[ CAS No. 39824-26-5 ] {[proInfo.proName]}

Name: 39824-26-5|6-Chloro-9-[2,3-O-(1-methylethylidene)-beta-D-ribofuranosyl]-9H-Purine|97%
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Quality Control of [ 39824-26-5 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 39824-26-5 ]

CAS No. :	39824-26-5	MDL No. :	MFCD03788833
Formula :	C₁₃H₁₅ClN₄O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	VDYNZOUPLVQLRV-WOUKDFQISA-N
M.W :	326.74	Pubchem ID :	11727150
Synonyms :

Calculated chemistry of [ 39824-26-5 ]

Physicochemical Properties

Num. heavy atoms :	22
Num. arom. heavy atoms :	9
Fraction Csp3 :	0.62
Num. rotatable bonds :	2
Num. H-bond acceptors :	7.0
Num. H-bond donors :	1.0
Molar Refractivity :	75.47
TPSA :	91.52 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	No
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-8.0 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.55
Log Po/w (XLOGP3) :	0.41
Log Po/w (WLOGP) :	0.57
Log Po/w (MLOGP) :	-0.84
Log Po/w (SILICOS-IT) :	0.33
Consensus Log Po/w :	0.6

Druglikeness

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

Water Solubility

Log S (ESOL) :	-2.29
Solubility :	1.66 mg/ml ; 0.00507 mol/l
Class :	Soluble
Log S (Ali) :	-1.9
Solubility :	4.13 mg/ml ; 0.0126 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.21
Solubility :	2.03 mg/ml ; 0.00622 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	0.0
Synthetic accessibility :	4.21

Safety of [ 39824-26-5 ]

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 [ 39824-26-5 ]

* 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 [ 39824-26-5 ]
Downstream synthetic route of [ 39824-26-5 ]

[ 39824-26-5 ] Synthesis Path-Upstream 1~7

1
[ 2004-06-0 ]
[ 67-64-1 ]
[ 39824-26-5 ]

Yield	Reaction Conditions	Operation in experiment
87%	With toluene-4-sulfonic acid In water	((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4- d][l,3]dioxol-4-yl)methanol-Toluenesulfonic acid monohydrate (19.8 g, 104 mmol) was added to a stirred suspension of (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran- 3,4-diol (3.0 g, 10.5 mmol) in dried acetone (300 mL). The solid dissolved 15 min later. 2 h later, the solution was poured into stirred aqueous NaHC0₃ (0.5 N, 300 mL) slowly. After removed acetone in vacuo, the mixture was extracted with DCM (100 mL x 5). The combined organic layers were washed with water (100 mL) and brine (100 mL), then dried over Na₂S0₄, filtered and concentrated to afford the target (3.0 g, yield: 87percent, purity >96percent) as a pale solid. 1H NMR (500 MHz, CD₃OD) δ 8.71 (d, J = 1.0 Hz, 1H), 8.65 (d, J = 1.5 Hz, 1H), 6.23 (d, J = 2.0 Hz, 1H), 5.29 (dd, J = 2.0, 6.0 Hz, 1H), 4.96 (dd, J = 2.0, 6.0 Hz, 1H), 4.31 (d, J = 2.0 Hz, 1H), 3.68-3.59 (m, 2H), 1.51 (s, 3H), 1.29 (s, 3H) ppm; LCMS (m/z): 327.1 [M+l]⁺.
86%	Stage #1: With toluene-4-sulfonic acid In water at 25℃; for 6 h; Stage #2: With sodium hydrogencarbonate In water	Compound 356l-(4-(tert-butyl)phenyl)-3-(3-((((2R,3S,4R,5R)-5-(6-(dimethylamino)-9H-purin-9-yl)-3,4- dihydroxytetrahydrofuran-2-yI)methyl)(isopropyl)amino)propyl)ureaStep 1. Preparation of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4-yl)methanolp-Toluenesulfonic acid monohydrate (134 g, 700 mmol) was added to a stirred suspension of (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran- 3,4-diol (20 g, 70 mmol) in acetone (100 mL). After stirred at 25° C for 6 h, the reaction mixture was poured into stirred aqueous NaHC0₃ (0.5 N, 2000 mL) slowly. After removed acetone in vacuo, the mixture was extracted with DCM (800 mL x 3). The combined organic layers were washed with water (500 mL) and brine (500 mL), then dried over Na₂S0₄ and concentrated to afford the title compound (19.5 g, yield: 86 percent) as a white solid. NMR(500 MHz, CDC1₃): δ 8.75 (s, 1H), 8.30 (s, 1H), 6.01 (d, J = 4.5 Hz, 1H), 5.19-5.17 (m, 1H), 5.10-5.09 (m, 1H), 4.54 (s, 1H), 3.96 (dd, J = 1.0, 12.5 Hz, 1H), 3.82 (dd, J = 2.0, 12.5 Hz, 1H), 1.64 (s, 3H), 1.37 (s, 3H) ppm; ESI (m/z): 327.1 [M+l]⁺.
74.1%	at 20℃; for 3 h;	200 mg (0.7 mmol) of the commercial precursor 6-chloropurine riboside and acetone (10 mL)were mixed under agitation at room temperature for 30 min. This was followed by the slowaddition of p-toluensulfonic acid (5.57 mmol). The solution was kept under stirring conditionsat room temperature for 3 h. The progress of the reaction was monitored by TLC. Sodiumbicarbonate (1.5 g) was added and maintained under agitation. Once the reaction was finished,the solid phase was removed and washed with ethyl acetate (2). The product was thenpurified by column chromatography with mixtures of CH2Cl2-MeOH, obtaining the compound[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol (A); Yellow solid,74.1percent yield; m.p. 155–158 °C 1H–NMR (CDCl3, 400.1 MHz) δ 8.72 (s, 1H, CH-Ar purine); 8.31 (s, 1H,CH-Ar purine); 6.01 (d, J = 8.0 Hz, 1H, CH-1'); 5.16 (m, 1H, CH-2'); 4.97 (d, J = 7.83 Hz, 1H, CH-3');4.52 (d, J = 1.22 Hz, 1H, CH-4'); 3.83 (m, 2H, CH2-5'); 5.06 (m, 1 OH); 1.62 (s, 3H, ketal); 1.35 (s, 3H,ketal). 13C–NMR (CDCl3, 100.6 MHz) δ 151.6, 151.4, 148.8, 144.4, 132.5, 114.0, 93.4, 86.2, 83.2, 81.1,62.7, 27.1, 24.8. IR (KBr) λ/cm1 3320, 2906, 2863, 959, 733. Anal. Cal. C13H15ClN4O4: C = 47.75percent,H = 4.59percent, Cl = 10.85percent, N = 17.14percent.

Reference： [1] Nucleosides and Nucleotides, 1996, vol. 15, # 1-3, p. 619 - 629
[2] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 7, p. 3848 - 3865
[3] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 8, p. 577 - 582
[4] Patent: WO2012/82436, 2012, A2, . Location in patent: Page/Page column 192-193
[5] Patent: WO2012/82436, 2012, A2, . Location in patent: Page/Page column 256-257
[6] Molecules, 2018, vol. 23, # 5,
[7] Journal of the American Chemical Society, 1961, vol. 83, p. 150,154
[8] Journal of the American Chemical Society, 1996, vol. 118, # 24, p. 5532 - 5543
[9] Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6880 - 6889
[10] Patent: WO2005/84653, 2005, A2, . Location in patent: Page/Page column 48
[11] Pr.IV.Congr.Biochem.Wien 1958,Bd.15,S.40,
[12] Organic Letters, 2015, vol. 17, # 6, p. 1513 - 1516
[13] Patent: WO2005/84653, 2005, A2, . Location in patent: Page/Page column 48

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Yield	Reaction Conditions	Operation in experiment
60%	With chloro-trimethyl-silane; tert.-butylnitrite In dichloromethane at 20℃; Inert atmosphere	To a solution of 2 (20.0 g, 65.2 mmol) in dry dichloromethane was dropwise added TMCS (57.7 ml, 456.1 mmol) under argon atmosphere at room temperature, after short time. To the solution was dropwis added tert-butyl nitrite (59.6 ml, 547.3 mmol), then stirred at room temperature for overnight. The mixture was quenched with saturated NaHCO₃, layers were separated, the water layer was extracted with chloroform (200 ml). The combined organic layers were dried with Na₂SO₄, filtered and partly evaporated. The residue was purified by column chromatography (CH₂Cl₂: MeOH=10:1) to give the compound 3 in 60percent yield, white solid (12.3 g). ¹H NMR (400 MHz, DMSO-d₆) δ 8.88 (s, 1H), 8.83 (s, 1H), 6.30 (d, J = 2.4 Hz, 1H), 5.43 (dd, J = 6.1, 2.4 Hz, 1H), 5.00 (dd, J = 6.1, 2.3 Hz, 1H), 4.38 – 4.29 (m, 1H), 3.58 (dd, J = 4.6, 3.0 Hz, 2H), 1.57 (s, 3H), 1.35 (s, 3H). ¹³C NMR (100 MHz, DMSO-d₆) δ 151.62, 150.95, 149.28, 145.52, 131.06, 113.24, 90.55, 87.13, 83.68, 81.12, 61.12, 26.66, 24.81.
60%	With chloro-trimethyl-silane; n-Butyl nitrite In dichloromethane for 0.25 h; Inert atmosphere; Darkness	20 g of 2 ', 3'-isopropylideneuridine (compound of formula II) was dissolved in anhydrous dichloromethane,In the argon protection,In the dark and under normal conditions, 63.4 ml of trimethylchlorosilane was slowly added dropwise,After stirring for 15 min, 59.3 ml of n-butyl nitrite was slowly added dropwise,Stir the reaction after overnight stirring.The organic phase was collected by extraction with chloroform. The organic phase was combined, dried over anhydrous NaSO4, filtered and evaporated to dryness. The residue was separated by silica gel column chromatography (eluent: dichloromethane: methanol = 10: 1v / V) to give 12.7 g of the white product (compound represented by the formula III) in a yield of 60percent. EI: 326.

Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 3, p. 190 - 193
[2] Patent: CN104497085, 2017, B, . Location in patent: Paragraph 0032; 0033

3
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[ 77-76-9 ]
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Yield	Reaction Conditions	Operation in experiment
99%	Stage #1: With toluene-4-sulfonic acid In acetone at 20℃; for 16 h; Stage #2: With water; sodium hydrogencarbonate In acetone	Example 1: ((2R_/3S_/4R_/5R)-5-{6-[(lS)-2_/3-dihydro-lH-inden-l-ylamino]9H-purin-9-yl}- 3,4-dmydroxytetrahydrofuran-2-yl)methyl sulfamate (1-2)Step a: [('3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2_>2-dimethyltetrahydrofuro- r3,4-diri,31dioxol-4-yllmethanol; [0162] 6-Chloro-β-D-ribofuranosylpurine (8.17g, 28.5mmol), p-toluenesulfonic acid monohydrate (5.42g, 28.5mmol) and 2,2~dimethoxypropane(17.5mL, 142.5mmol) were mixed in acetone(500mL). The reaction mixture was stirred at room temperature for lβhours. Saturated aqueous NaHCO₃ solution (40OmL) was then added and the mixture was evaporated under reduced pressure to remove most of the acetone. The remaining aqueous residue was then extracted with chloroform(4 x 20OmL). The combined organics were dried- 78 - EPO <DP n="79"/>over Na₂SO₄, and then evaporated to yield the product as a white amorphous solid (9.22g, 99percent).[0163] LCMS: R.t. 1.22 min ES+ 327 (formic acid).
97%	With toluene-4-sulfonic acid In acetone at 20℃;	To a stirred solution of chloropurine 23 (15.0 g, 52.2 mmol) in 175 mL of acetone was 2,2-dimethoxypropane (63.0mL, 538 mmol) followed by p-toluenesulfonic acid (10.9 g, 60 mmol). The resulting heterogeneous mixture wasstirred for 2.5 h at rt during which time the solution become homogenous and bright yellow. The volatiles were removed in vacuo to give a thick yellow oil. The oil was dissolved in 150 mL of EtOAc followed by the addition of 150 mL of saturated NaHCO3 over a period of 5 minutes during which time the yellow color disappeared. The resulting layers were separated and the aqueous layer was extracted with 2 × 150 mL of EtOAc. The combined organic layers were washed with 200 mL of brine, dried (Na2SO4) and concentrated in vacuo to give the acetonide S12
97%	With toluene-4-sulfonic acid In acetone at 20℃; for 2 h;	Next, electrophilic AMP analogs with two significantly different substituents at N6-position (i.e. a propargyl and phenyl alkyne) were synthesized following Scheme 2 and Scheme 3. Compound 2 that has a small hydrophobic group (propargyl alkyne) at the N6-position was prepared by coupling 2-chloroethanesulfonyl chloride with the 5-amino adenine moiety, followed by the deprotection of the acid labile acetonide (Scheme 2). The synthesis of compound 3, which has a large hydrophobic group (phenyl alkyne) at the N6-position, required tert-butyldimethylsilane (TI3DMS) protection and deprotection steps on the 5’ alcohol and Hoc protection on the N6-amine due to the instability of the reaction intermediates during the Mitsunobu reaction. Subsequent treatment with 2-chloroethanesulfonyl chloride and global deprotection of the acid labile protecting groups led to the formation of compound 3.

89.03%	With toluene-4-sulfonic acid In acetone at 20℃; for 4 h; Inert atmosphere	(2R, 5R) -2- (6- chloro -9H- purin-9-yl) -5- (hydroxymethyl) tetrahydrofuran-3,4-diol (4.8 g, 16.74 mmol) and 2,2 - dimethoxy-propane (10.26 mL, 83.71 mmol) toIn a nitrogen stream, and then p- toluene sulfonic acid monohydrate (3.18 g, 16.74 mmol) was dissolved in anhydrous acetone (120 mL) to It was added dropwise then stirred at room temperature for 4 hours.The completion of the reactionA check after the reaction with saturated aqueous sodium hydrogen carbonate solutionIt concludes.The reaction solutionThe organic layer was concentrated under reduced pressure with chloroform (4 X 20 mL) Extracted and washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate.Intermediate compound by separating the resulting residue was then concentrated under reduced pressure, by column chromatography ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-tetrahydrofuro[3,4-d] [1,3]dioxol-4-yl)methanol (4.87 g, 89.03percent a)Obtained.
83%	With toluene-4-sulfonic acid In acetone at 20℃; for 2 h;	Step 1 (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.47 g, yield: 72percent) was obtained according to the process described in the known method (Journal of Organic Chemistry (J. Org. Chem.), 2002, vol. 67, pp. 6708-67963 using (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (10.9 g, 26.4 mmol) synthesized by the method described in the known method [Journal of Medicinal Chemistry (J. Med. Chem.), 2012, vol. 55, pp. 1478-1489]. (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.48 g, 19.1 mmol) was suspended in acetone (200 mL), and 2,2-dimethoxypropane (11.7 mL, 95.5 mmol) and 4-toluenesulfonic acid monohydrate (9.09 g, 47.8 mmol) were added thereto, and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added a saturated aqueous sodium bicarbonate solution, and the solvent was evaporated under reduced pressure until the amount of the solvent was decreased to about half. Chloroform was added thereto, and the mixture was extracted with chloroform and dried over sodium sulfate. Then, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1.3]dioxol-4-yl)methanol (5.17 g, yield: 83percent). ESI-MS (m/z): 327 (M+1)
83%	With toluene-4-sulfonic acid In acetone at 20℃; for 2 h;	(2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.47 g, yield: 72percent) was obtained according to the process described in the known method [Journal of Organic Chemistry (J. Org. Chem.), 2002, vol. 67, pp. 6788-6796] using (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (10.9 g, 26.4 mmol) synthesized by the method described in the known method [Journal of Medicinal Chemistry (J. Med. Chem.), 2012, vol. 55, pp. 1478-1489]. (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.48 g, 19.1 mmol) was suspended in acetone (200 mL), and 2,2-dimethoxypropane (11.7 mL, 95.5 mmol) and 4-toluenesulfonic acid monohydrate (9.09 g, 47.8 mmol) were added thereto, and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added a saturated aqueous sodium bicarbonate solution, and the solvent was evaporated under reduced pressure until the amount of the solvent was decreased to about half. Chloroform was added thereto, and the mixture was extracted with chloroform and dried over sodium sulfate. Then, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (5.17 g, yield: 83percent). ESI-MS (m/z): 327 (M+1)
79%	Stage #1: With toluene-4-sulfonic acid In acetone at 20℃; for 45 h; Stage #2: With sodium hydroxide In water for 0.0333333 h;	To a 200-L reactor with moderate stirring were charged acetone (115 L, 23 vol) and 6-chloropurine-9-riboside (5.0 kg, 17.4 mol, 1.0 wt/1.0 vol). Subsequently, p- TsOH^"H₂O (166 g, 0.88 mol, 0.05 equiv, 0.033 wt) and 2,2-dimethoxypropane (7.6 L, 62 mol, 3.54 equiv, 1.52 vol) were added and the resulting yellow suspension stirred at ambient temperature. After 45 h, a sample of the resulting yellow-green solution was taken and analysis by HPLC revealed the starting material to be present at 0.42percent by conversion (overall purity 96.9 area percent). The batch was neutralized by the addition of IN NaOH (900 rnL, 0.90 mol, 0.05 equiv, 0.18 vol). This addition took approximately 2 min; the final pH was pH 7. The batch was allowed to stir for 1 h. The resulting cloudy yellow mixture was concentrated under reduced pressure at 35 + 5 ⁰C on the rotary evaporator over a period of 8 h, until a volume of 45 L (9.0 vol) was achieved. The concentrate was stored under N₂ at 2-8 °C.The concentrate was transferred to a 200-L reactor and stirring commenced. Water (45 L, 9.0 vol) was added and the resulting dilute suspension was stirred for 55 min. The batch was transferred portionwise to a 72-L reactor assembled in a heating mantle equipped for vacuum distillation. Distillation at 35 +/- 5 °C commenced and proceeded until a batch volume of 62 L (12.4 vol) was achieved (The distillation was conducted over a period of two days, and included 15 hours of aging at <30 ⁰C once complete). The batch was transferred to a 72-L reactor assembled in a cooling bath. The batch was chilled over a period of A¹A h until the temperature reached <5 ⁰C and was stirred for an additional 1 h. The solids were filtered employing Sharkskin filter paper and the cake was rinsed with chilled 2:1 water/acetone (7.5 L, 1.5 vol) (The total filtration time was approximately 1 hour 40 minutes and included pulling N₂ through the cake in order to help it dry). The damp solids (5.99 kg) were transferred into six glass <n="32"/>drying trays and dried under vacuum, in an oven at 40 +/- 5 ⁰C. After drying for 47 h, the batch was packaged in 4-mil LDPE (double bags) under N₂ and stored in a fiber drum. This afforded 6-chloropurine-9-riboside acetonide (4505 g, 79percent).
76%	With toluene-4-sulfonic acid In acetone at 20℃; for 4 h; Inert atmosphere	A mixture of 6-chloropurine riboside (1) (1.0 g, 3.5 mmol), p-toluenesulfonic acid monohydrate (1.0 g, 5.3 mmol) and 2,2-dimethoxypropane (10 mL) in acetone (20 mL) was stirred at room temperature under N2 for 3 h. Another portion of 2,2-dimethoxypropane (10 mL) was added, and the mixture was stirred for another 1 h. The mixture was concentrated by rotary evaporation under reduced pressure. The residue was diluted with CH2C12, and extracted with water. The aqueous phase was washed with CH2C12, and the combined organic layers were washed with saturated NaHCO3 and brine. The organic phase was dried over MgSO4, filtered, concentrated by rotatory evaporation under reduced pressure, and purified by column chromatography (silica gel, EtOAc/hexane gradients from 3:7 to 1:0) to give compound 23 (870 mg, 76percent yield). C,3H,5C1N404; [cx]D25 = —112.6 (CHC13, c = 2); JR Vx (neat) 1592, 1563, 1490, 1438, 1419, 1400, 1384, 1337, 1259, 1202, 1154, 1136, 1108, 1080 cm-’; ‘H NMR (CDC13, 600 MHz) ö 8.79 (1 H, s), 8.25 (1 H, s), 6.00 (1 H, d, J= 4.6 Hz), 5.24—5.21 (1 H, m), 5.14 (1 H, dd, J 5.6, 1.5 Hz), 4.93 (1 H, dd, J 10.6, 2.0 Hz), 4.57 (1 H, d, J= 1.5 Hz), 4.00 (1 H, dt, J 12.7, 2.0 Hz), 3.84 (1 H, ddd, J 12.7, 10.6, 2.3 Hz), 1.68 (3 H, s), 1.41 (3 H, s); ‘3C NMR (CDC13, 150 MHz) ö 152.4, 151.7, 150.4, 144.7, 133.4, 114.5,94.1, 86.3, 83.2, 81.5, 63.2, 27.6, 25.2; ESJ—HRMS calcd. for C13H1635C1N404: 327.0855, found: m/z327.0868 [M + Hj.
2.24 g	With (R)-10-camphorsulfonic acid In acetone at 20℃; for 11 h;	First step, 6-chloropurine riboside (2.0 g) and 2,2-dimethoxypropane (5.80 g) in dry acetone (100 ml), (1S)-(+)-camphor-10-sulfonic acid (1.60 g) was added as a catalyst. The reaction mixture was stirred at room temperature for 11 h. After evaporating the solvent, the mixture was dissolved in chloroform (200 ml), and a NaHCO₃ solution (3*30 ml) was added. The water layer was extracted with chloroform (30 ml), then the chloroform layer was dried by anhydrous sodium sulfate and filtered. After evaporation of the solvent, the mixture was separated by column chromatography over silica gel eluting with CHCl₃-CH₃OH (100:1) to yield 2',3'-O-isopropylidene-6-chloropurine riboside (2.24 g) as a white solid.

Reference： [1] Patent: WO2006/84281, 2006, A1, . Location in patent: Page/Page column 78-79
[2] Journal of the American Chemical Society, 2013, vol. 135, # 45, p. 16948 - 16962
[3] Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 20, p. 5433 - 5440
[4] Patent: US2017/312284, 2017, A1, . Location in patent: Paragraph 0093; 0098
[5] Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 9, p. 2470 - 2473
[6] Patent: KR2015/10195, 2015, A, . Location in patent: Paragraph 0221-0224
[7] Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2545 - 2551
[8] Molecules, 2012, vol. 17, # 11, p. 13036 - 13044
[9] Patent: US2015/376611, 2015, A1, . Location in patent: Paragraph 0474; 0475
[10] Patent: US2017/354673, 2017, A1, . Location in patent: Paragraph 0690; 0691
[11] ChemMedChem, 2011, vol. 6, # 8, p. 1390 - 1400
[12] Patent: WO2008/111082, 2008, A1, . Location in patent: Page/Page column 30-31; 36
[13] Patent: WO2018/140734, 2018, A1, . Location in patent: Paragraph 00138
[14] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 23, p. 6736 - 6739
[15] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 6, p. 695 - 698
[16] Patent: EP1589027, 2005, A1, . Location in patent: Page/Page column 18-19
[17] Patent: US5824657, 1998, A,
[18] Patent: EP2511283, 2012, A1, . Location in patent: Page/Page column 67
[19] Patent: US2013/45942, 2013, A1, . Location in patent: Paragraph 0258; 0266

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Reference： [1] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 6, p. 695 - 698

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Reference： [1] Tetrahedron Letters, 2017, vol. 58, # 3, p. 190 - 193

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[ 39824-26-5 ]

Reference： [1] Journal of Organic Chemistry, 2008, vol. 73, # 6, p. 2416 - 2419

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[ 5987-73-5 ]
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Reference： [1] Bioorganic and Medicinal Chemistry Letters, 1998, vol. 8, # 6, p. 695 - 698

[ 39824-26-5 ] Synthesis Path-Downstream 1~88

1
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[ 67-64-1 ]
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Yield	Reaction Conditions	Operation in experiment
87%	With toluene-4-sulfonic acid; In water;	((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4- d][l,3]dioxol-4-yl)methanol-Toluenesulfonic acid monohydrate (19.8 g, 104 mmol) was added to a stirred suspension of (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran- 3,4-diol (3.0 g, 10.5 mmol) in dried acetone (300 mL). The solid dissolved 15 min later. 2 h later, the solution was poured into stirred aqueous NaHC03 (0.5 N, 300 mL) slowly. After removed acetone in vacuo, the mixture was extracted with DCM (100 mL x 5). The combined organic layers were washed with water (100 mL) and brine (100 mL), then dried over Na2S04, filtered and concentrated to afford the target (3.0 g, yield: 87%, purity >96%) as a pale solid. 1H NMR (500 MHz, CD3OD) delta 8.71 (d, J = 1.0 Hz, 1H), 8.65 (d, J = 1.5 Hz, 1H), 6.23 (d, J = 2.0 Hz, 1H), 5.29 (dd, J = 2.0, 6.0 Hz, 1H), 4.96 (dd, J = 2.0, 6.0 Hz, 1H), 4.31 (d, J = 2.0 Hz, 1H), 3.68-3.59 (m, 2H), 1.51 (s, 3H), 1.29 (s, 3H) ppm; LCMS (m/z): 327.1 [M+l]+.
86%		Compound 356l-(4-(tert-butyl)phenyl)-3-(3-((((2R,3S,4R,5R)-5-(6-(dimethylamino)-9H-purin-9-yl)-3,4- dihydroxytetrahydrofuran-2-yI)methyl)(isopropyl)amino)propyl)ureaStep 1. Preparation of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4-yl)methanolp-Toluenesulfonic acid monohydrate (134 g, 700 mmol) was added to a stirred suspension of (2R,3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran- 3,4-diol (20 g, 70 mmol) in acetone (100 mL). After stirred at 25 C for 6 h, the reaction mixture was poured into stirred aqueous NaHC03 (0.5 N, 2000 mL) slowly. After removed acetone in vacuo, the mixture was extracted with DCM (800 mL x 3). The combined organic layers were washed with water (500 mL) and brine (500 mL), then dried over Na2S04 and concentrated to afford the title compound (19.5 g, yield: 86 %) as a white solid. NMR(500 MHz, CDC13): delta 8.75 (s, 1H), 8.30 (s, 1H), 6.01 (d, J = 4.5 Hz, 1H), 5.19-5.17 (m, 1H), 5.10-5.09 (m, 1H), 4.54 (s, 1H), 3.96 (dd, J = 1.0, 12.5 Hz, 1H), 3.82 (dd, J = 2.0, 12.5 Hz, 1H), 1.64 (s, 3H), 1.37 (s, 3H) ppm; ESI (m/z): 327.1 [M+l]+.
74.1%	With toluene-4-sulfonic acid; at 20℃; for 3h;	200 mg (0.7 mmol) of the commercial precursor 6-chloropurine riboside and acetone (10 mL)were mixed under agitation at room temperature for 30 min. This was followed by the slowaddition of p-toluensulfonic acid (5.57 mmol). The solution was kept under stirring conditionsat room temperature for 3 h. The progress of the reaction was monitored by TLC. Sodiumbicarbonate (1.5 g) was added and maintained under agitation. Once the reaction was finished,the solid phase was removed and washed with ethyl acetate (2). The product was thenpurified by column chromatography with mixtures of CH2Cl2-MeOH, obtaining the compound[6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-yl]-methanol (A); Yellow solid,74.1% yield; m.p. 155-158 C 1H-NMR (CDCl3, 400.1 MHz) delta 8.72 (s, 1H, CH-Ar purine); 8.31 (s, 1H,CH-Ar purine); 6.01 (d, J = 8.0 Hz, 1H, CH-1'); 5.16 (m, 1H, CH-2'); 4.97 (d, J = 7.83 Hz, 1H, CH-3');4.52 (d, J = 1.22 Hz, 1H, CH-4'); 3.83 (m, 2H, CH2-5'); 5.06 (m, 1 OH); 1.62 (s, 3H, ketal); 1.35 (s, 3H,ketal). 13C-NMR (CDCl3, 100.6 MHz) delta 151.6, 151.4, 148.8, 144.4, 132.5, 114.0, 93.4, 86.2, 83.2, 81.1,62.7, 27.1, 24.8. IR (KBr) lambda/cm1 3320, 2906, 2863, 959, 733. Anal. Cal. C13H15ClN4O4: C = 47.75%,H = 4.59%, Cl = 10.85%, N = 17.14%.

With perchloric acid; at 0℃; for 2h;

To a suspension of 6-chloro-adenosine in acetone at 0C was added HC104 and stirring continued for 2h. Aq. NH3 was then added and the solution concentrated in vacuo. The solution was cooled to-20C and the resulting white precipitate of 2'3'-O- isopropylidene-6-chloro-adenosine was collected and washed with acetone

Reference： [1]Nucleosides and Nucleotides,1996,vol. 15,p. 619 - 629
[2]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 3848 - 3865
[3]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582
[4]Patent: WO2012/82436,2012,A2 .Location in patent: Page/Page column 192-193
[5]Patent: WO2012/82436,2012,A2 .Location in patent: Page/Page column 256-257
[6]Molecules,2018,vol. 23
[7]Journal of the American Chemical Society,1961,vol. 83,p. 150,154
[8]Journal of the American Chemical Society,1996,vol. 118,p. 5532 - 5543
[9]Journal of the American Chemical Society,1996,vol. 118,p. 6880 - 6889
[10]Pr.IV.Congr.Biochem.Wien 1958,Bd.15,S.40,
[11]Organic Letters,2015,vol. 17,p. 1513 - 1516
[12]Patent: WO2005/84653,2005,A2 .Location in patent: Page/Page column 48

2
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[ 77-76-9 ]
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Yield	Reaction Conditions	Operation in experiment
99%		Example 1: ((2R/3S/4R/5R)-5-{6-[(lS)-2/3-dihydro-lH-inden-l-ylamino]9H-purin-9-yl}- 3,4-dmydroxytetrahydrofuran-2-yl)methyl sulfamate (1-2)Step a: [('3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2>2-dimethyltetrahydrofuro- r3,4-diri,31dioxol-4-yllmethanol; [0162] 6-Chloro-beta-D-ribofuranosylpurine (8.17g, 28.5mmol), p-toluenesulfonic acid monohydrate (5.42g, 28.5mmol) and 2,2~dimethoxypropane(17.5mL, 142.5mmol) were mixed in acetone(500mL). The reaction mixture was stirred at room temperature for lbetahours. Saturated aqueous NaHCO3 solution (40OmL) was then added and the mixture was evaporated under reduced pressure to remove most of the acetone. The remaining aqueous residue was then extracted with chloroform(4 x 20OmL). The combined organics were dried- 78 - EPO <DP n="79"/>over Na2SO4, and then evaporated to yield the product as a white amorphous solid (9.22g, 99%).[0163] LCMS: R.t. 1.22 min ES+ 327 (formic acid).
97%	With toluene-4-sulfonic acid; In acetone; at 20℃;	To a stirred solution of chloropurine 23 (15.0 g, 52.2 mmol) in 175 mL of acetone was 2,2-dimethoxypropane (63.0mL, 538 mmol) followed by p-toluenesulfonic acid (10.9 g, 60 mmol). The resulting heterogeneous mixture wasstirred for 2.5 h at rt during which time the solution become homogenous and bright yellow. The volatiles were removed in vacuo to give a thick yellow oil. The oil was dissolved in 150 mL of EtOAc followed by the addition of 150 mL of saturated NaHCO3 over a period of 5 minutes during which time the yellow color disappeared. The resulting layers were separated and the aqueous layer was extracted with 2 × 150 mL of EtOAc. The combined organic layers were washed with 200 mL of brine, dried (Na2SO4) and concentrated in vacuo to give the acetonide S12
97%	With toluene-4-sulfonic acid; In acetone; at 20℃; for 2h;	Next, electrophilic AMP analogs with two significantly different substituents at N6-position (i.e. a propargyl and phenyl alkyne) were synthesized following Scheme 2 and Scheme 3. Compound 2 that has a small hydrophobic group (propargyl alkyne) at the N6-position was prepared by coupling 2-chloroethanesulfonyl chloride with the 5-amino adenine moiety, followed by the deprotection of the acid labile acetonide (Scheme 2). The synthesis of compound 3, which has a large hydrophobic group (phenyl alkyne) at the N6-position, required tert-butyldimethylsilane (TI3DMS) protection and deprotection steps on the 5? alcohol and Hoc protection on the N6-amine due to the instability of the reaction intermediates during the Mitsunobu reaction. Subsequent treatment with 2-chloroethanesulfonyl chloride and global deprotection of the acid labile protecting groups led to the formation of compound 3.

89.03%	With toluene-4-sulfonic acid; In acetone; at 20℃; for 4h;Inert atmosphere;	(2R, 5R) -2- (6- chloro -9H- purin-9-yl) -5- (hydroxymethyl) tetrahydrofuran-3,4-diol (4.8 g, 16.74 mmol) and 2,2 - dimethoxy-propane (10.26 mL, 83.71 mmol) toIn a nitrogen stream, and then p- toluene sulfonic acid monohydrate (3.18 g, 16.74 mmol) was dissolved in anhydrous acetone (120 mL) to It was added dropwise then stirred at room temperature for 4 hours.The completion of the reactionA check after the reaction with saturated aqueous sodium hydrogen carbonate solutionIt concludes.The reaction solutionThe organic layer was concentrated under reduced pressure with chloroform (4 X 20 mL) Extracted and washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate.Intermediate compound by separating the resulting residue was then concentrated under reduced pressure, by column chromatography ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-tetrahydrofuro[3,4-d] [1,3]dioxol-4-yl)methanol (4.87 g, 89.03% a)Obtained.
83%	With toluene-4-sulfonic acid; In acetone; at 20℃; for 2h;	Step 1 (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.47 g, yield: 72%) was obtained according to the process described in the known method (Journal of Organic Chemistry (J. Org. Chem.), 2002, vol. 67, pp. 6708-67963 using (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (10.9 g, 26.4 mmol) synthesized by the method described in the known method [Journal of Medicinal Chemistry (J. Med. Chem.), 2012, vol. 55, pp. 1478-1489]. (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.48 g, 19.1 mmol) was suspended in acetone (200 mL), and 2,2-dimethoxypropane (11.7 mL, 95.5 mmol) and 4-toluenesulfonic acid monohydrate (9.09 g, 47.8 mmol) were added thereto, and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added a saturated aqueous sodium bicarbonate solution, and the solvent was evaporated under reduced pressure until the amount of the solvent was decreased to about half. Chloroform was added thereto, and the mixture was extracted with chloroform and dried over sodium sulfate. Then, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1.3]dioxol-4-yl)methanol (5.17 g, yield: 83%). ESI-MS (m/z): 327 (M+1)
83%	With toluene-4-sulfonic acid; In acetone; at 20℃; for 2h;	(2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.47 g, yield: 72%) was obtained according to the process described in the known method [Journal of Organic Chemistry (J. Org. Chem.), 2002, vol. 67, pp. 6788-6796] using (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate (10.9 g, 26.4 mmol) synthesized by the method described in the known method [Journal of Medicinal Chemistry (J. Med. Chem.), 2012, vol. 55, pp. 1478-1489]. (2R,3R,4S,5R)-2-(6-Chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (5.48 g, 19.1 mmol) was suspended in acetone (200 mL), and 2,2-dimethoxypropane (11.7 mL, 95.5 mmol) and 4-toluenesulfonic acid monohydrate (9.09 g, 47.8 mmol) were added thereto, and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added a saturated aqueous sodium bicarbonate solution, and the solvent was evaporated under reduced pressure until the amount of the solvent was decreased to about half. Chloroform was added thereto, and the mixture was extracted with chloroform and dried over sodium sulfate. Then, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (5.17 g, yield: 83%). ESI-MS (m/z): 327 (M+1)
79%		To a 200-L reactor with moderate stirring were charged acetone (115 L, 23 vol) and 6-chloropurine-9-riboside (5.0 kg, 17.4 mol, 1.0 wt/1.0 vol). Subsequently, p- TsOH«H2O (166 g, 0.88 mol, 0.05 equiv, 0.033 wt) and 2,2-dimethoxypropane (7.6 L, 62 mol, 3.54 equiv, 1.52 vol) were added and the resulting yellow suspension stirred at ambient temperature. After 45 h, a sample of the resulting yellow-green solution was taken and analysis by HPLC revealed the starting material to be present at 0.42% by conversion (overall purity 96.9 area %). The batch was neutralized by the addition of IN NaOH (900 rnL, 0.90 mol, 0.05 equiv, 0.18 vol). This addition took approximately 2 min; the final pH was pH 7. The batch was allowed to stir for 1 h. The resulting cloudy yellow mixture was concentrated under reduced pressure at 35 + 5 0C on the rotary evaporator over a period of 8 h, until a volume of 45 L (9.0 vol) was achieved. The concentrate was stored under N2 at 2-8 C.The concentrate was transferred to a 200-L reactor and stirring commenced. Water (45 L, 9.0 vol) was added and the resulting dilute suspension was stirred for 55 min. The batch was transferred portionwise to a 72-L reactor assembled in a heating mantle equipped for vacuum distillation. Distillation at 35 +/- 5 C commenced and proceeded until a batch volume of 62 L (12.4 vol) was achieved (The distillation was conducted over a period of two days, and included 15 hours of aging at <30 0C once complete). The batch was transferred to a 72-L reactor assembled in a cooling bath. The batch was chilled over a period of A1A h until the temperature reached <5 0C and was stirred for an additional 1 h. The solids were filtered employing Sharkskin filter paper and the cake was rinsed with chilled 2:1 water/acetone (7.5 L, 1.5 vol) (The total filtration time was approximately 1 hour 40 minutes and included pulling N2 through the cake in order to help it dry). The damp solids (5.99 kg) were transferred into six glass <n="32"/>drying trays and dried under vacuum, in an oven at 40 +/- 5 0C. After drying for 47 h, the batch was packaged in 4-mil LDPE (double bags) under N2 and stored in a fiber drum. This afforded 6-chloropurine-9-riboside acetonide (4505 g, 79%).
76%	With toluene-4-sulfonic acid; In acetone; at 20℃; for 4h;Inert atmosphere;	A mixture of 6-chloropurine riboside (1) (1.0 g, 3.5 mmol), p-toluenesulfonic acid monohydrate (1.0 g, 5.3 mmol) and 2,2-dimethoxypropane (10 mL) in acetone (20 mL) was stirred at room temperature under N2 for 3 h. Another portion of 2,2-dimethoxypropane (10 mL) was added, and the mixture was stirred for another 1 h. The mixture was concentrated by rotary evaporation under reduced pressure. The residue was diluted with CH2C12, and extracted with water. The aqueous phase was washed with CH2C12, and the combined organic layers were washed with saturated NaHCO3 and brine. The organic phase was dried over MgSO4, filtered, concentrated by rotatory evaporation under reduced pressure, and purified by column chromatography (silica gel, EtOAc/hexane gradients from 3:7 to 1:0) to give compound 23 (870 mg, 76% yield). C,3H,5C1N404; [cx]D25 = -112.6 (CHC13, c = 2); JR Vx (neat) 1592, 1563, 1490, 1438, 1419, 1400, 1384, 1337, 1259, 1202, 1154, 1136, 1108, 1080 cm-?; ?H NMR (CDC13, 600 MHz) oe 8.79 (1 H, s), 8.25 (1 H, s), 6.00 (1 H, d, J= 4.6 Hz), 5.24-5.21 (1 H, m), 5.14 (1 H, dd, J 5.6, 1.5 Hz), 4.93 (1 H, dd, J 10.6, 2.0 Hz), 4.57 (1 H, d, J= 1.5 Hz), 4.00 (1 H, dt, J 12.7, 2.0 Hz), 3.84 (1 H, ddd, J 12.7, 10.6, 2.3 Hz), 1.68 (3 H, s), 1.41 (3 H, s); ?3C NMR (CDC13, 150 MHz) oe 152.4, 151.7, 150.4, 144.7, 133.4, 114.5,94.1, 86.3, 83.2, 81.5, 63.2, 27.6, 25.2; ESJ-HRMS calcd. for C13H1635C1N404: 327.0855, found: m/z327.0868 [M + Hj.
		Example 2 2',3'-Isopropylidene-6-chloropurineriboside 6-Chloropurineriboside (10.0 g) was suspended in acetone (70 ml), 2,2-dimethoxypropane (7.3 g) and p-toluenesulfonic acid monohydrate (3.3 g) was added thereto, and the mixture was stirred at 10C for 3 hr. The reaction mixture was added to a solution of sodium hydrogen carbonate (1.8 g) and water (70 ml). The mixture was concentrated under reduced pressure, and stirred at 20C for 3 hr. The precipitate was collected by filtration, washed with water, and dried overnight at 40C under reduced pressure to give 2',3'-isopropylidene-6-chloropurineriboside (9.7 g). 1H-NMR(DMSO-d6, ppm) delta: 1.34 (3H, s), 1.55(3H, s), 3.50-3.58(2H, m), 4.30-4.32(1H, m), 4.97-4.99(1H, m), 5.09-5.11(1H, s), 5.41-5.43(1H, s), 6.28(1H, d, J=2.4Hz), 8.82(1H, s), 8.87(1H, s). ; Reference Example 12',3'-Isopropylidene-6-chloropurineriboside 6-Chloropurineriboside (640 g, 2.23 mol) was suspended in acetone (5120 ml), and dimethoxypropane (494 g) and p-toluenesulfonic acid monohydrate (212 g) were added. The mixture was stirred at 17-23C for 5 hr. This reaction mixture was added to an aqueous solution of sodium hydrogen carbonate (99 g) and water (4480 ml). The aqueous solution was concentrated under reduced pressure, and stirred at 60C for 2 hr and further at room temperature for about 17 hr. The obtained slurry was filtered, and the separated crystals were washed with water to give 2',3'-isopropylidene-6-chloropurineriboside as crystals (612 g, 1.87 mol).
	With (1S)-10-camphorsulfonic acid; In acetone;	Example 1 Preparation of 5'-deoxy-6-N-phenyl-adenosine 5'-N-(N-L-phenylalanyl)sulfamide To a slurry of 6-chloropurine riboside (5.015 g) in acetone (100 ml) was added 2,2-dimethoxypropane (10 ml) and 10-camphorsulfonic acid (100 mg). The mixture was stirred at room temperature for 1 day. The mixture was diluted with ethyl acetate (500 ml) washed with saturated sodium chloride (2*200 ml) and dried over anhydrous magnesium sulfate. Evaporation gave a white solid which was purified by silica gel chromatography (1:1 ethylacetate hexanes) to give 6-chloro-2',3'-O-(1-methylethylidene)purine riboside as a white crystalline solid (5.06 g)
	(1S)-10-camphorsulfonic acid; In acetone; at 20℃; for 11h;Product distribution / selectivity;	First step, 6-chloropurine riboside (2.0 g) and 2, 2-dimethoxypropane (5.80 g) in dry acetone (100 ml), (1S)-(+)-camphor-10-sulfonic acid (1.60 g) was added as a catalyst. The reaction mixture was stirred at room temperature for 11 h. After evaporating the solvent, the mixture was dissolved in chloroform (200 ml), and a NaHCO3 solution (3× 30 ml) was added. The water layer was extracted with chloroform (30 ml), then the chloroform layer was dried by anhydrous sodium sulfate and filtered. After evaporation of the solvent, the mixture was separated by column chromatography over silica gel eluting with CHCl3-CH3OH (100 : 1) to yield 2',3'-O-isopropylidene-6-chloropurine riboside (2.24 g) as a white solid. Second step, a mixture of hydrochloric salt of 1-(3,4,5-trimethoxyphenyl)- ethylamine (2.0 g) prepared in the above example, 2',3'-O-isopropylidene-6-chloropurine riboside (1.60 g) and triethylamine (1.20 g) in EtOH (70 ml) was refluxed for 10 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (100 : 1) to yield 2',3'-O--isopropylidene-N6-(3,4,5-trimethoxybenzyl)-adenosine(1.4 g) as a white solid. Third step, a mixture of N6-(3,4,5-trimethoxybenzyl)-adenosine(700 mg), caprylic acid (241 mg), EDCI (537 mg), and DMAP (427.6 mg) in dry CH2Cl2 (60 ml) was stirred at room temperature for 3 h. After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (100 : 1) to yield N6-[(+/-)-1-(3,4,5-trimethoxyphenyl)-ethyl]-2',3'-O--isopropylidene-adenosine-5'-caprylate (450 mg). Fourth step, N6-[(+/-)-1-(3, 4, 5-trimethoxyphenyl)-ethyl]-2',3'-O-isopropylidene-adenosine-5'-caprylate (450 mg) was added to a formic acid solution (20 ml, 50% V/V), and the mixture was stirred at room temperature for 12 h, After evaporation of the reaction mixture, the residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (50 : 1) to yield N6-[(+/-)-1-(3, 4, 5-trimethoxyphenyl)-ethyl]- adenosine -5'-caprylate (360 mg) as a white solid: positive ESIMS m/z 588[M + H]+, 610[M + Na]+ and 626 [M + K]+; 1H NMR (300MHz, DMSO-d6): positive delta 8.35 (1H, s, H-8), 8.23 (1H, s, H-2), 8.18 (1H, brd, J = 8.1 Hz, NH), 5.97 (1H, d, J = 4.2 Hz, H-1'), 5.61 (1H, brs, -OH), 5.41 (1H, brs, -OH), 4.70 (1H, m, H-2'), 4.34 (1H, dd, J= 11.7, 1.8 Hz, H-5'a), 4.32 (1H, m, H-3'), 4.22 (1H, dd, J = 11.7, 5.7 Hz, H-5'b), 4.15 (1H, m, H-4'); the 1-(3, 4, 5-trimethoxyphenyl)-ethyl moiety delta 6.83 (2H, s, H-2", H-6"), 5.50 (1H, m, H-7"), 3.75 (6H, s, -OMe), 3.62 (3H, s, -OMe), 1.52 (3H, d, J = 6.6 Hz, H-8"); the capryl moiety delta 2.25 (2H, t, H-2'"), 1.45 (2H, m, H-3'"), 1.14 (8H, m, H-4'" - H-7"'), 0.77 (3H, t, H-8'"). 13C NMR (75 MHz, DMSO-d6): the adenosine moiety delta 153.8 (C-6), 152.6 (C-4), 148.5 (C-2), 140.9 (C-8), 119.8 (C-5) 88.1 (C-1'), 81.6 (C-4'), 73.1 (C-3'), 70.4 (C-2'), 63.8 (C-5'); the 1-(3,4,5-trimethoxyphenyl)-ethyl moiety delta 152.8 (C-3", C-5"), 139.6 (C-1"), 136.3 (C-4"), 103.8 (C-2", C-6"), 59.9 (MeO-4"), 55.9 (MeO-3'",5'"), 49.2 (C-7"), 22.8 (C-8'"); the capryl moiety delta 172.8 (C-1'"), 33.4 (C-2'"), 31.2 (C-3'"), 28.4 (C-4'"), 28.4 (C-5"'), 24.5 (C-6'"), 22.1 (C-7'"), 13.9 (C-8'").
2.24 g	With (R)-10-camphorsulfonic acid; In acetone; at 20℃; for 11h;	First step, 6-chloropurine riboside (2.0 g) and 2,2-dimethoxypropane (5.80 g) in dry acetone (100 ml), (1S)-(+)-camphor-10-sulfonic acid (1.60 g) was added as a catalyst. The reaction mixture was stirred at room temperature for 11 h. After evaporating the solvent, the mixture was dissolved in chloroform (200 ml), and a NaHCO3 solution (3*30 ml) was added. The water layer was extracted with chloroform (30 ml), then the chloroform layer was dried by anhydrous sodium sulfate and filtered. After evaporation of the solvent, the mixture was separated by column chromatography over silica gel eluting with CHCl3-CH3OH (100:1) to yield 2',3'-O-isopropylidene-6-chloropurine riboside (2.24 g) as a white solid.

Reference： [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 78-79
[2]Journal of the American Chemical Society,2013,vol. 135,p. 16948 - 16962
[3]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5433 - 5440
[4]Patent: US2017/312284,2017,A1 .Location in patent: Paragraph 0093; 0098
[5]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2470 - 2473
[6]Patent: KR2015/10195,2015,A .Location in patent: Paragraph 0221-0224
[7]Antibiotics,2019,vol. 8
[8]Journal of Medicinal Chemistry,1990,vol. 33,p. 2545 - 2551
[9]Molecules,2012,vol. 17,p. 13036 - 13044
[10]Patent: US2015/376611,2015,A1 .Location in patent: Paragraph 0474; 0475
[11]Patent: US2017/354673,2017,A1 .Location in patent: Paragraph 0690; 0691
[12]ChemMedChem,2011,vol. 6,p. 1390 - 1400
[13]Patent: WO2008/111082,2008,A1 .Location in patent: Page/Page column 30-31; 36
[14]Patent: WO2018/140734,2018,A1 .Location in patent: Paragraph 00138
[15]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6736 - 6739
[16]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 695 - 698
[17]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 18-19
[18]Patent: US5824657,1998,A
[19]Patent: EP2511283,2012,A1 .Location in patent: Page/Page column 67
[20]Patent: US2013/45942,2013,A1 .Location in patent: Paragraph 0258; 0266

3
[ 110-87-2 ]
[ 39824-26-5 ]
[ 139574-39-3 ]

Yield	Reaction Conditions	Operation in experiment
91%	With pyridinium p-toluenesulfonate In dichloromethane for 15h; Ambient temperature;

Reference： [1]Hamamichi, Norimitsu; Miyasaka, Tadashi [Journal of Organic Chemistry, 1994, vol. 59, # 6, p. 1525 - 1531]

4
[ 39824-26-5 ]
[ 120355-42-2 ]

Yield	Reaction Conditions	Operation in experiment
92%	With sodium hypochlorite; sodium dihydrogenphosphate;2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In water; acetonitrile; at 5℃; for 2h;pH 7 - 7.5;	Example 5 2',3'-Isopropylidene-6-chloropurineriboside-5'-carboxylic acid 2',3'-Isopropylidene-6-chloropurineriboside (0.5 g, 1.53 mmol) was suspended in acetonitrile (3.5 ml) and water (3 ml), and sodium dihydrogen phosphate (0.4 g) was added to adjust its pH to 7. 2,2,6,6-Tetramethylpiperidin-1-oxy (TEMPO) (8 mg, 0.05 mmol) was added. An aqueous sodium hypochlorite solution (effective chlorine concentration 111%, 2.86 g, 3.87 mmol) was added dropwise over 60 min while stirring at 5C, and the mixture was further stirred for 1 hr. During the reaction, the reaction mixture was maintained at pH 7.0-7.5. The reaction mixture was analyzed by HPLC. As a result, 2',3'-isopropylidene-6-chloropurineriboside-5'-carboxylic acid was produced in a yield of 92%, and the content of the impurity was 2%.
91%	With calcium hypochlorite; sodium hydrogencarbonate;2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; In water; acetonitrile; at 5℃; for 2h;pH 7 - 9.5;	Example 6 2',3'-Isopropylidene-6-chloropurineriboside-5'-carboxylic acid 2',3'-Isopropylidene-6-chloropurineriboside (0.6 g, 1.8 mmol) was suspended in acetonitrile (3.5 ml) and water (3 ml), and sodium hydrogen carbonate (0.2 g) and tetramethylpyridyl oxy (TEMPO) (8 mg, 0.05 mmol) were added. 60% Calcium hypochlorite (0.57 g, 4.39 mmol) was added in 4 portions over 1 hr while stirring at 5C, and the mixture was further stirred for 1 hr. The pH immediately after the start of the reaction was 9.5, and it was adjusted to 7 to 8 in about 10 min after addition of the calcium hypochlorite. Thereafter, this pH value was maintained. The reaction mixture was analyzed by HPLC. As a result, 2',3'-isopropylidene-6-chloropurineriboside-5'-carboxylic acid was produced in a yield of 91%, and the content of the impurity was 3%.
85%		Comparative Example 1 2',3'-Isopropylidene-6-chloropurineriboside (0.5 g, 1.5 mmol) was suspended in acetonitrile (3.5 ml) and water (3 ml), and sodium hydrogen carbonate (0.35 g) and 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) (8 mg, 0.05 mmol) were added. An aqueous sodium hypochlorite solution (effective chlorine concentration 11%, 2.86 g) was added dropwise over 10 min while stirring at 5C, and the mixture was further stirred for 1 hr. During the reaction, the pH of the reaction mixture was between 8.0 and 12.0. The reaction mixture was analyzed by HPLC. As a result, 2',3'-isopropylidene-6-chloropurineriboside-5'-carboxylic acid was produced in a yield of 85%, and the content of the impurity was 9%

82%		To a 72-L reactor supported in a cooling bath, was charged CH3CN (37 L, 14.8 vol). Stirring commenced at ambient temperature. To this was added 6-chloropurine acetonide (2234 g and 266 g, total = 2500 g = 1.0 wt = 1.0 vol, 7.65 mol), ruthenium(III) chloride hydrate (25 g, 0.121 mol, 0.016 equiv, 0.010 wt), water (10 L, 4.0 vol), and TBAI (25 g, 0.068 mol, 0.009 equiv, 0.010 wt). The resulting mixture was cooled to 50C over 1 h employing an ice-water cooling bath, and NaIO4 (3750 g, 17.5 mol, 2.3 equiv, 1.5 wt) was added over 2 min while maintaining the internal batch temperature <10 C. The ice/solvent bath was emptied after 50 min and the batch was allowed to warm to ambient temperature (The batch temperature reached a maximum of 33 0C over a period of two hours. A cold-water bath was applied to prevent the batch temperature from exceeding this temperature). The resulting thick brown-orange suspension was stirred at 15-30 0C for 21 h. Analysis by TLC (IPAc, UV detection) showed the disappearance of the 6-chloropurine-9-riboside acetonide. The yellow suspension (21C) was filtered over a period of 30 min until dripping ceased; CH3CN (15 L, 6.0 vol) was employed as a rinse of the reactor and cake. The filtrate was concentrated in three portions on the rotary evaporator with the water bath set at 40+5 C over a period of 11 h.To a 72-L reactor were charged the resultant residue (7.7 kg) and purified water (22.5 L, 9 vol). Stirring at ambient temperature was commenced. After 1 h, the batch (23 0C) was filtered, and the reactor and the cake were rinsed with purified water (7.5 L, 3 vol). The damp cake (4.7 kg) was transferred to six drying trays and dried in the vacuum oven set at 40 C for six days. The IPC KF (specification set at <0.6%) and 1H NMR (DMSO-J6) showed acceptable material. This afforded 6-chloropurine acid (2145 g, 82%) which was stored under N2 in amber glass jars with Teflon lined lids.
80.5%	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene; In water; acetonitrile;	For oxidation of 5?-OH, 100 mg of A (0.31 mmol) were added to H2O/CH3CN (1:1 mixture)and placed in an ultrasound bath for 30 min. The solvent was removed by vacuum, andthe residue obtained was stirred with diethyl ether (50 mL), filtered and then dried beforebeing purified by a SiO2 column chromatography with mixtures of CH2Cl2-MeOH, obtaining6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid (B), yellow solid,80.5% yield; m.p. 209-211 C. 1H-NMR (DMSO-d6, 400.1 MHz) delta 9.20 (s, 1H, CH-Arpurine); 8.73 (s,1H, CH-Ar purine); 6.31 (s, 1H, CH-1'); 5.28 (d, J = 5.62, 1H, CH-2'); 5.20 (d, J = 5.62 Hz, 1H, CH-3');4.54 (s, 1H, CH-4'); 1.52 (s, 3 H, ketal); 1.31 (s, 3H, ketal). 13C-NMR (DMSO-d6, 100.6 MHz) delta 173.1,151.9, 150.9, 149.1, 147.3, 131.4, 112.8, 91.7, 88.2, 84.9, 84.4, 27.2, 25.5. IR (KBr) /cm1 3409, 2990, 2937,1592, 1336, 1206, 1086, 635. Anal. Cal. C13H13ClN4O5: C = 45.79%, H = 3.82%, Cl = 10.40%, N = 16.44%.
		Example 3 2',3'-Isopropylidene-6-chloropurineriboside-5'-carboxylic acid 2',3'-Isopropylidene-6-chloropurineriboside (605 g, 1.085 mol) was added to a mixed solvent of acetonitrile (3630 ml) and water (1025 ml). Sodium hydrogen carbonate (106 g) and 2,2,6,6-tetramethylpiperidin-1-oxy (TEMPO, 5.8 g) were added thereto. An aqueous sodium hypochlorite solution (effective chlorine concentration 11%, 3034 g) was added dropwise over 3.4 hr while stirring at 5C, and the mixture was further stirred for 1 hr. While the pH immediately after the start of the reaction was 9.5, it dropped to not more than 9 within 10 min after dropwise addition of the aqueous sodium hypochlorite solution. Thereafter, the pH was adjusted to 7 to 8 and this pH value was maintained during the reaction. After the completion of the reaction, 20% aqueous sodium hydrogen sulfite solution (1650 g) was added, and the mixture was stirred for 1 hr. At this time point, complete decomposition of the oxidant was confirmed using a peroxide test paper (Merckoquant, trademark, manufactured by Merck). The content of the impurity in the reaction mixture was confirmed by HPLC and found to be 3%. Then, ethyl acetate (4880 ml) was added to the reaction mixture, and the aqueous layer was adjusted to pH 2.8 with 6N hydrochloric acid, whereby extraction was carried out at 25C. The organic solvent layer was separated, ethyl acetate (1120 ml) was added to the residual aqueous layer, which was then extracted again. The organic solvent layer was separated and combined with the organic solvent layer obtained earlier. Water (5064 ml) was added to the organic solvent layer and, after the aqueous layer was adjusted to pH 6.7 with aqueous sodium hydroxide solution, the mixture was subjected to a back-extraction at 25C. The aqueous layer containing the extracted object product was separated. The aqueous layer was adjusted to pH 2.8 with 6N hydrochloric acid and the mixture was subjected to neutralization to allow crystal precipitation at 30C. After crystal precipitation with stirring for about 17 hr, the slurry was filtered. The separated crystals were washed with water and dried overnight at 50C under reduced pressure to give 2',3'-isopropylidene-6-chloropurineriboside-5'-carboxylic acid as crystals (493 g, 1.45 mol). 1H-NMR(DMSO-d6, ppm) delta: 1.37 (3H, s), 1.53 (3H, s), 4.79(1H, d, J=1.6Hz), 5.55(1H, dd, J=1.6, 5.9Hz), 5.61(1H, d, J=5.9Hz), 6.50(1H, s), 8.76(1H, s), 8.83(1H, s). ; Example 42',3'-Isopropylidene-6-chloropurineriboside-5'-carboxylic acid 2',3'-Isopropylidene-6-chloropurineriboside (605 g, 1.85 mol) was added to a mixed solvent of acetonitrile (3630 ml) and water (3025 ml), and sodium hydrogen carbonate (106 g) and 2,2,6,6-tetramethylpiperidine-1-oxy (TEMPO) (5.8 g, 0.037 mol) were added. An aqueous sodium hypochlorite solution (effective chlorine concentration 11%, 3034 g, 4.25 mol) was added dropwise over 3.4 hr while stirring at 5C, and the mixture was further stirred for 1 hr. While the pH immediately after the start of the reaction was 9.5, it dropped to not more than 9 within 10 min after dropwise addition of the aqueous sodium hypochlorite solution. Thereafter the pH was adjusted to 7 to 8 and this pH value was maintained during the reaction. After the completion of the reaction, 20% aqueous hydrogen sulfite sodium solution (1650 g) was added, and the mixture was stirred for 1 hr. At this time point, complete decomposition of the oxidant was confirmed using a peroxide test paper (Merckoquant, trademark, manufactured by Merck). The content of the impurity in the reaction mixture was confirmed by HPLC and found to be 3% (reaction yield was 95%). Then, ethyl acetate (4880 ml) was added to the reaction mixture, the aqueous layer was adjusted to pH 2.8 with 6N hydrochloric acid, whereby extraction was carried out at 25C. The organic solvent layer was separated, ethyl acetate (1120 ml) was added to the residual aqueous layer, which was then extracted again. The organic solvent layer was separated and combined with the organic solvent layer obtained earlier. Water (5064 ml) was added to the organic solvent layer, and the aqueous layer was adjusted to pH 6.7 with aqueous sodium hydroxide solution. The mixture was subjected to a back-extraction at 25C. The aqueous layer containing the extracted object product was separated, and the aqueous layer was adjusted to pH 2.8 with 6N hydrochloric acid. The mixture was subjected to neutralization to allow crystal precipitation at 30C. After crystal precipitation with stirring for about 17 hr, the slurry was filtered. The separated crystals were washed with water and dried overnight at 50C under reduced pressure to give 2',3'-isopropylidene-6-chloropurineriboside-5'-carboxylic acid as crystals (493 g, 1.45 mol). The content of the impurity in the crystals was confirmed by HPLC and found to be 0.1%.
	With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; [bis(acetoxy)iodo]benzene; In water; acetonitrile; at 0 - 20℃;	A mixture of 6-Chloro-9-(2,3-0-isopropylidene-beta-D-ribofuranosyl)-9H-purine (5.g, 14.69 mmol) in MeCN (15 mL) and Water (15 mL) was cooled to 0 C. (Diacetoxyiodo)benzene (10.4 g, 32.32 mmol) and TEMPO (462 mg, 2.94 mmol) was added portionwise. The resulting mixture was stirred at RT overnight. TLC (9: 1 DCM/MeOH) showed completion of the reaction. The solid was filtered and quickly rinsed with EtOAc to give (3aR,4R,6S,6aS)-4-(6- chloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][l,3]dioxole-6-carboxylic acid (2.68 g, 7.87 mmol, 53.5% yield) as an off-white solid. The aq. layer of the filtrates was extracted with EtOAc and the combined organic layers were washed with sat. aq. sodium thiosulfate, water, brine, dried over sodium sulfate, filtered and concentrated to give (3aR,4R,6S,6aS)-4-(6-chloropurin-9-yl)-2,2- dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][l,3]dioxole-6-carboxylic acid (6.7 g, 7.9 mmol, 54% yield) as a brown solid, estimated to be -40% purity based on TLC
		KOH (2. 5eq) and KMn04 (2. 5eq) were added to a suspension of 2'3'-O- isopropylidene-6-chloro-adenosine (leq) in water and stirring continued for 4h. The reaction mixture was then quenched with hydrogen peroxide, concentrated and cooled to-20C. The resulting precipitate was collected and washed with water to afford 2'3'-O-isopropylidene-6-chloro-adenosine-5'-carboxylic acid

Reference： [1]Tetrahedron Letters,1992,vol. 33,p. 2307 - 2310
[2]Bioorganic and Medicinal Chemistry,2006,vol. 14,p. 1618 - 1629
[3]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 20
[4]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 20
[5]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 21
[6]Patent: WO2008/111082,2008,A1 .Location in patent: Page/Page column 31; 36
[7]Molecules,2018,vol. 23
[8]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 19; 19-20
[9]ChemMedChem,2011,vol. 6,p. 1390 - 1400
[10]Patent: WO2018/152548,2018,A1 .Location in patent: Paragraph 00511
[11]Patent: WO2005/84653,2005,A2 .Location in patent: Page/Page column 48

5
[ 1623-08-1 ]
[ 39824-26-5 ]
Phosphoric acid dibenzyl ester (3aR,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With triphenylphosphine; diethylazodicarboxylate In pyridine Ambient temperature;

Reference： [1]Saady; Lebeau; Mioskowski [Tetrahedron Letters, 1995, vol. 36, # 13, p. 2239 - 2242]

6
[ 101523-04-0 ]
[ 39824-26-5 ]
Methyl-phosphonic acid benzyl ester (3aR,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With triphenylphosphine; diethylazodicarboxylate In pyridine Ambient temperature;

Reference： [1]Saady; Lebeau; Mioskowski [Tetrahedron Letters, 1995, vol. 36, # 13, p. 2239 - 2242]

7
[ 39824-26-5 ]
[ 18162-48-6 ]
[ 139301-94-3 ]

Yield	Reaction Conditions	Operation in experiment
68%	With 1H-imidazole; In N,N-dimethyl-formamide; at 0 - 20℃; for 2.5h;	Example 126: (2R,3S,4R,5JR)-3,4-dihydroxy-5-[6-(2-methoxyethyl)-9H-purin-9-yl]tetrahydro- furan-2-yl}methyl sulfamate (1-137)Step a: 9-[(3aR/4R>6R,6aR)-6-(\|[f°rf--butyl(dimethyl)silylloxy}methyl)-2/2-dimethyl- tetrahydrofuror3,4-rf]ri;3]dioxol-4-yl]-6-chloro-9H-purine; [0878] To a solution of [(3aR,4R,6R,6aR)-6-(6-cMoro-9H-purin-9-yl)-2,2-dimethyl- tetrahydrofuro[3,4-d][l,3]dioxol-4-yl]methanol (2.00 g, 6.12 mmol) and imidazole (0.83 g, 12.24 mmol) in DMF (40 mL) at 00C was added TBSCl in DMF (10 mL) dropwise. The solution was stirred for 30 minutes at 0 0C and r.t. for 2 h. The reaction was concentrated and the residue was diluted with DCM and washed with water. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (0 to 30% EtOAc/hexanes) to yield the title compound (1.82 g, 68%).

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 4483 - 4499
[2]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 695 - 698
[3]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 180

8
[ 76-83-5 ]
[ 39824-26-5 ]
[ 249757-27-5 ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine In dichloromethane for 20h; Heating;

Reference： [1]Kumamoto, Hiroki; Tanaka, Hiromichi; Tsukioka, Ryota; Ishida, Yumiko; Nakamura, Akiko; Kimura, Satoe; Hayakawa, Hiroyuki; Kato, Keisuke; Miyasaka, Tadashi [Journal of Organic Chemistry, 1999, vol. 64, # 21, p. 7773 - 7780]

9
[ 39824-26-5 ]
5'-fluoro-5'-deoxy-2',3'-O-isopropylidene-6-fluoro-nebularine [ No CAS ]
[ 862672-09-1 ]

Yield	Reaction Conditions	Operation in experiment
87%	With p-toluenesulfonyl fluoride; tetrabutyl ammonium fluoride In tetrahydrofuran for 18h; Reflux;
	With p-toluenesulfonyl fluoride; tetrabutyl ammonium fluoride In tetrahydrofuran at 66℃; for 18.5h; Title compound not separated from byproducts;

Reference： [1]D'Errico, Stefano; Oliviero, Giorgia; Borbone, Nicola; Amato, Jussara; D'Alonzo, Daniele; Piccialli, Vincenzo; Mayol, Luciano; Piccialli, Gennaro [Molecules, 2012, vol. 17, # 11, p. 13036 - 13044]
[2]Ashton, Trent D.; Scammells, Peter J. [Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 14, p. 3361 - 3363]

10
[ 39824-26-5 ]
[ 449205-33-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 3361 - 3363

11
[ 683-08-9 ]
[ 39824-26-5 ]
[ 1498-51-7 ]
O-ethyl O'-[2,3-O-isopropylidene-1-(6-chloropurin-9-yl)-β-D-ribofuranosyl][(diethoxyphosphinyl)methyl]phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	Stage #1: Diethyl methylphosphonate With sec.-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.333333h; Stage #2: ethyl phosphodichloridite In tetrahydrofuran; hexane at -78℃; for 2h; Stage #3: 6-chloro-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)-9H-purine In tetrahydrofuran; hexane at -78 - 20℃;

Reference： [1]Grison, Claude; Joliez, Stephane; De Clercq; Coutrot, Philippe [Carbohydrate Research, 2006, vol. 341, # 9, p. 1117 - 1129]

12
[ 39824-26-5 ]
[ 98-88-4 ]
[ 3249-96-5 ]

Yield	Reaction Conditions	Operation in experiment
99.72%	With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 2h;	An intermediate compound (2.8 g 8.56 mmol) prepared in Step 1One was dissolved in dry methylene chloride (100 mL) cooled to 0 and then triethylamine (3.6 mL, 25.70 mmol) andDimethylaminopyridine (21 mg, 0.17 mmol) toDrop-wise.Benzoyl chloride (1.5 mL, 12.85 mmol) toSlowly added dropwise at the same temperature and then stirred at room temperature for 2 hours.After checking the completion of the reaction and the reaction was terminated by a saturated sodium bicarbonate solution.The organic layer was extracted with methylene chloride The reaction mixture was concentrated under reduced pressure and washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate.Intermediate compound by separating the resulting residue was then concentrated under reduced pressure, by column chromatography ((3aR, 4R, 6R, 6aR) -6- (6- chloro -9H- purin-9-yl) -2,2-dimethyl-tetrahydro a hydrofuro [3,4-d] [1,3] dioxol-4-yl) methyl benzoate (3.68 g, to give a 99.72%).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 2470 - 2473
[2]Patent: KR2015/10195,2015,A .Location in patent: Paragraph 0221; 0222; 0227; 0228

13
[ 3181-38-2 ]
[ 39824-26-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1998,vol. 8,p. 695 - 698

14
[ 39824-26-5 ]
[ 39824-27-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 2,6-lutidine / dioxane / 3 h / Ambient temperature 2: Pb(OAc)4 / dioxane / 0.5 h / Ambient temperature

Reference： [1]Schmitt, Lutz; Tampé, Robert [Journal of the American Chemical Society, 1996, vol. 118, # 24, p. 5532 - 5543]

15
[ 39824-26-5 ]
[ 178960-40-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: ethanol / Heating 2: 74 percent / diethyl azodicarboxylate, PPh₃ / tetrahydrofuran / 1 h / Ambient temperature 3: 83 percent / hydrazine hydrate / ethanol / 1 h / Heating

Reference： [1]Reinhoudt, David N.; Rudkevich, Dmitry M.; De Jong, Feike [Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6880 - 6889]

16
[ 39824-26-5 ]
[ 176747-13-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 2,6-lutidine / dioxane / 3 h / Ambient temperature 2: Pb(OAc)4 / dioxane / 0.5 h / Ambient temperature 3: H₂O / 2 h / 130 °C

Reference： [1]Schmitt, Lutz; Tampé, Robert [Journal of the American Chemical Society, 1996, vol. 118, # 24, p. 5532 - 5543]

17
[ 39824-26-5 ]
[ 176747-08-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 2,6-lutidine / dioxane / 3 h / Ambient temperature 2: Pb(OAc)4 / dioxane / 0.5 h / Ambient temperature 3: H₂O / 2 h / 130 °C

Reference： [1]Schmitt, Lutz; Tampé, Robert [Journal of the American Chemical Society, 1996, vol. 118, # 24, p. 5532 - 5543]

18
[ 39824-26-5 ]
[ 178960-41-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: ethanol / Heating 2: 74 percent / diethyl azodicarboxylate, PPh₃ / tetrahydrofuran / 1 h / Ambient temperature

Reference： [1]Reinhoudt, David N.; Rudkevich, Dmitry M.; De Jong, Feike [Journal of the American Chemical Society, 1996, vol. 118, # 29, p. 6880 - 6889]

19
[ 39824-26-5 ]
[ 176747-20-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: 2,6-lutidine / dioxane / 3 h / Ambient temperature 2: Pb(OAc)4 / dioxane / 0.5 h / Ambient temperature 3: H₂O / 2 h / 130 °C 4: Et₃N / dioxane / 70 °C 5: conc. H₂SO₄ / CHCl₃; methanol / 0.5 h / Ambient temperature

Reference： [1]Schmitt, Lutz; Tampé, Robert [Journal of the American Chemical Society, 1996, vol. 118, # 24, p. 5532 - 5543]

20
[ 39824-26-5 ]
[ 35847-70-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1: 81.6 percent / ethanol; dimethylformamide / 0.5 h 2: dicyclohexylcarbodiimide (DCC), dichloroacetic acid / dimethylsulfoxide / 0.5 h 3: dimethylsulfoxide / 1 h 4: 72.9 percent / methanol / 1 h 5: Et₃N / CH₂Cl₂ / 0.67 h 6: methanol; diethyl ether 7: liquid ammonia / 48 h / 140 - 145 °C 8: Raney nickel / ethanol / 1 h / Heating

Reference： [1]Kappler, Francis; Hampton, Alexander [Journal of Medicinal Chemistry, 1990, vol. 33, # 9, p. 2545 - 2551]

21
[ 39824-26-5 ]
[ 1003-03-8 ]
[ 103626-58-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In ethanol; for 16h;Heating / reflux;	To a solution of (2S,1R,4R,5R)-2-hydroxymethyl-5-(6-chloropurin-9-yl)-tetrahydrofuran-3,4-diol acetonide, the compound of formula (2) in which R2 is hydrogen (4.98 g, 15 mmol) in ethanol (80 ml) was added cyclopentylamine (0.6 ml, 30 mmol), and triethylamine (6.27 ml, 45 mmol), and the mixture was refluxed for 16 hours. The solvent was then removed under reduced pressure, and the residue partitioned between ethyl acetate and 10% citric acid in water, followed by water. Ethyl acetate was removed from the organic layer, to yield {(1R,2R,4R,5R)-4-[6-(cyclopentylamino)purin-9-yl]-7,7-dimethyl-3,6,8-trioxabicyclo[3.3.0]oct-2-yl}methan-1-ol, a compound of formula (3).

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 6736 - 6739
[2]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582
[3]Patent: US2004/43960,2004,A1 .Location in patent: Page/Page column 15-16

22
[ 39824-26-5 ]
sodium 2',3'-isopropylidene-5'-carboxyl-6-chloropurineriboside-5'-acetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		Example 7 Sodium 2',3'-isopropylidene-5'-carboxyl-6-chloropurineriboside-5'-acetate 2',3'-Isopropylidene-6-chloropurineriboside (6.05 g, 18.5 mmol) was added to acetonitrile (36 ml) and water (21 ml), and sodium hydrogen carbonate (0.4 g) and tetramethylpyridyloxy (TEMPO) (0.058 g, 0.37 mmol) were added. The mixture was stirred at 5C. An aqueous sodium chlorite solution (effective chlorine concentration 11%, 30.4 g, 41.1 mmol) was added over 3 hr, during which the pH was maintained at 6.5-7.5 by the addition of 20% aqueous sodium hydrogen carbonate solution. The mixture was further stirred overnight, and the pH was maintained at 6.5-7.5. Sequentially, 20% aqueous sulfite hydrogen sodium solution (5.1 g) was added, and the mixture was stirred for 1 hr. At this time point, complete decomposition of the oxidant was confirmed using a peroxide test paper (Merckoquant, trademark, manufactured by Merck). The content of the impurity in the reaction mixture was confirmed by HPLC and found to be 1.8% (reaction yield was 97%). Ethyl acetate (49 ml) was added to the reaction mixture, and the mixture was adjusted to pH 2.7 with 6N hydrochloric acid. After layer separation, the aqueous layer was extracted with ethyl acetate (11 ml). Water (30 ml) was added to the combined organic layer and the mixture was adjusted to pH 6.7 with aqueous sodium hydroxide solution. The layers were separated and the aqueous layer was concentrated. Toluene (30 ml) was added and the mixture was stirred overnight. The precipitate was collected by filtration, washed with toluene, and dried overnight at 50C under reduced pressure to give sodium 2',3'-isopropylidene-5'-carboxyl-6-chloropurineriboside-5'-acetate (6.5 g, 15.7 mmol). The content of the impurity in the crystal was confirmed by HPLC and found to be 1.4%. 1H-NMR(DMSO-d6) delta (ppm): 1.32(3H, s), 1.54(3H, s), 4.43(1H, s), 5.08(1H, d, J=5.9Hz), 5.18(1H, d, J=5.9Hz), 6.30(1H, s), 8.77(1H, s), 9.51(1H, s).

Reference： [1]Patent: EP1589027,2005,A1 .Location in patent: Page/Page column 20

23
[ 871108-12-2 ]
[ 39824-26-5 ]
[ 309725-38-0 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In ethanol for 48h; Heating / reflux;	14 2',3'-Isopropylidene-N6-(R)-(3-tetrahydrofuranyl) adenosine: 2',3'-isopropylidene- 6-chloroadenosine (0.750 gm, 0.0023 mol) was diluted with ethanol (20 mL) and to the resultant solution was added R-(3-aminotetrahydrofuranylan-iineNo.MeSO3H (0.630 gm, 0.0035 mol), followed by triethylamine (0.9 mL). The resultant reaction was heated at refluxed for 2 days, then cooled to room temperature and the resultant reaction mixture was concentrated in vacuo, diluted with water (25 mL) and ethyl acetate (25 mL), and transferred to a separatory funnel. The organic layer was separated, dried over sodium sulfate and concentrated in vacuo to provide a crude residue which was recrystalized from EtOAc-hexane to provide 2',3'-Isopropylidene-N6-(R)-(3-tetrahydrofuranyl) adenosine (0.680 gm).

Reference： [1]Current Patent Assignee: ROCKET PHARMACEUTICALS INC - WO2005/117910, 2005, A2 Location in patent: Page/Page column 143

24
[ 10277-74-4 ]
[ 39824-26-5 ]
[ 905580-13-4 ]

Yield	Reaction Conditions	Operation in experiment
66%	With triethylamine; In ethanol; at 140℃; for 0.166667h;Microwave irradiation;	Step b: ((3aR,4R,6R,6aR)-6-{6-r(lS)-2,3-dihydro-lH-inden-l-ylamino1-9H-purin-9-yl)-2/2- dimemyltetrahydrofuror3,4-diri3idioxol-4-yl)methanol; [0164] [(3aR/4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2/2-dimethyltetrahydrofuro-[3,4-d][l,3]dioxol-4-yl]methanol(736mg, 2.26mmol), (S)-(+)-l-aminoindane (360mg, 2.71mmol) and triethylamine(380 muL, 2.71mmol) were added to ethanol (2.5mL) and the mixture was heated at 140 0C for lOminutes using microwave irradiation. The cooled mixture was diluted with diethyl ether (5mL) and the precipitated product isolated by filtration. Further product was isolated from the filtrates by evaporation, followed by recrystallization from ethanol / ether. Total yield was 630mg, 66%.[0165] LCMS: R.t. 1.64 min ES+ 424 (formic acid).

Reference： [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 79

25
[ 39824-26-5 ]
[ 148017-28-1 ]
[ 905580-17-8 ]

Yield	Reaction Conditions	Operation in experiment
63%	With di-isopropyl azodicarboxylate; triphenylphosphine; In ethyl acetate; for 2h;	Step b: fert-Butyl (aminosulf onyl) f r(3aR,4R<6R,6aR)-6-(6-chloro-9H-purin-9-yl)- 2,2-dimethyltetrahydrofuror3,4-rfiri31dioxol-4-yl1memyl)carbamate; [0237] (2R/3R,4S,5R)-2-(6-chloro-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol (6.352g, 0.01944mol), N-Boc-sulfamide (5.717g, 0.02913mol) and triphenylphosphine (6.119g, 0.02333mol) were dissolved in ethyl acetate (20OmL) under nitrogen and diisopropyl azodicarboxylate (5.742mL, 0.02916mol) was added dropwise. The solution was stirred for 2h, and then concentrated in vacuo. The residue was purified by flash chromatography (Hex/EtOAc 25% to 65%) to afford 5.46Og of product as a white solid and 1.4Og of product with triphenylphosphine oxide impurity. This second batch was purified by flash chromatography (Hex/EtOAc 20% to 60%). The product was obtained as a white solid (6.16Og, 63%).[0238] LCMS: R.t. 1.66 min ES+ 505 (formic acid).

Reference： [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 87

26
[ 108-24-7 ]
[ 39824-26-5 ]
[ 905580-65-6 ]

Yield	Reaction Conditions	Operation in experiment
84%	With pyridine;dmap; In dichloromethane; at 20℃; for 1h;	Example 60: { (2R,3S,4R,5R)-5-[6-(4-Fluorobenzyl)-9H-purin-9-yl]-3,4-dihydroxytetrahydro- furan-2-yl}methyl sulfamate (1-41)Step a: r(3aR,4R,6R,6aR)-6-(6-Chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuror3,4-dl- [131dioxol-4-yl]methyl acetate; [0469] [(3aR,4R,6R,6ai?)-6-(6-Chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro-[3,4-d][l,3]dioxol-4-yl]methanol (1.00Og, 0.003060mol), pyridine (495.1 muL, 0.006121mol), 4- dimethylaminopyridine (0.0748g, 0.000612mol) and acetic anhydride (577.5 muL, 0.006121mol) were stirred in methylene chloride (2OmL) at room temperature for Ih. The solution was diluted with Methylene chloride, extracted with HCl IN, dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/DCM 0% to 25%) to obtain the product (1.129g, 84%) as an oil.[0470] LCMS: R.t. 1.38 ES+ 477 (formic acid).

Reference： [1]Nucleosides, nucleotides and nucleic acids,2009,vol. 28,p. 642 - 656
[2]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 120

27
[ 39824-26-5 ]
[ 52719-20-7 ]

Yield	Reaction Conditions	Operation in experiment
86%	With Dess-Martin periodane; In dichloromethane; at 0 - 20℃; for 2 - 5h;Product distribution / selectivity;	Example 49: 2-((2R/3S,4R,5K)-5-{6-[(lS)-2,3-Dihydro-lH-inden-l-ylamino]-9H-purin-9-yl}- 3,4-dihydroxytetrahydrofuran-2-yl)ethanesulfonamide (1-31)Step a: [(SaR^^.R^aR'l--fe-Chloro-gH-purin-g-yn-Sigma^-dimethyltetrahydrofurorS^-rfi- [1 ,31dioxol-4-carbaldehyde[0388] To a suspension of Dess-Martin periodinane (16.42 g, 0.03872 mol) in anhydrous methylene chloride (88.0 mL) cooled in an ice/water bath was added [(3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4- yl]methanol (11.50 g, 0.03520 mol) in methylene chloride (200 mL). The reaction was stirred under an atmosphere of nitrogen and allowed to warm to ambient temperature. After 2 hours, a further portion of Dess-Martin periodinane (1.00 g, 0.00236 mol) was added. After 3 hours, a solution (200 mL) of sodium thiosulfate (5Og in 200 mL of saturated aqueous sodium bicarbonate) was added and the mixture stirred for 10 min. The aqueous was extracted 2 x 250 mL methylene chloride and 8 x 5OmL of chloroform. The combined organics were washed with water and dried over magnesium sulfate and concentrated in vacuo to dryness. The residue was taken up in dry toluene (20OmL) and concentrated in vacuo, and then taken up in dry methylene chloride and concentrated in vacuo to yield the product as a foam (9.83g, 86%).; Example 58: (R)-l-((2S,3S,4R,5R)-5-(6-((S)-2,3-Dihydro-lH-inden-l-ylamino)-9H-purin-9- yl)-3,4-dihydroxy-tetrahydrofuran-2-yl)ethyl sulfamate (1-58)Step a: l-((3aR,4R,6R,6aR)-6-(6-Chloro-9H-purin-9-yl)-2,2-dimethyl-tetrahydro- furor3,4-din,31dioxol-4-yl)ethanol; [0444] To a suspension of Dess-Martin periodinane (1.4g, 3.3 iranol) in methylene chloride (8 ml), cooled in an ice /water bath, was added dropwise a solution of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-tetrahydrofuro[3,4-d][l,3]dioxol-4- yl)methanol (0.978g, 3.0 mmol) in methylene chloride (10 mL). The reaction was allowed to warm to ambient temperature while stirring for 2h.[0445] A solution of sodium thiosulfate (25 %) in sat. sodium bicarbonate (25 mL) was added and the mixture stirred for 15 min and extracted with methylene chloride (3 x 15 mL). The organic was dried (MgSO4) and evaporated to give a colorless foam, 0.66g.[0446] To a solution of the aldehyde (0.65 g, 2.0 mmol) in anhydrous THF (20 mL) at-78 0C was added dropwise a 3.0 M solution of methylmagnesium bromide in diethylether (1.2 mL, 4.0 mmol) and the reaction was allowed to warm to -20 C over 2 h while being stirred under a stream of nitrogen.[0447] The reaction was quenched with saturated ammonium chloride solution (20 mL) containing acetic acid (0.5 mL) and extracted with ethyl acetate (3 x 50 mL).[0448] Flash chromatography (3:2 methylenechloride : EtOAc) gave the title compound (0.32 g, 27% yield).[0449] LCMS: R.t. 1.36 ES+ 339, 341 (ammonium acetate).

Reference： [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 108

28
[ 39824-26-5 ]
[ 905580-15-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sulphamoyl chloride; triethylamine; In N,N-dimethyl-formamide; at 0℃; for 3.58333h;Product distribution / selectivity;	Example 6: ((2R,3S,4R,5R)-3,4-Dihydroxy-5-{6-[(3-methoxybenzyl)amino]-9H-purin-9-yl}- tetrahydrofuran-2-yl)methyl-sulfamate (1-11); Step a: Sulfamic acid 6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo\|'3,4-diriy31- dioxol4-yl methyl ester[0185] [6-(6-Chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][l,3]dioxol-4-yl]- methanol (6.53g, 20mmol) and triethylamine (4.17mL, 30mmol) were dissolved in DMF (3OmL) under nitrogen and cooled on an ice bath. Chlorosulfonamide solution (1OmL, 20mmol) was then added over 5 minutes and the mixture stirred for 90 minutes. Two further portions of chlorosulfonamide (5mL, lOmmol) were added with the reaction mixture stirred for a 60 minutes after each addition. The mixture was then evaporated under vacuum at 50 0C and the residue was purified by column chromatography on silica (12Og) using ethyl acetate gradient 0 to 100% in hexane to give the desired product, as a foam (6.88g, 85%).

Reference： [1]Patent: WO2006/84281,2006,A1 .Location in patent: Page/Page column 81
[2]Antibiotics,2019,vol. 8

29
[ 39824-26-5 ]
[ 213554-28-0 ]

Yield	Reaction Conditions	Operation in experiment
	With aniline In <i>N</i>-methyl-acetamide; ethyl acetate	1 Preparation of 5'-deoxy-6-N-phenyl-adenosine 5'-N-(N-L-phenylalanyl)sulfamide 6-chloro-2',3'-O-(1-methylethylidene)purine riboside (972 mg) and aniline (1.08 ml) in dry dimethylformamide (8 ml) were heated to 90° C. under an atmosphere of nitrogen for 16 hours. The mixture was then poured into ethylacetate (200 ml) washed with water (2*100 ml) dried over anhydrous magnesium sulfate and evaporated to a brown oil. The oil was purified by silica gel chromatography (30-50% ethylacetate in hexanes) to yield 2',3'-O-(1-methylethylidene)-6-N-phenyl adenosine as a brown foam (757 mg).

Reference： [1]Current Patent Assignee: MERCK & CO INC - US5824657, 1998, A

30
[ 124-09-4 ]
[ 64-17-5 ]
[ 15715-58-9 ]
[ 39824-26-5 ]
[ 73122-07-3 ]

Yield	Reaction Conditions	Operation in experiment
74%	In methanol	2.I 2-I. 2-I. PREPARATION OF THE LABELED CONJUGATE 6-(6-Aminohexyl)amino-9-(2',3'-O-isopropylidene-β-D-ribofuranosyl) purine (2). 16.0 g (50 mmol) of 6-chloro-9-(2',3'-O-isopropylidene-β-D-ribofuranosyl) purine (1) [Hampton et al, J. Am. Chem. Soc. 83:1501 (1961)] was added with stirring to a molten (70° C.) sample of freshly distilled 1,6-diaminohexane (58 g, 500 mmol). The resulting mixture was stirred under argon at 40° C. for 18 hours. The excess diamine was removed by distillation under reduced pressure (60° C., 0.01 mm Hg). The resulting pale yellow residue was adsorbed onto 150 g of silica gel 60 (E. Merck, Darmstadt, West Germany) and used to top a chromatographic 9:1 (v:v) mixture of absolute ethyl alcohol and triethylammonium bicarbonate (pH 7.5, l M). The column was eluted with the above 9:1 (v:v) solvent mixture and 900 20 ml fractions were collected. The fractions were examined by thin layer chromatography (TLC) on silica gel 60 eluding with a 7:3 (v:v) mixture of absolute ethyl alcohol and triethylammonium bicarbonate (pH 7.5, l M). Fractions numbered 391 through 900 from the column chromatography were combined and evaporated in vacuo leaving 15.0 g of a glassy residue (74% yield). A 1 g sample of the glass was dissolved in a small volume of methyl alcohol and applied to the top of a column prepared from 80 g of Sephadex LH-20 (Pharmacia Fine Chemicals, Uppsala, Sweden) preswollen in methyl alcohol. The column was eluted with methyl alcohol. A total of ninety 8 ml fractions were collected. The fractions were examined by TLC on silica gel 60 eluding with a 7:3 (v:v) mixture of absolute ethyl alcohol and triethylammonium bicarbonate (pH 7.5, l M). Fractions numbered 19 through 27 from the column chromatography were combined and evaporated in vacuo leaving 910 mg (91% recovery) of a white glass. Analysis: Calculated for C19 H30 N6 O4: C, 56.14; H, 7.44; N, 20.68. Found: C, 53.91; H, 7.33; N, 19.18 NMR (60 MHz, CDCl3): δ1.40 (s, 3H, isopropylidene), 1.63 (s, 3H, isopropylidene) 5.98 (d, 1H, 1'-ribose), 7.92 (s, 1H, purine), 8.36 (s, 1H, purine)

Reference： [1]Current Patent Assignee: BAYER AG - US4213893, 1980, A

31
[ 39824-26-5 ]
[ 110-60-1 ]
[ 871793-10-1 ]

Reference： [1]ChemBioChem,2010,vol. 11,p. 256 - 265
[2]Bioorganic and Medicinal Chemistry,2008,vol. 16,p. 40 - 48

32
[ 2140-11-6 ]
[ 39824-26-5 ]

Reference： [1]Journal of Organic Chemistry,2008,vol. 73,p. 2416 - 2419

33
[ 39824-26-5 ]
[ 10068-07-2 ]
[ 851046-31-6 ]

Yield	Reaction Conditions	Operation in experiment
95%		To a solution of [6- (6-Chloro-purin-9-yl)-2, 2-dimethyl-tetrahydro-furo [3,4- d] [1, 3] dioxol-4-yl] -methanol (0.570 g, 1.74 mmol) in 16 mL of dry dichloromethane was added polymer-bound triphenylphosphine (PS-TPP; Argonaut Tech. , 2.14 mmol/g, 0.91 g, 1.2 eq), followed by methyl-3-hydroxy-5-isoxazolecarboxylate (0.248 g, 1 eq). The mixture was sonicated for 15 minutes then stirred at room temperature for lh under argon. The reaction mixture was cooled to 0 C and under argon flow diethylazodicarboxylate (0.33 g, 1.1 eq), dissolved in 1 ml of dichloromethane, was added dropwise via syringe. The mixture was protected from light and stirred at 0 C for 30 min. then at room temperature for 20 h. The resin was washed liberally with dichloromethane and methanol. The organic solution obtained from the washes was concentrated to give, after flash chromatography purification, 0.740 g of the product as a white solid (95% yield).'H NMR (300 MHz, CDC13) 6 8.76 (s, 1H), 8.23 (s, IH), 6.42 (s, 1H), 6.23 (d, J= 2. 1Hz, 1H), 5.43 (dd, J= 2.1 Hz, IH), 5.14 (dd, J = 3. 6 Hz, 1H), 4.7 (m, 1H), 4.61 (dd, J= 3. 9Hz, IH), 4.49 (dd, J= 5. 7Hz, IH), 3.93 (s, 3H), 1.65 (s, 3H), 1.42 (s, 3H). MW calculated for C18Hl8CIN507 (MH+) 452, found 452 by LCMS.

Reference： [1]Patent: WO2005/39590,2005,A1 .Location in patent: Page/Page column 58

34
[ 39824-26-5 ]
[ 124-40-3 ]
[ 19083-21-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	In tert-butyl alcohol; at 85℃; for 3h;	To a stirred solution of 6-chloro-9-(2',3'-O-isopropylidene-beta-D-ribofuranosyl)purine in tert-BuOH (20 mL) in sealed tube was added N,N-dimethylamine (1 mL) and the reaction heated at 85 C. for 3 hours. The solvent was removed under vacuum. Purification by flash chromatography (1:1 EtOAc/hexane) afforded the title compound (198 mg, 96%) as white solid: Rf 0.4 (EtOAc); [alpha]20D -62.4 (c 0.5, MeOH); 1H NMR (600 MHz, CD3OD) delta 1.51 (s, 3H), 1.77 (s, 3H), 3.65 (br s, 6H), 3.89 (dd, J=12.6, 3.6 Hz, 1H), 4.00 (dd, J=12, 3 Hz, 1H), 4.56 (d, J=2.4 Hz, 1H), 5.18 (dd, J=6.6, 1.8 Hz, 1H), 5.34 (t, J=6 Hz, 1H), 6.21 (d, J=4.2 Hz, 1H), 8.27 (s, 1H), 8.34 (s, 1H); 1H NMR (600 MHz, CDCl3) delta 1.37 (s, 3H), 1.64 (s, 3H), 3.49 (br s, 6H), 3.79 (d, J=13.2 Hz, 1H), 3.98 (d, J=12.6 Hz, 1H), 4.53 (s, 1H), 5.12 (d, J=5.4 Hz, 1H), 5.24 (t, J=5.4 Hz, 1H), 5.82 (d, J=4.8 Hz, 1H), 7.36 (s, 1H), 8.26 (s, 1H); 13C NMR (150 MHz, CDCl3) delta 25.4, 27.9, 63.7, 81.9, 82.8, 86.2, 94.6, 105.0, 105.0, 114.0, 121.8, 138.2, 148.9, 151.9, 155.3; MS (APCI+) calcd for C15H22N5O4 [M+H]+ 336.1, found 336.1

Reference： [1]Patent: US2008/293666,2008,A1 .Location in patent: Page/Page column 51

35
[ 39824-26-5 ]
[ 765-30-0 ]
[ 883743-30-4 ]

Yield	Reaction Conditions	Operation in experiment
94%	In tert-butyl alcohol; at 85℃; for 3h;	To a stirred solution of 6-chloro-9-(2',3'-O-isopropylidene-beta-D-ribofuranosyl)purine in tBuOH (20 mL) in sealed tube was added cyclopropyl amine (1 mL) and heated at 85 C. for 3 hours. The solvent was removed under vacuum and purification of the crude residue by flash chromatography (EtOAc/hexane 50:50) afforded the title compound (200 mg, 94%) as a white solid: Rf 0.4 (EtOAc); [alpha]20D -230 (c 1.0, MeOH); 1H NMR (600 MHz, CDCl3) delta 0.67 (br s, 2H), 0.95 (q, J=6.0 Hz, 2H), 1.37 (s, 3H), 1.63 (s, 3H), 3.78 (d, J=12.6 Hz, 1H), 3.96 (d, J=13.2 Hz, 1H), 4.53 (s, 1H), 5.11 (d, J=6.0 Hz, 1H), 5.19 (t, J=5.4 Hz, 1H), 5.86 (d, J=4.2 Hz, 1H), 7.81 (s, 1H), 8.40 (s, 1H); 13C NMR (150 MHz, CDCl3) delta 7.6, 23.9, 25.4, 27.8, 63.5, 81.9, 83.2, 86.3, 94.5, 114.2, 121.5, 140.0 (3 Aromatic carbons are missing For this I have given more no. of scans and increased relaxation time also); MS (APCI+) calcd for C16H20N5O4 [M+H]+ 346.1520, found 346.1551 (error 8.9).

Reference： [1]Patent: US2008/293666,2008,A1 .Location in patent: Page/Page column 51

36
[ 74-83-9 ]
[ 39824-26-5 ]
[ 223756-63-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.5h; Inert atmosphere;

Reference： [1]Williamson, Douglas S.; Borgognoni, Jenifer; Clay, Alexandra; Daniels, Zoe; Dokurno, Pawel; Drysdale, Martin J.; Foloppe, Nicolas; Francis, Geraint L.; Graham, Christopher J.; Howes, Rob; Macias, Alba T.; Murray, James B.; Parsons, Rachel; Shaw, Terry; Surgenor, Allan E.; Terry, Lindsey; Wang, Yikang; Wood, Mike; Massey, Andrew J. [Journal of Medicinal Chemistry, 2009, vol. 52, # 6, p. 1510 - 1513]

37
[ 100-39-0 ]
[ 39824-26-5 ]
C₂₀H₂₁ClN₄O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium hydride In N,N-dimethyl-formamide; mineral oil for 0.5h; Inert atmosphere;

38
[ 39824-26-5 ]
[ 17201-43-3 ]
[ 1134156-49-2 ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1510 - 1513
[2]Journal of Medicinal Chemistry,2019

39
[ 39824-26-5 ]
[ 402-49-3 ]
6-chloro-9-((3aR,4R,6R,6aR)-2,2-dimethyl-6-(((4-(trifluoromethyl)benzyl)oxy)methyl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purine [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1510 - 1513
[2]Chemical Communications,2017,vol. 53,p. 5167 - 5170

40
[ 39824-26-5 ]
[ 220141-72-0 ]
C₂₀H₁₈ClF₃N₄O₄ [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2009,vol. 52,p. 1510 - 1513

41
[ 110-91-8 ]
[ 39824-26-5 ]
[ 1310342-58-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;
80%	With N-ethyl-N,N-diisopropylamine In acetonitrile for 2h; Reflux;	11.4.2 Step 2: Synthesis of Compound ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-morpholino-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol The compounds ((3 aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyl-tetrahydrofuro[3,4-D][1,3]dioxol-4-yl)methanol (1.00 g, 3.06 mmol), morpholine (610 mg, 7.0 mmol) and DIPEA (900 mg, 7.0 mmol) were dissolved in CH3CN (20 mL), then refluxed and reacted for 2 hours. After the reaction was completed, the reaction mixture was cooled to RT, poured into ice-water and extracted with EA. The organic phase was washed with water, dried with Na2SO4 and concentrated. The crude product was purified and separated by column chromatography to give the desired product (912 mg, yield 80%).

Reference： [1]Lukkarila, Julie L.; Da Silva, Sara R.; Ali, Mohsin; Shahani, Vijay M.; Xu, G. Wei; Berman, Judd; Roughton, Andrew; Dhe-Paganon, Sirano; Schimmer, Aaron D.; Gunning, Patrick T. [ACS Medicinal Chemistry Letters, 2011, vol. 2, # 8, p. 577 - 582]
[2]Current Patent Assignee: WIGEN BIOMEDICINE TECHNOLOGY SHANGHAI - US2020/190066, 2020, A1 Location in patent: Paragraph 0247; 0245

42
[ 38041-19-9 ]
[ 39824-26-5 ]
[ 223761-85-1 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

43
[ 4795-29-3 ]
[ 39824-26-5 ]
[ 1310342-48-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

44
[ 2744-08-3 ]
[ 39824-26-5 ]
[ 1310342-61-0 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582

45
[ 27757-85-3 ]
[ 39824-26-5 ]
[ 1310342-50-7 ]

Yield	Reaction Conditions	Operation in experiment
93%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

46
[ 30433-91-1 ]
[ 39824-26-5 ]
[ 1310342-51-8 ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

47
[ 3731-53-1 ]
[ 39824-26-5 ]
[ 1310342-56-3 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 75℃; for 17.5h; Inert atmosphere;

48
[ 5036-48-6 ]
[ 39824-26-5 ]
[ 1310342-52-9 ]

Yield	Reaction Conditions	Operation in experiment
98%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

49
[ 107-85-7 ]
[ 39824-26-5 ]
[ 1310342-35-8 ]

Yield	Reaction Conditions	Operation in experiment
83%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 115℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

50
[ 617-89-0 ]
[ 39824-26-5 ]
[ 185848-23-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

51
[ 107-45-9 ]
[ 39824-26-5 ]
[ 1310342-38-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 135℃; for 4.33h; Inert atmosphere; Microwave irradiation;

52
[ 39824-26-5 ]
[ 83585-56-2 ]
[ 1310342-62-1 ]

Yield	Reaction Conditions	Operation in experiment
70%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 1h; Inert atmosphere; Microwave irradiation;

53
[ 39824-26-5 ]
[ 19961-27-4 ]
[ 1310342-45-0 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582

54
[ 39824-26-5 ]
[ 75-31-0 ]
[ 1052239-26-5 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; at 20℃; for 1h;	General procedure: Compound 5 was synthesized using modified methods described in references e and f. A solution of <strong>[39824-26-5]((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol</strong> (1.05g, 3.21 mmol) in 2M Methylamine in THF (10.0 mL, 20.0 mmol) was stirred at rt for 1h. The THF was removed under vacuum, and the resulting solids were dissolved in DCM and washed with Sat. Aq. NaHCO3. The Aqueous layer was extracted with DCM (2Xs) and the combined DCM layers were dried over Na2SO4 and concentrated under vacuum to give ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol as a white foam (1.00g, 97%).

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582
[2]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 1532 - 1537

55
[ 39824-26-5 ]
[ 108-00-9 ]
[ 1310342-43-8 ]

Yield	Reaction Conditions	Operation in experiment
55%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

56
[ 39824-26-5 ]
[ 62-53-3 ]
[ 213554-28-0 ]

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582
[2]Antibiotics,2019,vol. 8

57
[ 39824-26-5 ]
[ 107-11-9 ]
[ 1310342-31-4 ]

Yield	Reaction Conditions	Operation in experiment
91%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

58
[ 39824-26-5 ]
[ 74-89-5 ]
[ 4566-77-2 ]

Yield	Reaction Conditions	Operation in experiment
97%	In tetrahydrofuran; at 20℃; for 1h;	Compound 5 was synthesized using modified methods described in references e and f. A solution of <strong>[39824-26-5]((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol</strong> (1.05g, 3.21 mmol) in 2M Methylamine in THF (10.0 mL, 20.0 mmol) was stirred at rt for 1h. The THF was removed under vacuum, and the resulting solids were dissolved in DCM and washed with Sat. Aq. NaHCO3. The Aqueous layer was extracted with DCM (2Xs) and the combined DCM layers were dried over Na2SO4 and concentrated under vacuum to give ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol as a white foam (1.00g, 97%). 1HNMR (400 MHz, METHANOL-d4) d 8.26 (s, 1H), 8.25 (br. s., 1H), 6.14 (d, J=3.54Hz, 1H), 5.27 (dd, J=3.54, 6.06 Hz, 1H), 5.04 (dd, J=2.27, 6.06Hz, 1H), 4.35-4.39 (m, 1H), 3.80 (dd, J=3.54, 12.13 Hz, 1H), 3.71 (dd, J=4.04,12.38 Hz, 1H), 3.11 (br. s, 3H), 1.62 (s, 3H), 1.38 (s, 3H). LCMS:[M+H]+ = 322.

Reference： [1]ACS Medicinal Chemistry Letters,2011,vol. 2,p. 577 - 582
[2]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 1532 - 1537
[3]Antibiotics,2019,vol. 8

59
[ 39824-26-5 ]
[ 109-85-3 ]
[ 1310342-41-6 ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In dimethyl sulfoxide at 105℃; for 0.666667h; Inert atmosphere; Microwave irradiation;

60
[ 930-45-0 ]
[ 39824-26-5 ]
[ 124555-37-9 ]

Reference： [1]Patent: WO2011/119969,2011,A1 .Location in patent: Page/Page column 31

61
[ 39824-26-5 ]
[ 67604-85-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With palladium 10% on activated carbon; hydrogen; potassium carbonate; In tetrahydrofuran; at 20℃; under 760.051 Torr; for 18h;	To a stirred solution of S12 (7.00 g, 21.5 mmol) in 80 mL of THF was added K2CO3 (5.90 g, 42.9 mmol) followed by 1.5 g of 10% Pd/C. The solution was purged with Ar for 30 min before being stirred under H2 (1 atm) for 18 h. The solution was then filtered through Celite and concentrated in vacuo to give a yellow oil. The oil was purified by flash chromatography (10% MeOH/DCM) to give the product 29
95%	With hydrogen; potassium carbonate;palladium 10% on activated carbon; In tetrahydrofuran; at 20℃; for 15h;	Step 1. Preparation of ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(9H-purin-9- yI)tetrahydrofuro[3,4-d][l,3]dioxol-4-yl)methanolTo a solution of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-d][l ,3]dioxol-4-yl)methanol (7 g, 21.5 mmol) in THF (80 mL) was added K2C03 (5.9 g, 42.9 mmol) and 10% Pd/C (1.5 g). The mixture was stirred under H2 atmosphere at rt for 15 h, then filtered and the filtrate was concentrated to obtain the target product (6 g, yield: 95%) as a light yellow oil. 1H NMR (500 MHz, CDC13): delta 9.14 (s, IH), 8.91 (s, IH), 8.12 (s, IH), 5.92 (d, 7 = 4.5 Hz, IH), 5.39-5.36 (m, IH), 5.19-5.16 (m, IH), 5.08-5.05 (m, IH), 4.49 (s, IH), 3.93-3.90 (m, IH), 3.78-3.73 (m, IH), 1.59 (s, 3H), 1.32 (s, 3H) ppm; ESI-MS (m/z): 293.2 [M+l]+.

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5433 - 5440
[2]Patent: WO2012/82436,2012,A2 .Location in patent: Page/Page column 211
[3]Green Chemistry,2014,vol. 16,p. 1077 - 1081

62
[ 109-83-1 ]
[ 39824-26-5 ]
[ 19083-21-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	at 60℃;	Step 2. Preparation of ((3aR,4R,6R,6aR)-6-(6-(dimethylamino)-9H-purin-9-yl)- 2,2-dimethyltetrahydrofuro[3,4-d][l,3]dioxol-4-yl)methanoIO. ,0((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4- d][l ,3]dioxol-4-yl)methanol (2 g, 6.13 mmol) was dissolved in 30 % methylamine ethanol solution (120 mL) and the mixture was stirred at 60 C overnight. The mixture was concentrated to dryness, the residue was dissolved in DCM (150 mL), then washed with sat. K2C03 solution (50 mL), brine (50 mL). The organic phase was dried over Na2S04, filtered and concentrated to afford the title compound (1.9 g, yield: 92 %) as a white solid. NMR (500 MHz, CDC13): delta 8.26 (s, 1H), 7.73 (s, 1H), 6.90 (d, J = 1 1.5 Hz, 1H), 5.82 (d, / = 5.0 Hz, 1H), 5.25-5.23 (m, 1H), 5.13-5.11 (m, 1H), 4.53 (s, 1H), 3.98 (d, i = 12.5 Hz, 1H), 3.78(t, J = 12.0 Hz, 1H), 3.48 (br s, 6H), 1.65 (s, 3H), 1.38 (s, 3H) ppm; ESI (m/z): 336.3 [M+l]+

Reference： [1]Patent: WO2012/82436,2012,A2 .Location in patent: Page/Page column 257

63
1-(3,4,5-trimethoxyphenyl)ethylamine hydrochloride [ No CAS ]
[ 39824-26-5 ]
N⁶-[1-(3,4,5-trimethoxyphenyl)ethyl]-2',3'-O-isopropylideneadenosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1.24 g	With triethylamine In ethanol for 8h; Reflux;	55 Second step, a mixture of 1-(3,4,5-trimethoxyphenyl)-ethylamine (0.730 g), 2',3'-O-isopropylidene-6-chloropurine riboside (0.80 g) and triethylamine (1.20 g) in 95% EtOH (50 ml) was refluxed for 8 h. After evaporation of the reaction mixture, the residue was suspended in EtOAc (150 ml), and filtered. The filtrate was evaporated. The residue was separated by column chromatography over silica gel and eluted with CHCl3-CH3OH (100:1) to yield N6-[(+/-)-1-(3,4,5-trimethoxyphenyl)-ethyl]-2',3'-O-isopropylidene-adenosine (1.24 g) as a pale yellowish solid.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF MEDICAL SCIENCES - US2013/45942, 2013, A1 Location in patent: Paragraph 0267

64
[ 39824-26-5 ]
[ 2450-71-7 ]
N6-(prop-2"-ynyl)-2',3'-(O-isopropylidene)adenosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
54%	With triethylamine; In butan-1-ol; at 95℃; for 5h;	Next, electrophilic AMP analogs with two significantly different substituents at N6-position (i.e. a propargyl and phenyl alkyne) were synthesized following Scheme 2 and Scheme 3. Compound 2 that has a small hydrophobic group (propargyl alkyne) at the N6-position was prepared by coupling 2-chloroethanesulfonyl chloride with the 5-amino adenine moiety, followed by the deprotection of the acid labile acetonide (Scheme 2). The synthesis of compound 3, which has a large hydrophobic group (phenyl alkyne) at the N6-position, required tert-butyldimethylsilane (TI3DMS) protection and deprotection steps on the 5? alcohol and Hoc protection on the N6-amine due to the instability of the reaction intermediates during the Mitsunobu reaction. Subsequent treatment with 2-chloroethanesulfonyl chloride and global deprotection of the acid labile protecting groups led to the formation of compound 3.

Reference： [1]Patent: US2017/312284,2017,A1 .Location in patent: Paragraph 0093
[2]Journal of the American Chemical Society,2013,vol. 135,p. 16948 - 16962

65
[ 39824-26-5 ]
[ 814-49-3 ]
[ 1622143-79-6 ]

Yield	Reaction Conditions	Operation in experiment
76%	In pyridine; at 0℃; for 2h;Inert atmosphere;	To a solution of 6-chloro-9-(2,3-O-isopropylidene--d-ribofuranosyl)-9H-purine [21] (2.56g, 7.83mmol) in anhydrous pyridine (32mL), diethylchlorophosphate (2.8mL, 19.58mmol) was added dropwise at 0C under argon atmosphere. The resulting solution was stirred at this temperature. After completion (2h), MeOH (10mL) was added and the solvents were removed under reduced pressure. The crude product was purified by flash column chromatography (200g SiO2, CH2Cl2/MeOH: 100/0 to 98/2) to afford compound 3 (2.76g, 76%) as a yellow oil. 1H NMR (400.13MHz, DMSO-d6): delta 1.14 (2td, 4JH,P=0.9, J=7.1, 2×3H, CH3), 1.35 (s, 3H, (CH3)2C), 1.57 (s, 3H, (CH3)2C), 3.85-3.94 (m, 4H, O-CH2), 4.05-4.19 (m, 2H, H-5?), 4.42-4.46 (m, 1H, H-4?), 5.08 (dd, J3?,4?=3.1, J2?,3?=6.2, 1H, H-3?), 5.53 (dd, J1?,2?=2.0, J2?,3?=6.2, 1H, H-2?), 6.38 (d, J1?,2?=2.1, 1H, H-1?), 8.84 (s, 2H, H-2, H-8); 13C NMR (100.62MHz, DMSO-d6): delta 16.3 (d, 3JC,P=6.4, 2C, CH3), 25.6 ((CH3)2C), 27.3 ((CH3)2C), 63.3 (d, 2JC,P=5.7, 2C, O-CH2-CH3), 66.8 (d, 2JC,P=5.3, C-5?), 81.2 (C-3?), 83.8 (C-2?), 85.6 (d, 3JC,P=7.7, C-4?), 90.5 (C-1?), 114.0 ((CH3)2C), 132.0 (C-5), 146.5 (C-8), 149.9 (C-6), 151.6 (C-4), 152.2 (C-2); 31P NMR (161.62MHz, DMSO-d6): delta-0.90; HRMS (ESI-TOF): m/z calcd for [C17H2435ClN4O7P+H]+ 463.1149, found 463.1168.

Reference： [1]European Journal of Medicinal Chemistry,2014,vol. 85,p. 418 - 437

66
[ 39824-26-5 ]
[ 98-80-6 ]
((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-phenyl-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
134.3 mg	With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In toluene at 100℃;
	With potassium carbonate In toluene at 110℃; Inert atmosphere;
	With tetrakis-(triphenylphosphine)-palladium; potassium carbonate In toluene for 18h; Inert atmosphere;

Reference： [1]Ali, Md Ashif; Yao, Xiayin; Sun, Hao; Lu, Hongjian [Organic Letters, 2015, vol. 17, # 6, p. 1513 - 1516]
[2]Liang, Lei; Xie, Ming-Sheng; Wang, Hai-Xia; Niu, Hong-Ying; Qu, Gui-Rong; Guo, Hai-Ming [Journal of Organic Chemistry, 2017, vol. 82, # 11, p. 5966 - 5973]
[3]Yang, Qi-Liang; Liu, Ying; Liang, Lei; Li, Zhi-Hao; Qu, Gui-Rong; Guo, Hai-Ming [Journal of Organic Chemistry, 2022, vol. 87, # 9, p. 6161 - 6178]

67
[ 39824-26-5 ]
[ 100-46-9 ]
[ 78188-38-2 ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran at 20℃; for 1h;	Compound 5 General procedure: Compound 5 was synthesized using modified methods described in references e and f. A solution of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (1.05g, 3.21 mmol) in 2M Methylamine in THF (10.0 mL, 20.0 mmol) was stirred at rt for 1h. The THF was removed under vacuum, and the resulting solids were dissolved in DCM and washed with Sat. Aq. NaHCO3. The Aqueous layer was extracted with DCM (2Xs) and the combined DCM layers were dried over Na2SO4 and concentrated under vacuum to give ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(methylamino)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol as a white foam (1.00g, 97%).

Reference： [1]Kung, Pei-Pei; Huang, Buwen; Zehnder, Luke; Tatlock, John; Bingham, Patrick; Krivacic, Cody; Gajiwala, Ketan; Diehl, Wade; Yu, Xiu; Maegley, Karen A. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 7, p. 1532 - 1537]

68
[ 6783-05-7 ]
[ 39824-26-5 ]
((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-((E)-styryl)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 3h;Inert atmosphere;	Step 2 1,4-Dioxane (2 mL) and water (one drop) were added to <strong>[39824-26-5]((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol</strong> (150 mg, 0.459 mmol) obtained in Step 1, (E)-styrylboronic acid (136 mg, 0.918 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (37.5 mg, 0.031 mmol), and cesium carbonate (449 mg, 1.38 mmol), and the mixture was stirred at 80 C. for 3 hours under a nitrogen atmosphere. After the reaction solution was cooled to room temperature, saturated brine was added thereto, and the mixture was extracted with ethyl acetate and dried over sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-((E)-styryl)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (90.1 mg, yield: 50%). ESI-MS (m/z): 395 (M+1)
50%	With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In 1,4-dioxane; water; at 80℃; for 3h;Inert atmosphere;	Step 2 1,4-Dioxane (2 mL) and water (one drop) were added to <strong>[39824-26-5]((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol</strong> (150 mg, 0.459 mmol) obtained in Step 1, (E)-styrylboronic acid (136 mg, 0.918 mmol), 1,1'-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (37.5 mg, 0.031 mmol), and cesium carbonate (449 mg, 1.38 mmol), and the mixture was stirred at 80 C. for 3 hours under a nitrogen atmosphere. After the reaction solution was cooled to room temperature, saturated brine was added thereto, and the mixture was extracted with ethyl acetate and dried over sodium sulfate. The residue obtained by evaporating the solvent under reduced pressure was purified by column chromatography (heptane/ethyl acetate) to obtain ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-((E)-styryl)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol (90.1 mg, yield: 50%). ESI-MS (m/z): 395 (M+1)

Reference： [1]Patent: US2015/376611,2015,A1 .Location in patent: Paragraph 0477; 0478
[2]Patent: US2017/354673,2017,A1 .Location in patent: Paragraph 0692; 0693; 0694

69
[ 110-85-0 ]
[ 39824-26-5 ]
((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(piperazin-1-yl)-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With potassium carbonate; In acetonitrile; at 20℃; for 6h;	To a solution of piperazine (5.0 g, 58.1 mmol) and K2CO3 (10.8 g, 78.3 mmol) in acetonitrile was added the solution of 3 (12.7 g, 39.0 mmol) in acetonitrile, then stirred 6h at room temperature. The solution was filtered and evaporated. The residue was purified by column chromatography (CH2Cl2: MeOH=70:1) to give the compound 4 in 90% yield, white solid (13.4 g). 1H NMR (400 MHz, DMSO-d6) delta 8.38 (s, 1H), 8.25 (s, 1H), 6.16 (d, J = 3.0 Hz, 1H), 5.34 (dd, J = 6.1, 3.0 Hz, 1H), 4.98 (dd, J = 6.1, 2.4 Hz, 1H), 4.43 - 3.91 (m, 5H), 3.66 - 3.50 (m, 2H), 2.86 - 2.73 (m, 4H), 1.55 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, DMSO-d6) delta 153.19, 151.92, 149.90, 138.45, 119.30, 112.98, 89.68, 86.49, 83.34, 81.35, 61.55, 45.95, 45.67, 27.03, 25.16.
90%	With potassium carbonate; In acetonitrile; at 20℃; for 6h;	Weigh 5.0 g of piperazine and 10.8 g of K2CO3,100 ml of acetonitrile was added, and 12.7 g of the compound represented by the formula III dissolved in acetonitrile was added dropwise with stirring at room temperature,Continue to stir for 6h,(Eluent: dichloromethane: methanol = 70: 1, v / v) to give 13.1 g of the white product (compound of formula IV) as a white product,The yield was 90%. EI: 376

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 190 - 193
[2]Patent: CN104497085,2017,B .Location in patent: Paragraph 0034; 0035

70
[ 362-75-4 ]
[ 39824-26-5 ]

Yield	Reaction Conditions	Operation in experiment
60%	With chloro-trimethyl-silane; tert.-butylnitrite; In dichloromethane; at 20℃;Inert atmosphere;	To a solution of 2 (20.0 g, 65.2 mmol) in dry dichloromethane was dropwise added TMCS (57.7 ml, 456.1 mmol) under argon atmosphere at room temperature, after short time. To the solution was dropwis added tert-butyl nitrite (59.6 ml, 547.3 mmol), then stirred at room temperature for overnight. The mixture was quenched with saturated NaHCO3, layers were separated, the water layer was extracted with chloroform (200 ml). The combined organic layers were dried with Na2SO4, filtered and partly evaporated. The residue was purified by column chromatography (CH2Cl2: MeOH=10:1) to give the compound 3 in 60% yield, white solid (12.3 g). 1H NMR (400 MHz, DMSO-d6) delta 8.88 (s, 1H), 8.83 (s, 1H), 6.30 (d, J = 2.4 Hz, 1H), 5.43 (dd, J = 6.1, 2.4 Hz, 1H), 5.00 (dd, J = 6.1, 2.3 Hz, 1H), 4.38 - 4.29 (m, 1H), 3.58 (dd, J = 4.6, 3.0 Hz, 2H), 1.57 (s, 3H), 1.35 (s, 3H). 13C NMR (100 MHz, DMSO-d6) delta 151.62, 150.95, 149.28, 145.52, 131.06, 113.24, 90.55, 87.13, 83.68, 81.12, 61.12, 26.66, 24.81.
60%	With chloro-trimethyl-silane; n-Butyl nitrite; In dichloromethane; for 0.25h;Inert atmosphere; Darkness;	20 g of 2 ', 3'-isopropylideneuridine (compound of formula II) was dissolved in anhydrous dichloromethane,In the argon protection,In the dark and under normal conditions, 63.4 ml of trimethylchlorosilane was slowly added dropwise,After stirring for 15 min, 59.3 ml of n-butyl nitrite was slowly added dropwise,Stir the reaction after overnight stirring.The organic phase was collected by extraction with chloroform. The organic phase was combined, dried over anhydrous NaSO4, filtered and evaporated to dryness. The residue was separated by silica gel column chromatography (eluent: dichloromethane: methanol = 10: 1v / V) to give 12.7 g of the white product (compound represented by the formula III) in a yield of 60%. EI: 326.

Reference： [1]Tetrahedron Letters,2017,vol. 58,p. 190 - 193
[2]Patent: CN104497085,2017,B .Location in patent: Paragraph 0032; 0033

71
[ 23530-40-7 ]
[ 39824-26-5 ]
N-(((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N-methyl-2-nitrobenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	With di-isopropyl azodicarboxylate; triphenylphosphine; In tetrahydrofuran; at 0 - 20℃; for 24h;	To a stirred solution of chloropurine S12 (10.0 g, 30.6 mmol) in 115 mL of THF was added sulfonamide (6.23 g,33.7 mmol). The solution was then cooled to 0 C before triphenylphosphine (12.0 g, 45.9 mmol) was added in one portion followed by the addition of DIAD (9.03 mL, 45.9 mmol) dropwise by syringe. The residual yellow solution was stirred for 2 h during which time the solution was allowed to warm to rt. The volatiles were removed in vacuo togive a thick brown oil. To this oil was added 150 mL of MeOH and the solution was cooled to 0 C for 0.5 h during which time a white precipitate formed. This precipitate was collected by suction filtration and washed with Et2O (3 ×50 mL) to give the sulfonamide 24

Reference： [1]Bioorganic and Medicinal Chemistry,2017,vol. 25,p. 5433 - 5440

72
[ 54060-30-9 ]
[ 39824-26-5 ]
C₂₁H₂₁N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With triethylamine; In butan-1-ol; at 95℃; for 5h;	Next, electrophilic AMP analogs with two significantly different substituents at N6-position (i.e. a propargyl and phenyl alkyne) were synthesized following Scheme 2 and Scheme 3. Compound 2 that has a small hydrophobic group (propargyl alkyne) at the N6-position was prepared by coupling 2-chloroethanesulfonyl chloride with the 5-amino adenine moiety, followed by the deprotection of the acid labile acetonide (Scheme 2). The synthesis of compound 3, which has a large hydrophobic group (phenyl alkyne) at the N6-position, required tert-butyldimethylsilane (TI3DMS) protection and deprotection steps on the 5? alcohol and Hoc protection on the N6-amine due to the instability of the reaction intermediates during the Mitsunobu reaction. Subsequent treatment with 2-chloroethanesulfonyl chloride and global deprotection of the acid labile protecting groups led to the formation of compound 3.

Reference： [1]Patent: US2017/312284,2017,A1 .Location in patent: Paragraph 0093

73
[ 100-82-3 ]
[ 39824-26-5 ]
C₂₀H₂₂FN₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With triethylamine; In ethanol; at 20 - 40℃; for 5h;	To a stirred solution of compound 2 (3 g, 9.2 mmol) in EtOH(50 mL) was added Et3N (2.6 mL, 18.4 mmol) and 3-fluorobenzylamine (2.1 mL, 18.4 mmol) at room temperature. Themixture was stirred for 5 h at 40 C and concentrated. The residuewas purified by column chromatography over silica gel (DCM:MeOH: NH3H2O 200: 10: 0.1) to yield compound 3a (3.13 g, 82%)as a colorless oil; [a]20D167.77 (c 0.78, MeOH); 1H NMR(500 MHz, CDCl3) delta 8.39 (s, 1H, purin-H), 7.79 (s, 1H, purin-H),7.35e7.30 (m, 1H, Ar-H), 7.17 (d, J 7.5 Hz, 1H, Ar-H), 7.11 (d,J 9 Hz, 1H, Ar-H), 6.59 (brs, 1H, NH), 5.89 (s, 1H, tetrahydrofuro-H),5.24 (t, J 5.1 Hz, 1H, tetrahydrofuro-H), 5.14 (d, J 5.5 Hz, 1H,tetrahydrofuro-H), 4.89 (brs, 2H, benzyl-CH2), 4.58 (s, 1H,tetrahydrofuro-H), 4.00 (d, J 12.6 Hz, 1H, CH2OH-CH), 3.84 (d,J 12.6 Hz, 1H, CH2OH-CH), 1.68 (s, 3H, CH3), 1.42 (s, 3H, CH3); 13CNMR (400 MHz, CDCl3) delta 162.5 (d, J 242.6 Hz, Ar-C), 154.8 (purin-C), 152.8 (purin-C), 147.5 (purin-C), 140.7 (purin-C), 139.8 (Ar-C),130.2 (d, J 8.1 Hz, Ar-C), 123.12 (d, J 2.5 Hz, Ar-H), 121.2 (purin-C), 114.5 (d, J 21.8 Hz, Ar-C), 114.0 (Ar-C), 94.4 (tetrahydrofuro-C),86.1 (tetrahydrofuro-C), 83.1 (tetrahydrofuro-C), 81.7 (tetrahydrofuro-C), 63.4 (CH2-C), 43.8 (benzyl-CH2-C), 27.6 (CH3), 25.2(CH3); LRMS (ESI): m/z 438 [M Na]
82%	With triethylamine; In ethanol; at 40℃; for 6h;Inert atmosphere;	The preparation route of the compound 1aa was as shown in the above formula, and under a argon atmosphere, a solution of the compound 2 (3.0 g, 9.18 mmol) in ethanol (50 mL) was added 3-fluorobenzylamine (2.6 mL, 22.79 mmol) and triethylamine. (4.0 mL, 28.7 mmol), and the mixture was stirred at 40 C for 6 hr, and concentrated to silica gel column chromatography ( petroleum ether: ethyl acetate = 1:2) to give compound 3a (3.1 g, yield 82%).

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 994 - 1004
[2]Patent: CN108484705,2018,A .Location in patent: Paragraph 0042-0044; 0046

74
[ 39824-26-5 ]
[ 4152-90-3 ]
((3aR,4R,6R,6aR)-6-(6-((3-chlorobenzyl)amino)-9H-purin-9-yl)-2,2-dimethyl tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With triethylamine; In ethanol; at 20 - 40℃; for 5h;	General procedure: To a stirred solution of compound 2 (3 g, 9.2 mmol) in EtOH(50 mL) was added Et3N (2.6 mL, 18.4 mmol) and 3-fluorobenzylamine (2.1 mL, 18.4 mmol) at room temperature. Themixture was stirred for 5 h at 40 °C and concentrated. The residuewas purified by column chromatography over silica gel (DCM:MeOH: NH3H2O 200: 10: 0.1) to yield compound 3a (3.13 g, 82percent)as a colorless oil; [a]20D167.77 (c 0.78, MeOH); 1H NMR(500 MHz, CDCl3) delta 8.39 (s, 1H, purin-H), 7.79 (s, 1H, purin-H),7.35e7.30 (m, 1H, Ar-H), 7.17 (d, J 7.5 Hz, 1H, Ar-H), 7.11 (d,J 9 Hz, 1H, Ar-H), 6.59 (brs, 1H, NH), 5.89 (s, 1H, tetrahydrofuro-H),5.24 (t, J 5.1 Hz, 1H, tetrahydrofuro-H), 5.14 (d, J 5.5 Hz, 1H,tetrahydrofuro-H), 4.89 (brs, 2H, benzyl-CH2), 4.58 (s, 1H,tetrahydrofuro-H), 4.00 (d, J 12.6 Hz, 1H, CH2OH-CH), 3.84 (d,J 12.6 Hz, 1H, CH2OH-CH), 1.68 (s, 3H, CH3), 1.42 (s, 3H, CH3); 13CNMR (400 MHz, CDCl3) delta 162.5 (d, J 242.6 Hz, Ar-C), 154.8 (purin-C), 152.8 (purin-C), 147.5 (purin-C), 140.7 (purin-C), 139.8 (Ar-C),130.2 (d, J 8.1 Hz, Ar-C), 123.12 (d, J 2.5 Hz, Ar-H), 121.2 (purin-C), 114.5 (d, J 21.8 Hz, Ar-C), 114.0 (Ar-C), 94.4 (tetrahydrofuro-C),86.1 (tetrahydrofuro-C), 83.1 (tetrahydrofuro-C), 81.7 (tetrahydrofuro-C), 63.4 (CH2-C), 43.8 (benzyl-CH2-C), 27.6 (CH3), 25.2(CH3); LRMS (ESI): m/z 438 [M Na]
82%	With triethylamine; In ethanol; at 40℃; for 5h;	To compound 2 (3 g, 9.2 mmol) at room temperatureEthanol (50mL)Et3N (2.6 mL, 18.4 mmol) was added to the solution.And 3-chlorobenzylamine (2.1 mL, 18.4 mmol),The resulting mixture was stirred at 40 ° C for 5 h;Concentrated and the residue is purified by silica gel column(by volume ratio, DCM: MeOH: NH3·H2O=200:10:0.1),Obtaining colorless oily compound 3(3.13g, 82percent),

Reference： [1]European Journal of Medicinal Chemistry,2018,vol. 157,p. 994 - 1004
[2]Patent: CN108892693,2018,A .Location in patent: Paragraph 0099-0102

75
[ 39824-26-5 ]
[ 102607-00-1 ]
6-(4-methoxybenzylthio)purine-2‘,3‘-O-isopropylidene-riboside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With potassium carbonate; In tetrahydrofuran; methanol; at 0℃; for 2h;	A solution of compound 23 (163 mg, 0.5 mmol) and S-(4-methoxybenzyl) thioacetate (106 mg, 0.55 mmol) in MeOH (8 mL) and THF (2 mL) was stirred at 0 C while K2C03 (76 mg, 0.55 mmol) was added in one portion. The mixture was stirred at 0 C for 2 h, diluted with EtOAc, and washed with water and brine. The organic phase was dried over MgSO4, filtered, concentrated by rotatory evaporation under reduced pressure, and purified by column chromatography (silica gel, EtOAc/CH2C12 gradients from 0:1 to 1:2) to give compound 24a (168 mg, 76% yield). C21H24N405S; white foam; TLC (EtOAc/DCM (1:3)) R1= 0.33; ?H NMR (600 MHz, CDC13) D 8.71 (1 H, s), 8.13 (1 H, s), 7.36 (2 H, d, J= 8.4 Hz), 6.82 (2 H, d, J= 8.4 Hz), 5.96 (1 H, d, J 5.4 Hz), 5.19 (1 H, t, J = 5.4 Hz), 5.10 (1 H, d, J 5.4 Hz), 4.56 - 4.64 (2 H, m), 4.53 (1 H, s), 3.97 (1 H, d, J= 12.0 Hz), 3.81 (1 H, dd, J= 12.0, 2.0 Hz), 3.77 (3 H, s), 1.64 (3 H, s), 1.37 (3 H, s); ?3C NMR (CDC13, 100 MHz) oe 162.2, 158.8, 151.3, 146.9, 142.2, 132.0, 130.2, 128.8, 114.1, 113.9, 93.9, 86.3, 83.3, 81.5, 63.1, 55.2, 32.5, 27.5, 25.1; ESI-HRMS calcd. For C21H25N405S: 445.1540, found: m/z 445.1543 [M+Hj.

Reference： [1]Patent: WO2018/140734,2018,A1 .Location in patent: Paragraph 00139

76
S-[4-(4-methoxybenzyloxy)benzyl]thioacetate [ No CAS ]
[ 39824-26-5 ]
6-(4-methoxybenzylthio)purine-2‘,3‘-O-isopropylidene-riboside [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With potassium carbonate; In tetrahydrofuran; methanol; at 0℃; for 2h;	A solution of compound 23 (61.8 mg, 0.19 mmol) and S-[4-(4-methoxybenzyloxy)benzylj thioacetate (63 mg, 0.21 mmol) in MeOH (4 mL) and THF (1 mL) was stirred at 0 C while K2C03 (34.6 mg, 0.25 mmol) was added in one portion. The mixture was stirred at 0 C for 2 h, diluted with EtOAc, and washed with water and brine. The organic phase was dried over MgSO4, filtered, concentrated by rotatory evaporation under reduced pressure, and purified by column chromatography (silica gel, EtOAc/CH2C12 gradients from 0:1 to 2:3) to give compound 24a (85 mg, 81% yield). C28H30N4O6S; white foam; TLC (EtOAc/hexane (1:1)) R1 0.24; ?H NMR (600 MHz, CDC13) oe 8.72 (1 H, s), 8.06 (1 H, s), 7.38 (2 H, d, J 8.7 Hz), 7.34 (2 H, d, J= 8.7 Hz), 6.91 (4 H, d, J= 8.7, 2.0 Hz), 5.94 (1 H, d, J= 4.6 Hz), 5.23-5.19 (1 H, m), 5.13 (1 H, dd, J= 5.9, 1.4 Hz), 4.97(2 H, s), 4.65-4.58 (2 H, m), 4.55 (1 H, d, J= 1.4 Hz), 3.98 (1 H, dd, J= 12.5, 1.8 Hz), 3.83 (1 H, d,J= 1.8 Hz), 3.81 (3 H, s), 1.66 (3 H, s), 1.39 (3 H, s); ?3C NMR (CDC13, 100 MHz) oe 162.4, 159.3,158.1, 146.9, 142.2, 132.4, 130.2, 129.09, 129.06, 128.8, 114.8, 113.9, 93.9, 86.1, 83.1, 81.5, 69.7,63.2, 55.2, 32.4, 27.5, 25.1; ESI-HRMS calcd for C28H31N406S: 551.1959, found: m/z 551.2983 [M+Hj

Reference： [1]Patent: WO2018/140734,2018,A1 .Location in patent: Paragraph 00140

77
[ 39824-26-5 ]
[ 152918-18-8 ]

Reference： [1]Patent: WO2008/111082,2008,A1

78
[ 39824-26-5 ]
[ 10068-07-2 ]
[ 851046-32-7 ]

Reference： [1]Patent: WO2005/39590,2005,A1

79
[ 31618-90-3 ]
[ 39824-26-5 ]
diethyl ((((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methoxy)methyl)phosphonate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With magnesium 2-methylpropan-2-olate; In dimethyl sulfoxide; at 50℃; for 18h;	A mixture of ((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-(diethoxyphosphoryl)methyl 4-methylbenzenesulfonate (1.29 g, 4.0 mmol) and magnesium 2-methylpropan-2-olate (0.74 g, 4.34 mmol) in DMSO (15 mL) was stirred at 50 C for 18 hours. After cooling to ambient temperature, water (10 mL) and 1 : 1 MTBE/ethyl acetate (20 mL) were added. The mixture was passed through a short pad of celite. The organic layer was separated, washed with brine, dried (sodium sulfate), filtered and concentrated under reduced pressure. The residue obtained was purified by flash chromatography on silica gel 10: 1 ethyl acetate/methanol to give diethyl ((((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2- dimethyltetrahydrofuro[3,4-

Reference： [1]Patent: WO2018/183635,2018,A1 .Location in patent: Paragraph 0303-0304

80
1-([1,1'-biphenyl]-4-yl)piperazine hydrochloride [ No CAS ]
[ 39824-26-5 ]
((3aR,4R,6R,6aR)-6-(6-(4-([1,1'-biphenyl]-4-yl)piperazin-1-yl)-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In ethanol at 80℃; for 17h;

Reference： [1]Crespo, Roberto A.; Dang, Qun; Zhou, Nian E.; Guthrie, Liam M.; Snavely, Thomas C.; Dong, Wen; Loesch, Kimberly A.; Suzuki, Takao; You, Lanying; Wang, Wei; O'Malley, Theresa; Parish, Tanya; Olsen, David B.; Sacchettini, James C. [Journal of Medicinal Chemistry, 2019, vol. 62, # 9, p. 4483 - 4499]

81
[ 136918-14-4 ]
[ 39824-26-5 ]
2-(((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 25℃; for 17h;

82
[ 1545-96-6 ]
[ 39824-26-5 ]
N-(((3aR,4R,6R,6aR)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N-(4-fluorophenyl)-4-nitrobenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.8%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 25℃; for 17h;

83
[ 111-86-4 ]
[ 39824-26-5 ]
2',3'-isopropylidene-N6-octyladenosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With N-ethyl-N,N-diisopropylamine In water; dimethyl sulfoxide at 110℃; for 0.75h; Microwave irradiation;

Reference： [1]Nautiyal, Manesh; Gadakh, Bharat; De Graef, Steff; Pang, Luping; Khan, Masroor; Xun, Yi; Rozenski, Jef; Van Aerschot, Arthur [Antibiotics, 2019, vol. 8, # 4]

84
[ 124-22-1 ]
[ 39824-26-5 ]
2',3'-isopropylidene-N6-dodeceyladenosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With N-ethyl-N,N-diisopropylamine In water; dimethyl sulfoxide at 110℃; for 0.75h; Microwave irradiation;

Reference： [1]Nautiyal, Manesh; Gadakh, Bharat; De Graef, Steff; Pang, Luping; Khan, Masroor; Xun, Yi; Rozenski, Jef; Van Aerschot, Arthur [Antibiotics, 2019, vol. 8, # 4]

85
[ 39824-26-5 ]
[ 124-30-1 ]
2',3'-isopropylidene-N6-octadecyladenosine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With N-ethyl-N,N-diisopropylamine In water; dimethyl sulfoxide at 110℃; for 0.75h; Microwave irradiation;

Reference： [1]Nautiyal, Manesh; Gadakh, Bharat; De Graef, Steff; Pang, Luping; Khan, Masroor; Xun, Yi; Rozenski, Jef; Van Aerschot, Arthur [Antibiotics, 2019, vol. 8, # 4]

86
[ 383-63-1 ]
[ 39824-26-5 ]
[ 109-76-2 ]
2,2,2-trifluoro-N-(3-((9-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)amino)propyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	Stage #1: 6-chloro-9-(2,3-O-isopropylidene-β-D-ribofuranosyl)-9H-purine; Trimethylenediamine With TEA In ethanol at 60℃; for 2h; Stage #2: ethyl trifluoroacetate, With TEA In methanol at 20℃; for 12h;	2,2,2-Trifluoro-N-(3-((9-((3aR,4R,6R,6aR)-6-(hydroxymethyl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)-9H-purin-6-yl)amino)propyl)acetamide (3). To a solution of propane-1,3-diamine (450mg, 6.1mmol) and TEA (0.85mL, 6.1mmol) in EtOH (2mL) was added slowly a solution of 2 (500mg, 1.5mmol) in EtOH (20mL) and the reaction mixture was stirred at 60°C for 2h. The solvent and excess of reagents were removed under reduced pressure to give the crude nucleoside. The crude nucleoside was dissolved in dry MeOH (20mL) and TEA (0.42mL, 3.1mmol) and trifluoroacetic acid ethyl ester (1.1mL, 9.1mmol). The reaction mixture was stirred at room temperature for 12h. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (ethyl acetate 100%) to give the protected nucleoside 3 (625mg, 89%) as a white solid. 1H NMR (500MHz, CDCl3) δ 8.86 (s, 1H), 8.28 (s, 1H), 7.82 (s, 1H), 6.43 (t, J=11.1Hz, 2H), 5.85 (d, J=4.9Hz, 1H), 5.26-5.15 (m, 1H), 5.15-5.06 (m, 1H), 4.53 (s, 1H), 4.00-3.91 (m, 1H), 3.83-3.71 (m, 2H), 3.48-3.31 (m, 2H), 2.25 (s, 1H), 1.63 (s, 3H), 1.36 (s, 3H). 13C NMR (126MHz, CDCl3) δ 157.48, 157.19, 155.80, 152.44, 147.39, 140.01, 117.75, 115.59, 114.12, 94.33, 86.12, 83.03, 81.67, 63.37, 37.67, 35.56, 29.41, 27.64, 25.23. LCMS (ESI) m/z: [M + H]+ 461.2.

Reference： [1]Iyamu, Iredia D.; Huang, Rong [Analytical Biochemistry, 2020, vol. 604]

87
Nα-[2-(methoxyhydroxyphosphinyl)acetyl]-O-benzyl-L-threonine benzyl ester [ No CAS ]
[ 39824-26-5 ]
5'-O-[(methoxy)((2-oxo-2(O-benzyl-L-threonine benzyl ester))ethyl)phosphinyl]-6-chloro-9-(2',3'-O-isopropylidene-D-ribofuranosyl)purine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With triphenylphosphine; diethylazodicarboxylate In tetrahydrofuran; toluene at 20℃; for 20h; Inert atmosphere;

Reference： [1]Kopina, Brett J; Missoury, Sophia; Collinet, Bruno; Fulton, Mark G; Cirio, Charles; Van Tilbeurgh, Herman; Lauhon, Charles T [Nucleic Acids Research, 2021, vol. 49, # 4, p. 2141 - 2160]

88
C₃₈H₄₂O₇S [ No CAS ]
[ 39824-26-5 ]
C₄₇H₄₉ClN₄O₉ [ No CAS ]
C₄₇H₄₉ClN₄O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87.5 % de	With diammonium hydrogen orthophosphate; Triphenylphosphine oxide In acetonitrile at 20℃; for 24h; Irradiation; Inert atmosphere; Sealed tube; Overall yield = 65 percent; diastereoselective reaction;	Methods To an 8 ml screw-capped vial that contained a magnetic stir bar was sequentially added an allyl glycosyl sulfone (0.3 mmol, 1.5 equiv.), a nucleophile (0.2 mmol,1.0 equiv.), Ph3PO (0.06 mmol, 0.3 equiv.), (NH4)2HPO4 (1.0 mmol, 5.0 equiv.), C4F9I (1.0 mmol, 5.0 equiv.) and MTBE (1 ml) under a N2 atmosphere. The vial was tightly sealed with a Teflon-lined cap and allowed to stir for 24 h at room temperature, with irradiation from a 10 W, 455 nm LED bulb placed ~3 cm below it. The reaction mixture was then diluted with ethyl acetate (10 ml) and filtered through a pad of cotton. The combined organic phases were concentrated under reduced pressure. The residue was purified by silica gel chromatography to give the desired product.

Reference： [1]Zhang, Chen; Zuo, Hao; Lee, Ga Young; Zou, Yike; Dang, Qiu-Di; Houk; Niu, Dawen [Nature Chemistry, 2022, vol. 14, # 6, p. 686 - 694]

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P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
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. 39824-26-5 ] {[proInfo.proName]}

Quality Control of [ 39824-26-5 ]

Related Doc. of [ 39824-26-5 ]

Product Details of [ 39824-26-5 ]

Calculated chemistry of [ 39824-26-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 39824-26-5 ]

Application In Synthesis of [ 39824-26-5 ]

[ 39824-26-5 ] Synthesis Path-Upstream 1~7

[ 39824-26-5 ] Synthesis Path-Downstream 1~88

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry