[ 1609393-90-9 ]
N-(3-{5-[1-(4-chlorophenyl)ethyl]-3-methyl-4-oxo-4,5-dihydro[1,2]oxazolo[4,5-d]pyridazin-7-yl}-2-methoxyphenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: acetic acid / 16 h / 20 °C 2: sodium hydrogencarbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / toluene; ethanol; water / 0.5 h / 130 °C / Inert atmosphere; Microwave irradiation

Reference： [1]Current Patent Assignee: ABBVIE INC - US2017/73353, 2017, A1

11
[ 1609393-90-9 ]
[ 108-24-7 ]
N-(2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid at 20℃; for 16h;	33.1 Step 1: Step 1: N-(2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide A mixture of 2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (13 g, 52.2 mmol) and acetic anhydride (50 mL, 530 mmol) in acetic acid(10 mL) was stirred at room temperature for 16 hours. The mixture was concentrated, and the residue was triturated with diethyl ether. The solid was collected by filtration, washed with diethyl ether, and dried to give the titled compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 9.23 (s, 1H), 8.10 (d, J=7.8 Hz, 1H), 7.28 (d, J=6.6 Hz, 1H), 7.04 (t, J=7.5 Hz, 1H), 3.73 (s, 3H), 2.12 (s, 3H), 1.30 (s, 12H); MS (ESI+) m/z 292 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC - US2017/73353, 2017, A1 Location in patent: Paragraph 0491

12
[ 1609393-90-9 ]
C₄₅H₄₇N₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / N,N-dimethyl-formamide / 5 h / 110 °C / Inert atmosphere 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / N,N-dimethyl-formamide / 5 h / 110 °C / Inert atmosphere 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere

Reference： [1]He, Qing; Williams, Neil J.; Oh, Ju Hyun; Lynch, Vincent M.; Kim, Sung Kuk; Moyer, Bruce A.; Sessler, Jonathan L. [Angewandte Chemie - International Edition, 2018, vol. 57, # 37, p. 11924 - 11928][Angew. Chem., 2018, vol. 130, # 37, p. 12100 - 12104,5]
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM; GYEONGSANG NATIONAL UNIVERSITY - WO2019/226863, 2019, A1

13
[ 1609393-90-9 ]
C₅₁H₅₅N₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / N,N-dimethyl-formamide / 5 h / 110 °C / Inert atmosphere 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere 3: boron trifluoride diethyl etherate / 20 °C
	Multi-step reaction with 3 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium phosphate / N,N-dimethyl-formamide / 5 h / 110 °C / Inert atmosphere 2: 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; pyridine / dichloromethane / 24 h / 20 °C / Inert atmosphere 3: boron trifluoride diethyl etherate / 20 °C

Reference： [1]He, Qing; Williams, Neil J.; Oh, Ju Hyun; Lynch, Vincent M.; Kim, Sung Kuk; Moyer, Bruce A.; Sessler, Jonathan L. [Angewandte Chemie - International Edition, 2018, vol. 57, # 37, p. 11924 - 11928][Angew. Chem., 2018, vol. 130, # 37, p. 12100 - 12104,5]
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM; GYEONGSANG NATIONAL UNIVERSITY - WO2019/226863, 2019, A1

14
[ 626-05-1 ]
[ 1609393-90-9 ]
3, 3'-(pyridine-2,6-diyl)bis(2-methoxyaniline) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 110℃; for 5h; Inert atmosphere;
0.92 g	With potassium phosphate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide at 110℃; for 5h; Inert atmosphere;	2.b Synthesis of 3, 3'-(pyridine-2,6-diyl)bis(2-methoxyaniline) (S5): Compounds S3 (3.67 g, 14.7 mmol), S2 (1.75 g, 7.3 mmol), Pd(PPh3)4 (509 mg, 0.4 mmol), and K3PCU (10.23 g, 44.1 mmol) were dissolved in dry DMF (150 ml), heated to 1 l0°C under an N2 atmosphere, and then stirred for 5 h. After allowing the reaction mixture to cool to room temperature, the mixture was diluted with ethyl acetate (150 ml). The resulting solution was washed with water (3x200 ml). The combined organic phase was dried over anhydrous Na2S04 for 2 h. After evaporation off the volatiles under reduced pressure, the residue was subjected to flash column over silica gel eluting with ethyl acetate (EA)/hexanes (1:2, v/v) to obtain compound S5 (0.92 g, 63%) as an off-white solid. 1 H NMR (400 MHz, CDCb, ppm): d 7.73-7.80 (m, 3H, ArH), 7.24 (dd, J = 7.8, 1.6 Hz, 2H, ArH), 7.03 (t, J = 7.8 Hz, 2H, ArH), 6.79 (dd, J = 7.8, 1.6 Hz, 2H, ArH), 3.94 (br, J = 4H, NH2), 3.54 (s, 6H, OMe); 13C NMR (100 MHz, CDCb, ppm): <5 156.0, 145.3, 140.2, 136.3, 133.8, 124.8, 122.5, 120.8, 116.3, 60.18; HRMS (ESI) m/z 322.1556 [M+H]+ calcd for C19H20N3O2, found 322.1551.

Reference： [1]He, Qing; Williams, Neil J.; Oh, Ju Hyun; Lynch, Vincent M.; Kim, Sung Kuk; Moyer, Bruce A.; Sessler, Jonathan L. [Angewandte Chemie - International Edition, 2018, vol. 57, # 37, p. 11924 - 11928][Angew. Chem., 2018, vol. 130, # 37, p. 12100 - 12104,5]
[2]Current Patent Assignee: THE UNIVERSITY OF TEXAS SYSTEM; GYEONGSANG NATIONAL UNIVERSITY - WO2019/226863, 2019, A1 Location in patent: Page/Page column 39; 40; 41

15
[ 41731-83-3 ]
[ 1609393-90-9 ]
ethyl 2-(3-amino-2-methoxyphenyl)thiazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60.8%	With potassium phosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) In 1,4-dioxane; water at 100℃; for 1h; Inert atmosphere;	239.1 Step 1 : A stirred mixture of ethyl 2-bromothiazole-5-carboxylate (116 mg, 0.491 mmol) , 2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (135 mg, 0.540 mmol) and l,l'-bis(di-tert-butylphosphino)ferrocene palladium dichloride (16.01 mg, 0.025 mmol) in Dioxane (4 mL) was degassed by bubbling nitrogen through the mixture for 5 minutes. 2M K3PO4 (aq) (0.737 mL, 1.474 mmol) was quickly added and the reaction mixture heated at 100 °C for one hour. LC-MS showed complete conversion to the desired product mass. The reaction mixture was cooled to room temperature. The reaction mixture was diluted with EtOAc (75mL) and then dried over sodium sulfate, filtered, concentrated and purified by flash chromatography, eluting with 0-100% EtOAc in hexanes. This afforded ethyl 2-(3-amino-2-methoxyphenyl)thiazole-5-carboxylate (84 mg, 0.299 mmol, 60.8 % yield) as a yellow oil.. LCMS m/z 279.2 (M+H)+; HPLC /R 0.86 min (HPLC Method A).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/92196, 2020, A1 Location in patent: Page/Page column 134-135

16
[ 173841-06-0 ]
[ 1609393-90-9 ]
methyl 3-(3-amino-2-methoxyphenyl)-1-methyl-1H-pyrazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29.4%	With potassium phosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) In 1,4-dioxane; water at 125℃; for 1h; Inert atmosphere;	455.1 Step 1 : A stirred mixture of methyl 3-chloro-1-methyl-1H-pyrazole-5-carboxylate (200 mg, 1.146 mmol), 2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (499 mg, 2.005 mmol) and l,r-bis(di-tert-butylphosphino)ferrocene palladium dichloride (37.3 mg, 0.057 mmol) in Dioxane (6 ml) was degassed by bubbling nitrogen through the mixture for 5 minutes. 2M K3PO4 (aq) (1.718 ml, 3.44 mmol) was quickly added and the reaction mixture heated at 125 °C for 1Hr. The reaction mixture was partitioned between EtOAc (30 ml) and water (30 ml). The organic layer was washed with brine (30 ml), dried (Na2S04) and concentrated to afford a brown oil that was chromatographed on a 24 gm ISCO silica gel cartridge, eluting with a 0-50%EtO Ac/Hexanes gradient. The pure fractions were concentrated to afford methyl 3-(3-amino-2-methoxyphenyl)-1-ethyl-1H-pyrazole-5-carboxylate (89 mg, 0.337 mmol, 29.4 % yield) as a tan solid. LCMS m/z 262.2 (M+H)+; HPLC fe 0.65 min (analytical HPLC Method A).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/92196, 2020, A1 Location in patent: Page/Page column 212-213

17
[ 1609393-90-9 ]
tert-butyl (2-(4-bromo-1H-pyrazol-1-yl)ethyl)carbamate [ No CAS ]
tert-butyl (2-(4-(3-amino-2-methoxyphenyl)-1H-pyrazol-1-yl)ethyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With potassium phosphate; dichloro[1,1'-bis(di-t-butylphosphino)ferrocene]palladium(II) In water at 100℃; for 1h; Inert atmosphere;	556.1 Step 1 : A solution of tert-butyl (2-(4-bromo-1H-pyrazol-1-yl)ethyl)carbamate (0.18 g, 0.620 mmol), 2-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.170 g, 0.682 mmol), and l,l'-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.020 g, 0.031 mmol) was degassed by bubbling N2 through the solution for 5 minutes. Then 2M K3PO4 (aq) (0.931 mL, 1.861 mmol) was added and the mixture was stirred at 100 °C for lh. LC-MS showed complete conversion to the desired product mass. The reaction mixture was cooled to room temperature, then diluted with EtOAc (75mL). This solution was then dried over sodium sulfate, filtered, concentrated and purified by flash chromatography, eluting with 0-100% EtOAc in hexanes to afford tert-butyl (2-(4-(3-amino-2-methoxyphenyl)-1H-pyrazol-1-yl)ethyl (carbamate (177 rng, 0.532 mmol, 86 % yield) in total, a yellow solid. LCMS m/z 333.2 (M+H)+; HPLC fe 0.68 min (analytical HPLC Method A).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2020/92196, 2020, A1 Location in patent: Page/Page column 245-246

18
[ 1609393-90-9 ]
C₂₄H₂₆⁽²⁾H₃N₉O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: lithium hexamethyldisilazane / tetrahydrofuran / 0.33 h / 25 °C 2.1: tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; caesium carbonate / 1,4-dioxane / 0.5 h / 130 °C / Inert atmosphere 3.1: sodium azide; copper diacetate / methanol / 2.5 h / 65 °C 3.2: 2 h / 20 °C