76661-24-0|2,5-Dichloro-4-(3-nitrophenoxy)pyrimidine| Ambeed

CAS No. :	76661-24-0
Formula :	C₁₀H₅Cl₂N₃O₃
M.W :	286.07
SMILES Code :	O=[N+](C1=CC(OC2=NC(Cl)=NC=C2Cl)=CC=C1)[O-]
MDL No. :	MFCD22124565
InChI Key :	SEGZIOXGXFJLHD-UHFFFAOYSA-N
Pubchem ID :	12679950

Safety of [ 76661-24-0 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Application In Synthesis of [ 76661-24-0 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 76661-24-0 ]

[ 76661-24-0 ] Synthesis Path-Downstream 1~54

1
[ 100-02-7 ]
[ 5750-76-5 ]
[ 76661-24-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2.0h;	2,5-dichloro-4-(3-nitrophenoxy)pyrimidine Potassium carbonate (2.42 g, 17.5 mmol) and 2,4,5-trichloropyrimidine (1.0 mL, 8.72 mmol) were added to the solution of 3-nitrophenol (1.21 g, 8.72 mmol) in DMF (20 mL). The reaction was heated to 6O0C for 2 h. The reaction mixture was filtered, the filtrate was dilute with ethyl acetate and washed with water (20 mL) three times. The organic layer wad dried over anhydrous sodium sulfate and concentrated to afford 2.24 g (90%) of a light yellow solid, which was used without further purification. 1H NMR 600 MHz (DMSO d6) δ 8.87 (s, IH), 8.28 (m, IH), 8.21 (m, IH), 7.84 (m, 2H); MS m/z: 287.07 (M+1).

References: [1]Patent: WO2010/129053,2010,A2 .Location in patent: Page/Page column 122-123.

2
[ 122833-04-9 ]
[ 76661-24-0 ]
[ 1213269-25-0 ]

Yield	Reaction Conditions	Operation in experiment
81%		5-chloro-N-(2-methoxy-4-(4-methyIpiperazin-l-yl)phenyl)-4-(3-nitrophenoxy)pyrimidin- 2-amine A flask was charged with <strong>[76661-24-0]2,5-dichloro-4-(3-nitrophenoxy)pyrimidine</strong> (1.56 g, 5.45 mmol), 2-methoxy-4-(4-methylpiperazin-l-yl)benzenamine (1.21 g, 5.45 mmol), TFA ( 0.42 mL, 5.45 mmol uL), 2-BuOH (30 mL). The slurry was heated to 1000C for 2h. The reaction mixture was allowed to cool to room temperature and, was neutralized with a saturated aqueous sodium bicarbonate solution. The aqueous mixture was then extracted with ethyl acetate (50 mL) three times. The crude product was purified using flash chromatography with 30: 1 :0.3 (v/v/v) dichloromethane-methanol-triethylamine to afford 2.07 g brown solid (81%). 1H NMR 600 MHz (DMSO d6) δ 8.38 (s, IH), 8.28 (s, IH), 8.16 (m, 2H), 7.76 (m, 2H), 7.08 (s, I H), 6.46 (m, IH), 6.14 (m, I H), 3.72 (s, 3H), 3.33 (m, 4H), 3.05 (m, 4H), 2.28 (s, 3H); MS m/z: 471.91 (M+1).
75%	With trifluoroacetic acid; In iso-butanol; at 100℃; for 4.0h;	General procedure: To a mixture of pyrimidine analogues 34, 35 or 36 (1.56 g, 5.45 mmol), amino piperazine 38 (1.21 g, 5.45 mmol) and anhydrous 2-butanol (30 mL) was added trifluoroacetic acid (0.42 mL, 5.45 mmol). The reaction mixture was heated to 100 C and stirred for 4 h. Subsequently, it was cooled to room temperature and was basified (pH 8.0) by dropwise addition of saturated aqueous sodium bicarbonate solution. The 2-butanol was removed in vacuo to obtain a thick slurry which was dissolved in ethyl acetate (50 mL). The organic layer was washed with water (3 x 20 mL) and brine (1 x 20 mL). The combined organic extracts were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash silica gel chromatography using dichloromethane-methanol (25:1, v/v) as eluent to afford the nitro analogues as brown solids in yields ranging from 72 - 79%.
72%	With trifluoroacetic acid; In iso-butanol; for 5.0h;Reflux;	To a solution of <strong>[76661-24-0]2,5-dichloro-4-(3-nitrophenoxy)pyrimidine</strong> (0.9 g, 3.16 mmol), 2-methoxy-4-(4-methylpiperazin-1-yl)benzenamine (0.7 g, 3.16 mmol), in 2-butanol (20 mL) was added trifluoroacetic acid (0.25 mL, 3.16 mmol). The resultant slurry was refluxed for 5 hours. The reaction mixture was allowed to cool to room temperature and then was neutralized with a saturated aqueous sodium bicarbonate solution. The aqueous mixture was then extracted with ethyl acetate (3*500 mL) and the combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo to furnish an oil which was purified by column chromatography on silica gel (100-200 mesh) eluting with 2-3% (v/v) methanol in dichloromethane to produce as pale brown solid (1 g, yield 72%). 1H NMR 400 MHz (DMSO-d6) δ 8.37 (s, 1H), 8.29 (s, 1H), 8.17-8.16 (m, 2H), 7.75-7.74 (m, 2H), 7.08-7.06 (m, 1H), 6.48 (s, 1H), 6.14 (s, br, 1H), 3.69 (s, 3H), 3.03 (t, J=4.8 Hz, 4H), 2.46 (t, J=4.8 Hz, 4H), 2.23 (s, 3H); LCMS m/e: 471 [M+1]+.

65%

With trifluoroacetic acid; In butan-1-ol; at 100℃; for 18.0h;

To a solution of compound 8 (1.33 g, 4.66 mmol) and compound11 (1.03 g, 4.66 mmol) in anhydrous 1-butanol (20 mL), trifluoroacetic acid (0.36 mL, 4.66 mmol) was added. The reaction mixturewas heated to 100 C and stirred for 18 h. Subsequently, it wascooled to room temperature and saturated aqueous sodium bicarbonatesolution was added drop wise until basic pH was obtained.The volatiles were removed in vacuo and the obtained thick slurrywas dissolved in DCM (50 mL). The organic layer was washed withwater (20 mL), brine (20 mL), dried over anhydrous sodium sulfate,filtered and concentrated in vacuo. The crude was purified by flashsilica gel chromatography using DCM/MeOH (96:4, v/v) as eluentto afford 1.42 g of the desired product 12 (3.02 mmol, 65%) as white solid.

References: [1]Patent: WO2010/129053,2010,A2 .Location in patent: Page/Page column 123.
[2]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4832 - 4837.
[3]Patent: US2018/208564,2018,A1 .Location in patent: Paragraph 0381-0382.
[4]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 2767 - 2780.
[5]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.
[6]European Journal of Medicinal Chemistry,2014,vol. 77,p. 75 - 83.

3
[ 1246532-96-6 ]
[ 76661-24-0 ]
[ 1254783-97-5 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In iso-butanol; at 90℃; for 2.0h;	tert-butyl 4-(4-(5-chloro-4-(3-nitrophenoxy)pyrimidin-2-ylamino)-3- methoxyphenyl)piperazine-l-carboxylate A flask was charged with 2,5-dichloro-4-(3- nitrophenoxy)pyrimidine (200mg, 0.7mmol), tert-butyl 4-(4-amino-3- methoxyphenyl)piperazine-l-carboxylate (215mg, 0.7mmol), Pd2(dba)3(64mg, 0.07mmol)), X-Phos (33 mg, 0.07mmol), potassium carbonate (200mg, 1.4mmol) in 2-BuOH (1OmL). The mixture was degased and heated to 9O0C for 2 hours. The slurry was filtrated through celite and washed with ethyl acetate. The concentrated residue was purified by flash chromatography to afford the title compound. MS(M+1): 558.0.

References: [1]Patent: WO2010/129053,2010,A2 .Location in patent: Page/Page column 127-128.

4
[ 209960-91-8 ]
[ 76661-24-0 ]
5-chloro-N-(2-methoxy-4-morpholinophenyl)-4-(3-nitrophenoxy)pyrimidin-2-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75.2%	With trifluoroacetic acid; In iso-butanol; at 100℃;	General procedure: To a solution of 3a-r (1.50 mmol, 1 eq) and 6a-b (1.50 mmol, 1eq) in 2-BuOH (8 mL) were added TFA (2 mL). The slurrywas heatedto 100 C for 2e3 h. The reaction mixture was allowed to cool toroom temperature and was neutralized with a saturated aqueoussodium bicarbonate solution. The mixture was then extracted withethyl acetate (50 mL) three times. The crude was purified by flashchromatography with 25:1 (v/v) dichloromethane - methanol.

References: [1]European Journal of Medicinal Chemistry,2021,vol. 210.
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

5
2-methoxy-4-[4-(4-methylpiperazin-1-yl)-piperidin-1-yl]-phenylamine [ No CAS ]
[ 76661-24-0 ]
C₂₇H₃₂ClN₇O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

6
[ 694499-26-8 ]
[ 76661-24-0 ]
C₂₃H₂₂ClF₃N₆O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

7
[ 761440-87-3 ]
[ 76661-24-0 ]
C₂₂H₂₂ClN₅O₅ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

8
[ 1116228-62-6 ]
[ 76661-24-0 ]
C₂₃H₂₄ClN₅O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

9
[ 1124330-14-8 ]
[ 76661-24-0 ]
C₂₃H₂₄ClN₅O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

10
[ 76661-24-0 ]
C₁₃H₁₈N₂O [ No CAS ]
C₂₃H₂₂ClN₅O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

11
2-(4-aminophenyl)-1-(4-methylpiperazin-1-yl)ethanone [ No CAS ]
[ 76661-24-0 ]
C₂₃H₂₃ClN₆O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

12
[ 76661-24-0 ]
[ 1233094-59-1 ]
C₂₃H₂₃ClN₆O₅ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

13
[ 76661-24-0 ]
[ 1001346-50-4 ]
C₂₄H₂₅ClN₆O₆ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

14
[ 50534-11-7 ]
[ 76661-24-0 ]
C₂₃H₂₃ClN₆O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

15
[ 876126-60-2 ]
[ 76661-24-0 ]
C₂₄H₂₅ClN₆O₅ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

16
[ 76661-24-0 ]
[ 1265526-86-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

17
[ 76661-24-0 ]
[ 1265526-88-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

18
[ 76661-24-0 ]
C₁₇H₁₄ClFN₄O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

19
[ 76661-24-0 ]
C₂₂H₁₈ClN₅O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

20
[ 76661-24-0 ]
4-(3-aminophenoxy)-5-chloro-N-(2-methoxy-4-morpholinophenyl)pyrimidin-2-amine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.
[2]European Journal of Medicinal Chemistry,2021,vol. 210.

21
[ 76661-24-0 ]
C₂₂H₂₄ClN₅O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

22
[ 76661-24-0 ]
[ 1254783-32-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

23
[ 76661-24-0 ]
C₂₃H₂₆ClN₅O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

24
[ 76661-24-0 ]
C₂₃H₂₆ClN₅O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

25
[ 76661-24-0 ]
C₂₃H₂₄ClN₅O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

26
[ 76661-24-0 ]
[ 1265527-57-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.
[2]European Journal of Medicinal Chemistry,2021,vol. 210.

27
[ 76661-24-0 ]
[ 1213269-26-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.
[2]European Journal of Medicinal Chemistry,2014,vol. 77,p. 75 - 83.
[3]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 2767 - 2780.
[4]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4832 - 4837.
[5]Patent: US2018/208564,2018,A1 .

28
[ 76661-24-0 ]
C₂₇H₃₄ClN₇O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

29
[ 76661-24-0 ]
C₂₃H₂₅ClN₆O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

30
[ 76661-24-0 ]
C₂₃H₂₅ClN₆O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

31
[ 76661-24-0 ]
C₂₄H₂₇ClN₆O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

32
[ 76661-24-0 ]
C₂₃H₂₅ClN₆O₂ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

33
[ 76661-24-0 ]
[ 1254783-16-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

34
[ 76661-24-0 ]
C₂₄H₂₇ClN₆O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

35
[ 76661-24-0 ]
C₂₂H₂₅ClN₆O [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

36
[ 76661-24-0 ]
C₂₃H₂₄ClF₃N₆O [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

37
[ 76661-24-0 ]
[ 1254783-12-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

38
[ 76661-24-0 ]
[ 1254783-30-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

39
[ 76661-24-0 ]
[ 1265526-94-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

40
[ 76661-24-0 ]
[ 1214265-56-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

41
[ 76661-24-0 ]
[ 1213269-23-8 ]

42
[ 76661-24-0 ]
[ 1254783-11-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

43
[ 76661-24-0 ]
[ 1254783-18-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

44
[ 76661-24-0 ]
[ 1254783-58-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

45
[ 76661-24-0 ]
[ 1254783-19-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

46
[ 76661-24-0 ]
[ 1254783-20-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

47
[ 76661-24-0 ]
[ 1265527-04-5 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

48
[ 76661-24-0 ]
[ 1265527-06-7 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

49
[ 76661-24-0 ]
[ 1265527-08-9 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

50
[ 16153-81-4 ]
[ 76661-24-0 ]
[ 1265527-54-5 ]

Yield	Reaction Conditions	Operation in experiment
71.5%	With trifluoroacetic acid; In iso-butanol; at 100℃;	General procedure: To a solution of 3a-r (1.50 mmol, 1 eq) and 6a-b (1.50 mmol, 1eq) in 2-BuOH (8 mL) were added TFA (2 mL). The slurrywas heatedto 100 C for 2e3 h. The reaction mixture was allowed to cool toroom temperature and was neutralized with a saturated aqueoussodium bicarbonate solution. The mixture was then extracted withethyl acetate (50 mL) three times. The crude was purified by flashchromatography with 25:1 (v/v) dichloromethane - methanol.

References: [1]European Journal of Medicinal Chemistry,2021,vol. 210.
[2]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

51
[ 76661-24-0 ]
[ 450-91-9 ]
C₁₇H₁₂ClFN₄O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

52
[ 76661-24-0 ]
[ 70261-82-4 ]
C₂₂H₂₃ClN₆O₃ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

53
[ 76661-24-0 ]
[ 103348-14-7 ]
C₂₂H₁₆ClN₅O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.

54
[ 554-84-7 ]
[ 5750-76-5 ]
[ 76661-24-0 ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2.0h;	Dissolve 2,4,5-trichloropyrimidine (1.82g, 10mmol) and m-nitrophenol (1.39g, 10mmol) in DMF (30ml), add potassium carbonate (1.38g, 10mmol), stir at room temperature for 2 hours, After the reaction solution was concentrated in vacuo, it was extracted three times with EA (20 ml). The organic layer was separated, dried over anhydrous sodium sulfate, concentrated, and passed through column chromatography to obtain Intermediate 1-4 with a yield of 90%.
87%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3.0h;	To a stirred solution of 77 (20.0 g, 109.0 mmol), in DMF (100.0 mL) wasadded 3-nitrophenol (15.10 g, 109.0 mmol) and K2C03 (16.0 g, 116.0 mmol) and the reaction mixture was heated at 60C for 3h. It was then cooled, ice cooled water (150 mL) was added, precipitation was observed that was filtered through sintered funnel. Filter cake was washed with ether (50 mL) and concentrated under reduced pressure. The residue obtained was further purified via column chromatography (Si02, 100- 200 mesh,10% EtOAc-hexane) to obtain 2,5-dichloro-4-(3-nitrophenoxy)pyrimidine 116 (27 g,87% yield) as white solid. 1HNMR (400 MHz, DMSO): 9.88 (s, 1H), 8.29 (t, 1H), 8.23(dd, 1H), 8.02 (dd, 1H), 7.68 (t, 1H).
87%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2.0h;	Potassium carbonate (2.26 g, 16.4 mmol) and 2,4,5-trichloropyrimidine (1.5 g, 8.19 mmol) were added to a solution of 3-nitrophenol (1.2 g, 8.19 mmol) in N,N-dimethylformamide (20 mL). The reaction mixture was heated to 60 C. for 2 hours and after cooling was filtered and the filtrate was dilute with ethyl acetate (3*500 mL) and washed with water (20 mL) three times. The organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to afford 2.0 g (yield 87%) of a light yellow solid. 1H NMR 400 MHz (DMSO-d6) δ 8.88 (s, 1H), 8.30 (d, J=2 Hz, 1H), 8.29-8.21 (m, 1H), 7.85-7.81 (m, 2H); LCMS m/e: 286 [M]+.

86%	With potassium carbonate; In N,N-dimethyl-formamide; for 2.0h;Heating;	Potassium carbonate (0.75 g, 5.45 mmol) and 2,4,5-trichloropyrimidine(0.50 g, 2.72 mmol) were added to a solution of 3-nitrophenol(0.38 g, 2.72 mmol) in DMF (10 mL). The reaction washeated to 60 C and stirred for 2 h. Then it was cooled to ambienttemperature and filtered through celite. The filtrate was dilutedwith ethyl acetate (20 mL) and washed with 1 M HCl (20 mL),water (10 mL) and brine (10 mL). The organic layer was dried overanhydrous sodium sulfate and concentrated to afford 0.67 g of titlecompound 8 (2.34 mmol, 86%) as light yellow solid. The productwas used without further purification.
86.9%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2.0h;	General procedure: To a solution of 3-nitrophenol (CAS: 554-84-7) (14.3 mmol,1 eq)in DMF (40 mL) was added potassium carbonate (28.6 mmol, 2 eq)and 2, 4, 5-trichloropyrimidine (CAS: 5750-76-5) or 2, 4-dichloropyrimidine (CAS: 3934-20-1) (14.3 mmol, 1 eq). The reactionwas heated to 60 C for 2 h. The reaction liquid was cooled toroom temperature and then added to the ice water while stirring.The mixture was filtered, and the solid was washed three timeswith ethyl acetate. The white solid was obtained, which was usedwithout further purification. 4.1.3.1. 2, 5-dichloro-4-(3-nitrophenoxy)pyrimidine (6a, CAS: 76661-24-0). White solid, 86.9% yield; 1H NMR (500 MHz, DMSO-d6)d 8.89 (s, 1H), 8.30 (t, J 2.2 Hz, 1H), 8.23 (ddd, J 8.0, 2.2, 1.2 Hz,1H), 7.85 (ddd, J 8.2, 2.3, 1.2 Hz, 1H), 7.82 (t, J 8.1 Hz, 1H).
78%	With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 2.0h;	General procedure: To a solution of ortho, meta or para nitrophenol (1.21 g, 8.72 mmol) in DMF (20 mL) was added potassium carbonate (2.42 g, 17.5 mmol) and 2,4,5-trichloropyrimidine (1.0 mL, 8.72 mmol). The mixture was heated at 90 C with stirring for 2 h until the reaction was completed. The reaction mixture was filtered, the filtrate was diluted with ethyl acetate (30 mL) and washed three times with water (3 x 20 mL). The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated to afford a light yellow solid. The crude product was then purified by flash silica gel chromatography using hexane and ethyl acetate (7:3) to obtain the desired products in yields ranging from 78 - 83%.
280 g	With potassium carbonate; In N,N-dimethyl-formamide; at 27 - 50℃; for 3.0h;	The control temperature is 27 C lower, will 198g type 1 illustrated compound 2, 4, 5-trichloro pyrimidine containing to 300g of potash 750mlDMF in the solvent, then adding 150g type 2 compound 3-nitro phenol, then the control temperature is 50 C, reaction 3 hours. TLC in the reaction process (PE:EA=10:1) monitoring after the reaction is complete, the reaction solution is poured into the 15 times in volume of water, drying the concentrated precipitate takes organizing compound layer solid; then filtering, the filter cake is washed with methanol after washing eluviation drying, by preparing 280g formula 3 illustrated compound 2,5-dichloro-4 - (3-nitrophenoxy) pyrimidine.
	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2.0h;Inert atmosphere;	Will be a meta-nitro phenol (5 g, 35.9 mmol) dissolved in N, N - dimethyl formamide (80 ml) in, adding potassium carbonate (9.9 g, 71.8 mmol), the reaction bottle slowly dropping in the 2, 4, 5 - trichloro pyrimidine (1 A) (6.6 g, 35.9 mmol), 60 C reaction 2 hours. After the reaction, cooling to room temperature, adding ethyl acetate (80 ml), washed with water (80 ml × 3), saturated salt water washing (80 ml × 1), anhydrous sodium sulfate drying, filtering, the filtrate is concentrated under reduced pressure to get the yellow solid of 2, 5 - dichloro -4 - (3 - nitrophenoxy) pyrimidine (1 B) the crude product (9.5 g, yield 92.2%), without further purification directly used for the next step reaction.

References: [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 4738 - 4748.
[2]Patent: CN111393377,2020,A .Location in patent: Paragraph 0071; 0074; 0084-0086.
[3]Patent: WO2015/25197,2015,A1 .Location in patent: Paragraph 000204.
[4]Patent: US2018/208564,2018,A1 .Location in patent: Paragraph 0379-0380.
[5]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 2767 - 2780.
[6]European Journal of Medicinal Chemistry,2021,vol. 210.
[7]Bioorganic and Medicinal Chemistry Letters,2017,vol. 27,p. 4832 - 4837.
[8]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 638 - 643.
[9]Patent: WO2013/169401,2013,A1 .Location in patent: Page/Page column 48.
[10]European Journal of Medicinal Chemistry,2014,vol. 77,p. 75 - 83.
[11]Patent: CN105777652,2016,A .Location in patent: Paragraph 0025; 0026.
[12]Patent: CN106916112,2017,A .Location in patent: Paragraph 0038; 0060; 0061; 0062; 0063; 0064; 0065.

Historical Records

Technical Information

• Alkyl Halide Occurrence • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Hiyama Cross-Coupling Reaction • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Nomenclature of Ethers • Preparation of Alkylbenzene • Preparation of Ethers • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Ethers • Stille Coupling • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Vilsmeier-Haack Reaction

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P401
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Health hazards
Code	Phrase
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H302	Harmful if swallowed
H303	May be harmful if swallowed
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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

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CAS No.: 76661-24-0

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CAS No.: 76661-24-0

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