* 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.
Stage #1: With potassium carbonate In chloroform at 0℃; for 0.25 h; Stage #2: With bromine In chloroform at 0℃; for 2.5 h;
A mixture of 1-methylcyclopentanol (4.00 g, 39.94 mmol) and K2CO3 (33.11 g, 239.6 mmol) in CHCl3 (130 mL) was stirred at 0° C. for 15 min., and then bromine (10.23 mL, 199.7 mmol) was then added. The reaction mixture was stirred at 0° C. for 2.5 hours, then poured slowly into an ice-chilled saturated aqueous Na2S2O3 solution (100 mL). The organic layer was separated, washed with water (2×100 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column (pet ether:EtOAc 3:1) give the desired product 6-bromohexan-2-one as a colorless oil (4 g). Yield 56percent (98percent purity, UV=214 nm, ESI no found). 1H— NMR (400 MHz, CDCl3) δ 1.66-1.80 (m, 2H), 1.82-1.93 (m, 2H), 2.15 (s, 3H), 2.48 (t, J=7.3 Hz, 2H), 3.41 (t, J=6.5 Hz, 2H)
Reference:
[1] Journal of Organic Chemistry, 2000, vol. 65, # 18, p. 5831 - 5833
[2] Patent: US2018/244648, 2018, A1, . Location in patent: Page/Page column 0289; 0290
[3] Russian Chemical Bulletin, 1999, vol. 48, # 11, p. 2080 - 2082
[4] Patent: WO2009/77990, 2009, A1, . Location in patent: Page/Page column 63-64
[5] Patent: US2011/34516, 2011, A1, . Location in patent: Page/Page column 34
[6] Patent: WO2011/53519, 2011, A1, . Location in patent: Page/Page column 31
2
[ 1073-06-9 ]
[ 10226-29-6 ]
[ 396-64-5 ]
Reference:
[1] Patent: CN106431824, 2017, A, . Location in patent: Paragraph 0067; 0068; 0069; 0070
Reference:
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1983, vol. 32, p. 1394 - 1398[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1983, # 7, p. 1541 - 1545
[3] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1983, vol. 32, p. 1394 - 1398[4] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1983, # 7, p. 1541 - 1545
13
[ 80345-55-7 ]
[ 10226-29-6 ]
Reference:
[1] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1961, p. 1164 - 1167[2] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1961, p. 1252 - 1256
14
[ 6407-36-9 ]
[ 109-64-8 ]
[ 10226-29-6 ]
Reference:
[1] Justus Liebigs Annalen der Chemie, 1975, p. 719 - 730
15
[ 10226-28-5 ]
[ 10035-10-6 ]
[ 10226-29-6 ]
[ 15719-64-9 ]
Reference:
[1] Journal of the Chemical Society, 1887, vol. 51, p. 725
[2] Journal of the Chemical Society, 1889, vol. 55, p. 335,338[3] Journal of the Chemical Society, 1890, vol. 57, p. 26
16
[ 21856-89-3 ]
[ 10035-10-6 ]
[ 10226-29-6 ]
Reference:
[1] Justus Liebigs Annalen der Chemie, 1896, vol. 289, p. 229[2] Chemische Berichte, 1898, vol. 31, p. 591
(1R,2R,4S)-2-[(E)-2-Benzenesulfonyl-6-benzyloxy-1-(diphenoxy-phosphoryloxy)-hept-1-enyl]-4-methoxymethoxy-cyclopentanecarboxylic acid methoxymethyl ester[ No CAS ]
EXAMPLE 2 Preparation of 1-(5-oxohexyl)-3-methyl-7-n-propylxanthine (Compound 1) 437.2 g of 3-methyl-7-propylxanthine, suspended in a mixture of 240 g of methanol and 321 g of water, are brought into solution at elevated temperature using 160 g of 50% strength sodium hydroxide solution, 358 g of 1-bromo-5-hexanone are subsequently added at boiling point and the mixture is heated under reflux for 41/2 hours. After cooling, unreacted 3-methyl-7-propylxanthine is separated off and the alcohol is removed by distillation. The aqueous solution is adjusted to pH 11 with sodium hydroxide solution and extracted with methylene chloride. After recrystallizing from 5.2 l of diisopropyl ether, 1-(5-oxohexyl)-3-methyl-7-propylxanthine of melting point 69-70 C. is obtained from the residue of the methylene chloride solution in about 90% yield (based on reacted 3-methyl-7-propylxanthine).
90%
In methanol; water;
EXAMPLE 2 Preparation of 1-(5-oxohexyl)-3-methyl-7-n-propylxanthine (compound 1) 437.2 g of 3-methyl-7-propylxanthine are suspended in a mixture of 240 g of methanol and 321 g of water and induced to dissolve at elevated temperature with 160 g of 50% strength sodium hydroxide solution, and subsequently at the boiling point 358 g of 1-bromo-5-hexanone are added and the mixture is heated to reflux for 41/2 hours. After cooling, unreacted 3-methyl-7-propylxanthine is separated off and the alcohol is removed by distillation. The aqueous solution is adjusted to pH 11 with sodium hydroxide solution and extracted with methylene chloride. 1-(5-Oxohexyl)-3-methyl-7-propylxanthine is obtained with melting point 69-70 C. in approximately 90% yield (based on reacted 3-methyl-7-propylxanthine) from the residue of the methylene chloride solution after recrystallization from 5.2 of diisopropyl ether.
1-(5-oxohexyl)-3-methyl-7-(methylpivaloyl)xanthine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
49%
With NaH; In water; dimethyl sulfoxide;
3-Methyl-7-(methylpivaloyl)xanthine (406 mg, 1.5 mmol) was added to a stirring suspension of NaH (36 mg, 1.5 mmol) in DMSO (20 ml) and stirred for 15 min. <strong>[10226-29-6]6-Bromo-2-hexanone</strong> (260 mg, 1.5 mmol) was added and the reaction mixture was stirred for 20 hrs. The reaction mixture was poured into 100 ml of water and extracted with 25% ethanol/dichloromethane (3*40 ml). The combined organic extracts were combined, dried with magnesium sulfate and the solvent was removed under vacuum to give a brown oil. The brown oil was chromatographed (10 g silica gel, ethyl acetate) to give 1-(5-oxohexyl)-3-methyl-7-(methylpivaloyl)xanthine (270 mg, 49% yield)
3-n-butyl-1-(5-oxohexyl)-7-(2-oxopropyl)xanthine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In N-methyl-acetamide; water;
1-(5'-oxohexyl)-3-butyl-7-(2'-oxopropyl)-xanthine (2) 3-butyl-7-(2'-oxopropyl)-xanthine (7,9 g), potassium carbonate (4,2 g) and dimethylformamide (51 ml) were stirred together and 1-bromhexane-5-one (8,1 g), freshly distilled, was added dropwise at room temperature. The mixture was then heated to 120, under a stream of nitrogen, for 30 min. to complete the reaction. After cooling, the mixture was treated with ca. 100 ml of water and extracted several times with chloroform. The chloroform phase was washed with water, dried over sodium sulphate and filtered and the chloroform was removed in vacuo. The residue was recrystallized from ether to yield 1-(5'-oxohexyl)-3-butyl-7-(2'-oxopropyl)-xanthine. Melting point: 87 C. Yield: 7,4 g=68,0% of the theory
3-cyclopropyl-3,7-dihydro-7-(4-methoxybenzyl)-1-(5-oxohexyl)-1H-purine-2,6-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With potassium carbonate; In water; N,N-dimethyl-formamide;
Example 1 3-Cyclopropyl-3,7-dihydro-7-(4-methoxybenzyl)-1-(5-oxohexyl)-1H-purine-2,6-dione A mixture of 4.00 g of 3-cyclopropyl-3,7-dihydro-7-(4-methoxybenzyl)-1H-purine-2,6-dione, 2.75 g of 5-oxohexyl bromide and 2. 13 g of potassium carbonate in 26 ml of N,N-dimethylformamide was stirred at 60C for 9.5 hours. The reaction mixture was concentrated under the reduced pressure, and water was added to the residue. Precipitates formed were collected by filtration and washed with water and n-hexane, successively, to give 5.00 g of colorless crystals, which were recrystallized from ethyl acetate-n-hexane to give colorless needles, mp 113 - 114.5C.