[ CAS No. 22536-62-5 ] {[proInfo.proName]}

Name: 22536-62-5|2-Chloro-5-phenylpyrimidine|97%
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Quality Control of [ 22536-62-5 ]

COA NMR CNMR HPLC LC-MS

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Product Details of [ 22536-62-5 ]

CAS No. :	22536-62-5	MDL No. :	MFCD04035567
Formula :	C₁₀H₇ClN₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JJNIWMPNOFGQEA-UHFFFAOYSA-N
M.W :	190.63	Pubchem ID :	605320
Synonyms :

Safety of [ 22536-62-5 ]

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 [ 22536-62-5 ]

* 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 [ 22536-62-5 ]
Downstream synthetic route of [ 22536-62-5 ]

[ 22536-62-5 ] Synthesis Path-Upstream 1~9

1
[ 32779-36-5 ]
[ 98-80-6 ]
[ 22536-62-5 ]

Yield	Reaction Conditions	Operation in experiment
86%	Stage #1: With dichloro bis(acetonitrile) palladium(II); sodium carbonate In ethanol; water at 45℃; for 0.5 h;	General procedure: Catalyst (2 molpercent), aryl halide (1 equiv.) and Na₂CO₃ (1.1 equiv.) were stirred in H₂O (5 mL) taken in the round bottom flask. The aryl boronic acid (1.1 equiv.) was added to the stirring solution. Stirring was continued for required time at 45 °C. After the requisite time, the reaction mixture was diluted with water and the product was extracted with ethyl acetate. The ethyl acetate extract was passed through celite bed and then analyzed by GC. Authentic samples of both reactant and product were used to verify the retention time and to confirm the product formation. The ethyl acetate extract was concentrated and chromatographed on a silica gel column using hexane and ethylacetate as eluent to afford coupled product. The products are characterized by NMR, GC MS and UPLC analyses.

Reference： [1] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 4, p. 1077 - 1081
[2] Journal of Molecular Catalysis A: Chemical, 2013, vol. 371, p. 118 - 124
[3] European Journal of Medicinal Chemistry, 2018, vol. 150, p. 30 - 38
[4] Patent: WO2004/22556, 2004, A1, . Location in patent: Page 16-17

2
[ 3958-47-2 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1] Organic Letters, 2008, vol. 10, # 17, p. 3745 - 3748

3
[ 32779-36-5 ]
[ 71-43-2 ]
[ 22536-62-5 ]

Reference： [1] Chemical Communications, 2016, vol. 52, # 11, p. 2326 - 2329

4
[ 960-16-7 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1] Acta Chemica Scandinavica, 1989, vol. 43, # 1, p. 62 - 68

5
[ 100-59-4 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1] Angewandte Chemie - International Edition, 2017, vol. 56, # 6, p. 1581 - 1585[2] Angew. Chem., 2017, vol. 129, # 6, p. 1603 - 1607,5

6
[ 27956-19-0 ]
[ 22536-62-5 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1479 - 1482

7
[ 33266-26-1 ]
[ 22536-62-5 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1479 - 1482

8
[ 56863-46-8 ]
[ 22536-62-5 ]

Reference： [1] Journal of Medicinal Chemistry, 1999, vol. 42, # 4, p. 730 - 741

9
[ 33266-29-4 ]
[ 22536-62-5 ]

Reference： [1] Journal of Heterocyclic Chemistry, 1980, vol. 17, p. 1479 - 1482

[ 22536-62-5 ] Synthesis Path-Downstream 1~77

1
[ 110-89-4 ]
[ 22536-62-5 ]
[ 22539-51-1 ]

Reference： [1]Zeitschrift fur Naturforschung, Teil B: Anorganische Chemie, Organische Chemie,1980,vol. 35,p. 463 - 467
[2]Zeitschrift fur Naturforschung, Teil B: Anorganische Chemie, Organische Chemie,1980,vol. 35,p. 463 - 467

2
[ 110-85-0 ]
[ 22536-62-5 ]
[ 76972-11-7 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

3
[ 27956-19-0 ]
[ 22536-62-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

4
[ 960-16-7 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1]Acta Chemica Scandinavica,1989,vol. 43,p. 62 - 68

5
[ 124-40-3 ]
[ 22536-62-5 ]
N,N-dimethyl-5-phenyl-2-pyrimidinamine [ No CAS ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1983,vol. 32,p. 265 - 270
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1983,p. 299 - 304

6
[ 108-00-9 ]
[ 22536-62-5 ]
N-(2'-dimethylaminoethyl)-5-phenylpyrimidin-2-amine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1985,vol. 38,p. 825 - 833

7
[ 623-51-8 ]
[ 22536-62-5 ]
[ 58668-15-8 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

8
sodium salt of ethyl cyanoacetate [ No CAS ]
[ 22536-62-5 ]
[ 104355-17-1 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1984,vol. 20,p. 676 - 680
Khimiya Geterotsiklicheskikh Soedinenii,1984,vol. 20,p. 827 - 831

9
[ 609-08-5 ]
[ 22536-62-5 ]
[ 76972-24-2 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

10
[ 64-17-5 ]
[ 22536-62-5 ]
2-ethoxy-5-phenylpyrimidine [ No CAS ]

Reference： [1]Australian Journal of Chemistry,1985,vol. 38,p. 825 - 833

11
[ 623-50-7 ]
[ 22536-62-5 ]
[ 58668-16-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

12
[ 22536-62-5 ]
[ 109-77-3 ]
[ 151673-95-9 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1993,vol. 29,p. 427 - 431
Khimiya Geterotsiklicheskikh Soedinenii,1993,p. 503 - 508

13
[ 22536-62-5 ]
[ 75-50-3 ]
5-phenylpyrimidinium-2-trimethylammonium chloride [ No CAS ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1983,vol. 32,p. 265 - 270
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1983,p. 299 - 304

14
[ 22536-62-5 ]
[ 126382-47-6 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1989,vol. 25,p. 805 - 811
Khimiya Geterotsiklicheskikh Soedinenii,1989,vol. 25,p. 962 - 968

15
[ 33266-26-1 ]
[ 22536-62-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

16
[ 33266-29-4 ]
[ 22536-62-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

17
[ 27578-60-5 ]
[ 22536-62-5 ]
(5-phenyl-pyrimidin-2-yl)-(2-piperidin-1-yl-ethyl)-amine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 730 - 741

18
[ 56863-46-8 ]
[ 22536-62-5 ]

Reference： [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 730 - 741

Yield	Reaction Conditions	Operation in experiment
70%	With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In 1,4-dioxane; water; at 90℃; for 18h;Inert atmosphere;	General procedure: To an Argon-flushed mixture of 5-bromo-2-chloropyrimidine (600 mg, 3.10 mmol), (2-chlorophenyl)- boronic acid (485 mg, 3.10 mmol) and Na2CO3 (493 mg, 4.65 mmol) in 1,4-dioxane (4 mL)IWater(1.5 mL) was added Pd(PPh3)4 (90 mg, 0.078 mmol) and the mixture was stirred at 90C for 18 h. A white precipitate was formed. Water was added, an off-white precipitate remained. The solid was filtered off, washed with water and air-dried. Purification by column chromatography (silica, 5% -> 25% EtOAc inheptane) gave pyrimidine INT-7 (2) (504 mg, 2.24 mmol, 72%) as an off-white solid.

21
[ 87120-72-7 ]
[ 22536-62-5 ]
[ 951004-32-3 ]

Yield	Reaction Conditions	Operation in experiment
48%	With triethylamine; In acetonitrile; at 150℃; for 0.5h;microwave irradiation;	A mixture of <strong>[22536-62-5]2-chloro-5-phenyl-pyrimidine</strong> (1.2 g, 6.29 mmol, 1.0 equiv; commercially available from Acme Bioscience Inc., USA), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.52 g, 12.59 mmol, 2.0 equiv; commercially available) and triethylamine (1.75 mL, 1.27 g, 12.59 mmol, 2.0 equiv) in anhydrous acetonitrile (5 mL) was heated by microwave irradiation to 150 C. for 30 min. The organic phase was concentrated under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluding with a gradient of heptane/ethyl acetate providing 1.06 g (48%) of the title compound. MS (ISP): 355.5 [M+H]+.

Reference： [1]Patent: US2007/225271,2007,A1 .Location in patent: Page/Page column 35-36

22
[ 1001398-03-3 ]
[ 22536-62-5 ]
[ 1001398-09-9 ]

Yield	Reaction Conditions	Operation in experiment
45%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 50℃; for 48h;	Compound 97 (50 mg, 0.12 mmol) was dissolved in 2 ml. methylene chloride and treated with 2 ml. of DIPEA followed by <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> (100 mg, 0.53 mmol). The reaction was then heated at 50 0C for 48 h while stirring. The reaction was cooled to room temperature and all the solvents were removed under reduced pressure. The crude reaction was then purified via column chromatography (5 ? 50% ethyl acetate/hexane) to give 30 mg (45%) of the title product 102 as a white solid. 1H NMR (400 MHz, DMSOd6): delta 1.79 - 1.92 (m, 2 H), 1.92 - 2.03 (m, 2 H), 3.05 (s, 3 H), 3.18 (t, J = 8.0 Hz, 2 H), 3.72 - 3.87 (m, 2 H), 3.96 - 4.10 (m, 4 H), 4.50 - 4.69 (m, 1 H), 6.51 (d, J = 8.0 Hz, 1 H), 6.91 (d, J = 8.0 Hz, 1 H), 7.06 - 7.35 (m, 8 H), 7.83 (d, J = 9.0 Hz, 2 H), 8.19 (s, 2 H); LCMS (ESI): m/z 527 (M + H)+.

Reference： [1]Patent: WO2008/8895,2008,A1 .Location in patent: Page/Page column 112; 113

23
[ 22536-62-5 ]
[ 85386-18-1 ]

Reference： [1]Bulletin of the Academy of Sciences of the USSR Division of Chemical Science,1983,vol. 32,p. 265 - 270
Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya,1983,p. 299 - 304

24
[ 22536-62-5 ]
[ 76972-13-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

25
[ 22536-62-5 ]
[ 58668-18-1 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

26
[ 22536-62-5 ]
[ 58668-17-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1479 - 1482

27
[ 22536-62-5 ]
[ 126382-60-3 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1989,vol. 25,p. 805 - 811
Khimiya Geterotsiklicheskikh Soedinenii,1989,vol. 25,p. 962 - 968

28
[ 22536-62-5 ]
[ 126382-53-4 ]

Reference： [1]Chemistry of Heterocyclic Compounds,1989,vol. 25,p. 805 - 811
Khimiya Geterotsiklicheskikh Soedinenii,1989,vol. 25,p. 962 - 968

29
[ 32779-36-5 ]
[ 98-80-6 ]
[ 22536-62-5 ]

Yield	Reaction Conditions	Operation in experiment
86%		General procedure: Catalyst (2 mol%), aryl halide (1 equiv.) and Na2CO3 (1.1 equiv.) were stirred in H2O (5 mL) taken in the round bottom flask. The aryl boronic acid (1.1 equiv.) was added to the stirring solution. Stirring was continued for required time at 45 C. After the requisite time, the reaction mixture was diluted with water and the product was extracted with ethyl acetate. The ethyl acetate extract was passed through celite bed and then analyzed by GC. Authentic samples of both reactant and product were used to verify the retention time and to confirm the product formation. The ethyl acetate extract was concentrated and chromatographed on a silica gel column using hexane and ethylacetate as eluent to afford coupled product. The products are characterized by NMR, GC MS and UPLC analyses.
80%	With palladium diacetate; sodium carbonate; In ethanol; water; at 45℃; for 0.5h;	Based on a literature method [31] 76 5-bromo-2-chloropyrimidine (1.00mg, 5.17mmol), 68 phenylboronic acid (1.26g, 10.34mmol), 69 Pd(OAc)2 (58mg, 0.26mmol) and 77 Na2CO3 (1.10g, 10.34mmol) in 78 H2O/34 EtOH (4:1, 50mL) were heated at 45C for 30min. The reaction was then allowed to cool at rt, and it was added to brine, extracted with CH2Cl2 (3×50mL), dried over Na2SO4 and concentrated in vacuo. Purification via flash column chromatography (eluent CH2Cl2) gave 8 as a white solid (1.57g, 80%). mp 132C (lit. 132C [32]; 131-133C [33]), 1H NMR (400MHz, CDCl3) delta 8.82 (s, 2H), 7.62-7.44 (m, 5H).
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In methanol; toluene; for 0.5h;Microwave irradiation; Sealed tube; Inert atmosphere;	General procedure: 5-bromo-2-chloropyrimidine (400 mg, 2.06 mmol, 1 eq), (2-fluoropyridin-3-yl) boronic acid (319 mg, 2.26 mmol, 1.1 eq), Pd(PPh3)4 (120 mg, 0.1 mmol, 0.05 eq) and K2CO3(855 mg, 6 mmol, 3 eq) were dissolved in a 4:1 mixture of toluene (12 mL)/ MeOH (3 mL) in a microwave vial. The sealed vial was heated at 110 C for 30 min in a microwave reactor. Then the mixture was diluted with dichloromethane and washed with water. The organic phase was evaporated in vacuo and the residue was purified by flash chromatography to yield compound S19a as white solid (256 mg, 54%).

With tetrakis(triphenylphosphine) palladium(0); sodium carbonate; In ethanol; water; toluene; at 90℃; for 19h;

[5-BROMO-2-CHLORO-PYRIMIDINE] (400 mg, 2.03 [MMOL),] phenylboronic acid (253 mg, 2.07 [MMOL)] and tetrakis (triphenylphosphine) palladium (118 mg, 0.102 [MMOL)] are dissolved in toluene/EtOH 9: 1 (50 [ML).] Na2CO3 (861 mg, 8.12 [MMOL)] is dissolved in water (4 [ML)] and added to the reaction mixture. The mixture is stirred at [90C] for 19h, cooled to rt and filtered over celite. The toluene layer is separated and washed with brine. The aq. layers are re- extracted with AcOEt; the combined organic extracts are dried over [MGS04] and filtered. The filtrate is evaporated to give a yellow solid (503 mg), which is purified by FC (silica gel, eluents cyclohexane and [ACOET/CYCLOHEXANE] 1: 9) to give 2-chloro-5-phenyl-pyrimidine. [()-3-QUINUCLIDINOL] (478 mg, 3.76 [MMOL)] is added to a suspension of NaH (164 mg of a 60% dispersion in mineral oil, 4.09 [MMOL)] in DMF (10 [ML).] The mixture is stirred for [1H] at rt. 2- Chloro-5-phenyl-pyrimidine (177 mg, 0.93 [MMOL)] is added and the mixture is heated for 3.5 h at [90C.] The reaction mixture is diluted with toluene and washed with 1 M aq. [NAOH] solution and brine. The aq. layers are re-extracted with toluene (3x). The combined organic extracts are dried over [MGS04] and filtered. The filtrate is evaporated to give a yellow solid (310 mg), which is purified by FC (silica gel, eluents : AcOEt, then [ACOET/MEOH/NET3] 80: 18: 2). A second purification is done by RP-HPLC (Phenomenex RP18 column, gradient 0.08% aq. [HCOOH I 0.] 08% aq. HCOOH/CH3CN 80: 20 in [10', O CH3CN] in 15') to give [(R)-3- (5-] [PHENYL-PYRIMIDIN-2-YLOXY)-1-AZA-BICYCLO] [2.2. 2] -octane as its formate salt, HPLC rt (min): 5.4 ; [MP C] : 108-110; [a] [DRT +8.] 6 (1.03, MeOH), M+H+ 282.2.

Reference： [1]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 1077 - 1081
[2]Journal of Molecular Catalysis A: Chemical,2013,vol. 371,p. 118 - 124
[3]Tetrahedron,2018,vol. 74,p. 5280 - 5288
[4]European Journal of Medicinal Chemistry,2018,vol. 150,p. 30 - 38
[5]Patent: WO2004/22556,2004,A1 .Location in patent: Page 16-17

30
[ 328083-82-5 ]
[ 22536-62-5 ]
[ 328083-59-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In toluene; for 8h;Heating / reflux;	The title compound (20 mg) was prepared by heating at reflux N1-[1-(3,4-dichlorobenzyl)-4-piperidinyl]-1,2-ethanediamine (100 mg) and <strong>[22536-62-5]2-chloro-5-phenypyrimidine</strong> (100 mg) and Hunigs' base (100 mg) in toluene for 8 hours. The mixture was purified by chromatography on silica, with ethyl acetate methanol (9:1) as eluant to give the title compound as a yellow oil. MS [M+h]+ (ES+) 456/8 1H NMR: (CDCl3) delta 1.51 (2H, m), 1.75 (2H, m), 2.15 (2H, td), 2.9 (2H, m), 3.05 (1H, m), 3.15 (2H, m), 3.44 (2H, m), 3.8 (2H, m), 6.65 (1H, m), 7.0-7.4 (8H, m), 8.5 (2H, m).

Reference： [1]Patent: US6903085,2005,B1 .Location in patent: Page/Page column 88

31
5-phenyl-2-pyrimidinol [ No CAS ]
[ 22536-62-5 ]

Yield	Reaction Conditions	Operation in experiment
	With trichlorophosphate; In dichloromethane; water;	EXAMPLE 12 2-Chloro-5-phenylpyrimidine A mixture of 8.7 g. of 5-phenyl-2-pyrimidinol and 90 ml. of phosphorus oxychloride is heated under reflux for 5 hours. The residue obtained by evaporation of solvent is dissolved in water and to this solution is added an excess of aqueous sodium bicarbonate. The product is extracted in methylene chloride and the dried extract is evaporated. A solution of the residue in methylene chloride is passed through a short column of alumina (Woelm, Activity II) and the residue obtained by evaporation of the elude is collected with the aid of hexane to give 6.0 g. of 2-chloro-5-phenylpyrimidine, m.p. 130-132 C. The procedure described above is used to prepare the 2-chloro-5-(substituted phenyl)pyrimidines listed in Table III.

Reference： [1]Patent: US4209621,1980,A

32
[ 22536-62-5 ]
[ 75175-43-8 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydrate; In pyridine; water;	EXAMPLE 13 2-Hydrazino-5-phenylpyrimidine To a solution of 5.4 g. of <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> in 25 ml. of pyridine is added 25 ml. of hydrazine hydrate. The mixture is heated on a steam bath for one hour with occasional swirling. Water is added and the material that is separated is collected and crystallized from methanol to give 4.5 g. of the product of the Example, m.p. 155 C. The procedure described above is used to prepare the 2-hydrazino-5-(substituted phenyl)pyrimidines of Table IV.

Reference： [1]Patent: US4209621,1980,A

33
[ 110-91-8 ]
[ 22536-62-5 ]
[ 350581-71-4 ]

Reference： [1]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 1077 - 1081

34
[ 75-31-0 ]
[ 22536-62-5 ]
[ 1048338-59-5 ]

Reference： [1]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 1077 - 1081

35
[ 62-53-3 ]
[ 22536-62-5 ]
[ 101987-05-7 ]

Reference： [1]Journal of Heterocyclic Chemistry,2008,vol. 45,p. 1077 - 1081
[2]Chemical Communications,2014,vol. 50,p. 1465 - 1468

36
[ 22536-62-5 ]
[ 25333-42-0 ]
(R)-3-(5-phenyl-pyrimidin-2-yloxy)-1-aza-bicyclo[2.2.2]-octane formate salt [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		[5-BROMO-2-CHLORO-PYRIMIDINE] (400 mg, 2.03 [MMOL),] phenylboronic acid (253 mg, 2.07 [MMOL)] and tetrakis (triphenylphosphine) palladium (118 mg, 0.102 [MMOL)] are dissolved in toluene/EtOH 9: 1 (50 [ML).] Na2CO3 (861 mg, 8.12 [MMOL)] is dissolved in water (4 [ML)] and added to the reaction mixture. The mixture is stirred at [90C] for 19h, cooled to rt and filtered over celite. The toluene layer is separated and washed with brine. The aq. layers are re- extracted with AcOEt; the combined organic extracts are dried over [MGS04] and filtered. The filtrate is evaporated to give a yellow solid (503 mg), which is purified by FC (silica gel, eluents cyclohexane and [ACOET/CYCLOHEXANE] 1: 9) to give <strong>[22536-62-5]2-chloro-5-phenyl-pyrimidine</strong>. [()-3-QUINUCLIDINOL] (478 mg, 3.76 [MMOL)] is added to a suspension of NaH (164 mg of a 60% dispersion in mineral oil, 4.09 [MMOL)] in DMF (10 [ML).] The mixture is stirred for [1H] at rt. 2- Chloro-5-phenyl-pyrimidine (177 mg, 0.93 [MMOL)] is added and the mixture is heated for 3.5 h at [90C.] The reaction mixture is diluted with toluene and washed with 1 M aq. [NAOH] solution and brine. The aq. layers are re-extracted with toluene (3x). The combined organic extracts are dried over [MGS04] and filtered. The filtrate is evaporated to give a yellow solid (310 mg), which is purified by FC (silica gel, eluents : AcOEt, then [ACOET/MEOH/NET3] 80: 18: 2). A second purification is done by RP-HPLC (Phenomenex RP18 column, gradient 0.08% aq. [HCOOH I 0.] 08% aq. HCOOH/CH3CN 80: 20 in [10', O CH3CN] in 15') to give [(R)-3- (5-] [PHENYL-PYRIMIDIN-2-YLOXY)-1-AZA-BICYCLO] [2.2. 2] -octane as its formate salt, HPLC rt (min): 5.4 ; [MP C] : 108-110; [a] [DRT +8.] 6 (1.03, MeOH), M+H+ 282.2.

Reference： [1]Patent: WO2004/22556,2004,A1 .Location in patent: Page 16-17

37
[ 3958-47-2 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1]Organic Letters,2008,vol. 10,p. 3745 - 3748

38
[ 120-72-9 ]
[ 22536-62-5 ]
[ 1394402-28-8 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 4614 - 4617

39
[ 120-72-9 ]
[ 22536-62-5 ]
[ 1394402-15-3 ]

Reference： [1]Organic Letters,2012,vol. 14,p. 4614 - 4617

40
[ 50541-93-0 ]
[ 22536-62-5 ]
(1-benzylpiperidin-4-yl)-(5-phenylpyrimidin-2-yl)-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In acetonitrile; at 190℃; for 1h;Microwave irradiation;	General procedure: Method A: A mixture of 4-amino-1-benzylpiperidine (0.11 mL, 0.53 mmol, 1.0 eq.), 2-chloro- 5-phenyl-pyrimidine (150 mg, 0.79 mmol, 1.5 eq.), and DIPEA (0.37 mL, 2.10 mmol, 4.0 eq.) in MeCN (2.0 mL) was stirred at 190 C under microvawe irradiations for 1 hour. The mixture was allowed to cool to r.t. and concentrated in vacuo. The residue was purified byflashmaster (column: 50 g, flow: 45 mL/min, 20 fractions of 45 mL, Hept/AcOEt-NEt3 (10% NEt3) 9:1 to HeptIAcOEt-NEt3 (10% NEt3) 3:7) to yield the desired product as a yellow solid.

Reference： [1]Patent: WO2015/28989,2015,A1 .Location in patent: Page/Page column 77

41
[ 22536-62-5 ]
(1-benzylpiperidin-4-yl)-(4-bromobenzyl)-(5-phenylpyrimidin-2-yl)amine [ No CAS ]

Reference： [1]Patent: WO2015/28989,2015,A1

42
[ 22536-62-5 ]
(1-benzylpiperidin-4-yl)-[4-(2-methylpyridin-4-ylamino)-benzyl]-(5-phenylpyrimidin-2-yl)-amine [ No CAS ]

Reference： [1]Patent: WO2015/28989,2015,A1

43
C₁₆H₂₇BrMgSSi [ No CAS ]
[ 22536-62-5 ]
C₂₆H₃₄N₂SSi [ No CAS ]

Reference： [1]Advanced Functional Materials,2015,vol. 25,p. 3943 - 3957

44
methyl 3-cyclopropyl-1H-indazole-6-carboxylate [ No CAS ]
[ 22536-62-5 ]
methyl 3-cyclopropyl-1-(5-phenylpyrimidin-2-yl)-1H-indazole-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
46%	With potassium tert-butylate; In N,N-dimethyl-formamide; at 20℃; for 16h;	Potassium tert-butylate (147 mg, 1.32 mmol, 1.5 eq) and <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> (167 mg, 0.88mmol, 1.0 eq) were added to a stirred solution of product 14d) (190 mg, 0.88 mmol, 1.0 eq) in DMF (10mL). The mixture was stirred at 120C for 16 h, then cooled to room temperature, diluted with water (10mL) and extracted with ethyl acetate (2x10 mL). The combined organic layers were washed with brine(10 mL), dried (Na2SO4) and evaporated. The residue was purified by column chromatography [100-200mesh silica gel; pet ether with 20% ethyl acetate]. Pale brown solid. Yield: 150 mg (46% of theory)IH NMR (400 MHz, DMSO-d6, ppm): 9.34 (s, lH), 9.29 (s, 2H), 8.12 (d, J = 8.1 Hz, IH), 7.94 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 7.5 Hz, 2H), 7.58-7.46 (m, 3H), 3.95 (s, 3H), 2.50-2.40 (m, IH), 1.16-1.14 (s, 4H).

Reference： [1]Patent: WO2016/8590,2016,A1 .Location in patent: Page/Page column 68; 69

45
methyl 3-(methylsulfanyl)-1H-indazole-6-carboxylate [ No CAS ]
[ 22536-62-5 ]
methyl-3-(methylthio)-1-(5-phenylpyrimidin-2-yl)-1H-indazole-6-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With potassium carbonate; In dimethyl sulfoxide; at 100℃; for 18h;	9a) Methyl 3-(methylthio)- I -(5-phenylpyrimidin-2-yl)- I H-indazole-6-carboxylateTo a solution of methyl 3-(methylthio)-1 K-indazole-6-carboxylate (2.2 g, 9.90 mmol) in dry DMSO (30mL) were added <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> (1.89 g, 9.90 mmol) and potassium carbonate (4.10 g, 29.7mmol) and the mixture was heated to 100C for 18 h. After cooling to room temperature, the reactionmixture was diluted with warm ethyl acetate and water. The layers were separated and the aqueous phasewas extracted first with warm ethyl acetate and then with dichloromethane. The combined ethyl acetate layers were washed with water and brine, and dried over sodium sulfate. The dichioromethane layer was washed with brine, dried over sodium sulfate, combined with the ethyl acetate fraction and evaporated. Purification by column chromatography [silica, dichloromethane with 0 to 3% methanol]. Yellow solid.Yield: 3.25 g (87% of theory). LCMS: calculated for [M+H]: 377, found: 377.

Reference： [1]Patent: WO2016/8590,2016,A1 .Location in patent: Page/Page column 65

46
[ 32779-36-5 ]
[ 71-43-2 ]
[ 22536-62-5 ]

Reference： [1]Chemical Communications,2016,vol. 52,p. 2326 - 2329

47
[ 4096-21-3 ]
[ 22536-62-5 ]
C₂₀H₁₉N₃ [ No CAS ]

Reference： [1]Chemical Science,2014,vol. 5,p. 4173 - 4178

48
[ 100-59-4 ]
[ 32779-36-5 ]
[ 22536-62-5 ]

Reference： [1]Angewandte Chemie - International Edition,2017,vol. 56,p. 1581 - 1585
Angew. Chem.,2017,vol. 129,p. 1603 - 1607,5

49
C₅₂H₄₇B₂NO₄ [ No CAS ]
[ 22536-62-5 ]
C₆₀H₃₇N₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; toluene; for 20h;Inert atmosphere; Reflux;	Under Ar protection, a 2000ml three-necked flask was added M2-113.3g (molecular weight 266, 0.05mol), S6112.14g (molecular weight 607,0.02mol), tetrakis (triphenylphosphine) palladium, 2.52g (0.0022mol ) and the resulting solution of THF 360ml, 240ml of toluene, 36g (molecular weight 138,0.26mol) of potassium carbonate were dissolved in 240ml water and added to the reaction flask. After repeated under reduced pressure ventilation, electric start stirring, the reaction was monitored by TLC (thin layer chromatography), refluxed for 20 hours, the reaction was complete. Allowed to cool, the reaction system divided into two layers, the organic layer was separated, evaporated to dryness to give a solid product, repeated recrystallization from toluene, to give 9.4g product, molecular weight 979, 48% yield.Prepared in Example 30, except that a starting material which 4,6-diphenyl-2-chloro-5-phenyl-pyrimidin changed to 2-chloropyrimidine, other materials and methods for preparing the same, to give a yellow solid.

Reference： [1]Patent: CN103664894,2016,B .Location in patent: Paragraph 0366-0372

50
[ 16502-01-5 ]
[ 22536-62-5 ]
C₂₁H₁₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 120℃; for 8h;Inert atmosphere;	General procedure: Compound S16a (2 g, 11.6 mmol, 1 eq) and 2-chloropyrimidine (1.45 g, 12.8 mmol, 1.1 eq) was dissolved in 20 mL DMF and heated to 120 C for 8 h. Themixture were cooled to room temperature and evaporated in vacuo to give the crude product. The solid weresuspended in EtOAc and filtered to provide compound (9a) as yellow solid (1.8 g, 62%).

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 150,p. 30 - 38

51
[ 22536-62-5 ]
1-(furan-2-yl)-2-(5-phenylpyrimidin-2-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 150,p. 30 - 38

52
[ 22536-62-5 ]
3-(furan-2-yl)-2-(5-phenylpyrimidin-2-yl)-1,2,3,4-tetrahydro-9H-pyrrolo[3,4-b]quinolin-9-one [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 150,p. 30 - 38

53
[ 22536-62-5 ]
¹⁵N-ethyl 6-phenylimidazo[1,2-a]pyrimidine-3-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

54
[ 22536-62-5 ]
[ 31408-23-8 ]

Yield	Reaction Conditions	Operation in experiment
61%	With (15N)-ammonium chloride; sodium hydroxide; In water; at 150℃; for 0.5h;Sealed tube; Microwave irradiation;	A solution of 1M aq NaOH (5.0mL), <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> 6 (100mg, 0.53mmol) and NH4Cl (253mg, 4.72mmol) were added to a 10-20mL vial, sealed with a crimp cap and placed in a CEM Discover Lab Mate reactor microwave cavity. After irradiation at 150C for 30min, the reaction mixture was cooled to rt and the precipitate was filtered, and washed with water to provide a white crystalline solid (55mg, 61%). mp 162-163C (lit. 158-159C [35]), 1H NMR (400MHz, MeOH-d4) delta 8.53 (s, 2H), 7.56-7.28 (m, 5H).

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

55
[ 22536-62-5 ]
ethyl 6-phenylimidazo[1,2-a]pyrimidine-2-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

56
[ 22536-62-5 ]
6-Phenylimidazo[1,2-a]pyrimidine-2-carboxylic acid [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

57
[ 22536-62-5 ]
¹⁵N-ethyl 6-phenylimidazo[1,2-a]pyrimidine-2-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

58
[ 22536-62-5 ]
¹⁵N-6-phenylimidazo[1,2-a]pyrimidine-2-carboxylic acid [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

59
[ 22536-62-5 ]
2-<SUP>15</SUP>N-amino-5-phenylpyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With (15N)-ammonium chloride; sodium hydroxide; In water; at 150℃; for 0.5h;Sealed tube; Microwave irradiation;	A solution of 1M aq NaOH (5.0mL), <strong>[22536-62-5]2-chloro-5-phenylpyrimidine</strong> 17 6 (100mg, 0.53mmol) and 90 15NH4Cl (257mg, 4.72mmol) were added to a 10-20mL vial, sealed with a crimp cap and placed in a CEM Discover Lab Mate reactor microwave cavity. After irradiation at 150C for 30min, the reaction mixture was cooled to rt and the precipitate was filtered, and washed with water to provide a white crystalline 91 solid (74mg, 81%). mp 161-163C, vmax 3146 (NH2) cm-1, 1H NMR (400MHz, MeOH-d4, 9:1 mixture delta 8.43 (s, 2H), 7.50-7.45 (m, 2H), 7.42-7.37 (m, 2H), 7.30-7.23 (m, 1H); 8.53 (s, 2H), 7.57-7.52 (m, 2H), 7.45-7.42 (m, 2H), 7.37-7.32 (m, 1H). HRMS (ESI+) C10H10N215N+ ([M+H]+) requires 173.08396; found 173.08406.

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

60
[ 22536-62-5 ]
ethyl 6-phenylimidazo[1,2-a]pyrimidine-3-carboxylate [ No CAS ]

Reference： [1]Tetrahedron,2018,vol. 74,p. 5280 - 5288

61
[ 22536-62-5 ]
3,5-bis(5-phenylpyrimidin-2-yl)phenol [ No CAS ]

Reference： [1]Patent: WO2019/166206,2019,A1

62
[ 22536-62-5 ]
3,5-bis(5-phenylpyrimidin-2-yl)phenyl trifluoromethanesulfonate [ No CAS ]

Reference： [1]Patent: WO2019/166206,2019,A1

63
[ 22536-62-5 ]
2,2'-(4',5',6'-triphenyl-[1,1':2',1'':3'',1'''-quaterphenyl]-3''',5'''-diyl)bis(5-phenylpyrimidine) [ No CAS ]

Reference： [1]Patent: WO2019/166206,2019,A1

64
2,2'-(5-(9,9-dimethyl-9H-fluoren-2-yl)-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) [ No CAS ]
[ 22536-62-5 ]
2,2'-(5-(9,9-dimethyl-9H-fluoren-2-yl)-1,3-phenylene)bis(5-phenylpyrimidine) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With tetrakis(triphenylphosphine) palladium(0); potassium carbonate; In tetrahydrofuran; water; for 46h;Inert atmosphere; Reflux;	reflux temperature under a nitrogen atmosphere for 46 h. After cooling down to ambient temperature, the resulting precipitate was isolated by suction filtration and washed with n-hexane. The obtained white solid was dissolved in dichloromethane and washed with water three times. After drying over MgS04, the organic phase was filtered over a pad of Florisil. After rinsing with additional dichloromethane, the colorless filtrate was concentrated in vacuo to a minimal volume and n-hexane was added. The resulting white precipitate was isolated by suction filtration and washed with n-hexane. Further purification was achieved by trituration with n- hexane/dichloromethane (9:1) and recrystallization from toluene to afford 8.6 g (78%) of a white solid after drying. Final purification was achieved by sublimation. F1PLC: 99.8%; ESI-MS: m/z = 579 ([M+H]+).

Reference： [1]Patent: WO2019/166206,2019,A1 .Location in patent: Page/Page column 39

65
2,2'-(5-methoxy-1,3-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) [ No CAS ]
[ 22536-62-5 ]
2,2'-(5-methoxy-1,3-phenylene)bis(5-phenylpyrimidine) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In ethanol; water; toluene; for 22h;Inert atmosphere; Reflux;	A flask was flushed with nitrogen and charged with 2-chloro-5- phenylpyrimidine (19.1 g, 100 mmol), 2,2'-(5-methoxy-l,3- phenylene)bis(4,4,5,5-tetramethyl-l,3,2-dioxaborolane) (15 g, 41.7 mmol), Pd(dppf)Cl2 (0.3l g, 0.4 mmol), and K2CO3 (23 g, 166.4 mmol). A mixture of deaerated toluene/ethanol/water (3: 1: 1, 410 mL) was added and the reaction mixture was stirred at reflux temperature under a nitrogen atmosphere for 22 h. After cooling down to ambient temperature, all volatiles were removed in vacuo and the resulting solid was dissolved in chloroform/water. The organic phase was washed with water three times, dried over MgS04 and filtered over a pad of Florisil. After rinsing with additional chloroform, the filtrate was concentrated in vacuo to a minimal volume and n-hexane was added. The resulting off-white precipitate was isolated by suction filtration and washed with n-hexane. Further purification was achieved by precipitation from dichloromethane by addition of n-hexane to afford 12.6 g (73%) of a white solid after drying. F1PLC: 99.8%; GC-MS: m/z = 416.

Reference： [1]Patent: WO2019/166206,2019,A1 .Location in patent: Page/Page column 40

66
[ 1448296-00-1 ]
[ 22536-62-5 ]
[ 2095071-20-6 ]

Yield	Reaction Conditions	Operation in experiment
60.3%	With dicyclohexyl({2’,6’-dimethoxy-[1,1‘-biphenyl]-2-yl})phosphane; palladium diacetate; sodium tertiary butoxide In toluene at 140℃; for 4h;	2 Preparation of Compound C-81 (0111) Compound 1-2 (2.7 g, 14.2 mmol), compound 2-1 (3.5 g, 10.9 mmol), Pd(OAc)2 (0.11 g, 0.5 mmol), s-phos (0.45 g, 1.1 mmol), NaOt-bu (2.8 g, 27.3 mmol), and 200 mL of toluene were added into a flask, and the mixture was refluxed for 4 hours at 140° C. After completion of the reaction, distilled water was added thereto, and the organic layer was extracted with dichloromethane. The residual moisture was removed with magnesium sulfate and dried, and the resulting product was purified by column chromatography to obtain compound C-81 (3.2 g, yield: 60.3%).
60.3%	With dicyclohexyl({2’,6’-dimethoxy-[1,1‘-biphenyl]-2-yl})phosphane; palladium diacetate; sodium tertiary butoxide In toluene at 140℃; for 4h;	1 Example 1: Preparation of Compound H2-1 In a flask, 2-chloro-5-phenylpyrimidine (2.7 g, 14.2 mmol) and 5-phenyl-5,7-dihydroindolo[2,3-b]carbazole (3.5 g, 10.9 mmol) were introduced into palladium(II)acetate (Pd(OAc)2) (0.11 g, 0.5 mmol), a ligand (2-dicyclohexylphosphino-2′, 6′-dimethoxybiphenyl) (0.45 g, 1.1 mmol), NaOt-bu (2.8 g, 27.3 mmol), and toluene (200 mL), and the mixture was refluxed at 140° C. for 4 hours. After completion of the reaction, distilled water was added to the reaction mixture, and an organic layer was extracted with dichloromethane. The remaining moisture of the organic layer was removed using magnesium sulfate, and the residue was dried. The residue was separated by column chromatography to obtain 3.2 g of compound H2-1 (yield: 60.3%) (m.p.: 231° C.).

Reference： [1]Current Patent Assignee: DUPONT DE NEMOURS INC - US2020/299274, 2020, A1 Location in patent: Paragraph 0109-0111
[2]Current Patent Assignee: DUPONT DE NEMOURS INC - US2022/181558, 2022, A1 Location in patent: Paragraph 0091-0092

67
[ 1002762-60-8 ]
[ 22536-62-5 ]
C₄₀H₂₈N₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%	With dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; palladium diacetate; sodium t-butanolate In toluene at 120℃; for 4h;	1 Preparation of Compound C-1 (0108) Compound 1-2 (3.3 g, 17.5 mmol), compound 1-3 (6 g, 14.6 mmol), palladium(II)acetate (Pd(OAc)2) (0.15 g, 0.7 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (s-phos) (0.61 g, 1.5 mmol), sodium-tert-butoxide (NaOt-bu) (3 g, 29.2 mmol), and 250 mL of toluene were added into a flask, and the mixture was refluxed for 4 hours at 120° C. After completion of the reaction, distilled water was added thereto, and the organic layer was extracted with dichloromethane. The residual moisture was removed with magnesium sulfate and dried, and the resulting product was purified by column chromatography to obtain compound C-1 (4.3 g, yield: 52%).

Reference： [1]Current Patent Assignee: DOW INC - US2020/299274, 2020, A1 Location in patent: Paragraph 0104; 0107-0108

68
[ CAS Unavailable ]
[ 22536-62-5 ]
[ CAS Unavailable ]

Yield	Reaction Conditions	Operation in experiment
23.81%	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran; 1-methyl-pyrrolidin-2-one at 170℃; for 0.333333h; Microwave irradiation;	8-7 Example 8-7: To (lR,3r,5S,8s)-3-((5-cyclopropyl-3-(2-(trifluoromethoxy)phenyl)isoxazol-4- yl)methoxy)bicyclo[3.2.1]octan-8-amine (3f) (0.197 ml, 0.047 mmol, 0.24 M in THF) in a microwave vial was added Hunig's base (0.025 ml, 0.142 mmol), 2-chloro-5- phenylpyrimidine (9.93 mg, 0.052 mmol) and NMP (0.2 ml). The resulting mixture was heated in microwave reactor at 170°C for 20 min. The mixture was cooled to RT, quenched with water, and extracted with MTBE. The organic layer was loaded on silica gel and eluted with 0-50% EtOAc/hexane to provide N-((lR,3r,5S,8s)-3-((5-cyclopropyl-3-(2- (trifluoromethoxy)phenyl)isoxazol-4-yl)methoxy)bicyclo[3.2.1]octan-8-yl)-5- phenylpyrimidin-2-amine (Example 8-7) (6.5 mg, 0.011 mmol, 23.81 % yield). LC/MS observed [M+H]+, 577.2.

Reference： [1]Current Patent Assignee: ENANTA PHARMACEUTICALS INC - WO2020/231917, 2020, A1 Location in patent: Page/Page column 68; 69

69
[ 22536-62-5 ]
[ CAS Unavailable ]
[ 2614133-28-5 ]

Yield	Reaction Conditions	Operation in experiment
55%	Stage #1: 2-chloro-5-phenypyrimidine; allylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 0.25h; Stage #2: With 2,3-dicyano-5,6-dichloro-p-benzoquinone In 1,4-dioxane at 0℃;

Reference： [1]Wang, Si-Qing; Liu, Zong-Ci; Yue, Wen-Jun; Yin, Liang [Angewandte Chemie - International Edition, 2021, vol. 60, # 9, p. 4604 - 4608][Angew. Chem., 2021, vol. 133, # 9, p. 4654 - 4658,5]

70
[ 223785-93-1 ]
[ 22536-62-5 ]
[ 2698339-95-4 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 2-chloro-5-phenypyrimidine With toluene-4-sulfonic acid In ethanol; water for 0.5h; Reflux; Stage #2: N<SUP>1</SUP>-(2-(dimethylamino)ethyl)-N<SUP>1</SUP>-methylbenzene-1,4-diamine In ethanol; water for 10h; Reflux;	29 Step A-2: Preparation of N-(4-fluoro-2-methoxy-5-nitrophenyl)-4-(1-methyl-1H-indol-3-yl)pyrimidin-2-amine General procedure: Add 3-(2-chloropyrimidin-4-yl)-1-methyl-1H-indole (2.4g, 10.0mmol) and p-toluenesulfonic acid (1.7g, 10.0mmol) into a 100mL reaction flask. 40 mL of water and ethanol, reflux for 30 min.4-fluoro-2-methoxy-5-nitroaniline (1.9g, 10.0mmol) was added, and the reflux reaction was continued for 10h.After the reaction solution was concentrated under reduced pressure, 40 mL of water and 40 mL of ethyl acetate were added, and after vigorous stirring for 5 min,Adjust pH=8 with saturated sodium hydroxide solution. The ethyl acetate phase was separated, dried with anhydrous sodium sulfate and concentrated to obtain a crude product. After silica gel column chromatography (petroleum ether: ethyl acetate = 8:1), 2.2 g of an orange solid was obtained, with a yield of 56.1%.
	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 80℃; for 12h;	ynthesis of N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin 2-yl)-2-nitrobenzene-1,4-diamine (X19): General procedure: A mixture of M2 (2.0 g, 5.1 mmol), N1,N1,N2-trimethylethane-1,2-diamine (0.5 g, 5.1 mmol) and N,N-diisopropylethylamine (0.7 g,5.1 mmol) was dissolved in 4 mL of N,N-dimethyl formamide and heatedto 80 C for 12 h. After cooling, the reaction liquid was added to 100 mLof water and extracted with ethyl acetate. The ethyl acetate layer wasseparated, washed with brine, dried with anhydrous sodium sulfate andconcentrated in vacuo. The crude product was purified by chromatographyon silica gel (dichloromethane:methanol = 50:1) to obtain X02(1.4 g, 58.5%) as an orange solid. 1H NMR (600 MHz, DMSO-d6) δ 8.63(s, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.32 (d, J = 5.3 Hz, 2H), 8.08 (s, 1H),7.52 (d, J = 8.2 Hz, 1H), 7.27-7.23 (m, 1H), 7.21 (dd, J = 5.3, 2.8 Hz,1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (s, 1H), 3.96 (d, J = 2.2 Hz, 3H), 3.88(s, 3H), 3.27 (t, J = 6.9 Hz, 2H), 2.86 (s, 3H), 2.48 (d, J = 6.8 Hz, 2H),2.16 (s, 6H). 13C NMR (151 MHz, DMSO-d6) δ 162.6, 160.6, 157.6,155.3, 144.3, 138.1, 133.5, 132.7, 125.9, 122.7, 122.5, 121.8, 121.3,119.8, 112.8, 110.9, 107.8, 102.6, 56.9, 56.8, 53.3, 45.9, 41.0, 33.5. HRMS(ESI): C25H29N7O3, [M + H] +: 476.2413.
	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 80℃; for 12h;	ynthesis of N1-(2-(dimethylamino)ethyl)-N1-methyl-N4-(4-(1-methyl-1H-indol-3-yl)pyrimidin 2-yl)-2-nitrobenzene-1,4-diamine (X19): General procedure: A mixture of M2 (2.0 g, 5.1 mmol), N1,N1,N2-trimethylethane-1,2-diamine (0.5 g, 5.1 mmol) and N,N-diisopropylethylamine (0.7 g,5.1 mmol) was dissolved in 4 mL of N,N-dimethyl formamide and heatedto 80 C for 12 h. After cooling, the reaction liquid was added to 100 mLof water and extracted with ethyl acetate. The ethyl acetate layer wasseparated, washed with brine, dried with anhydrous sodium sulfate andconcentrated in vacuo. The crude product was purified by chromatographyon silica gel (dichloromethane:methanol = 50:1) to obtain X02(1.4 g, 58.5%) as an orange solid. 1H NMR (600 MHz, DMSO-d6) δ 8.63(s, 1H), 8.35 (d, J = 7.8 Hz, 1H), 8.32 (d, J = 5.3 Hz, 2H), 8.08 (s, 1H),7.52 (d, J = 8.2 Hz, 1H), 7.27-7.23 (m, 1H), 7.21 (dd, J = 5.3, 2.8 Hz,1H), 7.12 (t, J = 7.4 Hz, 1H), 6.85 (s, 1H), 3.96 (d, J = 2.2 Hz, 3H), 3.88(s, 3H), 3.27 (t, J = 6.9 Hz, 2H), 2.86 (s, 3H), 2.48 (d, J = 6.8 Hz, 2H),2.16 (s, 6H). 13C NMR (151 MHz, DMSO-d6) δ 162.6, 160.6, 157.6,155.3, 144.3, 138.1, 133.5, 132.7, 125.9, 122.7, 122.5, 121.8, 121.3,119.8, 112.8, 110.9, 107.8, 102.6, 56.9, 56.8, 53.3, 45.9, 41.0, 33.5. HRMS(ESI): C25H29N7O3, [M + H] +: 476.2413.

Reference： [1]Current Patent Assignee: SHENYANG PHARMACEUTICAL UNIVERSITY - CN113354622, 2021, A Location in patent: Paragraph 0112; 0116-0118; 0139; 0146-0148
[2]Wang, Xinran; Zhang, Cai; Zhang, Xiangyu; Wang, Jiming; Zhao, Liyu; Zhao, Dongmei; Cheng, Maosheng [Bioorganic Chemistry, 2022, vol. 121]
[3]Wang, Xinran; Zhang, Cai; Zhang, Xiangyu; Wang, Jiming; Zhao, Liyu; Zhao, Dongmei; Cheng, Maosheng [Bioorganic Chemistry, 2022, vol. 121]

71
[ 51387-90-7 ]
[ 22536-62-5 ]
[ 2764906-54-7 ]

Yield	Reaction Conditions	Operation in experiment
18%	In N,N-dimethyl-formamide at 150℃; for 15h;	2 Example 2: N-(2-(1-methylpyrrolidin-2-yl)ethylV5-phenylpyrimidin-2-amine A solution of 2-chloro-5-phenylpyrimidine (0.20 g, 1.05 mmol) in dry DMF was treated with 2-(1-methylpyrrolidin-2-yl)ethan-1-amine (0.16 g, 1.248 mmol), stirred at 150 °C for 15 h, cooled to RT, quenched with ice H2O and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with H2O and brine, dried over Na2SO4 and concentrated under reduced pressure. Purification of the residue by column chromatography on amine silica (Davisil) gave the title compound (0.053 g, 18%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.52 (s, 2H), 7.49-7.42 (m, 4H), 7.36-7.33 (m, 1H), 5.83 (s, 1H), 3.59-3.48 (m, 2H), 3.10 (t, J = 7.6 Hz, 1H), 2.36 (s, 3H), 2.36-2.20 (m, 1H), 2.20-2.13 (q, J = 9.2 Hz, 1H), 2.05-1.90 (m, 2H), 1.85-1.55 (m, 4H). MS ES+: 283.32.
18%	In N,N-dimethyl-formamide at 150℃; for 15h;	2 Example 2: N-(2-(1-methylpyrrolidin-2-yl)ethylV5-phenylpyrimidin-2-amine A solution of 2-chloro-5-phenylpyrimidine (0.20 g, 1.05 mmol) in dry DMF was treated with 2-(1-methylpyrrolidin-2-yl)ethan-1-amine (0.16 g, 1.248 mmol), stirred at 150 °C for 15 h, cooled to RT, quenched with ice H2O and extracted with EtOAc (2 x 20 mL). The combined organic layers were washed with H2O and brine, dried over Na2SO4 and concentrated under reduced pressure. Purification of the residue by column chromatography on amine silica (Davisil) gave the title compound (0.053 g, 18%) as an off-white solid. 1H NMR (400 MHz, CDCl3): δ 8.52 (s, 2H), 7.49-7.42 (m, 4H), 7.36-7.33 (m, 1H), 5.83 (s, 1H), 3.59-3.48 (m, 2H), 3.10 (t, J = 7.6 Hz, 1H), 2.36 (s, 3H), 2.36-2.20 (m, 1H), 2.20-2.13 (q, J = 9.2 Hz, 1H), 2.05-1.90 (m, 2H), 1.85-1.55 (m, 4H). MS ES+: 283.32.

Reference： [1]Current Patent Assignee: CEREVANCE; CEREVANCE INC - WO2022/53823, 2022, A1 Location in patent: Page/Page column 64-65
[2]Current Patent Assignee: CEREVANCE; CEREVANCE INC - WO2022/53823, 2022, A1 Location in patent: Page/Page column 64-65

72
[ 96736-02-6 ]
[ 22536-62-5 ]
[ 2763587-46-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride In tetrahydrofuran at 20℃; for 6h;

Reference： [1]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 109

73
[ 2763587-56-8 ]
[ 22536-62-5 ]
[ 2763587-57-9 ]

Yield	Reaction Conditions	Operation in experiment
84%	Stage #1: tert-butyl (2S,4R)-2-((4-chlorobenzamido)methyl)-4-hydroxypyrrolidine-1-carboxylate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: 2-chloro-5-phenylpyrimidine In N,N-dimethyl-formamide; mineral oil at 20℃;	tert-Butyl (2S,4R)-2-((4-chlorobenzamido)methyl)-4-((5-phenylpyrimidin-2-yl)oxy) pyrrolidine-1-carboxylate (U2) To the solution of Ul (480 mg, 1.35 mmol) in DMF (15 mL) at 0°C, NaH (60% in mineral oil, 60 mg, 1.49 mmol, 1.1 eq) was added. The reaction mixture was stirred at 0°C for 15 min. 2-Chloro-5-phenylpyrimidine (260 mg, 1.35 mmol) was added and the reaction mixture was stirred at room temperature. After 20h, the mixture was poured onto ice. Precipitates were filtered, washed with water (50 mL) and dried to afford U2 (580 mg, 84%) as white solid. 1H NMR (400 MHz, CDCI3) 6: 8.72 (s, 2H), 8.64 (s, 1H), 7.87 - 7.78 (m, 2H), 7.56 - 7.35 (m, 7H), 5.58 - 5.52 (m, 1H), 4.84 - 3.82 (m, 1H), 4.43 - 4.34 (m, 1H), 3.89 - 3.82 (m, 1H), 3.78 - 3.65 (m, 2H), 3.44 (m, 1H), 2.58 - 2.47 (m, 1H), 2.22 -2.09 (m, 1H), 1.46 (s, 9H). LC-MS (m/z): 509.8 [M+H]+
84%	Stage #1: tert-butyl (2S,4R)-2-((4-chlorobenzamido)methyl)-4-hydroxypyrrolidine-1-carboxylate With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.25h; Stage #2: 2-chloro-5-phenylpyrimidine In N,N-dimethyl-formamide; mineral oil at 20℃;	tert-Butyl (2S,4R)-2-((4-chlorobenzamido)methyl)-4-((5-phenylpyrimidin-2-yl)oxy) pyrrolidine-1-carboxylate (U2) To the solution of Ul (480 mg, 1.35 mmol) in DMF (15 mL) at 0°C, NaH (60% in mineral oil, 60 mg, 1.49 mmol, 1.1 eq) was added. The reaction mixture was stirred at 0°C for 15 min. 2-Chloro-5-phenylpyrimidine (260 mg, 1.35 mmol) was added and the reaction mixture was stirred at room temperature. After 20h, the mixture was poured onto ice. Precipitates were filtered, washed with water (50 mL) and dried to afford U2 (580 mg, 84%) as white solid. 1H NMR (400 MHz, CDCI3) 6: 8.72 (s, 2H), 8.64 (s, 1H), 7.87 - 7.78 (m, 2H), 7.56 - 7.35 (m, 7H), 5.58 - 5.52 (m, 1H), 4.84 - 3.82 (m, 1H), 4.43 - 4.34 (m, 1H), 3.89 - 3.82 (m, 1H), 3.78 - 3.65 (m, 2H), 3.44 (m, 1H), 2.58 - 2.47 (m, 1H), 2.22 -2.09 (m, 1H), 1.46 (s, 9H). LC-MS (m/z): 509.8 [M+H]+

Reference： [1]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 120
[2]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 120

74
[ 2763587-58-0 ]
[ 22536-62-5 ]
[ 2763585-69-7 ]

Yield	Reaction Conditions	Operation in experiment
38%	With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 14h;	Compound 233 To solution of V2 (336 mg, 1.32 mmol) and 2-chloro-5-phenylpirimidine (5, 253 mg, 1.32 mmol) in THF (20 mL), NaH (60% on mineral oil, 106 mg, 2.65 mmol) was added at once. The resulting yellow suspension was stirred at room temperature for 14 h, and then poured into cold water (50 mL). Precipitates were filtered and re-crystallized from ethanol/water mixture (5/1) to afford the title compound as white solid (205 mg, 38%). XH NMR (400 MHz, DMSO) 6 8.98 (s, 2H), 8.91 (s, 2H), 8.08 -8.03 (m, 2H), 7.77 - 7.73 (m, 2H), 7.54 - 7.48 (m, 2H), 7.46 - 7.40 (m, 3H), 5.52 - 5.47(m, 1H), 3.69 -3.60 (m, 4H). ESI (m/z): 408.4 [M+H]+. Elemental analysis (%): Calculated: C 62.03, H 4.72, N 16.74 (with 0.1 molecule of H2O and 0.1 molecule of hexane). Found: C 61.93, H 4.46, N 16.67.
38%	With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 14h;	Compound 233 To solution of V2 (336 mg, 1.32 mmol) and 2-chloro-5-phenylpirimidine (5, 253 mg, 1.32 mmol) in THF (20 mL), NaH (60% on mineral oil, 106 mg, 2.65 mmol) was added at once. The resulting yellow suspension was stirred at room temperature for 14 h, and then poured into cold water (50 mL). Precipitates were filtered and re-crystallized from ethanol/water mixture (5/1) to afford the title compound as white solid (205 mg, 38%). XH NMR (400 MHz, DMSO) 6 8.98 (s, 2H), 8.91 (s, 2H), 8.08 -8.03 (m, 2H), 7.77 - 7.73 (m, 2H), 7.54 - 7.48 (m, 2H), 7.46 - 7.40 (m, 3H), 5.52 - 5.47(m, 1H), 3.69 -3.60 (m, 4H). ESI (m/z): 408.4 [M+H]+. Elemental analysis (%): Calculated: C 62.03, H 4.72, N 16.74 (with 0.1 molecule of H2O and 0.1 molecule of hexane). Found: C 61.93, H 4.46, N 16.67.

Reference： [1]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 121-122
[2]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 121-122

75
[ 2763587-60-4 ]
[ 22536-62-5 ]
[ 2763585-70-0 ]

Yield	Reaction Conditions	Operation in experiment
60%	With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 16h;	Compound 234 To solution of Wl (774 mg, 3.21 mmol) and 2-chloro-5-phenylpirimidine (612 mg, 3.21 mmol) in THF (30 mL), NaH (60% on mineral oil, 257 mg, 6.43 mmol) was added at once. The resulting suspension was stirred at room temperature for 16 h. The suspension was poured into cold water (50 mL) and extracted with EtOAc (2x30 mL). The organic extracts were combined, dried over NajSC and evaporated. The residue was purified by flash chromatography (eluent EtOH/DCM/O.1% HCI). Product containing fractions were combined and evaporated. The residue was dissolved in DMSO (1 mL) and solution was poured into cold water (10 mL). Filtration of the precipitates yielded the title compound as white solid (335 mg, 26%). XH NMR (400 MHz, DMSO) 6 10.42 (s, 2H), 9.00 (s, 2H), 7.89 - 7.83 (m, 2H), 7.79 - 7.73 (m, 4H), 7.55 - 7.49 (m, 2H), 7.47 - 7.41 (m, 1H), 5.77 - 5.68 (m, 1H), 3.92 - 3.79 (m, 4H). ESI (m/z): 365.4 [M+H]+. Elemental analysis (%): Calculated: C 56.56, H 4.89, N 13.19 (with 1.3 molecule of H2O). Found: C 56.52, H 4.69, N 13.02.
60%	With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 16h;	Compound 234 To solution of Wl (774 mg, 3.21 mmol) and 2-chloro-5-phenylpirimidine (612 mg, 3.21 mmol) in THF (30 mL), NaH (60% on mineral oil, 257 mg, 6.43 mmol) was added at once. The resulting suspension was stirred at room temperature for 16 h. The suspension was poured into cold water (50 mL) and extracted with EtOAc (2x30 mL). The organic extracts were combined, dried over NajSC and evaporated. The residue was purified by flash chromatography (eluent EtOH/DCM/O.1% HCI). Product containing fractions were combined and evaporated. The residue was dissolved in DMSO (1 mL) and solution was poured into cold water (10 mL). Filtration of the precipitates yielded the title compound as white solid (335 mg, 26%). XH NMR (400 MHz, DMSO) 6 10.42 (s, 2H), 9.00 (s, 2H), 7.89 - 7.83 (m, 2H), 7.79 - 7.73 (m, 4H), 7.55 - 7.49 (m, 2H), 7.47 - 7.41 (m, 1H), 5.77 - 5.68 (m, 1H), 3.92 - 3.79 (m, 4H). ESI (m/z): 365.4 [M+H]+. Elemental analysis (%): Calculated: C 56.56, H 4.89, N 13.19 (with 1.3 molecule of H2O). Found: C 56.52, H 4.69, N 13.02.

Reference： [1]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 122-123
[2]Current Patent Assignee: ERACAL THERAPEUTICS - WO2022/53541, 2022, A1 Location in patent: Page/Page column 122-123

76
[ 2824121-61-9 ]
[ 22536-62-5 ]
[ 2824122-23-6 ]

Yield	Reaction Conditions	Operation in experiment
79%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; for 48h;	12060 4-[[1-[[[1-[(2,4-Dimethoxyphenyl)methylamino]-5-isoquinolyl]amino]methyl]-2-(5-phenylpyrimidin-2- yl)-2-azabicyclo[2.1.1]hexan-4-yl]methoxy]-1-methyl-pyridin-2-one DIPEA (23 μL, 0.164 mmol) was added to a mixture of 4-[[4-[[[1-[(2,4-dimethoxyphenyl)methylamino]-5- isoquinolyl]amino]methyl]-2-azabicyclo[2.1.1]hexan-1-yl]methoxy]-1-methyl-pyridin-2-one (60 mg, 0.111 mmol) and 2-chloro-5-phenyl-pyrimidine (22 mg, 0.115 mmol) in DMF (1000 μL) at rt. The mixture was stirred at 100 °C for 48 h then concentrated. The product was purified by flash chromatography (Silica, 0- 40% MeOH in EtOAc to afford the product (61 mg, 79% yield). [M+H]+ = 696.4
79%	With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 100℃; for 48h;	12060 4-[[1-[[[1-[(2,4-Dimethoxyphenyl)methylamino]-5-isoquinolyl]amino]methyl]-2-(5-phenylpyrimidin-2- yl)-2-azabicyclo[2.1.1]hexan-4-yl]methoxy]-1-methyl-pyridin-2-one DIPEA (23 μL, 0.164 mmol) was added to a mixture of 4-[[4-[[[1-[(2,4-dimethoxyphenyl)methylamino]-5- isoquinolyl]amino]methyl]-2-azabicyclo[2.1.1]hexan-1-yl]methoxy]-1-methyl-pyridin-2-one (60 mg, 0.111 mmol) and 2-chloro-5-phenyl-pyrimidine (22 mg, 0.115 mmol) in DMF (1000 μL) at rt. The mixture was stirred at 100 °C for 48 h then concentrated. The product was purified by flash chromatography (Silica, 0- 40% MeOH in EtOAc to afford the product (61 mg, 79% yield). [M+H]+ = 696.4

Reference： [1]Current Patent Assignee: KALVISTA PHARMACEUTICALS INC - WO2022/175675, 2022, A1 Location in patent: Page/Page column 520-521
[2]Current Patent Assignee: KALVISTA PHARMACEUTICALS INC - WO2022/175675, 2022, A1 Location in patent: Page/Page column 520-521

77
[ 1007204-37-6 ]
[ 22536-62-5 ]
[ 1336916-79-0 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In acetonitrile at 180℃; Microwave irradiation; Inert atmosphere;

Reference： [1]Aissaoui, Hamed; Holdener, Martin; Gnerre, Carmela; Niggemann, Kerstin; Reber, Stefan; Richard, Sylvia; Siegrist, Romain; Boss, Christoph [ChemMedChem, 2023, vol. 18, # 10]

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Technical Information

• Acid-Catalyzed α -Halogenation of Ketones • Addition of a Hydrogen Halide to an Internal Alkyne • Alcohols from Haloalkanes by Acetate Substitution-Hydrolysis • Alkyl Halide Occurrence • Alkylation of an Alkynyl Anion • An Alkane are Prepared from an Haloalkane • Benzylic Oxidation • Birch Reduction • Birch Reduction of Benzene • Blanc Chloromethylation • Chloroalkane Synthesis with SOCI2 • Complete Benzylic Oxidations of Alkyl Chains • Complete Benzylic Oxidations of Alkyl Chains • Conversion of Amino with Nitro • Convert Haloalkanes into Alcohols by SN2 • Deprotonation of Methylbenzene • Directing Electron-Donating Effects of Alkyl • Electrophilic Chloromethylation of Polystyrene • Friedel-Crafts Alkylation of Benzene with Acyl Chlorides • Friedel-Crafts Alkylation of Benzene with Carboxylic Anhydrides • Friedel-Crafts Alkylation of Benzene with Haloalkanes • Friedel-Crafts Alkylation Using Alkenes • Friedel-Crafts Alkylations of Benzene Using Alkenes • Friedel-Crafts Alkylations Using Alcohols • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Groups that Withdraw Electrons Inductively Are Deactivating and Meta Directing • Halogenation of Alkenes • Halogenation of Benzene • Hiyama Cross-Coupling Reaction • Hydrogenation to Cyclohexane • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Methylation of Ammonia • Nitration of Benzene • Nucleophilic Aromatic Substitution • Nucleophilic Aromatic Substitution with Amine • Oxidation of Alkyl-substituted Benzenes Gives Aromatic Ketones • Preparation of Alkylbenzene • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reductive Removal of a Diazonium Group • Reverse Sulfonation——Hydrolysis • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Sulfonation of Benzene • Suzuki Coupling • The Acylium Ion Attack Benzene to Form Phenyl Ketones • The Claisen Rearrangement • The Nitro Group Conver to the Amino Function • Vilsmeier-Haack Reaction

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P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

[ CAS No. 22536-62-5 ] {[proInfo.proName]}

Quality Control of [ 22536-62-5 ]

Related Doc. of [ 22536-62-5 ]

Product Details of [ 22536-62-5 ]

Safety of [ 22536-62-5 ]

Application In Synthesis of [ 22536-62-5 ]

[ 22536-62-5 ] Synthesis Path-Upstream 1~9

[ 22536-62-5 ] Synthesis Path-Downstream 1~77

Technical Information

Related Functional Groups of [ 22536-62-5 ]

Aryls

Chlorides

Related Parent Nucleus of [ 22536-62-5 ]

Pyrimidines

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 22536-62-5 ]

Related Parent Nucleus of
[ 22536-62-5 ]