[ CAS No. 115899-38-2 ] {[proInfo.proName]}

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Quality Control of [ 115899-38-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 115899-38-2 ]

Product Details of [ 115899-38-2 ]

CAS No. :	115899-38-2	MDL No. :	MFCD28134647
Formula :	C₁₄H₁₅F₃N₄O₅	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	OKLUSVKQOCPUNW-IVZWLZJFSA-N
M.W :	376.29	Pubchem ID :	14768553
Synonyms :

Calculated chemistry of [ 115899-38-2 ]

Physicochemical Properties

Num. heavy atoms :	26
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.5
Num. rotatable bonds :	5
Num. H-bond acceptors :	9.0
Num. H-bond donors :	4.0
Molar Refractivity :	80.23
TPSA :	139.7 Å²

Pharmacokinetics

GI absorption :	Low
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) :	-9.4 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.15
Log Po/w (XLOGP3) :	-1.14
Log Po/w (WLOGP) :	-0.48
Log Po/w (MLOGP) :	-1.44
Log Po/w (SILICOS-IT) :	-0.36
Consensus Log Po/w :	-0.45

Druglikeness

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

Water Solubility

Log S (ESOL) :	-1.3
Solubility :	19.1 mg/ml ; 0.0506 mol/l
Class :	Very soluble
Log S (Ali) :	-1.3
Solubility :	18.8 mg/ml ; 0.0499 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.1
Solubility :	29.5 mg/ml ; 0.0785 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	4.24

Safety of [ 115899-38-2 ]

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 [ 115899-38-2 ]

* 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 [ 115899-38-2 ]
Downstream synthetic route of [ 115899-38-2 ]

[ 115899-38-2 ] Synthesis Path-Upstream 1~1

1
[ 14719-21-2 ]
[ 611-53-0 ]
[ 115899-38-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In N,N-dimethyl-formamide at 20℃; for 18 h; Inert atmosphere; Darkness	To a solution of 5-iodo-2'-deoxycytidine (10 g, 28.32 mmol) in DMF (200 ml) in a light protected round bottom flask under Argon atmosphere, was added CuI (1.08 g, 5.67 mmol), triethylamine (7.80 ml, 55.60 mmol), 2,2,2-trifluoro-N-prop-2-ynyl-acetamide (12.8 g, 84.76 mmol) and at last Pd(PPh)₃)₄ (3.27 g, 2.83 mmol). After 18 hours at room temperature, dowex bicarbonate (20 mg) was added and the mixture was stirred for a further 1 h. Filtration and evaporation of the volatiles under reduced pressure gave a residue that was purified by flash chromatography on silica gel (CH₂Cl₂, CH₂Cl₂:EtOAc 1:1, EtOAc:MeOH 9:1) .The expected product (7) was obtained as a beige solid in quantitative yield. ¹H NMR (D₂O) δ 2.24-2.17 (m, 1H, H-2'), 2.41-2.37 (m, 1H, H-2'), 3.68 (dd, J = 12.5, 5.0 Hz, 1H, H-5'), 3.77 (dd, J = 12.5, 3.2 Hz, 1H, H-5'), 3.99 (m, 1H, H-4'), 4.27 (s, 2H, CH₂N), 4.34 (m, 1H, H-3'), 6.11 (t, J = 6.3 Hz, 1H, H-1'), 8.1 (br s, 1H, NH) ; MS (ES) : m/z (percent) (M-H) 375 (100).
79%	Stage #1: With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾ In N,N-dimethyl-formamide for 0.166667 h; Stage #2: at 20℃;	To a solution of 5-iodocytidine C (7.5g, 21.2 mmol) in anhyd DMF (75 mL) CuT (0.30 g,1.57 mmol0 and Pd(PPh3)4 (0.62g, 0.053 mmol) were added. After stirring for 10 mm. triethylamine (6.0 mL, 42.9 mmol) and trifluoro-N-prop-2-ynyl-acetamide (9.6 g, 63.5 mmol) were added. The reaction mixture was stirred overnight at room temperature. All the volatiles were removed under vacuum and the residue was purified by flash chromatography on silica gel (EtOAc/MeOH (0-15percent)j to afford the desired product 35 as yellow solid 7.8g (79percent). 1H-NMR (DMSo-d6) 9.97 (brs, 1H, NH), 8.15 (s, 1H, H-6), 6.08-6. 12 (t, I = 6.4 Hz, 1H, H-i’), 5.20- 5.21 (d, I = 4 Hz, 1H, OHO, 5.05-5.07 (t, I = 4.8 Hz, 1H, OH), 4.28-4.29 (d, I = 5.2 Hz, 2H, NCH2), 4.15-4.19 (m, 1H, H-3’), 3.77-3.79 (m, 1H, H-4’), 2.11-2.16 (m, 1H, (H-2’), 1.92-1.96 (m, 1H, H-2’).
61%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In N,N-dimethyl-formamide at 20℃; Inert atmosphere	Add to a single mouth bottle.dU-I (0.7 mmol, 247 mg),Weigh 9.7mgCuI and 20.3mg Pd (PPh3) 4 added to the reaction flask, evacuated, nitrogen protection, aluminum foil, add 2.3ml DMF, stirred to dissolve, add 0.2ml TEA, weighed F2 (254mg, 1.7mmol) with DMF dissolved in the above reaction flask was added, stirred at room temperature, the reaction overnight. TLC plate monitoring, EA as developing solvent, Rf = 0.35 as the raw material F1, Rf = 0.32 for the product F3, two very close position. After the reaction was over, the solvent was evaporated to dryness under reduced pressure and directly separated by column chromatography. Elution with 20: 1 DCM: MeOH as eluant gave F3214 mg, 61percent yield.

58%

With copper(l) iodide; tetrakis(triphenylphosphine) palladium⁽⁰⁾; triethylamine In methanol; N,N-dimethyl-formamide at 20℃;

DC-I, 5-iodo-2'-deoxycytidine (0.70 mmol, 248 mg) was added to a one-necked flask and 10 mg of CuI (25.2 μmol) and 20 mg of Pd (PPh 3) 4 (17.6 μmol) In, evacuated, nitrogen protection, aluminum foil wrapped, add 1.5ml DMF, stirred to dissolve, add 0.2ml TEA,Weigh F2 (254mg, 1.68mmol) dissolved in 1ml DMF was added to the above reaction flask, stirred at room temperature, the reaction overnight. The solvent was spun off, and DCM: MeOH = 5: 1 was used as developing solvent. The residue was purified by TLC to give 153 mg, yield 58percent.

Reference： [1] Patent: EP2607369, 2015, B1, . Location in patent: Paragraph 0138
[2] Chemical Communications, 2005, # 36, p. 4551 - 4553
[3] Patent: WO2016/182984, 2016, A1, . Location in patent: Paragraph 00140
[4] Journal of the American Chemical Society, 2005, vol. 127, # 43, p. 15071 - 15082
[5] Patent: CN104693258, 2017, B, . Location in patent: Paragraph 0088; 0094; 0095
[6] Patent: CN104292117, 2016, B, . Location in patent: Paragraph 0443; 0452; 0455; 0456
[7] Patent: US5151507, 1992, A,
[8] Patent: US5047519, 1991, A,

[ 115899-38-2 ] Synthesis Path-Downstream 1~30

1
[ 115899-38-2 ]
N-{(Z)-3-[4-Amino-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-5-yl]-allyl}-2,2,2-trifluoro-acetamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 267 - 270

2
[ 14719-21-2 ]
[ 611-53-0 ]
[ 115899-38-2 ]

Yield	Reaction Conditions	Operation in experiment
100%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 20℃; for 18h;Inert atmosphere; Darkness;	To a solution of 5-iodo-2'-deoxycytidine (10 g, 28.32 mmol) in DMF (200 ml) in a light protected round bottom flask under Argon atmosphere, was added CuI (1.08 g, 5.67 mmol), triethylamine (7.80 ml, 55.60 mmol), 2,2,2-trifluoro-N-prop-2-ynyl-acetamide (12.8 g, 84.76 mmol) and at last Pd(PPh)3)4 (3.27 g, 2.83 mmol). After 18 hours at room temperature, dowex bicarbonate (20 mg) was added and the mixture was stirred for a further 1 h. Filtration and evaporation of the volatiles under reduced pressure gave a residue that was purified by flash chromatography on silica gel (CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1) .The expected product (7) was obtained as a beige solid in quantitative yield. 1H NMR (D2O) delta 2.24-2.17 (m, 1H, H-2'), 2.41-2.37 (m, 1H, H-2'), 3.68 (dd, J = 12.5, 5.0 Hz, 1H, H-5'), 3.77 (dd, J = 12.5, 3.2 Hz, 1H, H-5'), 3.99 (m, 1H, H-4'), 4.27 (s, 2H, CH2N), 4.34 (m, 1H, H-3'), 6.11 (t, J = 6.3 Hz, 1H, H-1'), 8.1 (br s, 1H, NH) ; MS (ES) : m/z (%) (M-H) 375 (100).
79%		To a solution of 5-iodocytidine C (7.5g, 21.2 mmol) in anhyd DMF (75 mL) CuT (0.30 g,1.57 mmol0 and Pd(PPh3)4 (0.62g, 0.053 mmol) were added. After stirring for 10 mm. triethylamine (6.0 mL, 42.9 mmol) and trifluoro-N-prop-2-ynyl-acetamide (9.6 g, 63.5 mmol) were added. The reaction mixture was stirred overnight at room temperature. All the volatiles were removed under vacuum and the residue was purified by flash chromatography on silica gel (EtOAc/MeOH (0-15%)j to afford the desired product 35 as yellow solid 7.8g (79%). 1H-NMR (DMSo-d6) 9.97 (brs, 1H, NH), 8.15 (s, 1H, H-6), 6.08-6. 12 (t, I = 6.4 Hz, 1H, H-i?), 5.20- 5.21 (d, I = 4 Hz, 1H, OHO, 5.05-5.07 (t, I = 4.8 Hz, 1H, OH), 4.28-4.29 (d, I = 5.2 Hz, 2H, NCH2), 4.15-4.19 (m, 1H, H-3?), 3.77-3.79 (m, 1H, H-4?), 2.11-2.16 (m, 1H, (H-2?), 1.92-1.96 (m, 1H, H-2?).
61%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In N,N-dimethyl-formamide; at 20℃;Inert atmosphere;	Add to a single mouth bottle.dU-I (0.7 mmol, 247 mg),Weigh 9.7mgCuI and 20.3mg Pd (PPh3) 4 added to the reaction flask, evacuated, nitrogen protection, aluminum foil, add 2.3ml DMF, stirred to dissolve, add 0.2ml TEA, weighed F2 (254mg, 1.7mmol) with DMF dissolved in the above reaction flask was added, stirred at room temperature, the reaction overnight. TLC plate monitoring, EA as developing solvent, Rf = 0.35 as the raw material F1, Rf = 0.32 for the product F3, two very close position. After the reaction was over, the solvent was evaporated to dryness under reduced pressure and directly separated by column chromatography. Elution with 20: 1 DCM: MeOH as eluant gave F3214 mg, 61% yield.

58%	With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0); triethylamine; In methanol; N,N-dimethyl-formamide; at 20℃;	DC-I, 5-iodo-2'-deoxycytidine (0.70 mmol, 248 mg) was added to a one-necked flask and 10 mg of CuI (25.2 mumol) and 20 mg of Pd (PPh 3) 4 (17.6 mumol) In, evacuated, nitrogen protection, aluminum foil wrapped, add 1.5ml DMF, stirred to dissolve, add 0.2ml TEA,Weigh F2 (254mg, 1.68mmol) dissolved in 1ml DMF was added to the above reaction flask, stirred at room temperature, the reaction overnight. The solvent was spun off, and DCM: MeOH = 5: 1 was used as developing solvent. The residue was purified by TLC to give 153 mg, yield 58%.
3.84 g (102%)	In methanol; dichloromethane;	B. Preparation of 5-(3-Trifluoroacetamido-1-propynyl)-2'-deoxycytidine (56) Iodide 55 (353.1 mg, 1.00 mmol) was coupled for 4 h to N-propargyltrifluoroacetamide following the general procedure given in Example 1C. Chomatography of the crude product with a 0-20% methanol in dichloromethane gradient afforded 3.84 g (102%) of white powder after vacuum drying overnight. This material was homogeneous by TLC, but tenaciously retained solvent. Recrystallization of this powder from boiling isopropanol (10 mL) and cooling to -20 afforded 299.6 mg (74%) alkynylamino nucleoside 56 as white needles (mp 168-170). NMR showed that the recrystallized product was homogeneous and that the crystals contained 0.5 molecules of isopropanol per molecule of product 56.
3.84 g, (102%)	In methanol; dichloromethane;	B. PREPARATION OF 5-(3-TRIFLUOROACETAMIDO1-PROPYNYL)2'-DEOXYCYTIDINE (56) Iodide 55 (353.1 mg, 1.00 mmol) was coupled for 4 h to N-propargyltrifluoroacetamide following the general procedure given in EXAMPLE 1C. Chomatography of the crude product with a 0-20% methanol in dichloromethane gradient afforded 3.84 g, (102%) of white powder after vacuum drying overnight. This material was homogeneous by TLC, but tenaciously retained solvent. Recrystallization of this powder from boiling isopropanol (10 mL) and cooling to -20 afforded 299.6 mg (74%) alkynylamino nucleoside 56 as white needles (mp 168-170). NMR showed that the recrystallized product was homogeneous and that the crystals contained 0.5 molecules of isopropanol per molecule of product 56.

Reference： [1]Patent: EP2607369,2015,B1 .Location in patent: Paragraph 0138
[2]Chemical Communications,2005,p. 4551 - 4553
[3]Patent: WO2016/182984,2016,A1 .Location in patent: Paragraph 00140
[4]Journal of the American Chemical Society,2005,vol. 127,p. 15071 - 15082
[5]Patent: CN104693258,2017,B .Location in patent: Paragraph 0088; 0094; 0095
[6]Patent: CN104292117,2016,B .Location in patent: Paragraph 0443; 0452; 0455; 0456
[7]Patent: US5151507,1992,A
[8]Patent: US5047519,1991,A

3
[ 115899-38-2 ]
C₁₄H₁₈F₃N₄O₁₄P₃ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 15071 - 15082
[2]Patent: CN104292117,2016,B

4
[ 115899-38-2 ]
5-[3-aminoprop-1-ynyl]-2'-deoxycytidine-5'-O-triphosphate [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2005,vol. 127,p. 15071 - 15082

5
[ 115899-38-2 ]
N-{3-[4-Amino-1-((2R,4S,5R)-4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-2-oxo-1,2-dihydro-pyrimidin-5-yl]-propyl}-2,2,2-trifluoro-acetamide [ No CAS ]

Reference： [1]Tetrahedron Letters,2000,vol. 41,p. 267 - 270

6
[ 18162-48-6 ]
[ 115899-38-2 ]
5'-O-(tert-butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With 1H-imidazole; In N,N-dimethyl-formamide; at 0℃; for 3h;	To a solution of the starting material (7) (1.0 g, 2.66 mmol) and imidazole (200 mg, 2.93 mmol) in DMF (3.0 ml) at 0 C, was slowly added TBDMSC1 (442 mg, 2.93 mmol) in four portions over 1 h. After 2 h, the volatiles were evaporated under reduced pressure and the residue was adsorbed on silica gel and purified by flash chromatography (EtOAc, EtOAc:MeOH 9.5:0.5). The expected product (8) was isolated as a crystalline solid (826 mg, 64%). 1H NMR (d6 DMSO) delta 0.00 (s, 1H, CH3); 0.01 (s, 1H, CH3), 0.79 (s, 9 H, tBu), 1.87-1.80 (m, 1H, H-2'), 2.12 (ddd, J = 13.0, 5.8 and 3.0 Hz, 1H, H-2'), 3.65 (dd, J = 11.5, 2.9 Hz, 1H, H-5'), 3.74 (dd, J = 11.5, 2.5 Hz, 1H, H-5'), 3.81-3.80 (m, 1H, H-4'), 4.10-4.09 (m, 1H, H-3'), 4.17 (d, 2H, J = 5.1 Hz, NCH2), 5.19 (d, 1H, J = 4.0 Hz, 3'-OH), 6.04 (t, J = 6.6 Hz, 1H, H-1'), 6.83 (br s, 1H, NHH), 7.78 (br s, 1H, NHH), 7.90 (s, 1H, H-6), 9.86 (t, J = 5.1 Hz, 1H, -H2CNH) ; MS (ES) : m/z (%) (MH)+ 491 (40%).

Reference： [1]Patent: EP2607369,2015,B1 .Location in patent: Paragraph 0139

7
[ 115899-38-2 ]
4-N-acetyl-5'-O-(tert-butyldimethylsilyl)-3'-O-(methylthiolmethyl)-5-[3-(2,2,2-trifluoroacetamide)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

8
[ 115899-38-2 ]
4-N-acetyl-3'-O-(azidomethyl)-5'-O-(tert-butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamide)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

9
[ 115899-38-2 ]
3'-O-(azidomethyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]
4-N-acetyl-3'-O-(azidomethyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

10
[ 115899-38-2 ]
4-N-benzoyl-5'-O-(tert-butyldimethylsilyl)-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

11
[ 115899-38-2 ]
4-N-benzoyl-5'-O-(tert-butyldimethylsilyl)-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

12
[ 115899-38-2 ]
4-N-benzoyl-5'-O-(tert-butyldimethylsilyl)-3'-O-azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

13
[ 115899-38-2 ]
4-N-benzoyl-3'-O-azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: EP2607369,2015,B1

14
[ 58479-61-1 ]
[ 115899-38-2 ]
5'-O-tert-butyldiphenylsilyl-5-[3-(2,2,2-trifluoroacetamido)prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
57%	With pyridine; at 0 - 20℃;Inert atmosphere;	Tert-butyldiphenylsilyl chloride (6.97 mL, 26.65 mmol) was added dropwise to a stirred solution of compound 35 (9.11 g, 24.23 mmmol) in dry pyridine (100 mL) at 0 C under N2. After 10 minutes, the solution was allowed to rise to room temperature and stirred overnight. The volatiles were removed under vacuum and the residue was purified by flash chromatography on silica using ethyl acetate in hexanes from 75-100% to afford the desired product 36 (8.42 g, 57%). 1H-NMR (DMSO-d6) 7.95 (s, 1H, H-6), 7.61-7.65 (m, 4H, Ar-H), 7.43-7.47 (m, 6H, Ar-H), 6.11-6.15 (t, J= 6.8 Hz, H-i?), 5.26-5.28 (m, 1H, OH), 4.20-4.27 (m,1H, H-3?), 4.13-4.15 (d, J= 4.8 Hz, NCH2), 3.84-3.90 (m, 3H, H-4 and CH2-5?), 3.70-3.74 (m,1H, CH2-5?), 1.00 (s, (H, C(CH3)3)

Reference： [1]Patent: WO2016/182984,2016,A1 .Location in patent: Paragraph 00142

15
[ 115899-38-2 ]
N-benzoyl-5'-O-tert-butyldiphenylsilyl-5-[3-(2,2,2-trifluoroacetamido)prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: WO2016/182984,2016,A1

16
[ 115899-38-2 ]
N-benzoyl-5'-O-tert-butyldiphenylsilyl-3'-O-methylthiomethyl-5-[3-(2,2,2-trifluoroacetamido)prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: WO2016/182984,2016,A1

17
[ 115899-38-2 ]
N-benzoyl-5'-O-tert-butyldiphenylsilyl-3'-O-azidomethyl-5-[3-(2,2,2-trifluoroacetamido)prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: WO2016/182984,2016,A1

18
[ 115899-38-2 ]
5'-O-tert-butyldiphenylsilyl-3'-O-azidomethyl-5-[3-(amino)prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: WO2016/182984,2016,A1

19
[ 115899-38-2 ]
5'-O-tert-butyldiphenylsilyl-3'-O-azidomethyl-5-[3-(2-((N-tertbutoxyamido-ethyl)-2-yl-disulfanyl)ethyloxy-carboxyamido)-prop-1-ynyl]-2'-deoxycytidine [ No CAS ]

Reference： [1]Patent: WO2016/182984,2016,A1

20
[ 115899-38-2 ]
tri-n-butylamine pyrophosphate [ No CAS ]
5-[3-aminoprop-1-ynyl]-2'-deoxycytidine-5'-O-triphosphate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		he compound dU-I 60 mg (0.16 mmol), tri-n-butylamine pyrophosphate 150 mg(0.32 mmol) and 66 mg (0.32 mmol) of 2-chloro-4H-1,3,2-benzodioxan-4-one were placed in three reaction tubes. The tri-n-butylamine pyrophosphate was dissolved in 0.5mL anhydrous DMF, then add 0.6mL of freshly distilled tri-n-butylamine, and stirred for half an hour. 2-chloro-4H-1,3,2-benzodioxan-4-one was dissolved in 0.5mL of anhydrous DMF, with stirring under stirring through the syringe was added tri-n-butylamine pyrophosphate solution, stirring for half an hour . The mixture was then poured into F3 and stirred for 1.5 h. Add 5 mL of 3% iodine (9: 1 Py / H20) solution. After 4 minutes 4mL water was added and stirred for 2h.Add 0.5mL3M NaCl solution, then add 30mL absolute ethanol, -20 frozen overnight, centrifugation 3200r / min, 25 ) 20min. Decant the supernatant, precipitate, drained the solvent. Then add TEAB solution and concentrated ammonia, followed by stirring at room temperature overnight. The solvent was evaporated to dryness under reduced pressure to give a white solid, giving dUTP (AP3). Analysis was carried out using an analytical PLC under the following conditions: Column: C18, 10 mum, 4.6 × 250 mm; Flow rate: 1 mL / min; Mobile phase: 20 mM triethylamine acetate and CH3CH2OH; UV detector: 254nm. Product peak generation at t = 13.5 min.

Reference： [1]Patent: CN104693258,2017,B .Location in patent: Paragraph 0088; 0089; 0098; 0099

21
[ 115899-38-2 ]
[ 937162-92-0 ]
C₁₆H₂₁N₂O₁₄P₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
24%		In a glove box, 51 mg (0.16 mmol) of compound dU-P and 150 mg (0.32 mmol) of tri-n-butylamine pyrophosphate were weighed out, and 2-chloro-4H-1,3,2-benzodioxo- 66 mg (0.32 mmol) of ketone were placed in three reaction tubesin. The tri-n-butylamine pyrophosphate was dissolved in 0.5mL anhydrous DMF, then add 0.6mL of freshly distilled tri-n-butylamine, and stirred for half an hour. 2-chloro-4H-1,3,2-benzodioxan-4-one was dissolved in 0.5mL of anhydrous DMF, with stirring under stirring through the syringe was added tri-n-butylamine pyrophosphate solution, stirring for half an hour . The mixture was then injected into compound F3 and stirred for 1.5 h. Add 5 mL of 3% iodine (9: 1 Py / H20) solution. After 4 minutes 4mL water was added and stirred for 2h. Add 0.5mL 3M NaCl solution, add 30mL absolute ethanol, freeze at -20 overnight, centrifuge (3200r / min, 25 ) 20min. Decant the supernatant, precipitate, drained the solvent. Then add TEAB solution and concentrated ammonia, followed by stirring at room temperature overnight. The solvent was evaporated to dryness under reduced pressure to give a white solid, giving dUTP-NH2. Analytical HPLC analysis, conditions: Column: C18, 10 mum, 4.6 × 250 mm; flow rate: 1 mL / min; flowPhase: 20 mM triethylamine acetate and CH3CH2OH, gradient wash, 0-20% ethanol (35 min); UV detector: 254 nm. Peak product at t = 16.5 min. Preparative HPLC product was isolated 22mg, that dUTP-P, the yield of 24%.

Reference： [1]Patent: CN104693258,2017,B .Location in patent: Paragraph 0140

22
C₇H₆O₁₀P₃^(1-) [ No CAS ]
[ 115899-38-2 ]
C₁₄H₁₆F₃N₄O₁₂P₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In N,N-dimethyl-formamide; for 1.5h;	In a glove box, 90 mg (0.24 mmol) of compound dC (AP3), 264 mg (0.48 mmol) of tri-n-butylamine pyrophosphate, -one 90 mg (0.48 mmol) were placed in three reaction tubes.Tri-n-butylamine pyrophosphate was dissolved in 0.75 mL of anhydrous DMF, then 0.9 mL of anhydrous tri-n-butylamine was added and stirred for half an hour.The 2-chloro-4H-1,3,2-benzodioxan-4-one was dissolved in 0.75mL of anhydrous DMF, with stirring under stirring through the syringe was added tri-n-butylamine pyrophosphate solution, stirring for half an hour .The mixture was then poured into 8 and stirred for 1.5 h.Add 4 mL of 3% iodine (9: 1 Py / H20) solution.After 4 minutes 4mL water was added and stirred for 2h.Add 1mL3M NaCl solution, add 35mL absolute ethanol, freeze at -20 overnight, centrifuge (3200r / min, 25 ) 20min.Decant the supernatant, precipitate, drained the solvent. Add 2ml concentrated ammonia and stir at room temperature for 6h.The solvent was discarded under reduced pressure and a brown solid appeared, RP-HPLC analysis [Conditions: Column: C18, 10 mum, 4.6 × 250 mm; Flow rate: 1 mL / min; Mobile phase: 20 mM TEAA and EtOH, gradient, 0% -20% EtOH (35min); UV detector:254 nm], retention time t = 11 min. RP-HPLC separation [Conditions: Column: C18, 5 mum, 9.4 × 250 mm; flow rate: 4 mL / min; mobile phase: 20 mM TEAA and MeOH,UV-Vis detector: 254nm], NaCl / EtOH to remove triethylamine acetate salt to give 42 mg of a white solid in 24.5% yield.

Reference： [1]Patent: CN104292117,2016,B .Location in patent: Paragraph 0443; 0452; 0457; 0458

23
[ 115899-38-2 ]
C₄₁H₄₅F₃N₄O₇Si [ No CAS ]