[ CAS No. 2450-08-0 ] {[proInfo.proName]}

Name: 2450-08-0|Methyl pyrimidine-4-carboxylate|97%
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Quality Control of [ 2450-08-0 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 2450-08-0 ]

CAS No. :	2450-08-0	MDL No. :	MFCD00234184
Formula :	C₆H₆N₂O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	GXZQHMHLHHUHAM-UHFFFAOYSA-N
M.W :	138.12	Pubchem ID :	254248
Synonyms :

Calculated chemistry of [ 2450-08-0 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.17
Num. rotatable bonds :	2
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	33.31
TPSA :	52.08 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-7.33 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.33
Log Po/w (XLOGP3) :	-0.27
Log Po/w (WLOGP) :	0.26
Log Po/w (MLOGP) :	-0.47
Log Po/w (SILICOS-IT) :	0.72
Consensus Log Po/w :	0.31

Druglikeness

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

Water Solubility

Log S (ESOL) :	-0.84
Solubility :	20.0 mg/ml ; 0.145 mol/l
Class :	Very soluble
Log S (Ali) :	-0.36
Solubility :	59.6 mg/ml ; 0.432 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.7
Solubility :	2.76 mg/ml ; 0.02 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.53

Safety of [ 2450-08-0 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 2450-08-0 ]

* 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 [ 2450-08-0 ]
Downstream synthetic route of [ 2450-08-0 ]

[ 2450-08-0 ] Synthesis Path-Upstream 1~1

1
[ 2450-08-0 ]
[ 39513-54-7 ]

Reference： [1] Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 6942 - 6990

[ 2450-08-0 ] Synthesis Path-Downstream 1~49

1
[ 79-20-9 ]
[ 2450-08-0 ]
[ 75399-06-3 ]

Yield	Reaction Conditions	Operation in experiment
23%	With sodium hydride In 1,2-dimethoxyethane Heating;

Reference： [1]Stekhova, S. A.; Zagulyaeva, O. A.; Lapachev, V. V.; Mamaeva, V. P. [Chemistry of Heterocyclic Compounds, 1980, vol. 16, # 6, p. 640 - 644][Khimiya Geterotsiklicheskikh Soedinenii, 1980, # 6, p. 822 - 826]

2
[ 401-78-5 ]
[ 2450-08-0 ]
4-pyrimidinyl(3-trifluoromethylphenyl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With n-butyllithium In tetrahydrofuran; diethyl ether; hexane -90 deg C to rt;

Reference： [1]Heinisch, Gottfried; Holzer, Wolfgang; Langer, Thierry; Lukavsky, Peter [Heterocycles, 1996, vol. 43, # 1, p. 151 - 172]

3
[ 626-55-1 ]
[ 2450-08-0 ]
pyridin-3-yl(pyrimidin-4-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With n-butyllithium 1.) ether, THF, hexane, -90 deg C, 15 min, 2.) ether, THF, hexane, from -90 deg C to RT, 12 h; Yield given. Multistep reaction;

Reference： [1]Heinisch, Gottfried; Langer, Thierry; Lukavsky, Peter [Journal of Heterocyclic Chemistry, 1997, vol. 34, # 1, p. 17 - 19]

Yield	Reaction Conditions	Operation in experiment
	+ LiAlH4, THF (-67grad) -> Pyrimidin-aldehyd-(4);
	Alk. Hydrolyse;
	With water In methanol at 20 - 30℃; alkaline hydrolysis; E(excit.), S(excit.), log A;

Yield	Reaction Conditions	Operation in experiment
	entspr. Saeure, sd.methanol.HCl (8h);
	(yield)86percent;
	Saeure (6), Diazomethan;

	4-Tribrommethylpyrimidin;
	4-Carboxy-pyrimidin, sd.MeOH, konz.H2SO4 oder methanol.HCl oder Diazomethan;
	With caesium carbonate In acetonitrile at 20℃; Cooling with ice;	395.6 Methyl 1-methyl-1H-pyrrole-3-carboxylate, Example 395.4 General procedure: To a mixture of 1H-pyrrole-3-carboxylic acid (1.0 g, 9.00 mmol) and cesium carbonate (1.58 mL, 19.80 mmol) in ACN (20 mL) colled in an ice bath, was added iodomethane (1.68 mL, 27.0 mmol). The resulting mixture was stirred at RT. The mixture was then filtered, and the solid was washed with EtOAc. The filtrate was concentrated and dried under reduced pressure to give methyl 1-methyl-1H-pyrrole-3-carboxylate (577 mg). LCMS- ESI (pos.): 140.1 (M+H)+.

6
[ 67-56-1 ]
[ 31462-59-6 ]
[ 2450-08-0 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sulfuric acid; for 16h;Heating / reflux;	Step B: Preparation of Pyrimidine-4-carboxylic acid methyl ester: A solution of the product of Preparation 2, Step A (6.17 g, 49.7 mmol), in MeOH (60 ml) was added to sulfuric acid (0.3 ml) and heated to refluxed for 16 hr. Excess solvent was removed under vacuum to obtain a residue, which was dissolved in 10% MeOH/CHCI3 (100 ml) and adsorbed onto silica gel. The crude material was purified by column chromatography over silica gel eluting with CHCl3 then 10% MeOH/CHCI3 to obtain the title compound as a yellow solid (5.8 g, 85%). 1H-NMR(DMSO): delta 9.4(s, 1 H), 9.0(d, J=4.9 Hz, 1H), 8.0(d, J=4.9 Hz, 1 H) and 4.0(s,3H). Mass: (M+H) 140 calculated for C6H7N2O2.

Reference： [1]Patent: WO2008/23239,2008,A1 .Location in patent: Page/Page column 21
[2]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990

7
[ 141-78-6 ]
[ 2450-08-0 ]
[ 64210-67-9 ]
[ 1093114-82-9 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethyl acetate; methyl pyrimidine-4-carboxylate With potassium <i>tert</i>-butylate In tetrahydrofuran for 40h; Heating / reflux; Stage #2: With hydrogenchloride In water	2.C Step C: S-Oxo-S-pyrimidin^-yl-propionic acid ethyl ester : To a solution of the product of Preparation 2, Step B (5.8 g, 42 mmol), in EtOAc (180 ml) was added 1M potassium ferf-butoxide in THF (85 ml, 85 mmol) in four portions, with mechanical stirring. The reaction was refluxed for 40 hr. Water (200 ml) was added and layers separated. The aqueous was washed with EtOAc (2 X 100 ml). The aqueous was acidified with cone. HCI to pH 2-3 then extracted with CHCI3 (3 X 100 ml). The organics were combined, washed with brine, dried over sodium sulfate, and concentrated to give the title compound as an orange solid (7.07g 86%). (Mixture of keto and enol form) Keto: 1H-NMR(CDCI3) δ ppm 12.22 (s, 1 H), 9.23(s, 1H), 8.89 (d, J=4.Q8 Hz, 1 H), 7.83 - 7.85 (m, 1 H), 7.26(s, 1H), 6.46(s, 1H), 4.30 (q, J=7.05 Hz, 2 H), 1.34 (t, J=7.26 Hz, 3 H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2008/23239, 2008, A1 Location in patent: Page/Page column 21; 22

8
[ 2450-08-0 ]
E-4-pyrimidinyl(3-trifluoromethylphenyl)methanone oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 80 percent / n-BuLi / diethyl ether; tetrahydrofuran; hexane / -90 deg C to rt 2: 42 percent / H₂NOH*HCl, CH₃CO₂Na / ethanol / 24 h / Ambient temperature

Reference： [1]Heinisch, Gottfried; Holzer, Wolfgang; Langer, Thierry; Lukavsky, Peter [Heterocycles, 1996, vol. 43, # 1, p. 151 - 172]

9
[ 2450-08-0 ]
Z-4-pyrimidinyl(3-trifluoromethylphenyl)methanone oxime [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 80 percent / n-BuLi / diethyl ether; tetrahydrofuran; hexane / -90 deg C to rt 2: 46 percent / H₂NOH*HCl, CH₃CO₂Na / ethanol / 24 h / Ambient temperature

Reference： [1]Heinisch, Gottfried; Holzer, Wolfgang; Langer, Thierry; Lukavsky, Peter [Heterocycles, 1996, vol. 43, # 1, p. 151 - 172]

10
[ 31462-59-6 ]
[ 2450-08-0 ]

Yield	Reaction Conditions	Operation in experiment
57.55%	With hydrogenchloride; methanol; In water; at 20℃;Heating / reflux;	To 4-Methyl pyrimidine (5.0 g, 0.053 mol) in pyridine (55ML) was added selenium dioxide (8.82 g, 0.079 mol) at RT with stirring. The reaction mixture was stirred at 55 C for 2 h and at 80 C for 3.5 hr. After cooling to RT and stirring over night, the reaction mixture was filtered and the residue was washed with pyridine. The combined pyridine solution was concentrated and the carboxylic acid obtained was washed with water to remove traces of selenium dioxide. Yield : 5.3 g, 80.5 %. [00157] To Pyrimidine-4-carboxylic acid (5.0 g, 0.04 mol) in methanol (170 ml) was added conc. HCI (2 ML) at RT. After refluxing overnight, the reaction mixture was cooled to RT and neutralized with 10 % sodium bicarbonate solution and concentrated. The ester was extracted with diethyl ether, dried over NA2SO4 AND concentrated to get the methyl ester as a yellow solid, yield : 3.3 g, 57.55 %. [00158] TRIMETHYL ACETYLCHLORIDE (11.30 g, 0.093 mol) was added to a benzene (500 ML) solution of triethylamine (15.75 g, 0.155 mol) and 4- CHLOROANILINE (10.0 g, 0.078 mol) at 0C. The reaction mixture was warmed to RT and stirred for 3h. The reaction mixture was then quenched with water, extracted with ethyl acetate, washed with water, brine solution and dried over NA2SO4. The solid product obtained was crystallized from pet ether. Yield : 14.0 g, 84. 43 %. [00159] To N- (4-chlorophenyl)-2, 2-dimethyl propanamide (3.5 g, 0.0165 mol) in THF (50 MI) at 0 C was added n-butyl lithium in hexane (2.64 g, 1.2 M, 0. 041 MOL). Stirring was continued at 0 C for 2 h, the reaction then cooled to-70 C, pyrimidine-4-methyl carboxylate (3.18 g, 0.023 mol) in THF (25 ML) was then added slowly and the solution was warmed to RT and stirred overnight. Diethyl ether (50 ml) and water (50 ml) were added and the organic layer was separated. The aqueous layer was further extracted with ether. The combined ether layers were washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield : 1.7 g, 32.69 %. [00160] The protected amino ketone (1.7 g, 0.0054 mol) in sulfuric acid (10 ML, 70 %) was heated at 95 C over night. The reaction mixture was cooled to RT and basified with 10% NAOH, extracted with DCM, washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography using basic alumina to yield title compound (0.20g, 16%).

Reference： [1]Patent: WO2004/46092,2004,A2 .Location in patent: Page 52-53

11
[ 14113-98-5 ]
[ 2450-08-0 ]
[ 60651-76-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium methylate In water; benzene	41 Preparation of 1-Cyclopropyl-3-(4-pyrimidinyl)-1,3-propanedione EXAMPLE 41 Preparation of 1-Cyclopropyl-3-(4-pyrimidinyl)-1,3-propanedione A stirred mixture of 1.4 g. of methyl-4-pyrimidinecarboxylate, 1.7 g. of cyclopropylmethyl ketone, 1.2 g. of sodium methoxide and 40 ml. of benzene is heated under reflux for 4 hours. The mixture is diluted with 40 ml. of water and the benzene phase is removed. The aqueous mixture is made weakly acidic with dilute hydrochloric acid and extracted with chloroform. The cloroform solution is dried over magnesium sulfate and concentrated under reduced pressure to give light brown crystals, which are recrystallized from hexane to provide straw-colored crystals, melting point 81°-84°C.

Reference： [1]Current Patent Assignee: PFIZER INC - US3957805, 1976, A

12
[ 65854-91-3 ]
[ 2450-08-0 ]
[ 698395-65-2 ]

Yield	Reaction Conditions	Operation in experiment
32.69%		To 4-Methyl pyrimidine (5.0 g, 0.053 mol) in pyridine (55ML) was added selenium dioxide (8.82 g, 0.079 mol) at RT with stirring. The reaction mixture was stirred at 55 C for 2 h and at 80 C for 3.5 hr. After cooling to RT and stirring over night, the reaction mixture was filtered and the residue was washed with pyridine. The combined pyridine solution was concentrated and the carboxylic acid obtained was washed with water to remove traces of selenium dioxide. Yield : 5.3 g, 80.5 %. [00157] To Pyrimidine-4-carboxylic acid (5.0 g, 0.04 mol) in methanol (170 ml) was added conc. HCI (2 ML) at RT. After refluxing overnight, the reaction mixture was cooled to RT and neutralized with 10 % sodium bicarbonate solution and concentrated. The ester was extracted with diethyl ether, dried over NA2SO4 AND concentrated to get the methyl ester as a yellow solid, yield : 3.3 g, 57.55 %. [00158] TRIMETHYL ACETYLCHLORIDE (11.30 g, 0.093 mol) was added to a benzene (500 ML) solution of triethylamine (15.75 g, 0.155 mol) and 4- CHLOROANILINE (10.0 g, 0.078 mol) at 0C. The reaction mixture was warmed to RT and stirred for 3h. The reaction mixture was then quenched with water, extracted with ethyl acetate, washed with water, brine solution and dried over NA2SO4. The solid product obtained was crystallized from pet ether. Yield : 14.0 g, 84. 43 %. [00159] To N- (4-chlorophenyl)-2, 2-dimethyl propanamide (3.5 g, 0.0165 mol) in THF (50 MI) at 0 C was added n-butyl lithium in hexane (2.64 g, 1.2 M, 0. 041 MOL). Stirring was continued at 0 C for 2 h, the reaction then cooled to-70 C, pyrimidine-4-methyl carboxylate (3.18 g, 0.023 mol) in THF (25 ML) was then added slowly and the solution was warmed to RT and stirred overnight. Diethyl ether (50 ml) and water (50 ml) were added and the organic layer was separated. The aqueous layer was further extracted with ether. The combined ether layers were washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography. Yield : 1.7 g, 32.69 %. [00160] The protected amino ketone (1.7 g, 0.0054 mol) in sulfuric acid (10 ML, 70 %) was heated at 95 C over night. The reaction mixture was cooled to RT and basified with 10% NAOH, extracted with DCM, washed with water, brine and dried over NA2SO4. The product obtained upon concentration was purified by column chromatography using basic alumina to yield title compound (0.20g, 16%).

Reference： [1]Patent: WO2004/46092,2004,A2 .Location in patent: Page 52-53

13
[ 251924-61-5 ]
[ 2450-08-0 ]
[ 317332-24-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 1-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -65℃; for 0.666667h; Stage #2: methyl pyrimidine-4-carboxylate In tetrahydrofuran; hexane at 20℃;	1 1-[1-(4-Fluorobenzyl)-1H-pyrrol-2-yl]-3-pyrimidin-4-yl-propan-1,3-dione (1C) 1-[1-(4-Fluorobenzyl)-1H-pyrrol-2-yl]-3-pyrimidin-4-yl-propan-1,3-dione (1C). To an oven dried 50 mL three necked round bottomed flask with a stirring bar, septum, argon inlet and thermometer was added THF (5 mL) and diisopropylamine (1.5 mmol, 0.21 mL). This solution was cooled to -78C. and n-butyllithium (1.5 mmol, 0.6 mL of a 1.5 M solution in hexane) was added. To this well stirred solution was added a solution of 1-[1-(4-fluorobenzyl)-1H-pyrrol-2-yl]ethanone (1.0 mmol, 0.217 g) in THF (5 mL), maintaining the temperature

Reference： [1]Current Patent Assignee: MERCK & CO INC; AMGEN INC - US2003/229079, 2003, A1 Location in patent: Page 27

14
[ 2450-08-0 ]
[ 1577251-23-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C 1.2: 16 h / 80 °C 2.1: hydrazine hydrate / ethanol / 18 h / 80 °C 3.1: sodium hydride / tetrahydrofuran / 0.5 h / 0 °C 3.2: 18 h / 80 °C

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1

15
[ 2450-08-0 ]
[ 1577252-01-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C 1.2: 16 h / 80 °C 2.1: hydrazine hydrate / ethanol / 18 h / 80 °C 3.1: iridium(III) chloride trihydrate / 1,2-dimethoxyethane / 24 h / 220 °C

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1

16
[ 2450-08-0 ]
[ 1050622-59-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 1 h / 0 °C 1.2: 16 h / 80 °C 2.1: hydrazine hydrate / ethanol / 18 h / 80 °C

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1

17
[ 2450-08-0 ]
[ 67-64-1 ]
[ 1577253-62-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	Stage #1: acetone With sodium hydride In tetrahydrofuran at 0℃; for 1h; Stage #2: methyl pyrimidine-4-carboxylate In tetrahydrofuran at 80℃; for 16h;	Following adding 1.0g (43.4 mmol) of NaH to 80 ml of anhydrous tetrahydrofuran, 2.6 ml (34.8 mmol) of acetone was slowly added thereto at 0°C. After 1 hour, 4.0g (29.0 mmol) of pyrimidine-4-carboxylic acid methyl ester was slowly added thereto and heated under reflux at about 80°C for about 16 hours. After completion of the reaction, 30 ml of distilled water was added thereto, 2.5 ml of acetic was then slowly added and stirred at room temperature for about 30 minutes. After 30 minutes, the resulting product was extracted with 100 ml of dichloromethane five times to obtain an organic layer, which was dried using magnesium sulfate and distilled under reduced pressure. The resulting product was separated and purified using column chromatography to obtain 1.8g (11.0 mmol, Yield 38%) of Intermediate 4(1). LC-MS m/z = 165(M+H)+

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1 Location in patent: Paragraph 0154

18
[ 564-04-5 ]
[ 2450-08-0 ]
[ 1577253-65-6 ]

Yield	Reaction Conditions	Operation in experiment
16%	Stage #1: 2,2-dimethyl-3-pentanone With sodium t-butanolate In tetrahydrofuran at 0 - 0.6℃; for 2h; Stage #2: methyl pyrimidine-4-carboxylate In tetrahydrofuran at 80℃; for 12h;	Following adding 1.9g (19.3 mmol) of NatOBu (sodium t-butoxide) to 50 ml of anhydrous tetrahydrofuran, 2.2 g (17.5 mmol) of 2,2-dimethyl-3-pentanone was slowly added thereto at 0°C. After heating the mixture at about 60°C for about 2 hours, 2.2g (15.7 mmol) of pyrimidine-4-carboxylic acid methyl ester was slowly added thereto and heated under reflux at about 80°C for about 12 hours. After completion of the reaction, 50 ml of distilled water was added, and a 4N diluted hydrochloric acid was added for neutralization, followed by extraction with 100 ml of dichloromethane about three times to obtain an organic layer, which was then dried using magnesium sulfate, distilled under reduced pressure, and then separated and purified using column chromatography to obtain 0.6g (2.5 mmol, Yield: 16%) of Intermediate 27(1). LC-MS m/z = 223(M+H)+

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1 Location in patent: Paragraph 0201

19
[ 564-04-5 ]
[ 2450-08-0 ]
[ 1577252-97-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium t-butanolate / tetrahydrofuran / 2 h / 0 - 0.6 °C 1.2: 12 h / 80 °C 2.1: hydrazine hydrate / ethanol / 18 h / 80 °C

Reference： [1]Current Patent Assignee: Samsung Display (in: Samsung); SAMSUNG ELECTRONICS CO.,LTD. - EP2706064, 2014, A1

20
[ 2450-08-0 ]
C₁₀H₁₁N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

21
[ 2450-08-0 ]
C₁₀H₁₀BrN₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C 3: N-Bromosuccinimide / dichloromethane / 1 h / 0 °C

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

22
[ 2450-08-0 ]
C₇H₆BrN₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C 3: N-Bromosuccinimide / dichloromethane / 1 h / 0 °C 4: triethylamine / methanol / 18 h / 20 °C

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

23
[ 2450-08-0 ]
C₉H₈BrN₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C 3: N-Bromosuccinimide / dichloromethane / 1 h / 0 °C 4: triethylamine / methanol / 18 h / 20 °C 5: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 18 h / 90 °C

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

24
[ 2450-08-0 ]
C₂₅H₂₅N₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C 3: N-Bromosuccinimide / dichloromethane / 1 h / 0 °C 4: triethylamine / methanol / 18 h / 20 °C 5: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 18 h / 90 °C 6: potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tri tert-butylphosphoniumtetrafluoroborate / water; 1,4-dioxane / 18 h / 60 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

25
[ 2450-08-0 ]
C₂₅H₂₄FN₅O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: potassium 2-methyl-2-butoxide / tetrahydrofuran; toluene / 18 h / 20 °C 2: hydrogenchloride / ethanol; water / 1 h / 50 °C 3: N-Bromosuccinimide / dichloromethane / 1 h / 0 °C 4: triethylamine / methanol / 18 h / 20 °C 5: N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 18 h / 90 °C 6: potassium phosphate; tris-(dibenzylideneacetone)dipalladium⁽⁰⁾; tri tert-butylphosphoniumtetrafluoroborate / water; 1,4-dioxane / 18 h / 60 °C / Inert atmosphere; Sealed tube

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1

26
[ 2450-08-0 ]
[ 75-05-8 ]
C₈H₇N₃O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium 2-methyl-2-butoxide In tetrahydrofuran; toluene at 20℃; for 18h;	A14.a a- Synthesis of intermediate 39: a- Synthesis of intermediate 39: To a solution of methyl pyrimidine-4-carboxylate (10.0 g, 72.4 mmol) and ACN (1.89 mL, 36.2 mmol) in dry THF (100 mL) was added slowly potassium 2-methyl-2- butoxide in toluene (16.8 mL, 29.0 mmol). The reaction was stirred at r.t. for 18h, quenched with water and evaporated in vacuo. The solid was taken up with a minimum of cold EtOH, filtered on a glass frit, washed with Et20 (3 times) and dried to give 5.55g of intermediate , brown solid (83%). Intermediate 39 was used without purification in the next reaction step.

Reference： [1]Current Patent Assignee: NOVALIX; JOHNSON & JOHNSON INC - WO2015/144801, 2015, A1 Location in patent: Page/Page column 93; 94

27
[ 3438-46-8 ]
[ 2450-08-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: pyridine; selenium(IV) oxide / 6 h / 60 - 85 °C 2: sulfuric acid / 16 h / Reflux

Reference： [1]Okawa, Tomohiro; Aramaki, Yoshio; Yamamoto, Mitsuo; Kobayashi, Toshitake; Fukumoto, Shoji; Toyoda, Yukio; Henta, Tsutomu; Hata, Akito; Ikeda, Shota; Kaneko, Manami; Hoffman, Isaac D.; Sang, Bi-Ching; Zou, Hua; Kawamoto, Tetsuji [Journal of Medicinal Chemistry, 2017, vol. 60, # 16, p. 6942 - 6990]

28
[ 2450-08-0 ]
3-(((4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methyl)amino)-N-(2-(trifluoromethyl)benzyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C

29
[ 2450-08-0 ]
N-(2,6-difluorobenzyl)-3-(((4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methyl)amino)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C 6: water; sodium hydroxide / ethanol; tetrahydrofuran / 11.5 h / 20 °C 7: triethylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; benzotriazol-1-ol / N,N-dimethyl-formamide / 18 h / 20 °C

30
[ 2450-08-0 ]
3-(((4-propyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methyl)amino)-N-(2-(trifluoromethyl)benzyl)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C

31
[ 2450-08-0 ]
CMPD₁₀₃A [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C

32
[ 2450-08-0 ]
[ 39513-54-7 ]

Reference： [1]Journal of Medicinal Chemistry,2017,vol. 60,p. 6942 - 6990

33
[ 2450-08-0 ]
ethyl 4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark

34
[ 2450-08-0 ]
ethyl 4-propyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark

35
[ 2450-08-0 ]
(4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C

36
[ 2450-08-0 ]
(4-propyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C

37
[ 2450-08-0 ]
C₈H₈ClN₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C

38
[ 2450-08-0 ]
C₁₀H₁₂ClN₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C

39
[ 2450-08-0 ]
ethyl 3-(((4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methyl)amino)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C

40
[ 2450-08-0 ]
3-(((4-methyl-5-(pyrimidin-4-yl)-4H-1,2,4-triazol-3-yl)methyl)amino)benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: hydrazine hydrate / ethanol / 16 h / Reflux 2: toluene / 16 h / 130 °C / Dean-Stark 3: calcium chloride; sodium tetrahydroborate / ethanol / 12.5 h / 0 °C 4: thionyl chloride / dichloromethane / 20 °C 5: N,N-dimethyl-formamide / 2 h / 90 °C 6: water; sodium hydroxide / ethanol; tetrahydrofuran / 11.5 h / 20 °C

41
[ 2450-08-0 ]
[ 503860-54-6 ]