[ CAS No. 1025708-31-9 ] {[proInfo.proName]}

Name: 1025708-31-9|2-Cyanopyrimidine-5-boronic Acid Pinacol Ester|95%
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Quality Control of [ 1025708-31-9 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 1025708-31-9 ]

CAS No. :	1025708-31-9	MDL No. :	MFCD08669562
Formula :	C₁₁H₁₄BN₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KJQVHJSIJTVCMN-UHFFFAOYSA-N
M.W :	231.06	Pubchem ID :	16414276
Synonyms :

Safety of [ 1025708-31-9 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 1025708-31-9 ]

* 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 [ 1025708-31-9 ]

[ 1025708-31-9 ] Synthesis Path-Downstream 1~29

1
[ 1025708-31-9 ]
[ 1272353-93-1 ]
[ 1272354-91-2 ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	165 To a solution of 2-chloro-5-phenyl-N-(pyridin-2-ylmethyl)quinazolin-4- amine (0.22 g, 0.65 mmol) in 1,4-dioxane (10 mL) and ¾0 (2 mL) under nitrogen was added 2-cyanopyrimidin-5-ylboronic ester (0.22 g, 0.97 mmol), and potassium carbonate (0.18 g, 1.30 mmol). Upon completion of addition, the mixture was degassed with nitrogen for 15 min. After this time, (l,l'-bis(diphenylphosphino)- ferrocene)palladium (II) chloride dichloromethane complex (0.048 mg, 0.06 mmol) was added and the reaction mixture was again degassed with nitrogen for 10 min.After this time, the reaction mixture was stirred heated to 90 °C where it stirred for 16 h. At the conclusion of this period, the reaction mixture was allowed to cool to room temperature and then quenched by the addition of water. The reaction mixture was transferred to a separation funnel and the aqueous layer was extracted with ethyl acetate. The combined organic portions were washed with water and saturated NaCl, dried over a2S04, filtered and concentrated under reduced pressure. The resulting concentrate was purified by silica gel column chromatography using adichloromethane / methanol mixture as the eluent to afford Example 165 (0.13 g, 49 % yield) as a brown solid. XH NMR (400 MHz, DMSO-i¾) δ (ppm): 9.86 (s, 2H), 8.22 (d, 1H, J=6.4 Hz), 7.94 (dd, 1H, J =1.6 Hz J=8.4 Hz), 7.89 (dd, 1H, J= 3.2 Hz, J=11.2 Hz), 7.74 (dt, 1H, J =1.6 Hz, 8 Hz,), 7.63-7.50 (m, 5H),7.40-7.32 (m, 2H), 7.25 (dd, 1H, J=5.2 Hz, 6.8 Hz), 7.08 (br t, 1H, J= 4Hz), 4.76 (d, 2H, J=4.4 Hz). LCMS Method U: retention time 1.85 min; [M+l] = 416.0; HPLC Method A4: purity 97.6%, retention time = 23.30 min.
49%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In water; N,N-dimethyl-formamide at 90℃; for 4h; Inert atmosphere;

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2011/28741, 2011, A1 Location in patent: Page/Page column 255
[2]Gunaga, Prashantha; Lloyd, John; Mummadi, Somanadham; Banerjee, Abhisek; Dhondi, Naveen Kumar; Hennan, James; Subray, Veena; Jayaram, Ramya; Rajugowda, Nagendra; Umamaheshwar Reddy, Kommuri; Kumaraguru, Duraimurugan; Mandal, Umasankar; Beldona, Dasthagiri; Adisechen, Ashok Kumar; Yadav, Navnath; Warrier, Jayakumar; Johnson, James A.; Sale, Harinath; Putlur, Siva Prasad; Saxena, Ajay; Chimalakonda, Anjaneya; Mandlekar, Sandhya; Conder, MaryLee; Xing, Dezhi; Gupta, Arun Kumar; Gupta, Anuradha; Rampulla, Richard; Mathur, Arvind; Levesque, Paul; Wexler, Ruth R.; Finlay, Heather J. [Journal of Medicinal Chemistry, 2017, vol. 60, # 9, p. 3795 - 3803]

2
[ 1025708-31-9 ]
[ 1354290-08-6 ]
[ 1354286-57-9 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate; tricyclohexylphosphine In 1,4-dioxane; water at 90℃; for 19h; Inert atmosphere;	103 N-(5-Bromo-2-morpholinopyridin-4-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)- quinolin-4-amine (56.7 mg, 0.11 mmol), 5-(4,4,5,5-tetramethyl-l ,3,2-dioxaboro- lan-2-yl)pyrimidine-2-carbonitrile (53.6 mg, 0.23 mmol), tricyclohexylphosphine (6.7 mg, 0.024 mmol), and tris(dibenzylideneacetone)dipalladium (0) (11.1 mg, 0.012 mmol) were added to a flask then degassed and backfilled with argon. To the flask, 1,4-dioxane (2.0 mL) and aq. 1.3M potassium phosphate tribasic (0.22 mL, 0.29 mmol) were added by syringe. The resulting reaction was heated to 90 °C and monitored with TLC and LC-MS. After 19 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on silica gel (0-40% of a premixed solution of 89:9: 1 DCM: MeOH: ammonium hydroxide in DCM) to afford a light yellow solid that was further purified with HPLC ( 10-90% of 0.1 % TFA acetonitrile solution in 0.1% TFA water solution.) The desired fractions were cond then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a light yellow solid as 5-(4-(5,7-difluoro-3-methyl-2-(pyridin-2- yl)quinolin-4-ylamino)-6-moi holinopyridin-3-yl)pyrimidine-2-carbonitrile.NMR (400 MHz, DMSO-d6) δ ppm 9.05 (2 H, s), 8.72 (1 H, ddd, J=4.9, 1.8, 1.0 Hz), 8.43 (1 H, br. s.), 8.04 (1 H, td, J=7.7, 1.8 Hz), 7.97 (1 H, s), 7.90 (1 H, dt, J=7.9, 1.1 Hz), 7.72 (1 H, m), 7.57 (2 H, m), 5.67 (1 H, s), 3.60 (4 H, t, J=4.7 Hz), 3.32 (4 H, m), 2.30 (3 H, s). Mass Spectrum (pos.) m/e: 537.1 (M+H)+.

Reference： [1]Current Patent Assignee: AMGEN INC - WO2012/3283, 2012, A1 Location in patent: Page/Page column 172-173

3
[ 14080-23-0 ]
[ 73183-34-3 ]
[ 1025708-31-9 ]

Yield	Reaction Conditions	Operation in experiment
54%	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 3,4,7,8-Tetramethyl-o-phenanthrolin In tetrahydrofuran at 20 - 80℃; for 19h; Inert atmosphere; Glovebox;
	With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 3,4,7,8-Tetramethyl-o-phenanthrolin In tetrahydrofuran at 80℃; for 24h; Glovebox; Inert atmosphere; Sealed tube;

Reference： [1]Larsen, Matthew A.; Hartwig, John F. [Journal of the American Chemical Society, 2014, vol. 136, # 11, p. 4287 - 4299]
[2]Herbert, Simon; Kinzel, Tom; Shen, Qilong; Zhang, Wei; Zhao, Haiwei [Journal of Organic Chemistry, 2020, vol. 85, # 5, p. 3596 - 3604]

4
[ 1025708-31-9 ]
[ 1620828-38-7 ]
[ 1620827-63-5 ]

Yield	Reaction Conditions	Operation in experiment
10 mg	With palladium diacetate; sodium carbonate; triphenylphosphine In 1,2-dimethoxyethane; water at 100℃; for 6h; Inert atmosphere;	43 Example 43 5-(5-((4S,6S)-2-Amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-l,3-oxazin-4- yl)thiophen-3-yl)pyrimidine-2-carbonitrile Example 43 5-(5-((4S,6S)-2-Amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-l,3-oxazin-4- yl)thiophen-3-yl)pyrimidine-2-carbonitrile To a solution of (4S,6S)-4-(4-bromothiophen-2-yl)-4-methyl-6-(trifluoromethyl)-5,6- dihydro-4H-l,3-oxazin-2-amine (XXIX-1) (50 mg) in 1 ,2-dimethoxyethane (1.0 ml) was added subsequently 2-cyanopyrimidine-5-boronic acid pinacolester (34 mg), triphenylphosphine (10 mg) and an aqueous solution of Na2CC>3 (2N, 0.2 ml). The mixture was flushed with argon for 5 min, treated with palladium(II)acetate (5 mg) and heated at 100 °C for 6 h. The mixture was evaporated and purified by chromatography (NH2-phase from Biotage, gradient EtOAc in heptane, 0% to 100% EtOAc) followed by another chromatography (Si02, gradient MeOH in dichloromethane, 0% to 10% MeOH) to give the title compound (10 mg) as a colorless foam. MS: m/z = 368.5 [M+H]

Reference： [1]Current Patent Assignee: SIENA BIOTECH S.P.A. SOCIETA' IN LIQUIDAZIONE; ROCHE HOLDING AG - WO2014/114532, 2014, A1 Location in patent: Page/Page column 114; 115

5
[ 1025708-31-9 ]
5-(bromomethyl)-3-(3-(difluoromethoxy)phenyl)-2-ethoxypyrazine [ No CAS ]
5-({6-[3-(difluoromethoxy)phenyl]-5-ethoxypyrazin-2-yl}methyl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
53%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium hydrogencarbonate In ethanol; benzene at 125℃; for 0.25h; Microwave irradiation; Sealed tube; Inert atmosphere;	1 5-({6-[3-(Difluoromethoxy)phenyl]-5-ethoxypyrazin-2-yl}methyl)pyrimidine-2-carbonitrile Example 1 5-({6-[3-(Difluoromethoxy)phenyl]-5-ethoxypyrazin-2-yl}methyl)pyrimidine-2-carbonitrile Into a 5 mL microwave vial was combined 5-(bromomethyl)-3-(3-(difluoromethoxy)phenyl)-2-ethoxypyrazine (Intermediate 1, 176.00 mg, 0.49 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (124.55 mg, 0.54 mmol), EtOH (2.45 mL), benzene (7.00 mL), tetrakis(triphenylphosphine)palladium(0) (56.63 mg, 0.05 mmol), and sodium bicarbonate (1.38 mL, 1.15 mol/L; 1.59 mmol). The vial was sealed, purged with nitrogen and heated to 125° C. under microwave conditions for 15 minutes. Water was removed from the reaction with a pipette, and the crude reaction mixture was filtered thru CELITE, and washed with EtOAc (3*5 mL). The combined organic layers were dried (Na2SO4), and the solvent was removed under reduced pressure. Purification (FCC, SiO2, 0-30%, EtOAc/hexanes) afforded the title compound as a white solid (100 mg, 53%). 1H NMR (400 MHz, CD3OD) δ 8.94 (s, 2H), 8.17 (s, 1H), 7.95-7.90 (m, 1H), 7.85 (t, J=1.8 Hz, 1H), 7.46 (t, J=8.2 Hz, 1H), 7.19 (dd, J=2.3, 7.8 Hz, 1H), 7.04-6.61 (m, 1H), 4.49 (q, J=7.0 Hz, 2H), 4.30-4.25 (m, 2H), 1.44 (t, J=7.0 Hz, 3H). [M+H]=384.15.

Reference： [1]Current Patent Assignee: DART NEUROSCIENCE LLC - US2014/275531, 2014, A1 Location in patent: Paragraph 0390; 0391

6
[ 1025708-31-9 ]
2-[(3,5-difluoropyridin-2-yl)methoxy]-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl trifluoromethanesulfonate [ No CAS ]
5-{2-[(3,5-difluoropyridin-2-yl)methoxy]-6,7-dihydro-5H-cyclopenta[b]pyridin-4-yl}pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
31 mg	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In 1,4-dioxane; water at 70℃; for 1h; Inert atmosphere;	44.5 Production of 5-{2-[(3,5-difluoropyridin-2-yl)methoxy]-6,7-dihydr o-5H-cyclopenta[b]pyridin-4-yl}pyrimidine-2-carboni trile [Step 5] Production of 5-{2-[(3,5-difluoropyridin-2-yl)methoxy]-6,7-dihydr o-5H-cyclopenta[b]pyridin-4-yl}pyrimidine-2-carboni trile To 2-[(3,5-difluoropyridin-2-yl)methoxy]-6,7-dihydro-5 H-cyclopenta[b]pyridin-4-yl trifluoromethanesulfonate (50 mg), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyri midine-2-carbonitrile (31 mg), Pd(dppf)Cl2·CH2Cl2 (10 mg) and potassium carbonate (50 mg) was added 1,4-dioxane/water (3/1, 1 mL), and the mixture was degassed, then stirred under Ar atmosphere at 70°C for 1 hour. After the reaction mixture was allowed to return to room temperature, the mixture was added with water and ethyl acetate, and subjected to extraction. The organic layer was dried over anhydrous sodium sulfate, filtered off and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography to give the title compound (31 mg) as a white solid. [MS (ESI) m/z 366.3 (M+H)+]

Reference： [1]Current Patent Assignee: NIPPON SHINYAKU CO LTD - EP2891656, 2015, A1 Location in patent: Paragraph 0172

7
[ 1025708-31-9 ]
[ 145343-76-6 ]
2-chloro-4-(2-cyanopyrimidin-5-yl)benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium phosphate In 1,2-dimethoxyethane; water at 100℃; for 2h;	22.A Step A. 2-Chloro-4-(2-cyanopyrimidin-5 -yl)benzoic acid Step A. 2-Chloro-4-(2-cyanopyrimidin-5 -yl)benzoic acidA mixture of 2-chloro-4-iodobenzoic acid (0.28 g, 0.99 mmol),5 -(4,4,5,5 -tetramethyl- 1,3 ,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (0.41 g, 1.8 mmol), andK3P04 (0.64 g, 3.0 mmol) in DME (4.2 mL) and water (1.4 mL) was stirred at 100 °C for 2 h.After cooling the mixture, it was diluted with water and CH2C12 and filtered. The aqueous layerwas washed with CH2C12 and neutralized with iN aq. HC1. The precipitate was collected and dried to give the title compound. MS (ESI) mlz = 260, 262 (M+H)‘H NMR (300 MHz, DMSO-d6) (5 (ppm): 9.46 (2H, s), 8.15 (1H, d, J= 1.4 Hz), 8.00-7.89 (2H,m)
	With potassium phosphate In 1,2-dimethoxyethane; water at 100℃; for 2h;	17.A Step A. 2-Chloro-4-(2-cyanopyrimidin-5-yl)benzoic acid A mixture of 2-chloro-4-iodobenzoic acid (0.28 g, 0.99 mmol), (0992) 5-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (0.41 g, 1.8 mmol), and K3PO4 (0.64 g, 3.0 mmol) in DME (4.2 mL) and water (1.4 mL) was stirred at 100 °C for 2 h. After cooling the mixture, it was diluted with water and CH2CI2 and filtered. The aqueous layer was washed with CH2CI2 and neutralized with IN aq. HC1. The precipitate was collected and dried to give the title compound. MS (ESI) m/z = 260, 262 (M+H) (0993) 1H NMR (300 MHz, OMSO-d6) δ (ppm): 9.46 (2H, s), 8.15 (1H, d, J = 1.4 Hz), 8.00-7.89 (2H, m)

Reference： [1]Current Patent Assignee: MOCHIDA PHARMACEUTICAL CO LTD; MERCK & CO INC - WO2015/160636, 2015, A1 Location in patent: Page/Page column 128; 129
[2]Current Patent Assignee: MERCK & CO INC; MOCHIDA PHARMACEUTICAL CO LTD - WO2015/160634, 2015, A1 Location in patent: Page/Page column 129-130

Yield	Reaction Conditions	Operation in experiment
1.40 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 80℃; for 4h;	1 Step-i: - Preparation of 2-chloro-4-(4,4,5 ,5-tetramethyl- i ,3 ,2-dioxaborolan-2-yl)benzonitrile General procedure: The title compound was prepared following the procedure described in step-3 of Intermediate- 33 by using 4-bromo-2-chlorobenzonitrile (1.0 g, 4.61 mmo), 4,4,4’,4’,5,5,5’,5’-octamethyl-2,2’-bi(1,3,2-dioxaborolane) (1.29 g, 4.33 mmol), potassium acetate (0.9063 g, 9.23 mmol),Pd(dppf)C12 (0.190 g, 0.23 mmol) in 1,4-dioxane to afford 0.850 g of title compound :_To a solution of ethyl 4-amino-3-bromobenzoate (5.0 g, 20.66 mmol), (4- cyanophenyl)boronic acid (3.33 g, 22.72 mmol) and Pd(dppf)C12 (0.843 g, 1.03 mmoi) indiglyme (10 mL) was added K2C03 (4.27 g, 30.99 mmol). The reaction mixture was heated at80°C for 4 h. The reaction mass was quenched with water and extracted with EtOAc. The organic layer was washed with water and brine. The organic layer was separated, dried, filtered and concentrated to afford 2.7 g of title product.

9
[ 1025708-31-9 ]
[ 62875-84-7 ]
ethyl 4-amino-3-(2-cyanopyrimidin-5-yl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
0.500 g	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In diethylene glycol dimethyl ether at 80℃; for 4h;	2 Step-2: - Preparation of ethyl 4-amino-3 -(2-cyanopyrimidin-5-yl)benzoate The title compound was prepared following the procedure described in step-3 of Intermediate-33 by using 5-(4,4,5 ,5-tetramethyl- 1,3 ,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (0.780 g,3.37 mmol), ethyl 4-amino-3-iodobenzoate (step-i of Intermediate-66, 1.17 g, 4.05 mmol),Pd(dpp/)C12(O.137 g. 0.168 minol), diglyme (10 mL), K2C03 (0.931 g, 6.74 mmol) to afford0.500 g of title product. ‘H NMR (300 MHz, DMSO-d6): 8.09-8.04 (t, J = 6.6 Hz, 1H), 7.73-7.70 (t, J = 8.1 Hz, 1H), 7.60-7.57 (t, J = 7.8 Hz, 1H), 5.03 (s, 2H), 3.30-3.19 (q, J = 7.5 Hz,4H), 1.17-1.13 (t, J= 7.5 Hz, 3H), 1.04-0.99 (t, J= 7.2 Hz, 3H); MS [M+Hj: 380:_To a solution of ethyl 4-amino-3-bromobenzoate (5.0 g, 20.66 mmol), (4- cyanophenyl)boronic acid (3.33 g, 22.72 mmol) and Pd(dppf)C12 (0.843 g, 1.03 mmoi) indiglyme (10 mL) was added K2C03 (4.27 g, 30.99 mmol). The reaction mixture was heated at80°C for 4 h. The reaction mass was quenched with water and extracted with EtOAc. The organic layer was washed with water and brine. The organic layer was separated, dried, filtered and concentrated to afford 2.7 g of title product. ‘H NMR (300 MHz, DMSO-d6): 7.92-7.89 (d, J = 7.8 Hz, 2H), 7.69-7.67 (d, J = 8.7 Hz, 1H), 7.63-7.60 (d, J = 7.8 Hz, 2H),7.56 (s, 1H), 6.8 1-6.78 (d, J = 8.4Hz, 1H), 5.83 (br s, 2H), 4.22-4.20 (q, J = 6.9 Hz, 2H),1.28-1.23 (t, J= 7.5 Hz, 3H).

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2016/55947, 2016, A1 Location in patent: Page/Page column 76; 77; 120

10
[ 1025708-31-9 ]
[ 17823-40-4 ]
5-(4-cyano-2,3,5,6-tetrafluorophenyl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); In tetrahydrofuran; at 115℃; for 16h;	A mixture of <strong>[17823-40-4]4-bromo-2,3,5,6-tetrafluorobenzonitrile</strong> (0.44 g, 1.73 mmol), 2-cyanopyrimidine-5-boronic acid pinacol ester (0.40 g, 1.73 mmol), Pd2(dba)3 (0.09g, 0.1 mmol), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (0.08 g, 0.2 mmol) and K3PO4 (0.575 g, 2.5 mmol) in anhydrous toluene (20 mL) was degassed and heated at 115 C for 16 hours. The resulting mixture was poured into ethyl acetate (100 mL), after filtered off precipitate, the solution was loaded on silica gel and purified by flash column using eluents of ethyl acetate/hexane (10% to 30%). The desired fractions were collected and concentrated to give white solid Compound22 (0.12 g, in 25% yield).

Reference： [1]Patent: JP2016/526025,2016,A .Location in patent: Paragraph 0104; 0143

11
[ 1025708-31-9 ]
2-chloro-7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine [ No CAS ]
5-(7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2,3-b:4,5-c']dipyridin-2-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With potassium fluoride; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; XPhos In 1,4-dioxane at 100℃; for 2h; Inert atmosphere;	41 5-(7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2, 3-6:4, 5-c]dipyridin-2- yl)pyrimidine-2-carbonitrile (i48): 5-(7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9H-pyrrolo[2, 3-6:4, 5-c]dipyridin-2- yl)pyrimidine-2-carbonitrile (i48): To a stirred solution of 2-chloro-7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9/-/-pyrrolo[2,3- b:4,5-c]dipyridine (i47) (0.17 g, 0.468 mmol) and 5-(4,4,5,5-tetramethyl-1 ,3,2-dioxaborolan-2- yl)pyrimidine-2-carbonitrile (0.162 g, 0.702 mmol) in dioxane (15 mL), KF (0.135 g, 2.341 mmol) was added and the reaction was degassed with argon for 20 min. Pd2(dba)3 (0.043 g, 0.046 mmol) and X-phos (0.067 g, 0.14 mmol) were added and the mixture was further degassed for another 10 min. The reaction was heated at 100°C for 2h. The progress of the reaction was monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure. The crude product was purified by silica gel (230:400 mesh) column chromatography using 0.5 % methanol in DCM to afford 5-(7-methoxy-9-((2-(trimethylsilyl)ethoxy)methyl)-9/-/- pyrrolo[2,3-b:4,5-c']dipyridin-2-yl)pyrimidine-2-carbonitrile (i48) (0.09 g, Yield 44%). 1H NMR (400 MHz, DMSO-d6) δ -0.18 (s, 9H), 0.86 (t, J = 7.9 Hz, 2H), 3.62 (t, J = 7.9 Hz, 2H), 3.97 (s, 3H), 5.92 (s, 2H), 7.06 (s, 1 H), 8.25 (d, J = 8.0 Hz, 1 H), 8.73 (d, J = 8.0 Hz, 1 H), 9.08 (s, 1 H), 9.80 (s, 2H). MS (ESI) m/e (M+1 )+: 433.05

Reference： [1]Current Patent Assignee: UCB - WO2016/124508, 2016, A1 Location in patent: Page/Page column 64; 65

12
[ 15862-37-0 ]
[ 1025708-31-9 ]
5-(5-bromo-3-nitropyridin-2-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
29%	With potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ In tetrahydrofuran; water at 65℃; Inert atmosphere; Sealed tube;	143.1 Step 1: 5-(5-Bromo-3-nitropyridin-2-yl)pyrimidine-2-carbonitrile To a 250 mL round bottom flask was added 5-(4,4,5,5-tetramethyl-l,3,2- dioxaborolan-2-yl)pyrimidine-2-carbonitrile (0.65 g, 2.81 mmol),2,5-dibromo-3- nitropyridine (0.793 g, 2.81 mmol) and 50 mL of THF. To this mixture was added 2M aqueous tripotassium phosphate (2.81 ml, 5.63 mmol) and PdCi2(dppf) CH2Ci2 (0.230 g, 0.281 mmol). The resulting solution was degassed by bubbling through argon gas while sonicating for 1 min. The flask was sealed and heated in an oil bath at 65°C overnight. The reaction mixture was concentrated to give a black residue. This material was purified on SiC (40 g) loaded on dry column in DCM and eluted using hexane (51 mL), 20% EtOAc/hexane (252 mL) , 20 to 50% EtOAc/hexane (357 mL, linear gradient). The product fractions gave the title compound (251 mg, 29%) as a white fluffy solid. NMR (400MHz, CDCh) δ 9.08 (d, J=2.0 Hz, 1H), 9.01 (s, 2H), 8.64 (d, J=2.0 Hz, 1H). LC/MS (306, [M+H]+). LCMS: Rt = 1.28 min; (ES): m/z (M+H)+ 306: (Waters Acquity SDS; Column Type: ACQUITY UPLC BEH C18 1.7μιη 2.1 x 50 mm; Run Time: 2.20 min; 0-100%B; Solvent A: 100% water /0.05%TFA; Solvent B: 100% ACN w/0.05%TFA; Flow: 0.8 mL/min;Detection: UV = 220 nm).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/183118, 2016, A1 Location in patent: Page/Page column 217; 218

13
[ 1025708-31-9 ]
5-(dimethyl-1H-1,2,3-triazol-5-yl)-8-[(S)-oxan-4-yl(phenyl)methyl]-3,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-1⁽⁹⁾,2⁽⁷⁾,3,5,10,12-hexaene-11-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / tetrahydrofuran; water / 65 °C / Inert atmosphere; Sealed tube 2: 1,2-bis-(diphenylphosphino)ethane / 1,2-dichloro-benzene / 0.58 h / 160 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine / dichloromethane / 17 h / Cooling with ice 4: copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine / N,N-dimethyl-formamide / 2 h / 100 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/183118, 2016, A1

14
[ 1025708-31-9 ]
7-bromo-9H-pyrido[2’,3’:4,5]pyrrolo[2,3-d]pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / tetrahydrofuran; water / 65 °C / Inert atmosphere; Sealed tube 2: 1,2-bis-(diphenylphosphino)ethane / 1,2-dichloro-benzene / 0.58 h / 160 °C

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/183118, 2016, A1

15
[ 1025708-31-9 ]
(S)-7-bromo-9-(phenyl(tetrahydro-2H-pyran-4-yl)methyl)-9H-pyrido[2’,3’:4,5]pyrrolo[2,3-d]pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium phosphate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / tetrahydrofuran; water / 65 °C / Inert atmosphere; Sealed tube 2: 1,2-bis-(diphenylphosphino)ethane / 1,2-dichloro-benzene / 0.58 h / 160 °C 3: di-isopropyl azodicarboxylate; triphenylphosphine / dichloromethane / 17 h / Cooling with ice

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - WO2016/183118, 2016, A1

16
[ 1025708-31-9 ]
4-chloro-6-(hydroxy(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methyl)-2-methoxyquinolin-3-yl trifluoromethanesulfonate [ No CAS ]
5-(4-chloro-6-{hydroxy(1-methyl-1H-imidazol-5-yl)[6-(trifluoromethyl)pyridin-3-yl]methyl}-2-methoxyquinolin-3-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In 1,4-dioxane at 65℃; for 15h;

Reference： [1]Kummer, David A.; Cummings, Maxwell D.; Abad, Marta; Barbay, Joseph; Castro, Glenda; Wolin, Ronald; Kreutter, Kevin D.; Maharoof, Umar; Milligan, Cynthia; Nishimura, Rachel; Pierce, Joan; Schalk-Hihi, Celine; Spurlino, John; Urbanski, Maud; Venkatesan, Hariharan; Wang, Aihua; Woods, Craig; Xue, Xiaohua; Edwards, James P.; Fourie, Anne M.; Leonard, Kristi [Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 9, p. 2047 - 2057]

17
[ 1025708-31-9 ]
N-(5-bromo-4-fluoro-2-((3S,5R)-3,4,5-trimethylpiperazin-1-yl)phenyl)-6-oxo-4-(trifluoromethyl)-1,6-dihydropyridine-3-carboxamide [ No CAS ]
N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-[(3S,5R)-3,4,5-trimethylpiperazin-1-yl]phenyl]-6-oxo-4-(trifluoromethyl)-1H-pyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With chloro(2-dicyclohexylphosphino-2’,4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2’-amino-1,1‘-biphenyl’)]palladium(II); sodium carbonate; XPhos In 1,4-dioxane; water at 120℃; for 1h; Inert atmosphere; Microwave irradiation;	31.2 N-[5-(2-cyanopyrimidin-5-yl)-4-fluoro-2-[(3S, 5RJ-3, 4, 5-trimethylpiperazin-1- yl]phenyl]-6-oxo-4-(trifluoromethyl)-lH-pyridine-3-carboxamide To a 5 mL microwave vial charged with N-(5-bromo-4-fluoro-2-((3R,5S)-3,4,5-trimethylpiperazin-1-yl)phenyl)-6-oxo-4-(trifluoromethyl)-l,6-dihydropyridine-3- carboxamide (29.85 mg, 0.059 mmol), prepared according to the method described in Example 29), 2-cyanopyrimidine-5-boronic acid pinacol ester (40.9 mg, 0.177 mmol), sodium carbonate, anhydrous (62.6 mg, 0.591 mmol) and XPhos (5.63 mg, 0.012 mmol), XPhos Pd G2 (9.30 mg, 0.012 mmol) was added in water (1846 μ) / 1,4-dioxane (1108 μ) to give a white suspension that was stirred for 5 min, degassed, purged with N2, and microwaved for 60 min at 120 °C. The solvent was evaporated and 15 ml of DCM was added. The suspension was sonicated and the organic phase was removed and concentrated (3X). The crude black oil was purified using a Biotage column, (100-0%, CH2C12: 10% MeOH in CH2C12 + NH4Ac; in 10 min and isocratic for 5min using KP-SIL lOg column. Collected at 0% of the CH2C12) to yield an impure product. The product was freeze dried for 2 days to yield the crude product that was purified via preparatory HPLC. The fractions were evaporated and the concentrate was slowly passed through a ionic exchange column Rxn CX 6cc with MeOH and NH4OH. The product was lyophilized to yield 8.1 mg (26% yield) of the title compound. -NMR (500 MHz, MeOD) δ 9.14 (s, 2H), 8.04 (d, J = 8.2 Hz, 1H), 7.96 (s, 1H), 7.16 (d, J = 12.4 Hz, 1H), 6.92 (s, 1H), 3.15 (d, J = 11.6 Hz, 2H), 2.65 (t, J = 11.2 Hz, 2H), 2.61 - 2.54 (m, 2H), 2.39 (s, 3H), 2.03 (s, 1H), 1.17 (d, J = 6.1 Hz, 6H); LCMS [M+H]+ 530.

Reference： [1]Current Patent Assignee: PROPELLON THERAPEUTICS - WO2017/147700, 2017, A1 Location in patent: Paragraph 00249

18
[ 1025708-31-9 ]
tert-butyl (1-(1'-((4-(2-cyanopyrimidin-5-yl)isoquinolin-3-yl)methyl)-2'-oxospiro[azetidine-3,3'-indolin]-1-yIcarbonyl)cyclopropyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,2-dimethoxyethane / 16 h / 90 °C / Inert atmosphere; Sealed tube 2.1: caesium carbonate / acetonitrile / 0.17 h / 20 °C 2.2: 16 h / 70 °C

Reference： [1]Current Patent Assignee: MEDIVIR AB - WO2018/38667, 2018, A1

19
[ 1025708-31-9 ]
5-(3-((1-(1-aminocyclopropanecarbonyl)-2'-oxospiro[azetidine-3,3'-indolin]-1'-yl)methyl)isoquinolin-4-yl)pyrimidine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂ / water; 1,2-dimethoxyethane / 16 h / 90 °C / Inert atmosphere; Sealed tube 2.1: caesium carbonate / acetonitrile / 0.17 h / 20 °C 2.2: 16 h / 70 °C 3.1: dihydrogen peroxide; potassium carbonate / water; dimethyl sulfoxide / 1 h / 0 - 20 °C 3.2: 8 h / 20 °C

Reference： [1]Current Patent Assignee: MEDIVIR AB - WO2018/38667, 2018, A1

20
4-iodo-3-methyl-isoquinoline [ No CAS ]
[ 1025708-31-9 ]
5-(3-(bromomethyl)isoquinolin-4-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; sodium carbonate In 1,2-dimethoxyethane; water at 90℃; for 16h; Inert atmosphere; Sealed tube;	2.a Step a) 5-(3-(Bromomethvnisoauinolin-4-vnpyrimidine-2-carbonitrile (2a) A stirred solution of 4-iodo-3-methylisoquinoline (1 .5 g), 5-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolan-2-yl)pyrimidine-2-carbonitrile (1 .67 g) and sodium carbonate (1 .47 g) in 1 ,2- dimethoxyethane (20 mL) and water (5 mL) was purged with argon for 5 minutes. [1 ,1 '- Bis(diphenylphosphino)ferrocene]palladium(ll) chloride FontWeight="Bold" FontSize="10" CH2CI2 (0.40 g) was added and the reaction mixture was purged again with argon for 10 minutes. The reaction mixture was stirred in sealed tube at 90 °C for 16 h, then filtered through Celite. The filtrate was diluted with water (25 mL) and extracted with ethyl acetate (2x40 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced. The afforded crude was purified by column chromatography using 100-200 silica mesh and eluted with 25-28% EtOAc : p. ether. Fractions containing desired product were concentrated under reduced pressure which gave the title compound (700 mg, 45%) as a solid. MS (ES+) 247.1 [M+H]+.

Reference： [1]Current Patent Assignee: MEDIVIR AB - WO2018/38667, 2018, A1 Location in patent: Page/Page column 51

21
[ 1025708-31-9 ]
1-[(2S)-4-[(2-[[(tert-butyldimethylsilyl)oxy]methyl]phenyl)methyl]-6-chloro-2-cyclopropyl-2,3-dihydroquinoxalin-1-yl]ethanone [ No CAS ]
(S)-5-(1-acetyl-4-(2-(((tert-butyldimethylsilyl)oxy)methyl)benzyl)-2-cyclopropyl-1,2,3,4-tetrahydroquinoxalin-6-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.3%	With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In 1,2-dimethoxyethane at 110℃; for 2h; Microwave irradiation; Inert atmosphere;	1B.1 Step 1: Synthesis of (S)-5-(l-acetyl-4-(2-(((tert-butyldimethylsilyl)oxy)methyl)benzyl)-2- cyclopropyl-l,2,3,4-tetrahydroquinoxalin-6-yl)pyrimidine-2-carbonitrile To a stirred solution of l-[(2S)-4-[(2-[[(tert-butyldimethylsilyl)oxy]methyl]phenyl)methyl]-6- chloro-2-cyclopropyl-2,3-dihydroquinoxalin-l-yl]ethanone (600.00 mg, 1.24 mmol, 1.00 equiv) in DME(12.00 ml) was added 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrimidine-2- carbonitrile (571.53 mg, 2.47 mmol, 2.00 equiv), CS2CO3 (1.20 g, 3.71 mmol, 3.00 equiv) and BrettPhos Pd G3 (112.11 mg, 0.12 mmol, 0.10 equiv) in portions at room temperature. The final reaction mixture was irradiated with microwave radiation for 2 h at 110 degrees C under N2 atmosphere. The resulting mixture was concentrated under vacuum. The residue was purified by silica gel column chromatography, eluted with PE: EA = 3:1 to afford 5-[(2S)-l-acetyl-4-[(2-[[(tert-butyldimethylsilyl)oxy]methyl]phenyl)methyl]-2-cyclopropyl-2,3- dihydroquinoxalin-6-yl]pyrimidine-2-carbonitrile (550.00 mg, 80.30%) as a yellow oil. LC/MS: mass calcd. For C32H39N5O2S1: 553.29, found: 554.40 [M+H]+.
42%	With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2’,4’,6’-triisopropyl-1,1‘-biphenyl)-2-(2‘-amino-1,1’-biphenyl)]palladium(II) methanesulfonate; caesium carbonate In 1,2-dimethoxyethane at 110℃; for 2h; Inert atmosphere; Sealed tube; Microwave irradiation;

Reference： [1]Current Patent Assignee: DESIGN THERAPEUTICS - WO2021/158707, 2021, A1 Location in patent: Paragraph 00616; 00793; 00794; 00795
[2]Law, Robert P.; Atkinson, Stephen J.; Bamborough, Paul; Chung, Chun-Wa; Demont, Emmanuel H.; Gordon, Laurie J.; Lindon, Matthew; Prinjha, Rab K.; Watson, Allan J. B.; Hirst, David J. [Journal of Medicinal Chemistry, 2018, vol. 61, # 10, p. 4317 - 4334]

22
[ 1025708-31-9 ]
C₂₁H₁₉BrClFN₄O₄ [ No CAS ]
C₂₆H₂₁ClFN₇O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
5.9 mg	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate In water at 100℃; for 2h;	52 Example 52 Compound 86 (20 mg, 0.038 mmol) was dissolved in 1,2-dioxane (0.2 mL), and then 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine-2-carbonitrile (11.4 mg, 0.049 mmol), PdCl2(dppf) (2.48 mg, 0.0038 mmol) and a 2 mol/L aqueous solution of potassium carbonate (38.0 ul, 0.076mmol) were added thereto, and the mixture was stirred at 100°C for 2 hours. After cooling, the reaction mixture was added to a saturated aqueous solution of ammonium chloride, and the mixture was extracted with ethyl acetate. The extract was dried with sodium sulfate, filtered and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain Compound (1-2-16) (5.9 mg, 0.0107mmol). Compound (1-2-16); Method B LC/MS retention time =1.82 min. MS (ESI) m/z =550.35 (M+H)+.

Reference： [1]Current Patent Assignee: SHIONOGI & CO., LTD. - EP3450435, 2019, A1 Location in patent: Paragraph 0410; 0411; 0412

23
[ 1025708-31-9 ]
benzyl ((R)-4-(4-bromophenyl)-1-((S)-1-(4-chloro-3 -(1-(difluoromethyl)-1H-1,2,4-triazol-5-yl)phenyl)-2-(((1-(trifluoromethyl)cyclopropyl)carbamoyl)oxy)ethyl)-4-neopentyl-5-oxoimidazolidin-2-ylidene)carbamate [ No CAS ]
C₃₅H₃₂ClF₅N₁₀O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate / 1,4-dioxane; water / 1 h / 85 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 60 °C

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2019/75291, 2019, A1

24
[ 1025708-31-9 ]
benzyl ((R)-4-(4-bromophenyl)-1-((S)-1-(4-chloro-3 -(1-(difluoromethyl)-1H-1,2,4-triazol-5-yl)phenyl)-2-(((1-(trifluoromethyl)cyclopropyl)carbamoyl)oxy)ethyl)-4-neopentyl-5-oxoimidazolidin-2-ylidene)carbamate [ No CAS ]
(S)-2-((R)-2-(((benzyloxy)carbonyl)imino)-4-(4-(2-cyanopyrimidin-5-yl)phenyl)-4-neopentyl-5-oxoimidazolidin-1-yl)-2-(4-chloro-3-(1-(difluoromethyl)-1H-1,2,4-triazol-5-yl)phenyl)ethyl (1-(trifluoromethyl)cyclopropyl)carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 85℃; for 1h;	50 Preparation of Compound 167: To a solution of benzyl ((R)-4-(4-bromophenyl)- 1 -((5)-i -(4-chloro-3 -(1 -(difluoromethyl)- 1-1 ,2,4-triazol-5 -yl)phenyl)-2-(((i -(trifluoromethyl)cyclopropyl)carbamoyl)oxy)ethyl)-4-neopentyl-5 - oxoimidazolidin-2-ylidene)carbamate (0.03 g, 0.034 mmol) in dioxane (4 mL) and water (0.6 mL) were added 2-cyanopyrimidine-5-boronic acid pinacol ester (0.04 g, 0.017 mol), tetrakis(triphenylphosphine)palladium(0) (6 mg, 0.0017 mol) and potassium carbonate (11 mg, 0.017 mmol) was stirred at 85 °C for 1 h. Thereaction mixture was treated with saturated ammonium chloride solution and extracted with DCM. The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The crude mixture was purified by silica gel column chromatography (EtOAc/hexanes) to give the product (S)-2-((R)-2- (((benzyloxy)carbonyl)imino)-4-(4-(2-cyanopyrimidin-5 -yl)phenyl)-4-neopentyl-5-oxoimidazolidin- 1 -yl)-2-(4-chloro-3-(i -(difluoromethyl)- 1-i ,2,4-triazol-5- yl)phenyl)ethyl (1 -(trifluoromethyl)cyclopropyl)carbamate. Then, this compound was dissolved in dichloromethane (1 mL) and trifluoroacetic acid (3 mL). The mixture was heated at 60 °C for 2 h. The mixture was concentrated down and purified by reverse phase HPLC (acetonitrile/water, both containing 0.1% TFA) togive the product.

Reference： [1]Current Patent Assignee: GILEAD SCIENCES INC - WO2019/75291, 2019, A1 Location in patent: Page/Page column 259

25
[ 1025708-31-9 ]
(R)-1-((5-bromopyridin-2-yl)methyl)-3-(2-((tert-butyldimethylsilyl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propyl)imidazolidin-2-one [ No CAS ]
(R)-5-(6-((3-(2-((tert-butyldimethylsilyl)oxy)-3-(3,4-dihydroisoquinolin-2(1H)-yl)propyl)-2-oxoimidazolidin-1-yl)methyl)pyridin-3-yl)pyrimidine-2-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54.77%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium carbonate In 1,2-dimethoxyethane; water at 70℃; for 12h; Sealed tube;	XIII.a Step-a: Synthesis of (R)-5-(6-((3-(2-((tert-butyldimethylsilyl)oxy)-3-(3,4- dihydroisoquinolin-2(lH)-yl)propyl)-2-oxoimidazolidin-l-yl)methyl)pyridin-3- yl)pyrimidine-2-carbonitrile To a sealed tube, were added (R)-l-((5-bromopyridin-2-yl)methyl)-3-(2-((tert- butyldimethylsilyl)oxy)-3-(3,4-dihydroisoquinolin-2(lH)-yl)propyl)imidazolidin-2-one (3.5 g, 6.254 mmol), DME/H20 (4:1) (70 mL), 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2- yl)pyrimidine-2-carbonitrile (1.589 g, 6.879 mmol), Sodium carbonate (1.657 g, 15.635 mmol) and Pd(dppf)Cl2 (0.51 g, 0.625 mmol) and the reaction mixture was degassed with Argon gas for 10 minutes, and stirred for l2h at 70 °C temperature. After completion of reaction (monitored by TLC, eluent: 5% methanol in DCM), the reaction mixture was filtered through celite bed and filtrate was diluted with water and extracted with ethyl acetate and the combined organics were washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The obtained residue was purified by column chromatography (Si02, 2-3% MeOH in DCM) to get (2.0 g, 54.77%) of (R)-5-(6-((3-(2-((tert- butyldimethylsilyl)oxy)-3-(3,4-dihydroisoquinolin-2(lH)-yl)propyl)-2-oxoimidazolidin-l- yl)methyl)pyridin-3-yl)pyrimidine-2-carbonitrile. LCMS: 281.3 [M+H] +.

Reference： [1]Current Patent Assignee: DR REDDY'S LABORATORIES LIMITED - WO2019/180631, 2019, A1 Location in patent: Page/Page column 107; 108

26
[ 1025708-31-9 ]
[(SIPr)Pd(CHF₂)Cl]₂ [ No CAS ]
[ 1416821-62-9 ]

Yield	Reaction Conditions	Operation in experiment
18 mg	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 12h; Inert atmosphere;

Reference： [1]Herbert, Simon; Kinzel, Tom; Shen, Qilong; Zhang, Wei; Zhao, Haiwei [Journal of Organic Chemistry, 2020, vol. 85, # 5, p. 3596 - 3604]

27
[ 1025708-31-9 ]
[ 7732-18-5 ]
(2-(aminomethyl)pyrimidin-5-yl)boronic acid hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; palladium 10% on activated carbon; hydrogen In methanol at 20℃;	15.1 Step 1: (2-(aminomethyl)pyrimidin-5-yl)boronic acid hydrochloride To a solution of 5-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)pyrimidine-2- carbonitrile in MeOH (10 mL) was added Pd/C (10%, 40 mg) and 0.5 mL concentrated hydrochloric acid under nitrogen atmosphere. The resulting mixture was stirred overnight at room temperature under hydrogen atmosphere using a hydrogen balloon. The reaction mixture was filtered through a Celite pad. The filtrate was concentrated under reduced pressure to give 200 mg (crude) of (2-(aminomethyl)pyrimidin-5-yl)boronic acid hydrochloride, which was used for the next step directly without further purification.

Reference： [1]Current Patent Assignee: RIBOSCIENCE LLC - WO2020/140001, 2020, A1 Location in patent: Paragraph 0193

28
[ 1025708-31-9 ]
2-((6,7-dimethoxyquinazolin-4-ylamino)methyl)pyrimidin-5-ylboronic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrogenchloride; palladium 10% on activated carbon; hydrogen / methanol / 20 °C 2: isopropyl alcohol / 2 h / 80 °C

Reference： [1]Current Patent Assignee: RIBOSCIENCE LLC - WO2020/140001, 2020, A1

29
[ 1025708-31-9 ]
C₁₉H₁₀F₃NO₇S₃ [ No CAS ]
C₂₃H₁₂N₄O₄S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In tetrahydrofuran; water monomer at 70℃; for 24h; Inert atmosphere;	5 add compound 1 (50 mg, 0.10 mmol) to a 25 mL solvent storage bottle,5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolane-2-yl)pyrimidine-2-carbonitrile (27 mg, 0.12 mmol), tetrakis(tri Phenylphosphine) palladium (11 mg, 0.010 mmol), anhydrous potassium carbonate (27 mg, 0.20 mmol), under argon atmosphere, 5 mL of ultra-dry tetrahydrofuran and 1 mL of deionized water were added, heated to 70 °C, and refluxed for 24 h. After cooling to room temperature, adding an appropriate amount of silica gel powder, removing the solvent by a rotary evaporator, column separation to obtain 20 mg of a white solid with a yield of 44%.

Reference： [1]Current Patent Assignee: SOUTH CHINA SCIENCE UNIV - CN114292284, 2022, A Location in patent: Paragraph 0053-0056

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2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.93

[ 1631981-66-2 ]

2-(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)acetonitrile

Similarity: 0.89

[ 1235450-87-9 ]

2-Ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.89

[ 2058051-01-5 ]

(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)methanol

Similarity: 0.89

[ 321724-19-0 ]

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.88

Related Parent Nucleus of
[ 1025708-31-9 ]

Pyrimidines

[ 1052686-67-5 ]

2-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.93

[ 1235450-87-9 ]

2-Ethyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.89

[ 321724-19-0 ]

5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.88

[ 1820679-54-6 ]

2-Isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

Similarity: 0.88

[ 1375301-91-9 ]

2-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine

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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

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. 1025708-31-9 ] {[proInfo.proName]}

Quality Control of [ 1025708-31-9 ]

Related Doc. of [ 1025708-31-9 ]

Product Details of [ 1025708-31-9 ]

Safety of [ 1025708-31-9 ]

Application In Synthesis of [ 1025708-31-9 ]

[ 1025708-31-9 ] Synthesis Path-Downstream 1~29

Related Functional Groups of [ 1025708-31-9 ]

Organoboron

Esters

Related Parent Nucleus of [ 1025708-31-9 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1025708-31-9 ]

Related Parent Nucleus of
[ 1025708-31-9 ]