[ CAS No. 6623-81-0 ] {[proInfo.proName]}

Name: 6623-81-0|2,4-Dihydroxy-5-methoxypyrimidine|96%
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SKU: A124929
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Quality Control of [ 6623-81-0 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 6623-81-0 ]

SDS Specification

Alternatived Products of [ 6623-81-0 ]

Product Details of [ 6623-81-0 ]

CAS No. :	6623-81-0	MDL No. :	MFCD00187903
Formula :	C₅H₆N₂O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	KELXHQACBIUYSE-UHFFFAOYSA-N
M.W :	142.11	Pubchem ID :	81100
Synonyms :		Chemical Name :	2,4-Dihydroxy-5-methoxypyrimidine

Calculated chemistry of [ 6623-81-0 ] Expand+

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.2
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	34.18
TPSA :	74.95 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) :	-7.74 cm/s

Lipophilicity

Log Po/w (iLOGP) :	0.69
Log Po/w (XLOGP3) :	-0.81
Log Po/w (WLOGP) :	-0.93
Log Po/w (MLOGP) :	-0.95
Log Po/w (SILICOS-IT) :	1.22
Consensus Log Po/w :	-0.16

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-0.59
Solubility :	36.6 mg/ml ; 0.258 mol/l
Class :	Very soluble
Log S (Ali) :	-0.28
Solubility :	73.8 mg/ml ; 0.519 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.57
Solubility :	3.83 mg/ml ; 0.027 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.96

Safety of [ 6623-81-0 ]

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 [ 6623-81-0 ]

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

Upstream synthesis route of [ 6623-81-0 ]
Downstream synthetic route of [ 6623-81-0 ]

[ 6623-81-0 ] Synthesis Path-Upstream 1~7

1
[ 6939-11-3 ]
[ 6623-81-0 ]

Yield	Reaction Conditions	Operation in experiment
94%	Stage #1: for 2 h; Heating / reflux Stage #2: for 16 h; Heating / reflux	Intermediate 17; 5-(Methoxy)-2,4(1H,3H)-pyrimidinedione A mixture of 5-(methoxy)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (21.5 g; 0.137 moles), chloroacetic acid (21.5 g; 0.227 moles), and water (585 mL) was refluxed for 2 h. Concentrated HCl (85 mL) was added and the mixture was then refluxed for 16 h. Upon cooling, a solid formed and was collected by filtration, washed with water and dried to yield the desired product (18.2 g; 94percent yield). MS: (M+H)⁺=143.

Reference： [1] Patent: US2008/182852, 2008, A1, . Location in patent: Page/Page column 15

2
[ 6939-11-3 ]
[ 6623-81-0 ]

Reference： [1] Journal of Medicinal Chemistry, 2010, vol. 53, # 16, p. 6129 - 6152

3
[ 6290-49-9 ]
[ 57-13-6 ]
[ 109-94-4 ]
[ 6623-81-0 ]

Reference： [1] Journal of Chemical and Engineering Data, 2010, vol. 55, # 3, p. 1402 - 1404

4
[ 50-00-0 ]
[ 66-22-8 ]
[ 6623-81-0 ]

Reference： [1] Chemical Research in Toxicology, 1999, vol. 12, # 9, p. 802 - 808

5
[ 6623-81-0 ]
[ 22536-65-8 ]

Reference： [1] Patent: WO2011/144577, 2011, A1,
[2] Patent: WO2011/144578, 2011, A1,

6
[ 6623-81-0 ]
[ 19646-07-2 ]

Yield	Reaction Conditions	Operation in experiment
75%	for 2 h; Reflux	Intermediate 2: 2,4-Dichloro- -methoxypyrimidine2,4-Dihydroxy-5-methoxypyrimidine (45g, 0.316mol), phosphorous oxychloride (225mL, 0.88mol), and Ν,Ν-dimethylaniline (45mL, 0.391mol) were heated under reflux for 2h. The mixture was poured onto crushed ice (80 g.), and the product collected in ether. Recrystallisation from light petroleum (b.p: 40-60 °C) gave 2,4- dichloro-5-methoxypyrimidine (43g, 75percent).Mass: (ES+) 179 (M+H)⁺
20.83%	Cooling with ice; Reflux	2,4-Dichloro-5-methoxy-pyrimidine[0082] In ice bath, dimethyl-phenyl-amine (6.58 ml, 51.65 mmol, 0.5 eq) was added dropwise to a slurry of 5-methoxy-pyrimidine-2,4-diol (14.68 g, 1.0 eq) in POCI3 (47.42 ml, 5.0 eq) and refluxed overnight. Excess POCl₃ was evaporated in vacuo and the residue was poured into ice-water. After formation of pink precipitates, the mixture was filtered and dried solid in vacuo. A product was obtained as a white solid (3.89 g , 20.83percent) NMR (500 MHz, CDCl₃-di): 68.18(s, 1H), 4.01

Reference： [1] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4149 - 4153
[2] Patent: WO2011/144577, 2011, A1, . Location in patent: Page/Page column 24
[3] Patent: WO2011/80568, 2011, A2, . Location in patent: Page/Page column 109-110
[4] Patent: WO2011/144578, 2011, A1, . Location in patent: Page/Page column 26; 27

7
[ 6623-81-0 ]
[ 19646-07-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	for 2 h; Heating / reflux	Intermediate 18; 2,4-Dichloro-5-(methoxy)pyrimidine 5-(Methoxy)-2,4(1H,3H)-pyrimidinedione (18 g; 0.128 moles), phosphorous oxychloride (90 mL) and dimethylaniline (18 mL) were heated to reflux for 2 h. The system was cooled to room temperature and carefully poured over ice. The white solid formed was separated by filtration. The aqueous filtrate was extracted with diethyl ether (4.x.). The ether layers were combined and dried over anhydrous sodium sulfate. Removal of the solvent in vacuo afforded Intermediate 18 (6 g; 40percent yield based on recovered starting material). MS: (M+H)⁺=179, 181 and 183.

Reference： [1] Journal of Medicinal Chemistry, 2010, vol. 53, # 16, p. 6129 - 6152
[2] Patent: US2008/182852, 2008, A1, . Location in patent: Page/Page column 15
[3] Journal of Chemical and Engineering Data, 2010, vol. 55, # 3, p. 1402 - 1404
[4] Journal of Medicinal Chemistry, 2011, vol. 54, # 2, p. 510 - 524

[ 6623-81-0 ] Synthesis Path-Downstream 1~50

1
[ 6974-32-9 ]
[ 6623-81-0 ]
[ 37805-86-0 ]

Reference： [1]Chemische Berichte,1981,vol. 114,p. 1279 - 1286

2
[ 109-64-8 ]
[ 6623-81-0 ]
[ 122182-77-8 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1988,vol. 61,p. 3619 - 3628

3
[ 117365-83-0 ]
[ 6623-81-0 ]
[ 117365-84-1 ]

Reference： [1]Canadian Journal of Chemistry,1988,vol. 66,p. 1027 - 1031

4
[ 169736-17-8 ]
[ 6623-81-0 ]
C₂₆H₂₆N₂O₇S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 789 - 795

5
[ 76513-69-4 ]
[ 6623-81-0 ]
[ 186388-05-6 ]

Reference： [1]Synlett,1997,vol. 1997,p. 1233 - 1234
[2]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1873 - 1878

8
[ 110-86-1 ]
[ 6623-81-0 ]
C₁₅H₁₄N₄O⁽²⁺⁾*2Cl^(1-) [ No CAS ]

Reference： [1]Polish Journal of Chemistry,2000,vol. 74,p. 659 - 671

9
[ 24424-99-5 ]
[ 6623-81-0 ]
5-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Synthetic Communications,2001,vol. 31,p. 3739 - 3746

10
[ 50-00-0 ]
[ 66-22-8 ]
[ 6623-81-0 ]

Reference： [1]Chemical Research in Toxicology,1999,vol. 12,p. 802 - 808

11
6-methoxy-3,9-diphenyl-6aH-bis[1,2,4]oxadiazolo[4,5-a:4',5'-c]pyrimidine [ No CAS ]
[ 6623-81-0 ]

Reference： [1]Heterocycles,2005,vol. 65,p. 1079 - 1097

12
[ 6623-81-0 ]
[ 186387-62-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1873 - 1878

13
[ 6623-81-0 ]
3-(3-{4-[4-fluoro-2-(2,2,2-trifluoro-ethoxy)-phenyl]-piperazin-1-yl}-propyl)-5-methoxy-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1873 - 1878

14
[ 6623-81-0 ]
[ 186385-78-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2003,vol. 13,p. 1873 - 1878

15
[ 6623-81-0 ]
3-allyl-5-methoxy-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Synthetic Communications,2001,vol. 31,p. 3739 - 3746

16
[ 6623-81-0 ]
3-allyl-5-methoxy-2,4-dioxo-3,4-dihydro-2H-pyrimidine-1-carboxylic acid tert-butyl ester [ No CAS ]

Reference： [1]Synthetic Communications,2001,vol. 31,p. 3739 - 3746

17
[ 6623-81-0 ]
2-(N-pyridinio)-5-methoxypyrimidin-4-olate [ No CAS ]

Reference： [1]Polish Journal of Chemistry,2000,vol. 74,p. 659 - 671

18
[ 6623-81-0 ]
3-Isobutyl-5-methoxy-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Synlett,1997,vol. 1997,p. 1233 - 1234

19
[ 6623-81-0 ]
3-Benzyl-5-methoxy-1H-pyrimidine-2,4-dione [ No CAS ]

Reference： [1]Synlett,1997,vol. 1997,p. 1233 - 1234

20
[ 6623-81-0 ]
[ 199444-56-9 ]

Reference： [1]Synlett,1997,vol. 1997,p. 1233 - 1234

21
[ 6623-81-0 ]
[ 199444-55-8 ]

Reference： [1]Synlett,1997,vol. 1997,p. 1233 - 1234

22
[ 6623-81-0 ]
[ 122182-78-9 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1988,vol. 61,p. 3619 - 3628

23
[ 6623-81-0 ]
[ 122193-97-9 ]

Reference： [1]Bulletin of the Chemical Society of Japan,1988,vol. 61,p. 3619 - 3628

24
[ 6623-81-0 ]
C₁₆H₁₈N₆O₃S [ No CAS ]

Reference： [1]Bulletin of the Chemical Society of Japan,1988,vol. 61,p. 3619 - 3628

25
[ 6623-81-0 ]
[ 117365-85-2 ]

Reference： [1]Canadian Journal of Chemistry,1988,vol. 66,p. 1027 - 1031

26
[ 6623-81-0 ]
[ 117365-86-3 ]

Reference： [1]Canadian Journal of Chemistry,1988,vol. 66,p. 1027 - 1031

27
[ 6939-11-3 ]
[ 6623-81-0 ]

Yield	Reaction Conditions	Operation in experiment
94%		Intermediate 17; 5-(Methoxy)-2,4(1H,3H)-pyrimidinedione A mixture of 5-(methoxy)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (21.5 g; 0.137 moles), chloroacetic acid (21.5 g; 0.227 moles), and water (585 mL) was refluxed for 2 h. Concentrated HCl (85 mL) was added and the mixture was then refluxed for 16 h. Upon cooling, a solid formed and was collected by filtration, washed with water and dried to yield the desired product (18.2 g; 94% yield). MS: (M+H)+=143.

Reference： [1]Patent: US2008/182852,2008,A1 .Location in patent: Page/Page column 15

28
[ 6623-81-0 ]
[ 19646-07-2 ]

Yield	Reaction Conditions	Operation in experiment
40%	With N,N-dimethyl-aniline; trichlorophosphate; for 2h;Heating / reflux;	Intermediate 18; 2,4-Dichloro-5-(methoxy)pyrimidine 5-(Methoxy)-2,4(1H,3H)-pyrimidinedione (18 g; 0.128 moles), phosphorous oxychloride (90 mL) and dimethylaniline (18 mL) were heated to reflux for 2 h. The system was cooled to room temperature and carefully poured over ice. The white solid formed was separated by filtration. The aqueous filtrate was extracted with diethyl ether (4×). The ether layers were combined and dried over anhydrous sodium sulfate. Removal of the solvent in vacuo afforded Intermediate 18 (6 g; 40% yield based on recovered starting material). MS: (M+H)+=179, 181 and 183.

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6129 - 6152
[2]Patent: US2008/182852,2008,A1 .Location in patent: Page/Page column 15
[3]Journal of Chemical and Engineering Data,2010,vol. 55,p. 1402 - 1404
[4]Journal of Medicinal Chemistry,2011,vol. 54,p. 510 - 524

29
[ 6290-49-9 ]
[ 57-13-6 ]
[ 109-94-4 ]
[ 6623-81-0 ]

Reference： [1]Journal of Chemical and Engineering Data,2010,vol. 55,p. 1402 - 1404

30
[ 6939-11-3 ]
[ 6623-81-0 ]

Reference： [1]Journal of Medicinal Chemistry,2010,vol. 53,p. 6129 - 6152

31
[ 6623-81-0 ]
[ 844843-40-9 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 510 - 524

32
[ 6623-81-0 ]
2-(2-chloro-5-methoxy-6-oxo-6H-pyrimidin-1-ylmethyl)benzonitrile [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 510 - 524

33
[ 6623-81-0 ]
[ 22536-65-8 ]

Reference： [1]Patent: WO2011/144577,2011,A1
[2]Patent: WO2011/144578,2011,A1

34
[ 2525-62-4 ]
[ 6623-81-0 ]
[ 1431627-81-4 ]

Yield	Reaction Conditions	Operation in experiment
56%	In dimethyl sulfoxide; at 50℃; for 4h;	Example 9./V-hexyl-5-methoxy-2,4-dioxo-pyrimidine-1 -carboxamide 5-Methoxyuracil (0.05 g, 0.33 mmol) was dissolved in dry DMSO (1 .6 mL) and hexyl isocyanate (0.09 mL, 0.59 mmol) was added. The mixture was heated at 50 C for 4 hrs. The reaction was poured into water (5 mL), the precipitate formed was filtered and washed with water and hexane. The crude was triturated with cyclohexane to afford the title compound (0.05 g, 56%) as white powder. 1H NMR (400 MHz, DMSO-de): delta 0.86 (t, J = 6.9 Hz, 3H), 1 .26-1 .31 (m, 6H), 1 .47-1 .54 (m, 2H), 3.27 (td, J = 7.0, 5.7 Hz, 2H), 3.66 (s, 3H), 7.71 (s, 1 H), 9.22 (t, J = 5.6 Hz, 1 H), 1 1 .94 (s, 1 H). 13C NMR (101 MHz, DMSO-d6): delta 13.86, 21 .97, 25.87, 28.67, 30.83, 40.35, 56.49, 1 16.17, 136.52, 150.13, 150.24, 158.78. MS (ESI) m/z: 270 [M-H]+, 287 [M-NH4]+, 308 [M-K]+. MS (ESI) m/z: 268 [M-H] .
56%	In dimethyl sulfoxide; at 50℃; for 4h;	5-Methoxyuracil (0.05 g, 0.33 mmol) was dissolved in dry DMSO (1.6 mL) and hexyl isocyanate (0.09 mL, 0.59 mmol) was added. The mixture was heated at 50 C. for 4 hrs. The reaction was poured into water (5 mL), the precipitate formed was filtered and washed with water and hexane. The crude was triturated with cyclohexane to afford the title compound (0.05 g, 56%) as white powder. 1H NMR (400 MHz, DMSO-d6): delta 0.86 (t, J=6.9 Hz, 3H), 1.26-1.31 (m, 6H), 1.47-1.54 (m, 2H), 3.27 (td, J=7.0, 5.7 Hz, 2H), 3.66 (s, 3H), 7.71 (s, 1H), 9.22 (t, J=5.6 Hz, 111), 11.94 (s, 1H). 13C NMR (101 MHz, DMSO-d6): delta 13.86, 21.97, 25.87, 28.67, 30.83, 40.35, 56.49, 116.17, 136.52, 150.13, 150.24, 158.78. MS (ESI) m/z: 270 [M-H]4, 287 [M-NH4]+, 308 [M-K]+. MS (ESI) m/z: 268 [M-H]-.

Reference： [1]Journal of Medicinal Chemistry,2013,vol. 56,p. 3518 - 3530
[2]Patent: WO2013/178576,2013,A1 .Location in patent: Page/Page column 68; 69
[3]Patent: US2015/111892,2015,A1 .Location in patent: Paragraph 0360

35
[ 22224-38-0 ]
[ 6623-81-0 ]
[ 37805-86-0 ]

Yield	Reaction Conditions	Operation in experiment
65%		To a solution of compound 104 (2.8 g, 20 mmol) in dry acetonitrile (30 ml_) was added BSA (21 g, 1 00 mmol, 5 eq). The reaction mixture was stirred at 60 C for 4 h and cooled to room temperature. To this reaction mixture were added compound 1 03 (1 0.1 g, 20 mmol), TMSOTf (10.8 m l_, 60 mmol, 3eq), and the resulted reaction mixture was stirred at 60 C for 4 h. Upon completion of the reaction as monitored by TLC, the reaction mixture was treated with methylene chloride and saturated sodium bicarbonate. The organic phase was separated, and the aqueous phase was extracted with dichloromethane. The combined organic phase was dried over anhydrous Na2S04. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column giving 1 1 g desired compound 105 in 95% yield.

Reference： [1]Patent: WO2014/93924,2014,A1 .Location in patent: Page/Page column 277; 278

36
[ 6623-81-0 ]
[ 1613530-29-2 ]

Reference： [1]Patent: WO2014/93924,2014,A1
[2]Patent: WO2015/196130,2015,A2
[3]Patent: WO2015/196128,2015,A2

37
[ 6623-81-0 ]
[ 1613530-30-5 ]

Reference： [1]Patent: WO2014/93924,2014,A1
[2]Patent: WO2015/196130,2015,A2
[3]Patent: WO2015/196128,2015,A2

38
[ 6623-81-0 ]
[ 37805-86-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5764 - 5773

39
[ 999-97-3 ]
[ 6623-81-0 ]
[ 37805-85-9 ]

Reference： [1]Bioorganic and Medicinal Chemistry,2015,vol. 23,p. 5764 - 5773

40
[ 1943-82-4 ]
[ 6623-81-0 ]
5-methoxy-N-(2-phenylethyl)-2,4-dioxopyrimidine-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; dmap; triethylamine; In toluene; at 90℃; for 3h;	General procedure: Compounds 1-15 were synthesized according to Scheme 1. The appropriately substitutedcarboxylic acid (0.5 mmol) was dissolved in dry CH2Cl2 (5 mL). Oxalyl chloride (0.6 mmol, 0.05 mL)and DMF (0.01 mL) were added, and the reaction mixture was stirred at 0 C for 1 h. The solventwas evaporated under reduced pressure, keeping the temperature below 30 C. The crude residuewas redissolved with anhydrous acetone (5 mL) and then dropwise added into a stirred and ice-coldsolution of NaN3 (1.0 mmol, 33 mg) in H2O (1 mL). The resulting mixture was stirred at 0 C for30 min, and extracted with EtOAc. The organic layer was washed with brine, dried over anhydrousNa2SO4, and concentrated under reduced pressure. The residue was then dissolved in toluene (15 mL),and refluxed for 2 h. The reaction solution was cooled to room temperature, and dropwise added toa solution of the corresponding uracil derivatives (0.5 mmol) in dry pyridine (0.5 mL). After beingstirred at 90 C for 3 h, the mixture was cooled and evaporated. The crude was purified by flashchromatography on silica gel to afford compounds 1-15. N-Hexyl-2,4-dioxo-pyrimidine-1-carboxamide (1). This compound was obtained in 84% yield as a whiteamorphous powder. Detailed MS, 1H- and 13C-NMR results were according to the literature data [19].

Reference： [1]Molecules,2016,vol. 21

41
[ 14215-97-5 ]
[ 6623-81-0 ]
[ 37805-86-0 ]

Yield	Reaction Conditions	Operation in experiment
65%		Compound 110: To a solution of compound 109 (1 .42 g, 10 mmol) in dry acetonitrile (30 mL) was added BSA (10.5 g, 50 mmol). The reaction mixture was stirred at 60 C for 4 h and cooled to room temperature. To the reaction mixture were added compound 103 (5.04 g, 1 0 mmol) andTMSOTf (2.7 mL, 15 mmol). The resulted reaction mixture was stirred at 60 CC for 4 h. Upon completion of the reaction as monitored by TLC, the reaction mixture was treated with methylene chloride and saturated sodium bicarbonate. The organic phase was separated, and the aqueous phase was extracted with methylene chloride. The combined organic phase was dried over anhydrous Na2504. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column giving 3.8 g desired compound 110 in 65% yield.
65%		Compound 1 1 0: To a solution of compound 1 09 (1 .42 g, 1 0 mmol) in dry acetonitrile (30 mL) s added BSA (1 0.5 g, 50 mmol). The reaction mixture was stirred at 60 C for 4 h and cooled to m temperature. To the reaction mixture were added compound 1 03 (5.04 g, 1 0 mmol) and SOTf (2.7 mL, 15 mmol). The resulted reaction mixture was stirred at 60 C for 4 h. Upon mpletion of the reaction as monitored by TLC, the reaction mixture was treated with methylene oride and saturated sodium bicarbonate The organic phase was separated and the aqueous ase was anhydrous N ressure. The crude product was purified by flash chromatography on a silica gel column giving 3.8 g sired compound 1 1 0 in 65% yield.

Reference： [1]Patent: WO2015/196130,2015,A2 .Location in patent: Page/Page column 610; 611
[2]Patent: WO2015/196128,2015,A2 .Location in patent: Page/Page column 618; 619

42
[ 28708-32-9 ]
[ 6623-81-0 ]
C₁₆H₂₀N₂O₁₀ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		The nucleobase 1A-D (2.0 equivalents) was dissolved in dry acetonitrile (2 mL per mmol). N,O-bis-trimethylsilylamide (4.0 equivalents) was added and the mixture stirred at room temperature until clear (1-24 hours). The solution was cooled to 0 C. A solution of ribose tetraacetate (2) (1.0 equiv.) in dry CH3CN (5 mL per mmol) was added slowly, followed by SnCl4 (1.2 equiv.). The solution was stirred at room temperature overnight. The reaction was quenched with the careful addition of saturated aqueous sodium bicarbonate. A solution of 1M aqueous HCl was then carefully added, and the mixture stirred for one hour. The solution was extracted three times with ethyl acetate. The combined organics were washed with 1M HCl, water, saturated sodium bicarbonate and brine. The organic fraction was then dried over Na2SO4, filtered, and condensed in vacuo to give a crude residue that was purified by flash column chromatography (gradient, 99:1 to 90:10 chloroform:methanol) to give triacetylated ribonucleoside 3A-D. 3A: 1H NMR (500 MHz, CDCl3) delta=9.56 (bs, 1H), 7.44 (t, J=1.5 Hz, 1H), 6.16 (d, J=4.0 Hz, 1H), 5.36-5.32 (m, 2H), 4.32 (s, 2H), 4.24 (dd, J=2.0, 13.0 Hz, 1H), 4.19 (dd, J=1.5, 13.0 Hz, 1H), 3.40 (s, 3H), 2.17 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H)

Reference： [1]Patent: US9382287,2016,B2 .Location in patent: Page/Page column 44; 45

43
[ 6623-81-0 ]
[ 37805-91-7 ]

Reference： [1]Patent: US9382287,2016,B2

44
[ 6974-32-9 ]
[ 6623-81-0 ]
C₃₁H₃₂N₂O₇ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
65%		Compound 110: To a solution of compound 109 (1.42 g, 10 mmol) in dry acetonitrile (30 mL) was added BSA (10.5 g, 50 mmol). The reaction mixture was stirred at 60 C for 4 h and cooled to room temperature. To the reaction mixture were added compound 103 (5.04 g, 10 mmol) and TMSOTf (2.7 mL, 15 mmol). The resulted reaction mixture was stirred at 60 C for 4 h. Upon completion of the reaction as monitored by TLC, the reaction mixture was treated with methylene chloride and saturated sodium bicarbonate. The organic phase was separated, and the aqueous phase was extracted with methylene chloride. The combined organic phase was dried over anhydrous Na2SO4. The drying agent was filtered off, and the filtrate was concentrated under reduced pressure. The crude product was purified by flash chromatography on a silica gel column giving 3.8 g desired compound 110 in 65% yield.

Reference： [1]Patent: EP2918275,2015,A1 .Location in patent: Paragraph 2131; 2132

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