[ CAS No. 26032-72-4 ] {[proInfo.proName]}

Name: 26032-72-4|2,4-Dichloro-6-phenylpyrimidine|97%
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Quality Control of [ 26032-72-4 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 26032-72-4 ]

CAS No. :	26032-72-4	MDL No. :	MFCD00234591
Formula :	C₁₀H₆Cl₂N₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VRNSMZDBMUSIFT-UHFFFAOYSA-N
M.W :	225.07	Pubchem ID :	241554
Synonyms :

Calculated chemistry of [ 26032-72-4 ]

Physicochemical Properties

Num. heavy atoms :	14
Num. arom. heavy atoms :	12
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	57.49
TPSA :	25.78 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-4.98 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.5
Log Po/w (XLOGP3) :	3.79
Log Po/w (WLOGP) :	3.45
Log Po/w (MLOGP) :	2.43
Log Po/w (SILICOS-IT) :	3.73
Consensus Log Po/w :	3.18

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.19
Solubility :	0.0145 mg/ml ; 0.0000644 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.03
Solubility :	0.0212 mg/ml ; 0.0000943 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-5.41
Solubility :	0.000878 mg/ml ; 0.0000039 mol/l
Class :	Moderately soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	2.0
Synthetic accessibility :	1.88

Safety of [ 26032-72-4 ]

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 [ 26032-72-4 ]

* 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 [ 26032-72-4 ]
Downstream synthetic route of [ 26032-72-4 ]

[ 26032-72-4 ] Synthesis Path-Upstream 1~13

1
[ 917-64-6 ]
[ 26032-72-4 ]
[ 32785-40-3 ]

Reference： [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 2, p. 109 - 114

2
[ 26032-72-4 ]
[ 13036-50-5 ]

Reference： [1] Yakugaku Zasshi, 1950, vol. 70, p. 137[2] Chem.Abstr., 1950, p. 5886

3
[ 3764-01-0 ]
[ 98-80-6 ]
[ 26032-72-4 ]

Yield	Reaction Conditions	Operation in experiment
82%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In tetrahydrofuran; water for 5 h; Inert atmosphere; Heating	Under nitrogen atmosphere, 2,4,6-trichloropyrimidine (40.0g, 0.218mol) and phenylboronic acid (26.6g, 0.218mol) completely dissolved in 250mL of tetrahydrofuran, was added 2M aqueous potassium carbonate solution (125mL) and tetrakis(triphenylphosphine)palladium (7.6g, 6.5mmol) then heated and stirred for 5 hours. The temperature was lowered to room temperature, the aqueous layer is removed, dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and treated with a column with 1:3 ratio of tetrahydrofuran and hexane to prepare the compound 6-A (40g, yield: 82percent).
72%	With sodium carbonate In 1,2-dimethoxyethane; water for 16 h; Inert atmosphere; Reflux	Under an Ar gas atmosphere, 2,4,6-trichloropyrimidine (25.0g, 136.3 mmol), phenylboronic acid (16.6g, 136.3 mmol), palladium acetate (1.53g, 6.82 mmol), triphenylphosphine (3.58g, 13.6 mmol), DME (1250 ml) and an aqueous solution of 2M sodium carbonate (211 ml) were stirred for 16 hours at a reflux temperature. The solvent was distilled away under reduced pressure. The obtained residue was extracted by dichloromethane. The residue obtained by concentrating the organic phase was refined by silica-gel column chromatography (a developing solvent: hexane-ethyl acetate) to provide an intermediate body X₄ as a white solid. A yield of the intermediate body X₄ was 22.1 g and a yield rate thereof was 72percent. (reference document : J.Org.Chem. 66 7125-7128 (2001))
72%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH₂Cl₂; potassium carbonate In 1,4-dioxane at 60℃; for 1 h;	A suspension of 2,4,6—trichloropyrimidine (1000 mg, 5.29mmol), phenyl boronic acid (665 mg, 5.29 mmol), PdC12(dppf) dichloromethane complex (204 mg, 0.26 mmcl) and K2C03 2 M solution (5.3 ml, 10.58 mmol) in 1,4—dioxane (26.4 ml) was stirred in a CEM® microwave apparatus at 60 °C for 1 hour.Resulting crude was portioned between dichloromethane (150 ml), NaHCO3 saturated solution (100 ml), the organic layer dried over Na2SO4 and concentrated to dryness at low pressure. Final normal phase purification (cyclohexane/DCM from 100/0 to 85/15) afforded pure title compound (857 mg,yield 72 percent) . Rt = 1.38 mm (analysis method 2); MS (ESI)m/z: 225.1 [M—H], [M—H] calculated: 225.0. ‘H NMR (400MHz, CDC13) 6 8.13 — 8.03 (m, 2H), 7.68 (s, 1H), 7.62 — 7.48(m, 3H)

70.3%	With potassium carbonate In tetrahydrofuran; water; toluene for 9 h; Reflux	75.0 g (409 mmol) of 2,4,6-trichloropyrimidine, 54.8 g (450 mmol) of phenylboronic acid, and 11.8 g (10 mmol) of tetrakis- (triphenylphosphine)palladium were suspended in a mixed solvent of 450 ml of tetrahydrofuran and 300 ml of toluene to provide a suspension. The suspension was added to a solution in which 113.0 g (818 mmol) of potassium carbonate was dissolved in 300 ml of water, and the obtained mixture was heated and refluxed for 9 hours. After separating the reaction fluid into two layers, an organic layer was washed with a saturated sodium chloride aqueous solution and dried with anhydrous sodium sulfate.<ii3> The organic solvent was disti Hated and removed under reduced pressure, and then the residue was recrystallized with toluene. The obtained crystal was separated by filtration and washed with toluene to obtain 64.7 g (yield: 70.3 percent) of intermediate product (A).
62%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In tetrahydrofuran; water at 80℃; Inert atmosphere	2,4,6-Trichloropyrimidine (1.00 g, 5.45 mmol) was dissolved in tetrahydrofuran (15 mL).Then tetrakis(triphenylphosphine)palladium (430 mg, 0.50 mmol) was added.Phenylboronic acid (0.66 g, 5.45 mol), aqueous sodium carbonate (1 M, 15 mL, 15 mmol),The resulting mixture was heated to 80 ° C under a nitrogen atmosphere to stir the reaction overnight.Water (50 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50mL×3).The combined organic layers were washed with brine (100 mL)Filter and filter the solution under reduced pressure.The residue obtained was purified by silica gel column chromatography (purified petroleum ether)The title compound was obtained as a green solid(0.76g, 62percent).
62%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; sodium carbonate In tetrahydrofuran; water at 60℃; for 6 h; Inert atmosphere	To a solution of 2,4,6-trichloropyrimidine (1.00 g, 5.45 mmol) in THF (15 mL) were added tetrakis(triphenylphosphine)palladium (430 mg, 0.50 mmol), benzeneboronic acid (0.66 g, 5.45 mol) and aqueous sodium carbonate solution (1 M, 15 mL, 15 mmol). The mixture was stirred at 80 °C overnight under nitrogen protection. To the reaction mixture was added water (50 mL), and the resulting mixture was extracted with ethyl acetate (50 mL x 3). The combined organic layers were washed with saturated brine (100 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel column chromatography (PE) to give the title compound as a green solid (0.76 g, 62percent).
61%	With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h;	[00299] To a solution of 2,4,6-trichloropyrimidine (0.29 mL, 2.5 mmol) in tetrahydrofuran (5 mL) were added palladium acetate (8 mg, 0.035 mmol), triphenylphosphine (18 mg, 0.065 mmol), phenylboronic acid (0.20 g, 1.6 mmol) and aqueous sodium carboante solution (1 M, 3.3 mL, 3.3 mmol). The mixture was stirred at 60 °C for 6 h, then cooled to rt and concentrated to remove the organic solvent. To the residue was added H20 (10 mL), and the mixture was extracted with EtOAc (10 mL x 3). The combined organic layers were washed with saturated brine (30 mL), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo to dry and the residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (0.225 g, 6 1percent).
61%	With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h;	To a solution of 2,4,6-trichloropyrimidine (0.29 mL, 2.5 mmol) in tetrahydrofuran (5mL) were added palladium acetate (8 mg, 0.035 mmol), triphenylphosphine (18 mg, 0.065mmol), phenylboronic acid (0.20 g, 1.6 mmol) and an aqueous sodium carbonate solution (1 M, 3.3 mL, 3.3 mmol). The mixture was heated to 60 °C and stirred for 6 h. The mixture was cooled to rt, and concentrated in vacuo to remove organic solvent. To the residue was added H20 (10 mL), and the mixture was extracted with EtOAc (lOmL x 3). The combined organic layers were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated in vacuoto dryness, and the residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (0.225 g, 6 1percent).MS: (ESI, pos. ion) m/z: 224.95 [M+H]‘H NMR (400 IVIFIz, CDC13) (ppm): 8.15—8.04 (m, 2H), 7.70 (s, 1H), 7.63—7.50 (m, 3H).
61%	With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 6 h;	To a solution of 2,4,6-trichloropyrimidine (0.29 mL, 2.5 mmol) in THF (5 mL) wereadded palladium acetate (8 mg, 0.035 mmol), triphenylphosphine (18 mg, 0.065 mmol),benzeneboronic acid (0.20 g, 1.6 mmol) and aqueous sodium carbonate solution (1 M, 3.3 mL,3.3 mmol). The mixture was stirred at 60 oc for 6 h under nitrogen protection. After the reactionwas completed, the mixture was cooled to rt, and concentrated in vacuo. To the residue wasadded H20 (10 mL), and the mixture was extracted with ethyl acetate (10 mL x 3). Thecombined organic layers were washed with saturated brine (10 mL), dried over anhydroussodium sulfate, filtered and concentrated. The residue was purified by silica gel columnchromatography (PE) to give the title compound as a white solid (0.225 g, 61 percent ).MS (ESI, pos. ion) m/z: 225.0 [M+Ht;1H NMR (400 MHz, CDCh) 8 (ppm): 8.15-8.04 (m, 2H), 7.70 (s, 1H), 7.63-7.50 (m, 3H).
61%	With palladium diacetate; sodium carbonate; triphenylphosphine In tetrahydrofuran; water at 60℃; for 5 h; Inert atmosphere	To a solution of 2, 4, 6-trichloropyrimidine (0.29 mL, 48.0 mmol) in THF (5 mL) were added palladium acetate (8 mg, 0.035 mmol) , triphenylphosphine (18 mg, 0.065 mmol) , benzeneboronic acid (0.20 g, 1.6 mmol) and aqueous sodium carbonate solution (1 M, 3.3 mL, 3.3 mmol) . The mixture was stirred at 60 for 5 h under nitrogen protection. The mixture was cooled to rt, and concentrated in vacuo. To the residue was added H₂O (10 mL) , and the mixture was extracted with ethyl acetate (10 mL × 3) . The combined organic layers were washed with saturated brine (20 mL) , dried over anhydrous sodium sulfate, filtered and the filtrate was concentrated in vacuo. The residue was purified by silica gel column chromatography (PE) to give the title compound as a white solid (0.225 g, 61percent) .MS (ESI, pos. ion) m/z: 225.0 [M+H]⁺;¹H NMR (400 MHz, CDCl₃) δ (ppm) : 8.15 –8.04 (m, 2H) , 7.70 (s, 1H) , 7.63 –7.50 (m, 3H) .
59%	With sodium carbonate In 1,2-dimethoxyethane; water for 5 - 6 h; Heating / reflux	Example 84 {4-[4-(4,5-Dihydro-lH-pyrrol-2-ylammo)-phenyl]-6-phenyl-pyrimidin-2-yl}- hexyl-methyl-amineStep a 2,4-Dichloro-6-phenyl-pyrirnidine 2,4,6-Trichloropyrimidine (1.Og, 5.5mmol) and phenylboronic acid (0.67g, 5.5mmol) were dissolved in DME (5OmL) under an Argon atmosphere. A solution OfNa₂CO₃ (1.81g, 17.1mmol) in H₂O (5mL) was added, followed by palladium acetate (61.2mg) and PPh₃ (143mg). The reaction mixture was refluxed for 5-6 h. The solution was evaporated and the residue suspended in between H₂O-DCM (3:5 / 8OmL). The separated organic layer was separated, washed with H₂O (3OmL) and dried (MgSO₄). Filtration and evaporation of the solvent gave the crude product which was purified by chomatography (Hexane-EtOAc (4.5:0.5)) (0.725g, 59percent). ¹H NMR (CDCl₃) 8.07 (2H, d), 7.68 (IH, s), 7.61-7.51 (3H, m).
53%	With tetrakis(triphenylphosphine) palladium⁽⁰⁾; potassium carbonate In 1,4-dioxane; water at 60℃; for 12 h; Inert atmosphere	100.0 g (545.2 mmol) of 1,3,5-trichloro pyrimidine, 59.83 g (490.68 mmol) of phenylboronic acid, 188.38 g (1.36 mol) of potassium carbonate, and 18.90 g (16.36 mmol) of tetrakis(triphenylphosphine) palladium (0) were added to 800 mL of 1,4-dioxane and 400 mL of water in a 2 L flask, and the mixture was heated at 60° C. under a nitrogen flow for 12 hours. The obtained mixture was added to 2000 mL of methanol to crystallize a solid, and the solid was filtered, dissolved in monochlorobenzene, filtered with silica gel/Celite, and then, recrystallized with methanol after removing an appropriate of the organic solvent to obtain Intermediate 8-1 (65.0 g, yield of 53percent). (0202) calcd. C10H6Cl2N2: C, 53.36; H, 2.69; Cl, 31.50; N, 12.45; found: C, 53.36; H, 2.69; Cl, 31.50; N, 12.44.
42%	With palladium diacetate; sodium carbonate; triphenylphosphine In water at 60℃; for 3 h;	Phenylboronic acid (5.00 mmol, 610 mg) and 2,4,6-trichloropyrimidine (6.00 mmol, 0.70 mL) are dissolved in a sodium carbonate solution (1 M in water, 10.0 mmol, 10.0 mL), and palladium(II) acetate (0.10 mmol, 22.5 mg) and triphenylphosphine (0.20 mmol, 52.5 mg) are added. The reaction mixture is heated to 60 °C and stirred for 3 hours. After cooling, the solution is extracted with diethyl ether (3 × 30 mL). The combined organic phases are washed with brine and dried over sodium sulphate. Subsequently, the solvent is removed under reduced pressure and the crude product is purified via column chromatography (SiO2, NEt3 (1 percent), hexane / dichloromethane = 2:1) to yield 9 (478 mg, 42percent) as white solid; Rf 0.3 (hexane / dichloromethane = 2:1) [UV]; 1H NMR (360 MHz, CDCl3): δ 7.50-7.60 (m, 3 H), 7.67 (s, 1 H), 8.07 (dd, J = 1.5 Hz, J = 8.3 Hz, 2 H); 13C NMR (151 MHz, CDCl3): δ 115.3 (CH), 127.6 (2 × CH), 129.2 (2 × CH), 132.4 (CH), 134.1 (Cq), 161.0 (Cq), 162.9 (Cq), 168.2(Cq)

Reference： [1] Organic Letters, 2006, vol. 8, # 3, p. 395 - 398
[2] Journal of Organic Chemistry, 2001, vol. 66, # 21, p. 7125 - 7128
[3] Patent: CN105579445, 2016, A, . Location in patent: Paragraph 0365; 0366; 0367; 0368; 0369
[4] Patent: EP2489664, 2012, A1, . Location in patent: Page/Page column 45
[5] Patent: WO2018/203256, 2018, A1, . Location in patent: Page/Page column 33; 34
[6] Patent: WO2010/24572, 2010, A2, . Location in patent: Page/Page column 21-22
[7] Organic Letters, 2016, vol. 18, # 9, p. 2180 - 2183
[8] Patent: CN108276401, 2018, A, . Location in patent: Paragraph 0825; 1218; 1222; 1223
[9] Patent: WO2018/127096, 2018, A1, . Location in patent: Paragraph 00344; 00449
[10] Patent: WO2017/97234, 2017, A1, . Location in patent: Paragraph 00239; 00299
[11] Patent: WO2018/33082, 2018, A1, . Location in patent: Paragraph 00223; 00340
[12] Patent: WO2018/108125, 2018, A1, . Location in patent: Paragraph 00310
[13] Patent: WO2018/157830, 2018, A1, . Location in patent: Paragraph 00251
[14] Patent: WO2008/9963, 2008, A2, . Location in patent: Page/Page column 96
[15] Patent: US2017/317293, 2017, A1, . Location in patent: Paragraph 0199-0202
[16] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 2, p. 292 - 300
[17] Patent: US2010/144722, 2010, A1, . Location in patent: Page/Page column 19
[18] Journal of Heterocyclic Chemistry, 2010, vol. 47, # 5, p. 1056 - 1061
[19] Patent: WO2010/120998, 2010, A1, . Location in patent: Page/Page column 49; 72
[20] Patent: WO2007/41130, 2007, A2, . Location in patent: Page/Page column 47; Sheet 3/9
[21] Patent: CN105408310, 2016, A, . Location in patent: Paragraph 0274

4
[ 13345-09-0 ]
[ 26032-72-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	at 116℃; Inert atmosphere	Step 2: 2,4-dichloro-6-phenylpyrimidine; A 50.0 ml. round bottom flask equipped with a magnetic stir bar and a reflux condenser was charged with argon prior to the addition of 6-phenyl-2,4(1 H,3H)- pyrimidinedione (2.22 g, 11.8 mmol) and phosphorus oxychloride (11.0 ml, 1 18 mmol) at room temperature. The flask was placed in a 1 16°C pre-heated oil bath and rapidly warmed to reflux. The mixture was stirred at 1 16°C under argon for 4 hours and allowed to cool to room temperature, after which time product was observed by LC-MS (m/e 225 [M+1]⁺). The flask was fitted with a short-path distillation head and excess POCI₃ was removed by vacuum distillation at 1 16°C. Excess starting material distilled off at approximately 70⁰C. The crude mixture was cooled to -3°C using an ice bath and monitored using an internal thermometer. The reaction mixture was quenched very slowly with ice while maintaining the temperature below 10⁰C. The flask was left in the ice bath for additional 60 min and a solid precipitated out of solution which was collected by vacuum filtration and confirmed to be the desired product, 2,4-dichloro-6-phenylpyrimidine (1.74 g, 7.7 mmol, 65 percent yield), by LC-MS. MS (ES) m/e 225 [M+H]+.

Reference： [1] Patent: WO2009/97474, 2009, A1, . Location in patent: Page/Page column 35
[2] Yakugaku Zasshi, 1950, vol. 70, p. 137[3] Chem.Abstr., 1950, p. 5886
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 2, p. 510 - 524

5
[ 3764-01-0 ]
[ 100-58-3 ]
[ 26032-72-4 ]

Reference： [1] Patent: US2012/22066, 2012, A1, . Location in patent: Page/Page column 12

6
[ 3934-20-1 ]
[ 591-51-5 ]
[ 26032-72-4 ]

Reference： [1] Journal of Chemical Research, 2006, # 12, p. 785 - 787

7
[ 86984-17-0 ]
[ 26032-72-4 ]

Reference： [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 2, p. 109 - 114

8
[ 86984-18-1 ]
[ 26032-72-4 ]

Reference： [1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1983, vol. 37, # 2, p. 109 - 114

9
[ 13345-09-0 ]
[ 26032-72-4 ]

Reference： [1] Patent: US6372751, 2002, B1, . Location in patent: Example Pr3
[2] Patent: WO2006/34473, 2006, A2, . Location in patent: Page/Page column 219-220
[3] Patent: WO2006/34473, 2006, A2, . Location in patent: Page/Page column 222; 227

10
[ 56642-53-6 ]
[ 26032-72-4 ]
[ 78664-18-3 ]

Reference： [1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, p. 383 - 386[2] Khimiya Geterotsiklicheskikh Soedinenii, 1981, vol. 17, # 4, p. 526 - 529

11
[ 56642-53-6 ]
[ 1006-65-1 ]
[ 26032-72-4 ]
[ 78664-18-3 ]

Reference： [1] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, p. 383 - 386[2] Khimiya Geterotsiklicheskikh Soedinenii, 1981, vol. 17, # 4, p. 526 - 529
[3] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, p. 383 - 386[4] Khimiya Geterotsiklicheskikh Soedinenii, 1981, vol. 17, # 4, p. 526 - 529
[5] Chemistry of Heterocyclic Compounds (New York, NY, United States), 1981, p. 383 - 386[6] Khimiya Geterotsiklicheskikh Soedinenii, 1981, vol. 17, # 4, p. 526 - 529

12
[ 56035-29-1 ]
[ 26032-72-4 ]

Reference： [1] Yakugaku Zasshi, 1950, vol. 70, p. 137[2] Chem.Abstr., 1950, p. 5886

13
[ 13345-09-0 ]
[ 10026-13-8 ]
[ 10025-87-3 ]
[ 26032-72-4 ]

Reference： [1] Journal fuer Praktische Chemie (Leipzig), 1893, vol. <2> 47, p. 203

[ 26032-72-4 ] Synthesis Path-Downstream 1~88

1
[ 26032-72-4 ]
[ 3438-48-0 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1940,vol. 60,p. 367,370
Chem.Abstr.,1941,p. 1404

2
[ 26032-72-4 ]
[ 13036-50-5 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1950,vol. 70,p. 137
Chem.Abstr.,1950,p. 5886

3
[ 26032-72-4 ]
2,4-diazido-6-phenyl-pyrimidine [ No CAS ]

Reference： [1]Journal of the American Chemical Society,1954,vol. 76,p. 1858,1860

5
[ 917-64-6 ]
[ 26032-72-4 ]
[ 32785-40-3 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

6
[ 26032-72-4 ]
[ 124-41-4 ]
2-chloro-4-methoxy-6-phenylpyrimidine [ No CAS ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

7
[ 10467-10-4 ]
[ 26032-72-4 ]
[ 86984-23-8 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

8
[ 10467-10-4 ]
[ 26032-72-4 ]
[ 86984-22-7 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

9
[ 26032-72-4 ]
phenylmagnesium bromide [ No CAS ]
[ 1666-86-0 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

10
[ 26032-72-4 ]
[ 105-56-6 ]
[ 108654-91-7 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1986,vol. 22,p. 774 - 779
Khimiya Geterotsiklicheskikh Soedinenii,1986,vol. 22,p. 963 - 969

11
[ 26032-72-4 ]
[ 109-77-3 ]
[ 108655-05-6 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1986,vol. 22,p. 774 - 779
Khimiya Geterotsiklicheskikh Soedinenii,1986,vol. 22,p. 963 - 969

12
2,4-Dichloro-6-phenyl-1,6-dihydro-pyrimidine [ No CAS ]
[ 26032-72-4 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4137 - 4140

13
[ 86984-18-1 ]
[ 26032-72-4 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

14
[ 86984-17-0 ]
[ 26032-72-4 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

15
[ 56642-53-6 ]
[ 1006-65-1 ]
[ 26032-72-4 ]
[ 78664-18-3 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1981,p. 383 - 386
    Khimiya Geterotsiklicheskikh Soedinenii,1981,vol. 17,p. 526 - 529
[2]Chemistry of Heterocyclic Compounds,1981,p. 383 - 386
    Khimiya Geterotsiklicheskikh Soedinenii,1981,vol. 17,p. 526 - 529
[3]Chemistry of Heterocyclic Compounds,1981,p. 383 - 386
    Khimiya Geterotsiklicheskikh Soedinenii,1981,vol. 17,p. 526 - 529

16
[ 56642-53-6 ]
[ 26032-72-4 ]
[ 78664-18-3 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1981,p. 383 - 386
Khimiya Geterotsiklicheskikh Soedinenii,1981,vol. 17,p. 526 - 529

17
[ 110-89-4 ]
[ 26032-72-4 ]
2-chloro-4-phenyl-6-piperidin-1-yl-pyrimidine [ No CAS ]
4-chloro-6-phenyl-2-piperidin-1-yl-pyrimidine [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 395 - 398

18
[ 110-91-8 ]
[ 26032-72-4 ]
4-(4-chloro-6-phenylpyrimidin-2-yl)morpholine [ No CAS ]
4-(2-chloro-6-phenyl-pyrimidin-4-yl)morpholine [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 395 - 398

19
[ 623586-00-5 ]
[ 26032-72-4 ]
(R)-4-(2-chloro-6-phenylpyrimidin-4-yl)-3-methyl-piperazine-1-carboxylic acid benzyl ester [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 395 - 398

20
[ 26032-72-4 ]
[ 1765-93-1 ]
2-chloro-4-(4'-fluorophenyl)-6-phenylpyrimidine [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2006,vol. 43,p. 127 - 131
[2]Journal of Pharmacology and Experimental Therapeutics,2019,vol. 370,p. 514 - 527

21
[ 26032-72-4 ]
[ 111-92-2 ]
dibutyl-(2-chloro-6-phenylpyrimidin-4-yl)amine [ No CAS ]
dibutyl-(4-chloro-6-phenylpyrimidin-2-yl)amine [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 395 - 398

22
[ 26032-72-4 ]
[ 100-61-8 ]
(4-chloro-6-phenylpyrimidin-2-yl)methylphenylamine [ No CAS ]
(2-chloro-6-phenylpyrimidin-4-yl)methylphenylamine [ No CAS ]

Reference： [1]Organic Letters,2006,vol. 8,p. 395 - 398

23
[ 109-01-3 ]
[ 26032-72-4 ]
4-chloro-2-(4'-methylpiperazin-1'-yl)-6-phenylpyrimidine [ No CAS ]
2-chloro-4-(4'-methylpiperazin-1'-yl)-6-phenylpyrimidine [ No CAS ]

Reference： [1]Journal of Chemical Research,2006,p. 785 - 787

24
[ 109-01-3 ]
[ 26032-72-4 ]
2,4-bis-(4'-methylpiperazin-1'-yl)-6-phenylpyrimidine [ No CAS ]

Reference： [1]Journal of Chemical Research,2006,p. 785 - 787

25
[ 3934-20-1 ]
[ 591-51-5 ]
[ 26032-72-4 ]

Reference： [1]Journal of Chemical Research,2006,p. 785 - 787

26
[ 26032-72-4 ]
[ 1679-18-1 ]
[ 873913-83-8 ]

Yield	Reaction Conditions	Operation in experiment
67%	With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; In 1,4-dioxane; water; for 8h;Reflux; Inert atmosphere;	In argon atmosphere, intermediate E (4.50g, 20 mmol), 4-chlorophenylborate (3.13g, 20 mmol), dichloro(bistriphenylphosphine)palladium complex (0.351g, 0.5 mmol), 1,4-dioxane (80 mL) and a 2M aqueous potassium carbonate solution (40 mL) were sequentially added. The resulting mixture was heated under reflux for 8 hours. After the reaction mixture was cooled to room temperature, the mixture was diluted by adding toluene and washed with water, followed by drying under reduced pressure. The residue obtained was purified by means of silica-gel chromatography to obtain intermediate P (4.03g, yield: 67%).

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 1369 - 1379
[2]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0189; 0190

27
[ 26032-72-4 ]
[3-(4,6-diphenyl-pyrimidin-2-yl)-propyl]-dimethyl-amine [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 1369 - 1379

28
[ 26032-72-4 ]
[ 873913-93-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,2005,vol. 42,p. 1369 - 1379

29
phenylmagnesium bromide [ No CAS ]
[ 26032-72-4 ]

Reference： [1]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114
[2]Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry,1983,vol. 37,p. 109 - 114

30
[ 591-51-5 ]
2-<5-chloro-1(3)<i>H</i>-benzimidazol-2-yl>-3-hydroxy-inden-1-one [ No CAS ]
[ 26032-72-4 ]

Reference： [1]Journal of Organic Chemistry,1988,vol. 53,p. 4137 - 4140

31
[ 26032-72-4 ]
[ 108655-14-7 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1986,vol. 22,p. 774 - 779
Khimiya Geterotsiklicheskikh Soedinenii,1986,vol. 22,p. 963 - 969

32
[ 26032-72-4 ]
[ 108655-06-7 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1986,vol. 22,p. 774 - 779
Khimiya Geterotsiklicheskikh Soedinenii,1986,vol. 22,p. 963 - 969

33
[ 56035-29-1 ]
[ 26032-72-4 ]

Reference： [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1950,vol. 70,p. 137
Chem.Abstr.,1950,p. 5886

34
[ 26032-72-4 ]
[ 194985-94-9 ]
3-[(6-chloro-4-phenylpyrimidin-2-yl)oxy]-4-(benzyloxy)benzonitrile [ No CAS ]

Reference： [1]Patent: US6372751,2002,B1 .Location in patent: Example Pr4

35
[ 26032-72-4 ]
[ 194985-94-9 ]
3-[(2-chloro-6-phenylpyrimidin-4-yl)oxy]-4-(benzyloxy)benzonitrile [ No CAS ]

Reference： [1]Patent: US6372751,2002,B1 .Location in patent: Example Pr4

36
[ 13345-09-0 ]
[ 26032-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; for 10h;Heating / reflux;Product distribution / selectivity;	A mixture of compound, 6-phenyl-pyrimidine-2,4-diol (11 g, 58.5 mmol) and phosphorus oxychloride (100 mL) was refluxed for 10 hours under anhydrous condition. Excess of phosphorus oxychloride was removed by distillation and the residue was treated with cold water (100-150 mL). The solid precipitated xvas filtered, washed with water, and dried under vacuum to give the desired compound (10 g) as a brown solid. M.P.: 80-850C. EPO <DP n="221"/>1H NMR (400 MHz, DMSO-J15): delta 8.07 (d, J = 7.9 Hz, 2H), 7.68 (s, IH), 7.61 (s, IH), 7.54 (d, J= 7.3 Hz, 2H). IR (KBr, cm"1): 3442, 1560. MS: m/z (CI) 225 (M+, 100).
	With trichlorophosphate;Product distribution / selectivity;	Examples 40-47Synthesis of Substituted Pyrimidine Compounds Scheme 5The following compounds presented in Examples 40-47 were prepared in accordance with Scheme 5, by a procedure analogous to that disclosed in Example 39, using starting materials with the appropriate substitution.; Examples 52-92Synthesis of substituted pyrimidine compounds Scheme 6The following compounds presented in Examples 52-92 w^ere prepared in accordance with Scheme 6, by a procedure analogous to that disclosed in Examples 39 and 48, using starting materials with the appropriate substitution.

Reference： [1]Patent: US6372751,2002,B1 .Location in patent: Example Pr3
[2]Patent: WO2006/34473,2006,A2 .Location in patent: Page/Page column 219-220
[3]Patent: WO2006/34473,2006,A2 .Location in patent: Page/Page column 222; 227

37
[ 26032-72-4 ]
[ 31230-17-8 ]
[ 438203-33-9 ]

Yield	Reaction Conditions	Operation in experiment
62%	With triethylamine; sodium iodide; In DMF (N,N-dimethyl-formamide); at 90℃; for 15h;	To a solution of <strong>[26032-72-4]2,4-dichloro-6-phenyl-pyrimidine</strong> (300 mg, 1.33 mmol) and 3-amino-5-methylpyrazole (129 mg, 1.33 mmol) in DMF (7 mL) is added triethylamine (195 muL, 1.40 mmol) followed by sodium iodide (200 mg, 1.33 mmol) and the reaction mixture is stirred for 15 hours at 90 C. The resulting solution is partitioned between ethyl acetate and water and the organic phase washed with brine, dried over MgSO4 then concentrated in vacuo. The residue is triturated in methanol and the resulting white solid collected by filtration to afford (2-chloro-6-phenyl-pyrimidin-4-yl)-(5-methyl-2H-pyrazol-3-yl)-amine (236 mg, 62%).

Reference： [1]Patent: US2005/38023,2005,A1 .Location in patent: Page/Page column 129
[2]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 3586 - 3592

38
[ 5382-16-1 ]
[ 26032-72-4 ]
[ 881194-69-0 ]

Yield	Reaction Conditions	Operation in experiment
		The following compounds presented in Examples 52-92 w^ere prepared in accordance with Scheme 6, by a procedure analogous to that disclosed in Examples 39 and 48, using starting materials with the appropriate substitution.

Reference： [1]Patent: WO2006/34473,2006,A2 .Location in patent: Page/Page column 227

39
[ 26032-72-4 ]
trans-4-hydroxycyclohexylamine hydrochloride [ No CAS ]
[ 881194-93-0 ]
[ 881194-94-1 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In butan-1-ol; at 120℃; for 12h;	A mixture of compound <strong>[26032-72-4]2,4-dichloro-6-phenyl-pyrimidine</strong> (0.5 g, 2.22 mmol), 4-aminocyclohexanol hydrochloride (0.12 g, 1.11 mmol), triethylamine (0.67 g, 6.62 mmol) in n-butanol (10 ml) was stirred at 1200C for 12 hours under a nitrogen atmosphere. The reaction mixture was then concentrated under vacuum, diluted with water (25 mL) and extracted with ethyl acetate (3 x 20 mL). The organic layers were collected, combined, washed with water (20 mL), dried over anhydrous sodium sulphate, and concentrated "under vacuum. The residue thus obtained was purified by column chromatography using ethyl acetate-petroleum ether to give the two compounds 4-(2-chloro-6-phenyl-pyrimidin-4-ylamino)-cyclohexanol and 4-(4- chloro-6-phenyl-pyrimidin-2-ylamino)-cyclohexanol in ratio 1:2 (overall yield: 63%). Spectral data for 4-(2-chloro-6-phenyl-pyrimidin-4-ylamino)-cyclohexanol: 1H NMR (200 MHz, DMSO-^): delta 10.71 (br s, IH), 7.64-7.50 (m, 5H), 6.49 (s, IH), 3.85-3.64 (m, 2H), 1.96-1.90 (m, 4H), 1.32-1.19 (m, 4H) IR (KBr, cm-1): 3325, 1554. MS: m/z (CI) 304 (M+, 100). Spectral data for 4-(4-chloro-6-phenyl-pyrimidin-2-ylamino)-cyclohexanol: 1H NMR (200 MHz, DMSO-rfd): delta 10.89 (br s, IH), 8.20-8.11 (m, 2H), 7.60-7.52 (m, 3H), 6.55 (s, IH), 3.86-3.70 (m, 2H), 2.02-1.88 (m, 4H), 1.34-1.21 (m, 4H). IR (KBr, cm-1): 3327, 1551. MS: m/z (CI) 304 (M+, 100).

Reference： [1]Patent: WO2006/34473,2006,A2 .Location in patent: Page/Page column 267

40
[ 26032-72-4 ]
[ 916201-86-0 ]
[ 934178-99-1 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 80℃;	As shown in Figure 3-step i, a mixture of phenylboronic acid (1.22 g),2,4,6-trichloropyrimidine (compound 1011), tetrakis(triphenylphosphine) palladium(O) and 2N sodium carbonate (15 mL) in DME (25 mL) was heated at 80 0C overnight. After cooling to it, addition of water (30 mL), extraction with dichloromethane (3 x 20 mL), drying and evaporation, purification by column chromatography (SiO2, 10-20% ethyl acetate in hexane) afforded the desired product, <strong>[26032-72-4]6-phenyl-2,4-dichloropyrimidine</strong> (compound 1012) (0.544 g). As shown in Figure 3-step ii, compound 1012 (0.34 g) was mixed with (,S)-2-amino-N-(2,2,2- trifluoroethylpropanamide (0.3 g) and diisopropylethylamine (0.63 mL) in isopropanol (5 mL) and the reaction mixture heated at 80 0C overnight. Evaporation gave a residue, which after aqueous workup and purification (SiO2, 20% ethyl acetate/hexane) produced 2-(2- chloro-6-phenyl-pyrimidin-4-ylamino)-nu-(2,2,2-trifluoro-ethyl)propionamide (compound 1013) (0.165 g). As shown in Figure 3-step iii, compound 1013 (29 mg), 5-(4,4,5,5- Tetramethyl-[l,3,2]dioxaborolan-2-yl)-7-(toluene-4-sulfonyl)-7H-pyrrolo[2,3-d]pyrimidine (compound 1005), PdCl2dppf2 (7 mg), and potassium phosphate (32 mg) were heated in 1,4- dioxane (2 mL) at 80 0C overnight. To the reaction was added aqueous lithium hydroxide solution (2 mL). After heating at 600C for Ih, water (20 mL) was added. Extraction with dichloromethane (3X), drying, evaporation and purification (SiO2, 50-100% ethyl acetate/hexane) gave 3.7 mg of 2-[6-phenyl-2-(7eta-pyrrolo[2,3-d]pyrimidin-5-yl)-pyrimidin- 4-ylamino]-N-(2,2,2-trifluoro-ethyl)-propionamide (compound 18).

Reference： [1]Patent: WO2007/41130,2007,A2 .Location in patent: Page/Page column 47; Sheet 3/9

41
[ 26032-72-4 ]
[ 74-89-5 ]
[ 76-05-1 ]
[ 1312185-22-0 ]
[ 1312185-12-8 ]

Yield	Reaction Conditions	Operation in experiment
14%; 26%		Step 3: 2-chloro-lambda/-methyl-6-phenyl-4-pyrimidinamine and 4-chloro-lambda/-methyl-6-phenyl-2- pyrimidinamine; To a 50 mL round bottom flask equipped with a magnetic stir bar and an internal thermometer was added <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (250 mg, 1.1 1 mmol), tetrahydrofuran (1.1 1 mL) and triethylamine (0.156 mL, 1.11 mmol) all under a blanket of argon. The flask was cooled to -5C before 2M methylamine in THF (0.56 mL, 1.1 1 mmol) was added slowly over a 1 hour period. Then, the flask was allowed to warm up to 00C and maintained at that temperature for 6 hours, after which time LC-MS indicated that two products had formed. An additional equivalent of methylamine in THF (0.56 mL, 1.11 mmol) was added and the reaction was allowed to warm up to room temperature. After 3.5 hours LC-MS indicated that the reaction was complete. The mixture was concentrated under vacuum, taken up in 2.5 mL of DMSO, and purified by prep HPLC (Phenomenex, 50mm x 100 mm, 90 mL/min, A: acetonitrile (0.1 % TFA) B: water (0.1% TFA), A: 10 to 99% over 30 min, UV detection at 214 nm) which separated the two products to give each of the title compounds, 2-chloro-N-methyl-6-phenyl-4-pyrimidinamine (95.8 mg, 0.288 mmol, 26 % yield) and 4-chloro-N-methyl-6-phenyl-2-pyrimidinamine (51 mg, 0.153 mmol, <n="37"/>14 % yield), as the TFA salts, in the form of pale-yellow solids. Structure confirmation was based on 2-D NMR data. MS (ES) m/e 220 [M+H]+.

Reference： [1]Patent: WO2009/97474,2009,A1 .Location in patent: Page/Page column 35-36

42
[ 26032-72-4 ]
[ 1116082-29-1 ]
[ 1214276-67-1 ]

Yield	Reaction Conditions	Operation in experiment
68.0%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; toluene; for 12h;Reflux;	2.3 g (10 mmol) of intermediate product (A), 7.5 g (22 mmol) of l-(4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)isoquinoline (D), and 0.6 g (0.5 mmol) of tetrakis-(triphenylphosphine)palladium were suspended in a mixed solvent of 70 ml of tetrahydrofuran and 50 ml of toluene to provide a suspension. The suspension was added to a solution in which 5.7 g (41 mmol) of potassium carbonate was dissolved in 50 ml of water. The obtained mixture was heated and refluxed for 12 hours. After separating the reaction fluid into two layers, an organic layer thereof was washed with a saturated sodium chloride aqueous solution and dried with anhydrous sodium sulfate. <134> The organic solvent was disti Hated and removed under reduced pressure, and then the residue was recrystallized with toluene. The extracted crystal was separated by filtration and washed with toluene to obtain 3.9 g (yield- 68.0 %) of compound (10).<135> 1H NMR (300MHz, CDCl3) 8.94 (d,2H), 8.68 (d,2H), 8.52 (d,2H), 8.39(d,2H), 8.21 (d,2H), 8.16 (s,lH), 7.94 (m,6H), 7.72 (m,4H), 7.61 (m,5H); MS[M+1] 563.

Reference： [1]Patent: WO2010/24572,2010,A2 .Location in patent: Page/Page column 24-25

43
[ 26032-72-4 ]
[ 1214278-12-2 ]
[ 1214276-77-3 ]

Yield	Reaction Conditions	Operation in experiment
64.7%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; toluene; for 12h;Reflux;	4.0 g (18 mmol) of intermediate product (A), 13.0 g (39 mmol) of 3-(4- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)quinoline (E), and 1.0 g (0.9 mmol) of tetrakis-(triphenylphosphine)palladium were suspended in a mixed solvent of 120 ml of tetrahydrofuran and 80 ml of toluene to provide a suspension. The suspension was added to a solution in which 9.8 g (71 mmol) of potassium carbonate was dissolved in 80 ml of water. The obtained mixture was heated and refluxed for 12 hours. After separating the reaction fluid into two layers, an organic layer thereof was washed with a sodium chloride saturated aqueous solution and dried with anhydrous sodium sulfate.<148> The organic solvent was disti Hated and removed under reduced pressure, and then the residue was recrystallized with toluene. The extracted crystal was separated by filtration and washed with toluene to obtain 6.5 g (yield: 64.7 %) of compound (19).<149> 1H NMR (300MHz, CDCl3) 9.31 (d,2H), 8.89 (d,2H), 8.40 (m,6H), 8.17(d,2H), 8.09 (s,lH), 7.92 (m,6H), 7.75 (m,2H), 7.59 (m,5H); MS[M+1] 563.

Reference： [1]Patent: WO2010/24572,2010,A2 .Location in patent: Page/Page column 26

44
[ 26032-72-4 ]
[ 1003-03-8 ]
[ 1215103-73-3 ]

Yield	Reaction Conditions	Operation in experiment
58%	With N-ethyl-N,N-diisopropylamine; In methanol; for 16h;Inert atmosphere; Reflux;	Step (i): Synthesis of (2-chloro-6-phenyl-pyrimidin-4-yl)-cyclopentyl-amine Cyclopentylamine (1.6 mL, 16 mmol) was added to a solution of <strong>[26032-72-4]2,4-dichloro-6-phenyl-pyrimidine</strong> (3.0 g, 13.3 mmol) and DIEA (2.7 mL, 16 mmol) in anhydrous methanol (20 mL) under nitrogen atmosphere. The mixture was heated at reflux under stirring for 16 h. After evaporation of the volatiles the concentrate was diluted with EtOAc, washed with water, brine, and dried over sodium sulfate. After concentrating under reduced pressure the material was purified by chromatography over silica gel to afford the title compound as a white powder (2.1 g, 58% yield).1H NMR (CDCl3, 300 MHz): delta 7.97-7.94 (m, 2H), 7.48-7.44 (m, 3H), 6.60 (s, 1H), 5.35 (b s, 1H), 4.10-4.02 (m, 1H), 2.11-2.04 (m, 2H), 1.80-1.68 (m, 4H), 1.56-1.52 (m, 2H).LC-MSD (ES+): m/z [274 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 35-36

45
[ 26032-72-4 ]
[ 3886-69-9 ]
[ 1215103-76-6 ]

Yield	Reaction Conditions	Operation in experiment
30.8%		Step (i): Synthesis of (2-chloro-6-phenyl-pyrimidin-4-yl)-((R)-1-phenyl-ethyl)-amine To <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (1.343 g, 6 mmol), dissolved in 30 mL methanol, was added DIEA (1.1 mL, 6 mmol) and was stirred for 23 min at about 20-35 C. under a nitrogen atmosphere. To this mixture was added (R)-(+)-alpha-methyl-benzylamine (0.76 mL, 6 mmol) and stirred for about 10-19 h. The mixture was concentrated by rotary evaporation and purification (Biotage Horizon HPFC system chromatography, SiO2, 20:80 EtOAc: hexane) gave the title compound as a white solid (570 mg, 30.8% yield).1H NMR (300 MHz, CDCl3, TMS): delta 7.81-7.90 (m, 2H), 7.46-7.25 (m, 8H), 6.43 (s, 1H), 5.57 (s, 1H), 4.88 (s, 1H), 1.60 (d, J=6.6 Hz, 3H).LC-MSD (ES+): m/z [310 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 38

46
[ 26032-72-4 ]
[ 2627-86-3 ]
[ 1215103-78-8 ]

Yield	Reaction Conditions	Operation in experiment
42%		Step (i): Synthesis of (2-chloro-6-phenyl-pyrimidin-4-yl)-((S)-1-phenyl-ethyl)-amine To <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (450.3 mg, 2 mmol), dissolved in 30 mL methanol, was added DIEA (0.35 mL, 2 mmol) and was stirred for 30 min at about 20-35 C. under a nitrogen atmosphere. To this mixture was added (S)-(-)-a-methyl-benzylamine (0.25 mL, 2 mmol) and stirred 8 h. An additional DIEA (0.12 mL, 0.68 mmol) was added, and the mixture was stirred for 16.5 h. The mixture was concentrated by rotary evaporation and purification (Biotage Horizon HPFC system chromatography, SiO2, 20: 80 EtOAc : hexane) gave the title compound as a white solid (260 mg, 42% yield).1H NMR (300 MHz, CDCl3, TMS): delta 7.81-7.79 (m, 2H), 7.42-7.27 (m, 8H), 6.43 (s, 1H), 5.56 (b s, 1H), 4.88 (b s, 1H), 1.60 (d, J=6.9 Hz, 3H).LC-MSD (ES+): m/z [310 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 39

47
[ 26032-72-4 ]
[ 20989-17-7 ]
[ 1215103-80-2 ]

Yield	Reaction Conditions	Operation in experiment
39%		Step (i): Synthesis of (S)-2-(2-chloro-6-phenyl-pyrimidin-4-ylamino)-2-phenyl-ethanol To <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (642 mg, 2.8 mmol), dissolved in 30 mL methanol, was added DIEA (0.41 mL, 3 mmol) and was stirred for 25 min at about 20-35 C. under a nitrogen atmosphere. To this mixture was added (S)-(+)-2-phenyl glycinol (411 mg, 3 mmol) and stirred for 22 h. An additional DIEA (0.41 mL, 3 mmol) was added, and the mixture was stirred for about 10-19 h. The mixture after concentrating by rotary evaporation and purification (Biotage Horizon HPFC system chromatography, SiO2, 35:65 EtOAc:hexane) gave the title compound as a white solid (367 mg, 39% yield).1H NMR (300 MHz, DMSO-d6): delta 8.43 (apt d, J=7.8 Hz, 1H), 7.92 (b s, 2H), 7.50-7.22 (m, 8H), 7.08 (s, 1H), 5.18 (b s, 1H), 5.03 (b s, 1H), 3.68 (b s, 2H).LC-MSD (ES+): m/z [326 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 40

48
[ 26032-72-4 ]
[ 6291-01-6 ]
[ 1215103-71-1 ]

Yield	Reaction Conditions	Operation in experiment
30.6%		Step (i): Synthesis of intermediate (2-chloro-6-phenyl-pyrimidin-4-yl)-cyclobutyl-amine To <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (630 mg, 2.8 mmol), dissolved in 30 mL MeOH, was added DIEA (0.7 mL, 4 mmol) and was stirred for 25 min at about 20-35 C. under a nitrogen atmosphere. To this mixture was added cyclobutylamine hydrochloride (323 mg, 3 mmol) and stirred 22 h. The mixture was concentrated by rotary evaporation and purification (Biotage Horizon HPFC chromatography system, SiO2, 30:70 EtOAc: hexane) gave the title compound as a thick light yellow oil (222 mg, 30.6% yield).1H NMR (300 MHz, CDCl3, TMS): delta 7.96-7.93 (m, 2H), 7.49-7.42 (m 3H), 6.51 (s, 1H), 5.44 (br s, 1H), 2.53-2.43 (m, 2H), 2.01-1.76 (m, 5H).LC-MSD (ES+): m/z [260 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 34

49
[ 26116-12-1 ]
[ 26032-72-4 ]
[ 1215103-56-2 ]
C₁₇H₂₁ClN₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With lithium hexamethyldisilazane; In tetrahydrofuran; at -60℃; for 0.166667h;	Step (i): Synthesis of (2-chloro-6-phenyl-pyrimidin-4-yl)-(1-ethyl-pyrrolidin-2ylmethyl)-amine To <strong>[26032-72-4]2,4-dichloro-6-phenyl-pyrimidine</strong> (1.508 g, 6.6 mmol), dissolved in THF (10 mL), was added 2-(aminomethyl)-1-ethylpyrrolidine (0.96 mL, 6.6 mmol). The resulting mixture was cooled to -60 C. and then treated with lithium bis (trimethylsilyl) amide (13.2 mL, 13.2 mmol, 1M). The resulting solution was allowed to stir at -60 C. for 10 min and was quenched with water slowly. The mixture was diluted with ethylacetate, and washed two times with water and one time with brine. The organic phase was dried over sodium sulfate, filtered, and concentrated by rotary evaporation. Purification (Biotage Horizon HPFC chromatography system, SiO2, 95:5 dichloromethane: MeOH) gave the title compound as a solid (1.1 g, 52% yield) in addition to C-2 regioisomer (not fully characterized).HPLC: Betasil ODS-3V C18, [KH2PO4 (0.01M, pH 3.2): CH3CN], gradient, 264 nm, Rt 10.1 & 10.7 min, 52.8, 43.8% purity respectively.1H NMR (300 MHz, CDC13, TMS): delta 7.98-7.94 (m, 2H), 7.48-7.44 (m, 3H), 6.96 (s, 1H), 6.02-5.87 (m, 1H), 3.75 (b s, 1H), 3.39-3.19 (m, 2H), 2.91-2.65 (m, 2H), 2.29-2.12 (m, 2H), 1.97-1.60 (m, 4H), 1.12 (t, J=7.5 Hz, 3H).LC-MSD (ES+): m/z [317 (M+H)+, 100].;

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 24

50
[ 26032-72-4 ]
[ 75-64-9 ]
[ 1215103-49-3 ]

Yield	Reaction Conditions	Operation in experiment
58%	for 1.5h;Inert atmosphere; Reflux;	Step (iii): Synthesis of tert-butyl-(2-chloro-6-phenyl-pyrimidin-4-yl)-amine 2,4-Dichloro-6-phenyl-pyrimidine (10.9 g, 45 mmol) was dissolved in tert-butylamine (40 mL, 379 mmol). The resulting mixture was stirred at reflux for 1.5 h under nitrogen atmosphere. The mixture was concentrated by rotary evaporation. The solid was triturated with ether and hexanes, filter, and dried under vacuum to give title compound as white solid (6.8 g, 58% yield).HPLC: Inertsil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 14.7 min, 98.6% purity.1H NMR (300 MHz, CDCl3, TMS): delta 7.94-7.90 (m, 2H), 7.46-7.44 (m, 2H), 6.62 (s, 1H), 1.48 (s, 9H).LC-MSD (ES+): m/z [262 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 19

51
[ 26032-72-4 ]
[ 75-64-9 ]
[ 1215104-19-0 ]

Yield	Reaction Conditions	Operation in experiment
	for 1.5h;Inert atmosphere; Reflux;	Step (i): Synthesis of tert-butyl-(4-chloro-6-phenyl-pyrimidin-2yl)-amine 2,4-Dichloro-6-phenyl pyrimidine (5.03 g, 22.2 mmol) was dissolved in tert-butylamine (19.5 mL, 184.26 mmol). The resulting mixture was stirred at reflux for 1.5 h under nitrogen atmosphere. The mixture was concentrated by rotary evaporation. The resulting solid was recrystallized using ether and hexane. The mother liquor was concentrated and purified (flash chromatography system, SiO2, 80:20 hexane:ethyl acetate) to give the title compound as gummy material (2.3 g, 40% yield).HPLC: Inertsil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 26.7 min, 88.5% purity.1H NMR (300 MHz, CDCl3, TMS): delta 8.00-7.97 (m, 2H), 7.49-7.45 (m, 3H), 6.95 (s, 1H), 1.49 (s, 9H).Mass: LC-MSD (ES+): m/z 262 (M+H, 100).

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 67

52
[ 26032-72-4 ]
[ 14610-37-8 ]
[ 1215103-65-3 ]
[ 1215103-64-2 ]

Yield	Reaction Conditions	Operation in experiment
19%	In N,N-dimethyl-formamide; at 60℃;Sealed tube;	Step (i): Synthesis of tert-butyl-(2-chloro-6-phenyl-pyrimidin-4yl)-methylamine and tert-butyl-(4-chloro-6-phenyl-pyrimidin-2yl)-methylamine 2,4-Dichloro-6-phenyl-pyrimidine (2.52 g, 11.1 mmol) was dissolved in N-methyl-tert-butylamine (2.6 mL, 17.58 mmol); then DMF (7 mL) was added. The resulting mixture was stirred at 60 C. in a sealed tube for about 10-19 h. The mixture was diluted with dichloromethane, and was washed two times with water and one time with brine. The organic phase was dried over sodium sulfate and concentrated by rotary evaporation. The resulting sample was dried for about 10-19 h under vacuum. Both regioisomers were isolated. Purification (Biotage Horizon HPFC system chromatography, SiO2, 80:20 hexane: EtOAc) gave the title compounds as colorless gummy solidstert-Butyl-(2-chloro-6-phenyl-pyrimidin-4yl)-methylamine (1.7 g, 55% yield):HPLC: Betasil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 19.2 min, 93.1% purity.1H NMR (300 MHz, CDCl3, TMS): delta 7.93 to 7.90 (m, 2H), 7.44-7.42 (m, 3H), 6.74 (s, 1H), 3.09 (s, 3H), 1.57 (s, 9H).LC-MSD (ES+): m/z [276 (M+H)+, 100].tert-Butyl-(4-chloro-6-phenyl-pyrimidin-2yl)-methylamine (600 mg, 19% yield):HPLC: Betasil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 53.3 min, 97.4% purity.1H NMR (300 MHz, CDCl3, TMS): delta 8.00-7.97 (m, 2H), 7.44-7.41 (m, 3H), 6.9 (s, 1H), 3.28 (s, 3H), 1.58 (s, 9H).LC-MSD (ES+): m/z [276 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 29-30

53
[ 26032-72-4 ]
exo-2-aminonorbornane [ No CAS ]
bicyclo[2.2.1]hept-2-yl-(2-chloro-6-phenyl-pyrimidin-4-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%	With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 35℃;	Step (i): Synthesis of bicyclo[2.2.1]hept-2-yl-(2-chloro-6-phenyl-pyrimidin-4-yl)-amine To <strong>[26032-72-4]2,4-dichloro-6-phenyl-pyrimidine</strong> (2.50 g, 11.3 mmol) dissolved in DMF (15 mL) was added exo-2-aminonorbornane (1.3 mL, 11.3 mmol) followed by addition of K2CO3 (4.70 g, 33.8 mmol). After stirring at about 20-35 C. for about 10-19 h, the reaction mixture was extracted 3 times with dichloromethane. The combined organic layers were washed with water and brine, dried over sodium sulfate, filtered and then concentrated under vacuum to give product. Purification (Biotage Horizon HPFC chromatography system, SiO2, 80:20 hexane: EtOAc) gave the title compound as a white solid (1.672 mg, 49% yield).HPLC: Inertsil ODS-3V C18, 30:70 [KH2PO4 (0.01M, pH 3.2): CH3CN], 264 nm, Rt 21.3 min, 99.3% purity.1H NMR (CDCl3, 300 MHz): delta 7.98-7.94 (m, 2H), 7.56-7.44 (m, 3H), 6.55 (s, 1H), 5.23 (b s, 1H), 3.50 (b s, 1H), 1.66-1.05 (m, 10H).LC-MSD (ES+): m/z [300 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 32

54
[ 26032-72-4 ]
2-cyclopropyl-2-propylamine toluenesulfonate salt [ No CAS ]
[ 1215103-82-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 17h;Sealed tube;	Step (i): Synthesis of (2-chloro-6-phenyl-pyrimidin-4-yl)-(1-cyclopropyl-1-methyl-ethyl)-amine To <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (674 mg, 3 mmol), dissolved in 3 mL DMF, was added 2-cyclopropyl-2-propylamine-p-toluenesulfonate salt (1 g, 3.68 mmol) followed by K2CO3 (1.026 g, 7.4 mmol). The sealed tube was heated in a 60 C. oil bath for 17 h. The mixture was cooled and diluted with EtOAc and water. The organic layer was separated and the aqueous layer was back extracted with EtOAc. The combined organic layers were washed two times with water, one time with brine, dried over anhydrous K2CO3, filtered, and concentrated by rotary evaporation. Purification (Biotage Horizon HPFC system chromatography, SiO2, 1:9 EtOAc: hexanes) gave a white solid as the title compound (572 mg, 66% yield).1H NMR (300 MHz, CDCl3, TMS): delta 7.95-7.92 (m, 2H), 7.47-7.45 (m, 3H), 6.81 (s, 1H), 5.34 (b s, 1H), 1.33-1.20 (m, 7H), 0.60-0.43 (m, 4H).LC-MSD (ES+): m/z [288 (M+H)+, 100].

Reference： [1]Patent: US2010/144722,2010,A1 .Location in patent: Page/Page column 41

55
[ 26032-72-4 ]
2-(2-chloro-6-oxo-4-phenyl-6H-pyrimidin-1-ylmethyl)benzonitrile [ No CAS ]
C₁₈H₁₂ClN₃O [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 510 - 524

56
[ 26032-72-4 ]
2-chloro-4-phenyl-3H-pyrimidin-4-one [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 510 - 524

57
[ 26032-72-4 ]
[ 1356485-11-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In 1,4-dioxane; at 20℃;	General Method 3 Step 2B. To a solution of <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (224 mg, 1 mmol) in 1 mL of 1,4-dioxane was added 300 uL of hydrazine hydrate. Stirring was continued at room temperature and the reaction monitored by thin layer chromatography (30% ethyl acetate/hexanes). When the starting material was consumed, 2 mL of water was added and the resultant precipitate was collected on a filter to afford 2-chloro-4-hydrazinyl-6-phenylpyrimidine as a yellow solid. The damp solid was suspended in 2 mL of ethanol, to which was added 220 mg of 4-trifluoromethoxybenzaldehyde. Within 5 minutes the solution became clear and then reprecipitated material. The product, 2-chloro-4-phenyl-6-(2-(4-(trifluoromethoxy)benzylidene)hydrazinyl)pyrimidine (XX), was collected by filtration and dried to afford 150 mg of a solid. ESI/MS 392.973, 395.002 (M+H).

Reference： [1]Patent: US2012/22066,2012,A1 .Location in patent: Page/Page column 13

58
[ 26032-72-4 ]
[ 106-47-8 ]
[ 1111126-48-7 ]

Yield	Reaction Conditions	Operation in experiment
	With lithium diisopropyl amide; In tetrahydrofuran;	General Method 2 Step 2A.2. To 1 mmol of <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (X) and 4-chloroaniline in 4 mL of dry THF was added 1 mmol (0.5 mL, 2M in THF/heptane/ethylbenzene) of lithium diisopropylamide. The reaction was followed by TLC (30% ethyl acetate/hexane). The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate and the organic layers were dried over magnesium sulfate and concentrated under reduced pressure. The mixture was purified by chromatography on silica gel with elution by 30% ethyl acetate/hexanes to afford 70 mg of 2-chloro-N-(4-chlorophenyl)-6-phenylpyrimidin-4-amine (XII) as an amorphous solid. ESI/MS 315.883, 317.915 (M+H).

Reference： [1]Patent: US2012/22066,2012,A1 .Location in patent: Page/Page column 12

59
[ 3764-01-0 ]
[ 100-58-3 ]
[ 26032-72-4 ]

Yield	Reaction Conditions	Operation in experiment
	bis-triphenylphosphine-palladium(II) chloride; In tetrahydrofuran; for 1h;Inert atmosphere;	General Method 2 Step 1A.3 A mixture of 2,4,6-trichloropyrimidine (1.834 g, 10 mmol) and bis(triphenylphosphine)palladium(II) dichloride (60 mg, 0.085 mmol) in dry THF (20 mL) under nitrogen was treated dropwise with a solution of PhMgBr in THF (11 mL, 1M, 11 mmol) which generated some heat. The mixture was stirred for 1 hour and then partitioned between saturated sodium bicarbonate and ethyl acetate. Separated layers and the aqueous layer was extracted twice with ethyl acetate. The combined organics was dried over magnesium sulfate, filtered and concentrated on a rotary evaporator to yield a film (2.32 g). The film was taken up in chloroform and loaded onto 100 g of silica gel. The silica gel was eluted with ethyl acetate/hexanes (2%, 2.5%, 3%, 5%). The appropriate fractions were concentrated on a rotary evaporator to yield a white solid. The solid was triturated with hexanes, filtered and washed with more hexanes to yield 2,4-dichloro-6-phenylpyrimidine (X) as a white solid (382.97 mg). ESI/MS 225.0, 227.0, 229.0 (M+H).

Reference： [1]Patent: US2012/22066,2012,A1 .Location in patent: Page/Page column 12

60
[ 5350-93-6 ]
[ 26032-72-4 ]
[ 1356485-08-9 ]

Yield	Reaction Conditions	Operation in experiment
		General Method 2 Step 2A.1. Cooled a solution of 5-amino-2-chloropyridine (218.55 mg, 1.7 mmol) in dry THF (4.3 mL) in a dry-ice/acetone bath under nitrogen. The mixture was treated with a solution of nBuLi in hexanes (0.68 mL, 2.5M, 1.7 mmol) dropwise and stirred cold for 10 minutes. Allowed to warm to room temperature and 1.7 mL of the mixture was added dropwise to a solution of <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (X) (190 mg, 0.844 mmol) in dry THF (2 mL). The mixture was stirred for 15 minutes and treated with an additional 0.3 mL of the lithium anilide solution and stirred for another 15 minutes. The reaction was poured into a mixture of saturated sodium bicarbonate and ethyl acetate. The layers were separated and the aqueous layer was extracted twice with ethyl acetate. The combined organics was dried over magnesium sulfate, filtered and concentrated to yield a film. The film was taken up in chloroform and loaded onto 100 g of silica gel. The silica gel was eluted with ethyl acetate/hexanes (10%, 20%, 30%, 40%). The appropriate fractions were concentrated on a rotary evaporator to yield 2-chloro-N-(6-chloropyridin-3-yl)-6-phenylpyrimidin-4-amine (XII) as a film (41.15 mg). ESI/MS 317.0756, 319.0810 (M+H).

Reference： [1]Patent: US2012/22066,2012,A1 .Location in patent: Page/Page column 12

61
[ 26032-72-4 ]
[ 1356484-85-9 ]

Reference： [1]Patent: US2012/22066,2012,A1

62
[ 26032-72-4 ]
[ 1356484-97-3 ]

Reference： [1]Patent: US2012/22066,2012,A1

63
[ 26032-72-4 ]
[ 1356485-09-0 ]

Reference： [1]Patent: US2012/22066,2012,A1

64
[ 26032-72-4 ]
[ 333432-28-3 ]
[ 1292291-85-0 ]

Yield	Reaction Conditions	Operation in experiment
70%	With sodium carbonate;palladium diacetate; triphenylphosphine; In 1,2-dimethoxyethane; water; for 8h;Inert atmosphere; Reflux;	Under an Ar gas atmosphere, <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (the intermediate body X₄) (6.0 g, 26.6 mmol), 9,9-dimethylfluorene-2-boronic acid (6.34 g, 26.6 mmol), palladium acetate (0.30 g, 1.33 mmol), triphenylphosphine (0.70 g, 2.66 mmol), DME (250 ml) and an aqueous solution of 2M sodium carbonate (42 ml) were stirred for 8 hours at a reflux temperature. The solvent was distilled away under reduced pressure. The obtained residue was extracted by toluene. The residue obtained by concentrating the organic phase was refined by silica-gel column chromatography (a developing solvent: hexane-toluene) to provide an intermediate body X₅ as a white solid. A yield of the was 7.2 g and a yield rate thereof was 70%

Reference： [1]Patent: EP2489664,2012,A1 .Location in patent: Page/Page column 46

65
[ 26032-72-4 ]
[ 1292291-86-1 ]

Reference： [1]Patent: EP2489664,2012,A1

66
[ 26032-72-4 ]
[ 1292291-89-4 ]

Reference： [1]Patent: EP2489664,2012,A1

67
[ 26032-72-4 ]
[ 1312206-15-7 ]
[ 1312205-88-1 ]

Reference： [1]Patent: US2012/256174,2012,A1

68
[ 26032-72-4 ]
[ 1312206-15-7 ]
[ 1312206-16-8 ]

Yield	Reaction Conditions	Operation in experiment
62.3%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃; for 12h;Inert atmosphere;	First Step: Synthesis of Intermediate Product (1)In a 500 mL round-bottomed flask having a thermometer, a reflux condenser, and an agitator, 8.0 g (14.3 mmol) of compound (H), 8.04 g (35.7 mmol) of compound (C), and 0.8 g (0.69 mmol) of tetrakis(triphenylphosphine)palladium were mixed with 300 mL tetrahydrofuran under a nitrogen atmosphere, and then the mixed solution was mixed with 100 mL of 2 M potassium carbonate (K2CO3) and agitated at 70 C. for 12 hours.By cooling to room temperature, the reaction was completed, and then the produced solid was filtered and washed with methanol several times. The final residue was purified by silica gel chromatography using a chloroform solvent to provide 6.1 g (yield: 62.3%) of an intermediate product (I).

Reference： [1]Patent: US2012/256174,2012,A1 .Location in patent: Page/Page column 19-20

69
[ 26032-72-4 ]
[ 1312206-17-9 ]
[ 1312206-18-0 ]

Yield	Reaction Conditions	Operation in experiment
69.8%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃; for 12h;Inert atmosphere;	First Step: Synthesis of Intermediate Product (F)In a 500 mL round-bottomed flask having a thermometer, a reflux condenser, and an agitator, 8.0 g (14.2 mmol) of compound (E), 8.03 g (35.6 mmol) of compound (C), and 0.8 g (0.69 mmol) of tetrakis(triphenylphosphine)palladium were mixed with 300 mL of tetrahydrofuran under the nitrogen atmosphere, and then the mixed solution was mixed with 100 mL of 2 M potassium carbonate (K2CO3) and agitated at 70 C. for 12 hours.By cooling to room temperature, the reaction was completed, and then the produced solid was filtered and washed with methanol several times. The final residue was purified by silica-gel chromatography using a chloroform solvent to provide an intermediate product (F) in 6.8 g (yield: 69.8%).

Reference： [1]Patent: US2012/256174,2012,A1 .Location in patent: Page/Page column 22-23

70
[ 26032-72-4 ]
[ 1312206-13-5 ]
[ 1312205-84-7 ]

Reference： [1]Patent: US2012/256174,2012,A1

71
[ 26032-72-4 ]
[ 1312206-13-5 ]
[ 1312206-14-6 ]

Yield	Reaction Conditions	Operation in experiment
67.4%	With potassium carbonate;tetrakis(triphenylphosphine) palladium(0); In tetrahydrofuran; water; at 70℃; for 12h;Inert atmosphere;	First Step: Synthesis of Intermediate Product (D)In a 500 mL round-bottomed flask having a thermometer, a reflux condenser, and an agitator, 8.0 g (14.3 mmol) of compound (A), 8.04 g (35.7 mmol) of compound (C), and 0.8 g (0.69 mmol) of tetrakis(triphenylphosphine)palladium were mixed with 300 mL of tetrahydrofuran under a nitrogen atmosphere, and then the mixed solution was mixed with 100 mL of 2 M potassium carbonate (K2CO3) and agitated at 70 C. for 12 hours.By cooling to room temperature, the reaction was completed, and then the produced solid was filtered and washed with methanol several times. The final residue was purified by silica-gel chromatography using a chloroform solvent to provide an intermediate product (D) in 6.6 g (yield: 67.4%).

Reference： [1]Patent: US2012/256174,2012,A1 .Location in patent: Page/Page column 17-18

72
[ 26032-72-4 ]
[ 86-74-8 ]
[ 1426818-83-8 ]

Yield	Reaction Conditions	Operation in experiment
35%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 12h;Inert atmosphere; Reflux;	9.0 g (40 mmol) of <strong>[26032-72-4]2,4-dichloro-6-phenylpyrimidine</strong> (synthesized in accordance with the method described in J. Org. Chem., p. 7125, 2001), 6.7 g (40 mmol) of carbazole, 0.37 g (0.4 mmol) of tris(dibenzylideneacetone)dipalladium, 0.46 g (1.6 mmol) of tri-t-butylphosphonium tetrafluoroborate, 5.4 g (56 mmol) of sodium t-butoxide, and 100 ml of anhydrous toluene were sequentially mixed in an argon atmosphere, and the mixture was refluxed for 12 hours with heating and stirring. The reaction solution was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (hexane/dichloromethane=3/2) to obtain 5.0 g (yield: 35%) of an intermediate G as a white solid.

Reference： [1]Patent: US2013/62597,2013,A1 .Location in patent: Paragraph 0149; 0150

73
[ 26032-72-4 ]
[ 86-74-8 ]
[ 1426818-84-9 ]

Reference： [1]Patent: US2013/62597,2013,A1

74
[ 26032-72-4 ]
[ 1345202-03-0 ]
C₇₀H₄₄N₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Reflux;	In argon atmosphere, intermediate D (2.04g, 5.0 mmol), intermediate E (0.56g, 2.5 mmol), tris(dibenzilideneacetone)dipalladium (0.092g, 0.10 mmol), tri-t-butylphosphonium tetrafluoro borate (0.116g, 0.40 mmol), t-butoxy sodium (0.67g, 7.0 mmol) and dehydrated toluene (25 mL) were sequentially added. The resulting mixture was heated under reflux for 8 hours. After the reaction mixture was cooled to room temperature, the organic phase was separated, and the organic solvent was distilled off under reduced pressure. The residue obtained was purified by means of silica-gel chromatography to obtain H-2 (2.18g, yield: 88%). HPLC: Purity 99.9% FD-MS: calcd for C70H44N6=969, found m/z=969 (M+, 100)

Reference： [1]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0152; 0153; 0154

75
[ 26032-72-4 ]
[ 1060735-14-9 ]
C₇₀H₄₄N₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Inert atmosphere; Reflux;	In argon atmosphere, intermediate G (2.04g, 5.0 mmol), intermediate E (0.56g, 2.5 mmol), tris(dibenzilideneacetone)dipalladium (0.092g, 0.10 mmol), tri-t-butylphosphonium tetrafluoro borate (0.116g, 0.40 mmol), t-butoxy sodium (0.67g, 7.0 mmol) and dehydrated toluene (25 mL) were sequentially added. The resulting mixture was heated under reflux for 8 hours. After the reaction mixture was cooled to room temperature, the organic phase was separated, and the organic solvent was distilled off under reduced pressure. The residue obtained was purified by means of silica-gel chromatography to obtain H-3 (1.95g, yield: 81%). HPLC: Purity 99.9% FD-MS: calcd for C70H44N6=969, found m/z=969 (M+, 100)

Reference： [1]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0155; 0156; 0157

76
[ 26032-72-4 ]
[ 1060735-14-9 ]
C₄₀H₂₅ClN₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Inert atmosphere; Reflux;	In argon atmosphere, intermediate G (12.25g, 30 mmol), intermediate E (6.75g, 30 mmol), tris(dibenzilideneacetone)dipalladium (0.275g, 0.30 mmol), tri-t-butylphosphonium tetrafluoro borate (0.348g, 1.20 mmol), t-butoxy sodium (4.04g, 42 mmol) and dehydrated toluene (150 mL) were sequentially added. The resulting mixture was heated under reflux for 8 hours. The reaction mixture was cooled to room temperature, the organic phase was separated, and the organic solvent was distilled off under reduced pressure. The residue obtained was purified by means of silica-gel chromatography, washed with methylene chloride and then dried under reduced pressure, thereby to obtain J (8.46g, yield: 47%).

Reference： [1]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0164; 0165

77
[ 26032-72-4 ]
C₃₀H₂₀N₂ [ No CAS ]
C₇₀H₄₄N₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 16h;Inert atmosphere;	In argon atmosphere, intermediate I (3.27g, 8.2 mmol), intermediate E (0.90g, 4.0 mmol) and potassium carbonate (1.16g, 8.4 mmol) were added to dehydrated dimethylformamide (60 mL). The resulting mixture was heated to 120C and stirred for 16 hours. After the reaction mixture was cooled to room temperature, the mixture was diluted by adding toluene, and washed with a saturated solution of ammonium chloride. Then, the organic phase was separated, and the organic solvent was distilled off under reduced pressure. The residue obtained was purified by means of silica-gel chromatography to obtain H-5 (2.10g, yield: 54%). HPLC: Purity 99.7% FD-MS: calcd for C70H44N6=969, found m/z=969 (M+, 100)

Reference： [1]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0161; 0162; 0163

78
[ 26032-72-4 ]
[ 1346669-46-2 ]
C₅₈H₃₄N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
84%	With tris-(dibenzylideneacetone)dipalladium(0); sodium t-butanolate; tri tert-butylphosphoniumtetrafluoroborate; In toluene; for 8h;Inert atmosphere; Reflux;	In argon atmosphere, intermediate A (1.67g, 5.0 mmol), intermediate E (0.56g, 2.5 mmol), tris(dibenzilideneacetone)dipalladium (0.092g, 0.10 mmol), tri-t-butylphosphonium tetrafluoro borate (0.116g, 0.40 mmol), t-butoxy sodium (0.67g, 7.0 mmol) and dehydrated toluene (25 mL) were sequentially added. The resulting mixture was heated under reflux for 8 hours. After the reaction mixture was cooled to room temperature, the organic phase was separated, and the organic solvent was distilled away under reduced pressure. The residue obtained was purified by means of silica-gel chromatography to obtain H-4 (1.72g, yield: 84%). HPLC: Purity 99.9% FD-MS: calcd for C70H44N6=819, found m/z=819 (M+, 100)

Reference： [1]Patent: EP2662368,2013,A1 .Location in patent: Paragraph 0158 - 0160

79
[ 26032-72-4 ]
[ 100-46-9 ]
[ 881194-67-8 ]

Yield	Reaction Conditions	Operation in experiment
39%	In N,N-dimethyl-formamide; at 40℃; for 18h;	General procedure: The respective dichloropyrimidine derivative 9 (between 60 mg and 120 mg) and 1.5 equivalents of the respective amine are dissolved in DMF (2.00 mL). The reaction mixture is heated to 40 C and stirred for 18 hours. Subsequently, the solvent is removed under reduced pressure and the crude product is purified via column chromatography (SiO2, dichloromethane / ethyl acetate = 20:1).