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[ CAS No. 2273-93-0 ] {[proInfo.proName]}

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Chemical Structure| 2273-93-0
Chemical Structure| 2273-93-0
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Product Details of [ 2273-93-0 ]

CAS No. :2273-93-0 MDL No. :MFCD00039690
Formula : C6H4Cl2N4 Boiling Point : -
Linear Structure Formula :- InChI Key :HVMUWHZAZGTMJK-UHFFFAOYSA-N
M.W : 203.03 Pubchem ID :75281
Synonyms :

Calculated chemistry of [ 2273-93-0 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 9
Fraction Csp3 : 0.17
Num. rotatable bonds : 0
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 46.61
TPSA : 43.6 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.13 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.78
Log Po/w (XLOGP3) : 1.98
Log Po/w (WLOGP) : 1.67
Log Po/w (MLOGP) : 0.93
Log Po/w (SILICOS-IT) : 1.75
Consensus Log Po/w : 1.62

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.9
Solubility : 0.255 mg/ml ; 0.00126 mol/l
Class : Soluble
Log S (Ali) : -2.52
Solubility : 0.611 mg/ml ; 0.00301 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.97
Solubility : 0.22 mg/ml ; 0.00108 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.72

Safety of [ 2273-93-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338-P310 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 2273-93-0 ]

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

  • Upstream synthesis route of [ 2273-93-0 ]
  • Downstream synthetic route of [ 2273-93-0 ]

[ 2273-93-0 ] Synthesis Path-Upstream   1~10

  • 1
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2382-10-7 ]
  • [ 2273-93-0 ]
YieldReaction ConditionsOperation in experiment
66% With potassium carbonate In acetonitrile at 20℃; for 70 h; 2, 6-dichloropurine (5.0 gram), methyl iodide (1. 1 eq. , 1.81 mL) and K.) C03 (1.2 eq. , 4.39 gram) were dissolved in 200 mL of MECN. After stirring for 70 hours at 20°C, the MECN was evaporated. Both isomers were separated by column chromatography using CH2C12/MEOH (90/10). Yield: 3.55 g (66percent) of intermediate 33 and 1.61 g (30percent) of intermediate 40.
66% With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 0.5 h; Inert atmosphere Step 1: Preparation of 2,6-dichloro-9-methyl-9H-purine and 2,6-dichloro-7-methyl-7H-purine (a-2) To a solution of 2,6-dichloropurine (1.10 g, 5.82 mmol) in anhydrous THF (5.0 mL) was added tetra-n-butylammonium fluoride (0.58 mL, 10.58 mmol, 1.8 eq; 1M in THF). Methyl iodide (0.40 mL, 6.42 mmol, 1.1 eq) was added, and the reaction mixture was stirred at RT under N2 for 30 minutes. The reaction mixture was then diluted with ethyl acetate (250 mL). The organic layer was washed with aqueous saturated sodium thiosulfate solution, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 5 to 100percent ethyl acetate in hexane) to give 2,6-dichloro-9-methyl-9H-purine (a-2) as a white solid (780 mg, 66percent) followed by gradient 0 to 30percent methanol in ethyl acetate to give 2,6-dichloro-7-methyl-7H-purine (a-3) as a white solid (346 mg, 29.3percent). 1H NMR of 2,6-dichloro-9-methyl-9H-purine (DMSO-d6, 400 MHz) δ ppm 8.75 (s, 1H), 3.83 (s, 3H). 1H NMR of 2,6-dichloro-7-methyl-7H-purine (DMSO-d6, 400 MHz) δ ppm 8.80 (s, 1H), 4.09 (s, 3H).
43%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5 h; Inert atmosphere
Stage #2: at 0 - 25℃; for 17 h; Inert atmosphere
Intermediate 12.2,6-Dichloro-7-methyl-7H-purine To a solution of 2,6-dichloro-7H-purine (1.05 g, 5.56 mmol) in THF (8 mL) at 0 °C under nitrogen was added NaH (60percent in mineral oil, 525 mg, 13.1 mmol) in one portion and, after stirring for 30 min at 0 °C, iodomethane (0.38 mL, 6.12 mmol) was added. The mixture was stirred at 0 °C for 1 h and then at room temperature for 16 h. After this time, the reaction mixture was diluted with EtOAc and washed with water and brine. The organic layer was concentrated under reduced pressure and the residue obtained was purified by column chromatography (silica, 0–30percent EtOAc in CH2Cl2) to provide isomers 2,6-dichloro-9-methyl-9H-purine (491 mg, 43percent) and 2,6-dichloro-7- methyl-7H-purine (312 mg, 28percent): ESI MS (M+H) 203; 2,6-dichloro-9-methyl-9H-purine 1H NMR (300 MHz, DMSO-d6) G 8.69 (s, 1H), 3.83 (s, 3H) and 2,6-dichloro-7-methyl- 7H-purine 1H NMR (300 MHz, DMSO-d6) G 8.81 (s, 1H), 4.07 (s, 3H).
11%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.5 h; Cooling with ice
Sodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice-cooled solution of 2,6-dichloropurine (10.0 g, 52,9 mmol) in tetrahydrofuran (75 ml_) and the mixture was stirred for 30 min. Methyl iodide (3.29 ml_, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7/-/-puhne (1.19 g, 11 percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl- 9H-puhne (3.0 g, 28percent)
28%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.5 h;
Sodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice-cooled solution of 2,6-dichloropurine (10.0 g, 52,9 mmol) in tetrahydrofuran (75 mL) and the mixture was stirred for 30 min. Methyl iodide (3.29 mL, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7H-purine (1.19 g, 11percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl-9H-purine (3.0 g, 28percent).

Reference: [1] Patent: WO2005/28479, 2005, A2, . Location in patent: Page/Page column 58
[2] Patent: US2011/86841, 2011, A1, . Location in patent: Page/Page column 25
[3] Patent: WO2016/115434, 2016, A1, . Location in patent: Page/Page column 222; 223
[4] Patent: WO2010/34707, 2010, A1, . Location in patent: Page/Page column 15
[5] Patent: US2011/251217, 2011, A1, . Location in patent: Page/Page column 6-7
[6] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 15, p. 4622 - 4626
[7] Patent: WO2010/34706, 2010, A1, . Location in patent: Page/Page column 15
[8] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 18, p. 5097 - 5104
  • 2
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2382-10-7 ]
  • [ 2273-93-0 ]
YieldReaction ConditionsOperation in experiment
27% With potassium carbonate In acetone at 20℃; for 1.5 h; To a solution of dichloropurine 27 (1.36 g, 7.20 mmol) was dissolved in acetone (22.7 mL) and potassium carbonate (1.49 mg, 10.8 mmol) was added at room temperature. Methyl iodide (537 i.il, 8.67 mmol) was added and the mixture was stirred for 1.5 h at room temperature. The reaction mixture was concentrated, water was added to the residue and stirred stirred for 5 mm, and then extracted with ethyl acetate (2 x 100 ml). The combined organic layers were dried on Mg504, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography. Compound 29 was the major product formed (952 mg, 65percent) and was obtained as off-white solid and compound 28 was the minor product (389 mg, 27percent) aslo isolated pure as an off-white solid; these results are consistant with the literature (for example WO 2010/034706)
30% With potassium carbonate In acetonitrile at 20℃; for 70 h; Example 1; Synthesis of 2,6-dichloro-7-methyl-7H-purine from 3,7 dimethyl-1H-purine 2,6(3H,7H) dione (theobromine) (a-2) 2,6 dichloro-7-methyl-7H-purine was prepared from theobromine (a-1) in 10percent yield following the procedure of Uretskaya,G. Ya., Rybinka, E. I., and Men'shikov, G. P. Zh. Obshch. Ki., 1960, 30, 327 with the modification of N,N, diethylaniline disclosed by Stanovik, B. et at in the Australian Journal of Chemistry, 1981, 34, 1729. 1H NMR was identical in all respects to the material prepared by alkylation of commercially available 2,6 dichloropurine with base and iodomethane. For example, the procedure reported by Feng et al. (WO2004/087053) utilizes 60percent NaH as base, dimethylformamide (DMF) as the solvent and iodomethane yielded a 1:1 mixture of the N-7/N-9 methylated products which were separated via silica chromatography. The procedure reported by Lewi et et al (WO2005/028479 A2) utilizes potassium carbonate as the base, acetonitrile as solvent (rt 70 h) and iodomethane and yielded a 2:1 isolated yield of methylated purines after silica chromatography (60percent yield N9Me/30percent yield N-7 Methylated). Similarly acetone can replace acetonitrile as the solvent and after refluxing with potassium carbonate and iodomethane for 24 h a 3:1 mixture of N9/N7 is obtained. The N-7 methylated product was isolated in 16.3percent purified yield after silica chromatography. A report by Chi-Huey Wong et al. (see, Bioorg Med Chem 13 (2005) 4622-4626) utilizes tetrabutylammonium fluoride as the base (1M solution THF) and iodomethane to give similarily a 3:1 ratio of the N-9/N-7 methylated purines which could be separated by silica chromatography. 1H NMR (400 MHz, DMSO d&6) 8.79 (s, 1H, H8), 4.06 (s, 3H, N7Me).
11%
Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 0.5 h;
Example 12,6-Dichloro-9-methyl-9/-/-purine and 2,6-Dichloro-7-methyl-7/-/-purineSodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice- cooled solution of 2,6-dichloropuhne (10.0 g, 52.9 mmol) in tetrahydrofuran (75 ml_) and the mixture was stirred for 30 min. Methyl iodide (3.29 ml_, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7/-/-purine (1.19 g, 11 percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl-9/-/-purine (3.0 g, 28percent).
Reference: [1] Patent: WO2018/137036, 2018, A1, . Location in patent: Paragraph 00231; 00232
[2] Patent: US2011/86840, 2011, A1, . Location in patent: Page/Page column 29
[3] Patent: WO2008/116909, 2008, A1, . Location in patent: Page/Page column 22
  • 3
  • [ 2273-93-0 ]
  • [ 16017-76-8 ]
Reference: [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 5, p. 846
[2] Chemische Berichte, 1897, vol. 30, p. 2414[3] Chemische Berichte, 1898, vol. 31, p. 545 Anm.
  • 4
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2382-10-7 ]
  • [ 2273-93-0 ]
YieldReaction ConditionsOperation in experiment
66% With potassium carbonate In acetonitrile at 20℃; for 70 h; 2, 6-dichloropurine (5.0 gram), methyl iodide (1. 1 eq. , 1.81 mL) and K.) C03 (1.2 eq. , 4.39 gram) were dissolved in 200 mL of MECN. After stirring for 70 hours at 20°C, the MECN was evaporated. Both isomers were separated by column chromatography using CH2C12/MEOH (90/10). Yield: 3.55 g (66percent) of intermediate 33 and 1.61 g (30percent) of intermediate 40.
66% With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; for 0.5 h; Inert atmosphere Step 1: Preparation of 2,6-dichloro-9-methyl-9H-purine and 2,6-dichloro-7-methyl-7H-purine (a-2) To a solution of 2,6-dichloropurine (1.10 g, 5.82 mmol) in anhydrous THF (5.0 mL) was added tetra-n-butylammonium fluoride (0.58 mL, 10.58 mmol, 1.8 eq; 1M in THF). Methyl iodide (0.40 mL, 6.42 mmol, 1.1 eq) was added, and the reaction mixture was stirred at RT under N2 for 30 minutes. The reaction mixture was then diluted with ethyl acetate (250 mL). The organic layer was washed with aqueous saturated sodium thiosulfate solution, water and brine, then dried (Na2SO4), filtered and evaporated in vacuo. The resultant residue was purified by column chromotagraphy (Si-PPC, gradient 5 to 100percent ethyl acetate in hexane) to give 2,6-dichloro-9-methyl-9H-purine (a-2) as a white solid (780 mg, 66percent) followed by gradient 0 to 30percent methanol in ethyl acetate to give 2,6-dichloro-7-methyl-7H-purine (a-3) as a white solid (346 mg, 29.3percent). 1H NMR of 2,6-dichloro-9-methyl-9H-purine (DMSO-d6, 400 MHz) δ ppm 8.75 (s, 1H), 3.83 (s, 3H). 1H NMR of 2,6-dichloro-7-methyl-7H-purine (DMSO-d6, 400 MHz) δ ppm 8.80 (s, 1H), 4.09 (s, 3H).
43%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.5 h; Inert atmosphere
Stage #2: at 0 - 25℃; for 17 h; Inert atmosphere
Intermediate 12.2,6-Dichloro-7-methyl-7H-purine To a solution of 2,6-dichloro-7H-purine (1.05 g, 5.56 mmol) in THF (8 mL) at 0 °C under nitrogen was added NaH (60percent in mineral oil, 525 mg, 13.1 mmol) in one portion and, after stirring for 30 min at 0 °C, iodomethane (0.38 mL, 6.12 mmol) was added. The mixture was stirred at 0 °C for 1 h and then at room temperature for 16 h. After this time, the reaction mixture was diluted with EtOAc and washed with water and brine. The organic layer was concentrated under reduced pressure and the residue obtained was purified by column chromatography (silica, 0–30percent EtOAc in CH2Cl2) to provide isomers 2,6-dichloro-9-methyl-9H-purine (491 mg, 43percent) and 2,6-dichloro-7- methyl-7H-purine (312 mg, 28percent): ESI MS (M+H) 203; 2,6-dichloro-9-methyl-9H-purine 1H NMR (300 MHz, DMSO-d6) G 8.69 (s, 1H), 3.83 (s, 3H) and 2,6-dichloro-7-methyl- 7H-purine 1H NMR (300 MHz, DMSO-d6) G 8.81 (s, 1H), 4.07 (s, 3H).
11%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.5 h; Cooling with ice
Sodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice-cooled solution of 2,6-dichloropurine (10.0 g, 52,9 mmol) in tetrahydrofuran (75 ml_) and the mixture was stirred for 30 min. Methyl iodide (3.29 ml_, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7/-/-puhne (1.19 g, 11 percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl- 9H-puhne (3.0 g, 28percent)
28%
Stage #1: With sodium hydride In tetrahydrofuran; mineral oil for 0.5 h;
Sodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice-cooled solution of 2,6-dichloropurine (10.0 g, 52,9 mmol) in tetrahydrofuran (75 mL) and the mixture was stirred for 30 min. Methyl iodide (3.29 mL, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7H-purine (1.19 g, 11percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl-9H-purine (3.0 g, 28percent).

Reference: [1] Patent: WO2005/28479, 2005, A2, . Location in patent: Page/Page column 58
[2] Patent: US2011/86841, 2011, A1, . Location in patent: Page/Page column 25
[3] Patent: WO2016/115434, 2016, A1, . Location in patent: Page/Page column 222; 223
[4] Patent: WO2010/34707, 2010, A1, . Location in patent: Page/Page column 15
[5] Patent: US2011/251217, 2011, A1, . Location in patent: Page/Page column 6-7
[6] Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 15, p. 4622 - 4626
[7] Patent: WO2010/34706, 2010, A1, . Location in patent: Page/Page column 15
[8] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 18, p. 5097 - 5104
  • 5
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2273-93-0 ]
YieldReaction ConditionsOperation in experiment
22% With potassium carbonate In acetonitrile at 40℃; for 6 h; A mixture of 2,6-dichloro-7H-purine (5.0 g, 26.7 mmol), K2C03 (5.52 g, 40 mmol) and Mel (7.58 g, 53.4 mmol) in acetonitrile (50 mL) was heated to 40 °C for 6 hrs. The reaction was cooled to r.t., filtered, and concentrated to provide a crude mixture of regioisomeric products which were separated by column chromatography. The desired isomer, 2,6-dichloro-7-methyl-7H-purine, was isolated as a white solid white solid (1.2 g, 22percent).
Reference: [1] Patent: WO2015/175813, 2015, A1, . Location in patent: Paragraph 00425; 00426
  • 6
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2273-93-0 ]
Reference: [1] Organic Letters, 2016, vol. 18, # 1, p. 16 - 19
  • 7
  • [ 5451-40-1 ]
  • [ 74-88-4 ]
  • [ 2382-10-7 ]
  • [ 2273-93-0 ]
YieldReaction ConditionsOperation in experiment
27% With potassium carbonate In acetone at 20℃; for 1.5 h; To a solution of dichloropurine 27 (1.36 g, 7.20 mmol) was dissolved in acetone (22.7 mL) and potassium carbonate (1.49 mg, 10.8 mmol) was added at room temperature. Methyl iodide (537 i.il, 8.67 mmol) was added and the mixture was stirred for 1.5 h at room temperature. The reaction mixture was concentrated, water was added to the residue and stirred stirred for 5 mm, and then extracted with ethyl acetate (2 x 100 ml). The combined organic layers were dried on Mg504, filtered and concentrated under reduced pressure. The crude residue was purified by column chromatography. Compound 29 was the major product formed (952 mg, 65percent) and was obtained as off-white solid and compound 28 was the minor product (389 mg, 27percent) aslo isolated pure as an off-white solid; these results are consistant with the literature (for example WO 2010/034706)
30% With potassium carbonate In acetonitrile at 20℃; for 70 h; Example 1; Synthesis of 2,6-dichloro-7-methyl-7H-purine from 3,7 dimethyl-1H-purine 2,6(3H,7H) dione (theobromine) (a-2) 2,6 dichloro-7-methyl-7H-purine was prepared from theobromine (a-1) in 10percent yield following the procedure of Uretskaya,G. Ya., Rybinka, E. I., and Men'shikov, G. P. Zh. Obshch. Ki., 1960, 30, 327 with the modification of N,N, diethylaniline disclosed by Stanovik, B. et at in the Australian Journal of Chemistry, 1981, 34, 1729. 1H NMR was identical in all respects to the material prepared by alkylation of commercially available 2,6 dichloropurine with base and iodomethane. For example, the procedure reported by Feng et al. (WO2004/087053) utilizes 60percent NaH as base, dimethylformamide (DMF) as the solvent and iodomethane yielded a 1:1 mixture of the N-7/N-9 methylated products which were separated via silica chromatography. The procedure reported by Lewi et et al (WO2005/028479 A2) utilizes potassium carbonate as the base, acetonitrile as solvent (rt 70 h) and iodomethane and yielded a 2:1 isolated yield of methylated purines after silica chromatography (60percent yield N9Me/30percent yield N-7 Methylated). Similarly acetone can replace acetonitrile as the solvent and after refluxing with potassium carbonate and iodomethane for 24 h a 3:1 mixture of N9/N7 is obtained. The N-7 methylated product was isolated in 16.3percent purified yield after silica chromatography. A report by Chi-Huey Wong et al. (see, Bioorg Med Chem 13 (2005) 4622-4626) utilizes tetrabutylammonium fluoride as the base (1M solution THF) and iodomethane to give similarily a 3:1 ratio of the N-9/N-7 methylated purines which could be separated by silica chromatography. 1H NMR (400 MHz, DMSO d&6) 8.79 (s, 1H, H8), 4.06 (s, 3H, N7Me).
11%
Stage #1: With sodium hydride In tetrahydrofuran at 0℃; for 0.5 h;
Example 12,6-Dichloro-9-methyl-9/-/-purine and 2,6-Dichloro-7-methyl-7/-/-purineSodium hydride (60percent in mineral oil, 2.53 g, 63.5 mmol) was added to an ice- cooled solution of 2,6-dichloropuhne (10.0 g, 52.9 mmol) in tetrahydrofuran (75 ml_) and the mixture was stirred for 30 min. Methyl iodide (3.29 ml_, 52.9 mmol) was added drop-wise and the reaction mixture was stirred over night. Water was added and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulphate, filtered and concentrated in vacuo. Dichloromethane was added and undissolved material was collected by filtration. The crystalline compound turned out to be 2,6-dichloro-7-methyl-7/-/-purine (1.19 g, 11 percent) The filtrate was concentrated in vacuo and purified by flash chromatography (ethyl acetate/hepatane) to give 2,6-dichloro-9-methyl-9/-/-purine (3.0 g, 28percent).
Reference: [1] Patent: WO2018/137036, 2018, A1, . Location in patent: Paragraph 00231; 00232
[2] Patent: US2011/86840, 2011, A1, . Location in patent: Page/Page column 29
[3] Patent: WO2008/116909, 2008, A1, . Location in patent: Page/Page column 22
  • 8
  • [ 83-67-0 ]
  • [ 2273-93-0 ]
Reference: [1] Chemistry of Heterocyclic Compounds, 2000, vol. 36, # 1, p. 74 - 76
[2] Chemische Berichte, 1897, vol. 30, p. 2414[3] Chemische Berichte, 1898, vol. 31, p. 545 Anm.
[4] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 18, p. 5097 - 5104
[5] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 5, p. 845,846
  • 9
  • [ 552-62-5 ]
  • [ 2273-93-0 ]
Reference: [1] Journal of the American Chemical Society, 1957, vol. 79, p. 6401,6405
  • 10
  • [ 83-67-0 ]
  • [ 10025-87-3 ]
  • [ 2273-93-0 ]
Reference: [1] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 5, p. 844
[2] Chemische Berichte, 1897, vol. 30, p. 2414[3] Chemische Berichte, 1898, vol. 31, p. 545 Anm.
[4] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 5, p. 845,846
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