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[ CAS No. 104227-87-4 ]

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Chemical Structure| 104227-87-4
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CAS No. :104227-87-4 MDL No. :MFCD00866964
Formula : C14H19N5O4 Boiling Point : 550.2°C at 760 mmHg
Linear Structure Formula :- InChI Key :N/A
M.W :321.33 g/mol Pubchem ID :3324
Synonyms :

1. Famciclovir

Safety of [ 104227-87-4 ]

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

Application In Synthesis of [ 104227-87-4 ]

  • Upstream synthesis route of [ 104227-87-4 ]
  • Downstream synthetic route of [ 104227-87-4 ]

[ 104227-87-4 ] Synthesis Path-Upstream   1~50

  • 1
  • [ 108-24-7 ]
  • [ 104227-86-3 ]
  • [ 104227-87-4 ]
YieldReaction ConditionsOperation in experiment
90% With triethylamine In dichloromethane at 20 - 30℃; for 10 h; To a dry 1 L flask were added the intermediate diol 5 (50 g, 21.5 mmol), dichloromethane (500 ml), triethylamine (31 g, 30.6 mmol) and catalytic dimethylaminopyridine (3.1 g). The acetic anhydride (120 g, 31 mmol) was then added dropwise, keeping the solution at 2530° C. The reaction mixture was stirred at room temperature for 10 hours. Water was added to dilute the reaction mixture, and 5percent Sodium hydroxyl solution (5percent) was added till the solution turned neutral. The separated organic layer was washed with water (200 ml.x.2), saturated brine and dried by sodium sulphate. The dichloromethane was then removed under reduced pressure, and residue was dissolved with boiling methanol (180 ml). The famciclovir crystallized out by keeping the methanol solution at 04° C. for 4 hours (60 g, yield 90percent).
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
[2] Patent: US2006/264629, 2006, A1, . Location in patent: Page/Page column 4; 5
[3] Nucleosides and Nucleotides, 1996, vol. 15, # 5, p. 981 - 994
[4] Patent: WO2008/72074, 2008, A1, . Location in patent: Page/Page column 12; 13; 13-14
[5] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
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YieldReaction ConditionsOperation in experiment
91%
Stage #1: With triethylamine In dichloromethane at 10 - 20℃;
Stage #2: With dmap In dichloromethane at 5 - 20℃;
Example 11Preparation of 9-[4-acetoxy-3-(acetoxymethyl)but-1-yl]-2-aminopurine (famciclovir)2-Amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine Hydrochloride (75 g) was suspended in methylene dichloride (300 ml) and cooled to 10-20° C. Triethylamine (91 g) diluted with methylene dichloride (50 ml) was added over a period of 15-20 min. 4-(dimethylamino pyridine) (DMAP, 0.5 g) was added at 10-20° C. and the slurry was cooled to 5-8° C. Acetic anhydride (65 g) diluted with methylene dichloride (200 ml) was added slowly over 60 min at 5-10° C. Reaction mass was stirred for 2 h at 5-10 and hydrogen chloride solution in ethanol (15 ml) was added. The solution was stirred for 10 min and methylene dichloride was evaporated under reduced pressure at 30-35° C. To the residue water (375 ml) was added and distilled to remove residual methylene dichloride. The aqueous solution was treated with activated carbon (4 g). The clear filtrate was cooled to 10-15° C. and seeded with famciclovir (0.10 g). Stirring was continued for 6 h to complete the crystallization of product. The product slurry was cooled to 5-10° C. and maintained for 2 h. Product was filtered and washed with chilled water (70 ml, 4-6° C.) and dried under reduced pressure at approximately at 50° C. till constant weight to give title compound.Yield: 73 gChromatographic purity (HPLC): 99.3percentThe above obtained product (73 g) was dissolved was dissolved in ethyl acetate (440 ml) at 50-60° C. and filtered through hyflo. The clear filtrate was concentrated under vacuum at 55-60° C. to distill out ethyl acetate (approximately 250 ml). To the concentrate, hexane (270 ml) was added at 40-45° C. and slurry was cooled to 5-8° C. It was stirred at 5-8° C. for 60 min and filtered. The product obtained was washed with chilled hexane (65 ml) and dried till constant weight.Yield: 66.5 g (91percent)
Reference: [1] Patent: US2010/137592, 2010, A1, . Location in patent: Page/Page column 8
[2] Tetrahedron, 2000, vol. 56, # 26, p. 4589 - 4595
[3] Patent: WO2008/155613, 2008, A1, . Location in patent: Page/Page column 17-18
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YieldReaction ConditionsOperation in experiment
90.9% With water; ammonium formate In ethyl acetate for 2 h; Into a jacketed reactor equipment with a mechanical stirrer, a reflux condenser and a thermocouple, under an inert atmosphere (N2), was added wet 10 percent PD/C (4 g, 50 percent HA0), EtOAc (220 ml), C1-FMC (20 g; 56.1 mmol) and ammonium formate (4.37 G ; 67.28 mmol ; 20 percent excess). The reaction was completed after 2 hours, as all the CL-FMC was consumed. The reaction mixture was filtered at 50°C and the filtrate was evaporated to dryness, leaving 16.4 g of solid (90.9 percent of the 18 g expected).
90% With ammonium formate In methanol; water Example 2
9-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-aminopurine
A suspension of 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-chloropurine (0.36g, 1.0mmol) and 10percent palladium-on-charcoal (30mg) in methanol containing ammonium formate (400mM , 10ml) was heated under reflux for 30 minutes.
The mixture was allowed to cool, filtered and the solvent removed.
The residue was taken up in water and the solution extracted twice with chloroform.
The organic layers were combined, dried (magnesium sulphate) and the solvent removed to afford 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-aminopurine (0.29g, 90percent).
Recrystallisation from ethyl acetate-hexane gave white shiny plates (0.25g, 78percent) m.p. 102-104°C; λmax (MeOH) 222 (27,500), 244 (4,890), and 309 (7,160)nm; νmax (KBr) 3340, 3170, 1745, 1730, 1660, 1615 and 1580cmmin1; δH(CDCl3) 1.90-2.05 (3H, m, 2'-H and 3'-H), 2.07 (6H, s, 2 x CH3), 4.15 (4H, d, J 5.2 Hz, 2x4'-H), 4.21 (2H, t, J 7.2Hz, 1'-H), 5.16 (2H, br s, 2-NH2), 7.79 (1H, s, 8-H), and 8.70 (1H, s, 6-H); (Found: C, 52.10; H, 6.00; N, 21.49percent. C14H19N5O4 requires C, 52.33; H, 5.96; N, 21.79percent).
90% With ammonium formate In methanol for 2 h; Heating / reflux A mixture of 9-[4-acetoxy-3-(acetoxymethyl)butyl]-2-amino-6-chloro-purine (28.1 mmoles, 10 g), prepared according to Example 3 or 4, 10percent palladium on charcoal (0.833 g) and ammonium formate (4 eq/mole, 7.08 g) in methanol (270 ml) is refluxed for 2 h under stirring. The mixture is cooled to room temperature and filtered and the filtrate is evaporated under reduced pressure to give a thick, colourless oil. The residue is then taken up into water (150 ml) and extracted with chloroform (2x100 ml). The combined organic phases are dried over anhydrous sodium sulfate and evaporated under reduced pressure. The crude is purified by crystallization from ethyl acetate/hexane to afford 9-[4-acetoxy-3-(acetoxymethyl)butyl]-2-aminopurine (8.19 g) in a 90percent yield.1H-NMR (CDC13) (d, ppm): 1.87-1.95 (m, 3H, CH and CH2) 2.00 (s, 6H, 2xCH3) 4.07 (d, 4H, 2xCH2O) 4.18 (t, 2H, CH2N) 5.17 (br, 2H, NH2) 7.72 (s, 1H, CH) 8.63 (s, 1H, CH).13C-NMR (CDC13) (d, ppm): 20.82 (2xCH3) 28.83 (CH2) 34.95 (CH) 40.79 (CH2N) 63.65 (2xOCH2) 128.21 () 142.16 (C) 149.90 (CH) 153.20 (C) 159.95 (C) 170.70 (2xCO). EI-MS: 321 m/z (M+).
75% With ammonium formate In ethyl acetate at 70℃; for 5 h; Cl-FMC (145 g), 10 percent PD/C (28. 92 g), and ammonium formate (31.7 g) were dissolved in EtOAc (1,450 ml) at 70°C. After 5 hours hot filtration was performed, the solution was concentrated by distillation of EtOAc (vacuum, 41°C). After complete dissolution of the precipitated solid at 60°C, the solution was cooled for 1 hour to 5°C and left overnight before separating the resulting product. Reaction yield-75 percent (based on Cl- FMC).

Reference: [1] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 10
[2] Patent: EP182024, 1991, B1,
[3] Patent: WO2004/7418, 2004, A1, . Location in patent: Page 17
[4] Nucleosides and Nucleotides, 1996, vol. 15, # 5, p. 981 - 994
[5] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
[6] Journal of Medicinal Chemistry, 1989, vol. 32, # 8, p. 1738 - 1743
[7] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 11
[8] Patent: EP1852435, 2007, A1, . Location in patent: Page/Page column 5
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YieldReaction ConditionsOperation in experiment
89.7% With water; ammonium formate In ethyl acetate at 50℃; for 5 h; Into a jacketed reactor equipped with a mechanical stirrer, a reflux condenser and a thermocouple, under an inert atmosphere (N2), was added wet 10 percent Pd/C (12 g, 50 percent H20), EtOAc (660 ml), CL-FMC (60 g; 168.6 mmol), and ammonium formate (32.8 g; 504.5 mmol; 97 percent pure). The reaction mixture was heated at 50°C. After 5 hours, all the CL-FMC was consumed, and the composition of the reaction mixture showed 99.6 percent FMC, 0. 1 percent, of MH-FMC and traces of the DH-FMC. The reaction mixture was filtered at 50°C and the filtrate was evaporated to dryness, leaving 51.5 g of solid (95 percent of the 54.2 g expected). The solid was crystallized from n-BuOH (61°C ; 155 ml). After cooling in ice-water bath, filtration and drying (6 hrs ; 60°C) 48.6 g of pure FMC (89.7 percent yield) was obtained (99.8 percent FMC; MH-FMC level was less than 0.1 percent HPLC area percent).
62% With water; ammonium formate In ethyl acetate at 50 - 70℃; for 4 - 5 h; Into a jacketed reactor equipped with a mechanical stirrer and a reflux condenser, under an inert atmosphere (N2), was added wet 10 percent Pd/C (18.9 g, 52 percent H20), EtOAc (423 ml) AND CL-FMC (90 g; 252.9 mmol). The reaction mixture was heated to 70°C. Ammonium formate (19.7 g; 312.4 mmol) was added in 11 portions. The portions were added every 20 min. After 4 hours, all the Cl-FMC was consumed. The reaction mixture was diluted to 720 ml and filtered at 40°C. A charcoal (4.5 g) was added to the filtrate and the mixture was stirred for 30 min. Then the charcoal was filtered out and washed (90 ml) EtOAc. The wash was added to the filtrate. The filtrate was distillated back to 423 ml of EtOAc. Precipitation occurred during the distillation. The mixture was heated until a clear solution was obtained. Then the solution was cooled (4 hrs; 10°C) and precipitation occurred during the cooling process. After 12 hrs of stirring, the material was filtered out and was washed with water, and a wet famciclovir was obtained. The material was dried 3 hr at 45°C and 3 hr at 65°C. FMC (62 percent yield) was obtained (MH- FMC level was 0.03 percent HPLC).Example 13 Preparation of Acetic ACID 2-ACETOXYMETHYL-4-(2-AMINO-PURIN-9-YL)-BUTYL ester (FMC) from Acetic acid 2-acetoxymethyl-4- (5-amino-7-chloro-imidazo [4,5- B] PYRIDIN-3-YL)-BUTYL ester (Cl-FMC) Into a jacketed reactor equipped with a mechanical stirrer and a reflux condenser, under an inert atmosphere (N2), was added wet 10 percent PD/C (68. 7 g, 52 percent H20), EtOAc (1550 ml) and Cl-FMC (330 g ; 927. 5 MMOL). The reaction mixture was heated to 50°C. Ammonium formate (71.2 g; 1130.3 mmol) was added in 11 portions. The portions were added every 20 min. After 5 hours, all the Cl-FMC was consumed. The reaction mixture was diluted to 2640 ml and filtered at 50°C. A charcoal (16.5 g) was added to the filtrate and the mixture was stirred for 30 min. Then the charcoal was filtered out and washed (330 ML) OF ETOAC. The wash was added to the filtrate. The filtrate was DISTILLATED back TO 1, 550 ML OF EOTAC. The mixture was heated until a clear solution obtained. Then the solution was cooled (5.5 hrs ;-10°C) and precipitation occurred during the cooling process. After 12 hr of stirring, the material was filtered out and was washed with water, and a wet famciclovir was obtained. The material was dried 3 hr at 45°C and 3 hr at 65°C. FMC (69.8 percent yield) was obtained (MH-FMC level was 0.06 percent HPLC).
0.27 - 0.29 %Chromat.
Stage #1: at 20 - 42℃;
Stage #2: With ammonium formate In water for 3.5 - 7 h;
A MIXTURE OF 6. 2 G wet "10 percent Pd/C"(wt Pd/wt Pd+C) 52.14 percent H2O (wt H2O/wt of Pd+C+H2O), H2O (120 ml) and Cl-FMC (30 g; 83.1 mmol) was added, under an inert atmosphere of nitrogen, into a JACKETED REACTOR EQUIPMENT with a mechanical stirrer, a reflux condenser and a THERMOCOUPLE. THE MIXTURE WAS HEATED TO 42°C. A solution of ammonium FBNNATE (6. 5 g; 99.7 MMOL; 20 percent excess) in 20 ml H20 was added dropwise for 2. 5 HOURS. AFTER 30 min., charcoal (3 G) was added and the solution was continued to be stirred for an additional time of 30 min. The reaction mixture was filtered, and the catalyst was washed with 10 ml H2O. The filtrate was stirred for 2 hours in an ice bath (2°C). The precipitated solid was filtered and washed WITH 15 ML cold 20, LEAVING 31. 5 g wet solid precipitate. Upon drying, 22. 4 G of a very white solid was obtained (83. 6percent of the expected). The MH-FMC LEVEL WAS 0. 29percent and the FMC yield was 83.3 percent (HPLC area percent). Example 2 Preparation of Acetic acid 2-acetoxymethyl-4-(2-amino-purin-9-yl)-butyl ester (FMC) from 9-[4-acetoxy-3(acetoxymethyl)but-1-yl]-2-amino-6-chloropurine-(Cl- FMC) A MIXTURE OF 6. 2 G WET"10percent PD/C" (BASED on the weight of Pd+C) with 52. 14 percent H2O (wt H2O/wt of Pd+C+H2O), H2O (120 ml) and Cl-FMC (30 g; 83.1 MMOL) WAS ADDED,-UNDER AN INERT ATMOSPHERE OF NITROGEN, INTO a JACKETED REACTOR equipment with a MECHANICAL STIRRER, a reflux condenser and a thermocouple. The mixture was preheated to 35°C. A solution of ammonium formte (5.4 g; 83.1 mmole; 8.4percent in excess) in 20 ml H2O was added dropwise for 2.5 hours. After 30 MIN., CHARCOAL (3 G) WAS ADDED AND the solution was stirred for 30 min. The reaction mixture was filtered, and the catalyst obtained was washed with 10 ml H2O. The filtrate was stirred for 2 hours in an ice bath (2°C). The precipitated solid was filtered and washed with 15 ml cold H2O, leaving 31.5 g wet solid precipitate. Upon drying, 22. 4 g of a very white solid was obtained (81.3percent OF THE EXPECTED). THE MH-FMC level was 0.27percent and the CL-FMC was 0. 08percent (HPLC area percent). All other impurities levels were less than 0. 06percent (HPLC AREA percent). Example 3 PREPARATION OF ACETIC ACID 2-ACETOXYMETHYL-4- (2-AMINO-PUNN-9-YL)-BUTYL ESTER (FOC) FROM 9- [4-ACETOXY-3- (ACETOXYMETHYL) BUT-L-YL]-2-AMINO-6-CHLOROPUNNE (CL- FMC) Into A JACKETED REACTOR EQUIPMENT with a mechanical STIRRER, a reflux condenser and a thermocouple, under an inert atmosphere (N2), a mixture of wet"10 percent P LIJC (D 2 g, wherein the 10percent is based on THE COMBINED WEIGHT OFPD AND C, HAVING 52. 14 percent I20 (WT OF NZO/WT OF P+C+H2C3)),,-HSO (120 ML) and C1-FMC (30 G ; 83. 1 MMO .) was added. The mixture was maintained at room temperature. A solution of ammonium formate (5.4 g; 83. 1 mmole ; 8.4percent in excess) in 20 ML H20 was added DROPWISE FOR 6 HOURS. AFTER 30 MIN. , CHARCOAL (3 G) WAS ADDED AND THE SOLUTION WAS stirred for 30 min. The reaction mixture was filtered, and the catalyst was washed with 10 ml H20. The filtrate was stirred for 2 hours in an ice bath (2°C). The precipitated solid was filtered and washed with 15 ml cold H20, leaving 31.5 g wet solid precipitate. Upon drying, 22.4 g of a very white solid was obtained (81.3percent of the expected). The MH-FMC level was 0.27percent and the CL-FMC was 0. 08percent (HPLC area percent). All other impurities were less than 0. 06percent (HPLC area percent).
Reference: [1] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 10
[2] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 11-12
[3] Patent: WO2005/26167, 2005, A1, . Location in patent: Page/Page column 6-8
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YieldReaction ConditionsOperation in experiment
91% With pyridine; dmap; acetic anhydride In tetrahydrofuran; methanol c)
9-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-aminopurine STR34
To a suspension of 2-amino-9-(4-hydroxy-3-hydroxymethylbut-1-yl)purine (0.13 g, 0.55 mmol) in dry tetrahydrofuran (40 ml), stirred at room temperature under dry nitrogen were added pyridine (117 μl, 1.45 mmol) and 4-dimethylaminopyridine (5 mg, 41 μmol) followed by acetic anhydride (108 μl, 1.14 mmol).
The mixture was stirred at room temperature for 5 h. giving a clear, colourless solution. T.1.c. [chloroform/methanol (9:1)] showed the major product to be the title compound, rf=0.40.
Methanol (5 ml) was added, the mixture stirred for 5 mins.
then evaporated to dryness.
The residue was partitioned between water (5 ml) and chloroform (10 ml).
The aqueous portion was extracted with chloroform (4*10 ml) then the combined organic portions dried over magnesium sulphate, filtered and evaporated to leave a pale yellow glassy material which was column chromatographed on silica (20 g) [eluant=chloroform/methanol (19:1)] to give the title compound (0.16 g, 91percent) as a colourless viscous oil, which was crystallized from n-butanol (0.6 ml) to give colourless crystals (118 mg., 67percent), m.p. 102° C.
1 H n.m.r(CDCl3) 61.90(m,3H,--CH2 --+>CH--), 2.00(s,6H,--CH3), 4.05(d,4H,3 JHH =5 Hz,--CH2 --O), 4.10(t,2H,3 JHH =6 Hz,>NCH2 --), 5.35(br.s,2H,--NH2), 7.70(s,1H,H-8), 8.60(s,1H,H-6).
Reference: [1] Patent: US5175288, 1992, A,
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  • [ 104227-86-3 ]
  • [ 120687-07-2 ]
YieldReaction ConditionsOperation in experiment
64% With ammonium formate In methanol; acetic acid methyl ester at 40℃; for 6.16667 h; Into a jacketed reactor equipped with a mechanical stirrer, a reflux condenser and a thermocouple, under an inert atmosphere (N2), was added dry 7 percent Pd/C (3.48 g), MeOAc (500 ml), MEOH (50 ml), Cl-FMC (50.1 g; 49.6 mmol), and ammonium formate (27. 18 g; 97 percent pure). The reaction mixture was heated at 40°C for 6 hours and 10 min. At this stage 98. 37 percent FMC, 0.82 percent MH-FMC and 0.63 percent DH-FMC and 0.18 percent Cl- FMC; were detected. Upon cooling the reaction mixture and filtering the black solid, the filtrate was evaporated to dryness leaving 43.77 g solid (almost the entire expected amount of FMC; assay 97.3 percent FMC). The composition of the solid was left unchanged from the above quotation. The solid was partitioned in EtOAc (365 ml) and water (150 ml). The organic phase was washed with H20 (45 ml), and kept aside. The combined aqueous phases were washed with EtOAc (3 x 40 ml). The combined EtOAc extracts were washed with H20 (40 ml), and kept aside. The aqueous phases were extracted again with EtOAc (2 x 40 ml). The EtOAc extracts were washed with HA0 (10 ml), and kept aside. The three organic phases were combined, dried with MGS04 and evaporated to dryness leaving 34.7 g white solid (-76. 8 percent yield). The solid was crystallized in BUOH (100 ml; 63°C) giving 28.9 g pure FMC (64 percent yield). Less then 0.1 percent impurities (each) were detected in the crystals.
Reference: [1] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 6-7
[2] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 6-7
[3] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 8
[4] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 7-8
[5] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 8-9
[6] Patent: WO2004/99208, 2004, A1, . Location in patent: Page 9
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Reference: [1] Patent: US6342603, 2002, B1, . Location in patent: Example II-5
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YieldReaction ConditionsOperation in experiment
52% at 15 - 20℃; for 84 h; 16.92 g (50 mmole) of 2-aminopurine-thallium salt was suspended in 140 ml of N, N-dimethylformamide, and the temperature of a reactor was maintained below [15 °C.] The suspension was added slowly with a solution of 16.03 g (60 mmole) of 2-acetoxymethyl-4-bromobut-1-yl-acetate in 30 ml of N, N-dimethylformamide, followed by stirring for 84 hours at room temperature. At the end of the reaction, the stirred mixture was cooled and filtered, and then the filtrate was added with 100 ml of water. The solution was extracted three times with 70 ml of [CHC13,] and dried over magnesium sulfate, and then concentrated under reduced pressure to evaporate the solvent. The residue was crystallized from a mixed solvent of ethyl acetate, hexane and tert-butanol, to give 8.35 g [(52percent)] of [9- [4-ACETOXY-3- (ACETOXYMETHYL)] but- [1-YL]-2-AMINOPURINE.] Spectrum data analyzed for the compound obtained in Example 3 were identical to Example 2.
Reference: [1] Patent: WO2004/7497, 2004, A1, . Location in patent: Page 11-12
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YieldReaction ConditionsOperation in experiment
61% at 15 - 20℃; for 84 h; 16.92 g (50 mmole) of 2-aminopurine-thallium salt was suspended in 140 ml of N, N-dimethylformamide, and the temperature of a reactor was maintained below [15 °C.] The suspension was added slowly with a solution of 16.03 g (60 mmole) of 2-acetoxymethyl-4-bromobut-1-yl-acetate in 30 ml of N, N-dimethylformamide, followed by stirring for 84 hours at room temperature. At the end of the reaction, the stirred mixture was cooled and filtered, and then the filtrate was concentrated under reduced pressure to evaporate the solvent. The residue was purified by silica gel chromatography [(CHCL3] : [MEOH=90] : 1) to give 9.80 g [(61percent)] of [9- [4-ACETOXY-3-] (acetoxymethyl) but-1-yl]-2-aminopurine (Rf=0.82). [MELTING POINT: 101-103 °C (DEC. )] IR: vmax [(CM~1)] : 3330,3163, 1746,1729, 1654,1612, 1582 1H NMR (DMSO-d6, [300MHZ)] [(PPM) :] 1.99-1. 95 (3H, m, =NCH2CH2CH=) 2. 00 (6H, s,-CH [(CH2OCOCH3)] 2) 4. 03 (4H, [D,-CH] [(CH20COCH3)] 2) 4.14 (2H, t, [=NCH2CH2CH=)] 6.45 (2H, [BRS,-NH2)] 8.09 [(1H,] s, H of C-8) 8.57 [(1H,] s, H of C-6) Also, 0.19 [G] (1. [2percent)] of [7- [4-ACETOXY-3-] (acetoxymethyl) but-1-yl]-2-aminopurine as a reaction byproduct was obtained [(RF=0.] 49). Melting point: [137-139 °C] IR : vmax [(CM~1) :] 3330,3160, 1743,1728, 1645,1606 1H NMR [(DMSO-D6,] [300MHZ)] [(PPM) :] 1. [86-2.] 03 (9H, m, [=NCH2CH2CH=] and-CH [(CH20COCH3)] [2)] [4. 07 (4H, D, -CH (CH20COCH3) 2)] 4.16 (2H, t, [=NCH2CH2CH=)] 6.38 (2H, [BRS,-NH2)] 8.06 [(1H,] s, H of C-8) 8.61 [(1H,] s, [H OF C-6)]
Reference: [1] Patent: WO2004/7497, 2004, A1, . Location in patent: Page 9-11
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YieldReaction ConditionsOperation in experiment
89% With triethylamine In ethanol; dichloromethane; water (b)
9-(4-Acetoxy-3-acetoxymethylbut-1-yl)-2-aminopurine, (BRL42810) STR18
A solution of 9-(4-acetoxy-3-acetoxymethylbut-1-yl)-2-amino-6-iodopurine (15.3 g) and triethylamine (3.8 cm3) in ethanol (200 cm3) was hydrogenated over 5percent palladium on charcoal (1.6 g, Englehard type 4573) at 50° and 50 psi for 4 hours.
The reaction mixture was filtered and residue washed with ethanol (200 cm3).
After evaporation of the filtrate to ca 50 cm3, water (150 cm3) and dichloromethane (75 cm3) was added.
The phases were separated and the aqueous layer extracted with dichloromethane (3*75 cm3).
The combined organic extract was dried over magnesium sulphate and evaporated to give the crude product.
Recrystallisation from boiling butan-1-ol (30 cm3) gave the title compound 9.8 g (89percent) m.p. 102° C.
1 H n.m.r. (CDCl3) and t.l.c. (60:40 ethylacetate: methanol) were consistent with the title compound.
Reference: [1] Patent: US5017701, 1991, A,
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Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
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Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
[2] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
[3] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
[4] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
  • 13
  • [ 172529-94-1 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
[2] Nucleosides and Nucleotides, 1996, vol. 15, # 5, p. 981 - 994
  • 14
  • [ 127047-77-2 ]
  • [ 452-06-2 ]
  • [ 131266-15-4 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1990, vol. 46, # 19, p. 6903 - 6914
  • 15
  • [ 17495-12-4 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 16
  • [ 17495-10-2 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 17
  • [ 19962-37-9 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 18
  • [ 39809-25-1 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 19
  • [ 118-00-3 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 20
  • [ 97845-72-2 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 21
  • [ 256945-18-3 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 22
  • [ 256945-19-4 ]
  • [ 104227-87-4 ]
Reference: [1] Synthesis, 2004, # 12, p. 2026 - 2034
  • 23
  • [ 55387-85-4 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 24
  • [ 21339-47-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 25
  • [ 333335-46-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 26
  • [ 333335-48-1 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 27
  • [ 333335-47-0 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 28
  • [ 333335-49-2 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 29
  • [ 333335-55-0 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 30
  • [ 333335-54-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 2001, vol. 42, # 9, p. 1781 - 1784
  • 31
  • [ 77661-80-4 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1990, vol. 46, # 19, p. 6903 - 6914
  • 32
  • [ 131266-10-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1990, vol. 46, # 19, p. 6903 - 6914
  • 33
  • [ 172529-93-0 ]
  • [ 104227-87-4 ]
Reference: [1] Nucleosides and Nucleotides, 1996, vol. 15, # 5, p. 981 - 994
  • 34
  • [ 126589-88-6 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
[2] Tetrahedron, 1990, vol. 46, # 19, p. 6903 - 6914
  • 35
  • [ 128139-38-8 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
[2] Tetrahedron, 1990, vol. 46, # 19, p. 6903 - 6914
  • 36
  • [ 158665-15-7 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
[2] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 37
  • [ 104227-89-6 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 2000, vol. 56, # 26, p. 4589 - 4595
  • 38
  • [ 246021-74-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 2000, vol. 56, # 26, p. 4589 - 4595
  • 39
  • [ 291279-59-9 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 2000, vol. 56, # 26, p. 4589 - 4595
  • 40
  • [ 225111-64-8 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 41
  • [ 225111-63-7 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 42
  • [ 225111-68-2 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 43
  • [ 225111-70-6 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 44
  • [ 225111-69-3 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron, 1999, vol. 55, # 16, p. 5239 - 5252
  • 45
  • [ 122497-20-5 ]
  • [ 104227-87-4 ]
Reference: [1] Nucleosides and Nucleotides, 1996, vol. 15, # 5, p. 981 - 994
  • 46
  • [ 122497-22-7 ]
  • [ 104227-87-4 ]
Reference: [1] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
  • 47
  • [ 10310-21-1 ]
  • [ 104227-87-4 ]
Reference: [1] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
  • 48
  • [ 177838-59-4 ]
  • [ 104227-87-4 ]
Reference: [1] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
  • 49
  • [ 214201-64-6 ]
  • [ 104227-87-4 ]
Reference: [1] Heterocycles, 2008, vol. 75, # 11, p. 2803 - 2808
  • 50
  • [ 108-24-7 ]
  • [ 122497-22-7 ]
  • [ 104227-87-4 ]
Reference: [1] Tetrahedron Letters, 1992, vol. 33, # 32, p. 4609 - 4612
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