147118-35-2|(R)-Methyl 3-((tert-butyldimethylsilyl)oxy)-5-oxo-6-(triphenylphosphoranylidene)hexanoate| Ambeed

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Quality Control of [ 147118-35-2 ] Purity: 97% SDS Specification

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Product Details of [ 147118-35-2 ]

CAS No. :	147118-35-2
Formula :	C₃₁H₃₉O₄PSi
M.W :	534.70
SMILES Code :	O=C(OC)C[C@H](O[Si](C)(C(C)(C)C)C)CC(C=P(C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)=O
MDL No. :	MFCD09753068
InChI Key :	LKFANOWXMJEZDI-AREMUKBSSA-N
Pubchem ID :	10007313

Safety of [ 147118-35-2 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P280-P305+P351+P338-P310

Computational Chemistry of [ 147118-35-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	37
Num. arom. heavy atoms	18
Fraction Csp3	0.32
Num. rotatable bonds	12
Num. H-bond acceptors	4.0
Num. H-bond donors	0.0
Molar Refractivity	160.39
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	62.41 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	6.03
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	5.7
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	4.75
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	6.37
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	4.57

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-6.52
Solubility	0.000161 mg/ml ; 0.000000301 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-7.12
Solubility	0.0000406 mg/ml ; 0.000000076 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Poorly soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-10.08
Solubility	0.0000000442 mg/ml ; 0.0000000001 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Insoluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	No
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	Yes
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	Yes
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	Yes
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-5.28 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	2.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	1.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.17

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	2.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<3.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	6.06

Application In Synthesis of [ 147118-35-2 ]

* 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.

Downstream synthetic route of [ 147118-35-2 ]

[ 147118-35-2 ] Synthesis Path-Downstream 1~35

1
[ 4166-53-4 ]
[ 1779-49-3 ]
[ 147118-35-2 ]

References: [1]Journal of Organic Chemistry,1994,vol. 59,p. 7849 - 7854.

2
[ 139993-90-1 ]
[ 147118-35-2 ]
[ 160204-82-0 ]

References: [1]Journal of Organic Chemistry,1994,vol. 59,p. 7849 - 7854.
[2]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

3
[ 147118-35-2 ]
4-(4-Fluoro-phenyl)-6-isopropyl-2-methoxy-pyrimidine-5-carbaldehyde [ No CAS ]
(E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2-methoxy-pyrimidin-5-yl]-5-oxo-hept-6-enoic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

4
[ 147118-35-2 ]
4-(4-Fluoro-phenyl)-6-isopropyl-2-methylsulfanyl-pyrimidine-5-carbaldehyde [ No CAS ]
(E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2-methylsulfanyl-pyrimidin-5-yl]-5-oxo-hept-6-enoic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

5
[ 147118-35-2 ]
4-(4-Fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-1H-pyrrole-3-carbaldehyde [ No CAS ]
(E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[4-(4-fluoro-phenyl)-2-isopropyl-1-methanesulfonyl-1H-pyrrol-3-yl]-5-oxo-hept-6-enoic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

6
[ 147118-35-2 ]
N-[4-(4-Fluoro-phenyl)-5-formyl-6-isopropyl-pyrimidin-2-yl]-N-methyl-acetamide [ No CAS ]
(E)-(R)-7-[2-(Acetyl-methyl-amino)-4-(4-fluoro-phenyl)-6-isopropyl-pyrimidin-5-yl]-3-(tert-butyl-dimethyl-silanyloxy)-5-oxo-hept-6-enoic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

7
[ 147118-35-2 ]
[ 849470-61-7 ]
(E)-(R)-3-(tert-Butyl-dimethyl-silanyloxy)-7-[4-(4-fluoro-phenyl)-6-isopropyl-2-methanesulfonyl-pyrimidin-5-yl]-5-oxo-hept-6-enoic acid methyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

8
[ 147118-35-2 ]
[ 147118-37-4 ]
[ 147118-38-5 ]

Yield	Reaction Conditions	Operation in experiment
100%	In toluene; for 30h;Heating / reflux;	A solution of 100g of pyrimidine aldehyde, 228g of phosphorane, methyl (3R)-3- (tert-butyldimethylsilyloxy)-5-oxo-6-triphenylphosphoranylidene hexanate and 1500 ml of toluene was refluxed for about 30 hours and the reaction mixture was concentrated under reduced pressure. Cyclohexane (1500 ml) was added and the solution was cooled to 10 C and stirred for 2 hours at 10 C-12 C. The solution was filtered and concentrated under vacuum. The concentrate so obtained was dissolved in cyclohexane (1000 ml) and the residue was discarded. The solution so obtained was concentrated to 500 ml, cooled and filtered. The filtrate was concentrated under vacuum to give thick oil. Yield: 100%
100%		Example (1); In a reaction vessel 4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)-5- pyrimidinecarbardehyde (100 g of formula III), methyl-(3R)-3[[ter-butyl- (dimethyl)silyl]oxy]-5-oxo-6-(triphenylphosphoranylidine) hexanate (228 g of formula IV) and acetonitrile (10OmL) was added, stirred well and heated to reflux for 10 to 12 hrs. After the completion of the reaction, the reaction mass was cooled to 45 (+/-5C), the solvent was distilled off completely under vacuum and diisopropyl ether was added to it at 3O0C and stirred at room temperature until the solid precipitates out. The precipitated mass was cooled to 0 to 5C and stirred for 2 hrs, the solid was filtered under vacuum and washed with cold diisopropyl ether. To the diisopropyl ether layer aqueous acetic acid was added and stirred for about 15 minutes at room temperature. The layers were separated and the organic layer was washed with 5% sodium bicarbonate solution (100 mL), water (100 mL) and brine (100 mL). The solvent was distilled completely under vacuum at 40C (+50C) to obtain a thick yellowish pasty mass of methyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methylsulfonylamino)pyrimidin-5-yl]-(3R)-3-(tert-butyIdimethylsilyloxy)-5-oxo-(E)-6- heptenate of formula (I) with 100 % yield and 88% of purity by HPLC.
100%	In acetonitrile; for 10 - 12h;Heating / reflux;Product distribution / selectivity;	Example (2); <n="9"/>In a reaction vessel 4-(4-fluorophenyl)-6-isopropyl-2-(N--methyl-N-methylsulfonylamino)-5- pyrimidinecarbardehyde (100 g of formula III) and methyl-(3R)-3[[ter-butyl- (dimethyl)silyl]oxy]-5-oxo-6-(triphenylphosphoranylidine) hexanate (228 g of formula IV) and acetonitrile (100 mL) was added stirred well and heated to reflux for 10 to 12 hrs. After the completion of reaction the reaction mass was cooled to 45 (+50C), the solvent was distilled off completely under vacuum and diisopropyl ether was added at 300C and stirred at room temperature until the solid precipitates out. The precipitated mass was cooled to 0 to 50C and stirred for 2 hrs, the solid was filtered under vacuum and washed with cold diisopropyl ether. The diisopropyl ether layer was distilled under vacuum completely, methanol (IVoI) and water (lOVol.) was added and stirred for 15 minutes at room temperature. The layers were separated and the organic layer was distilled completely under vacuum at 40C+/-5C to obtain a thick yellowish pasty mass of methyl 7-[4-(4-fluororhohenyl)- 6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl]-(3R)-3-(tert- butyldimethylsilyloxy)-5-oxo-(E)-6-heptenate of formula (I) with 100% yield and 95% of purity by HPLC.

92%	With N-butylammonium bromide; In toluene; acetonitrile; at 75℃; for 12h;	A mixture of 400 g of acetonitrile and 200 g of toluene was added to a 2 L reaction flask, and 100 g of the main chain Z8 and 160 g of the side chain J6 were charged with stirring, 2 g of 4-butylammonium bromide was added, and the mixture was heated to 75 C Reflux for 12 hours, the end of the reaction, 40 C, -0.08MPa under the conditions of concentration under reduced pressure to get the crude oil that is H1. b. Condensation product purification: Add 1400 ml of n-hexane and 1200 ml of petroleum ether mixture to the oil, heat to reflux, cool the solution to 0 C, stir for solid for 6 hours, continue to warm to 20 C, stir for 30 min , The filter was removed by filtration, the filter cake was washed with petroleum ether, the filtrate and the washing liquid were combined, and the filtrate was distilled under reduced pressure at 40 C and -0.08 MPa to remove the organic solvent to obtain the product as H1. The detection purity was 91.4% and the yield was 92%
71.3%	In acetonitrile; for 14h;Heating / reflux;	(3); A solution of 190 mg of FPP-OH (compound (i)), 450 mg of methyl (3R)-3-(tert-butyldimethylsilyloxy)-5-oxo-6-triphenylpliosplioranylidenehexanate5 (prepared in step 2 above) and 5 mL of acetonitrile is refluxed under heating for 14 hours and evaporated under reduced pressure to distill off acetonitrile. The resulting residue is subjected to column chromatography on silica gel eluting with methylene chloride to give 233 mg (Yield: 71.3%) of methyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)pyrimidin-5-yl)-(3R)-3-(tert-butyldimethylsilyloxy)-5-oxo-(E)-6-heptenate (compound ii) as a syrup.
		A 250 ml flask, protected from light and provided with N2 flow was charged with compound-14 (4.38 g, 12.5 mmol), compound 19M (10 g, 18.7 mmol), and extra dry toluene (100 ml). The reaction mixture was heated to about 1000C for 15 hrs. After the completion of the reaction, anhydrous MgCl2 (4.8 g, 2.7 eq.) was added to the reaction mixture and the reaction mixture was heated for 2 hours at about 1000C. The reaction mixture was cooled to O0C over a period of about 2 hours, filtered, and washed with 45ml of toluene, yielding 12.73g of a viscous oil.
	In toluene; at 110℃; for 24h;Product distribution / selectivity;	EXAMPLE 1 : PREPARATION OF METHYL-7- [4-(4-FLUOROPHENYL)-6-ISO- PROPYL-2- (N-METHYL-N-METHYLSULPHONYLAMINO) PYRIMIDIN-5-YL] - (3R)-3-HYDROXY-5-OXO- (E)-6-HEPTENATE (FORMULA V):; Methyl (3R)-3-(tert-butyl dimethyl silyloxy)-5-oxo-6-triphenyl- phosphoranyllidene hexanoate (10 g), N-[4-(4-Fluoro-phenyl)-5-formyl-6-isopropyl- pyrimidin-2-yl]-N-methyl-methanesulfonamide (6.9 g), toluene (100 ml) were taken into a round bottom flask and heated to about 110 0C. The reaction mass was maintained at the same temperature for about 24 hours. Reaction completion was checked using thin layer chromatography. After the reaction was completed, the reaction mass was distilled at a temperature of about 45 0C under low pressure. To the residue obtained, a 1 : 9 mixture of ethyl acetate and n-hexane (100 ml) was added and stirred at about 26 0C for about 1 hour. The mixture was then cooled to about 10 0C and maintained under stirring for another 1 hour. The separated solid was filtered, and the filtrate was distilled off completely under high vacuum at about 45 0C. To the residue obtained, acetonitrile (130 ml) was added at about 26 0C, and then further cooled to about 5 0C. The mixture was maintained at 5 0C for about 15 minutes and then a solution of 48% aqueous hydrogen fluoride in acetonitrile (13 ml) was added to it and maintained at the same temperature for about 1 hour. The reaction mass was then allowed to heat to 26 0C and maintained for about 1 hour. Reaction completion was checked using thin layer chromatography. After the reaction was completed, saturated sodium bicarbonate solution (140 ml) was added to the reaction mass until pH was adjusted to 7.0. Dichloromethane (300 ml) was added to the above reaction mass and stirred for about 10 minutes. The organic layer was separated and the aqueous layer was extracted into dichloromethane (100 ml). The combined dichloromethane layer was distilled off at about 39 0C under high vacuum to give 11.2 g of the title compound.
	In acetonitrile; at 80℃; for 24h;Product distribution / selectivity;	EXAMPLE 2: PREPARATION OF METHYL-7- [4-(4-FLUOROPHENYL)-6-ISO- PROPYL-2- (N-METHYL-N-METHYLSULPHONYLAMINO) PYRIMIDIN-5-YL] - (3R)-3-HYDROXY-5-OXO- (E)-6-HEPTENATE (FORMULA V):; Methyl (3R)-3-(tert-butyl dimethyl silyloxy)-5-oxo-6-triphenyl- phosphoranyllidene hexanate (100 g), N-[4-(4-fluoro-phenyl)-5-formyl-6-isopropyl- pyrimidin-2-yl]-N-methyl-methanesulfonamide (69 g), acetonitrile (1000 ml) were taken into a round bottom flask and heated to about 80 0C. The reaction mass was maintained at the same temperature for about 24 hours. Reaction completion was checked using thin layer chromatography. After the reaction was completed, the reaction mass was distilled at a temperature of about 48 0C under reduced pressure. To the residue obtained (175 g), acetonitrile (875 ml) was added and stirred at about 26 0C for about 1 hour. The mixture was then cooled to about 5 0C and a solution of 48% aqueous hydrogen fluoride (36 ml) was added to it. After the addition was completed, the reaction mass was then allowed to heat to about 26 0C and maintained for about 1 hour. After the reaction was completed, saturated sodium bicarbonate solution (610 ml) was added to the reaction mass until the pH was adjusted to 7.0. Dichloromethane (1750 ml) was added to the above reaction mass and stirred for about 10 minutes. The organic layer was separated and the aqueous layer was extracted into dichloromethane (855 ml). The combined dichloromethane layer was washed with saturated sodium chloride solution (885 ml) and then distilled off at about 39 0C under high vacuum to give 145 g of the title compound as a residue. To 8.0 g of the residue obtained, a 9:1 mixture of n- hexane in ethyl acetate (150 ml) was added and stirred at about 25 0C for about 1 hour. The separated solid was filtered and washed with a 9: 1 mixture of n-hexane in ethyl acetate (125 ml) to yield 5.5 g of the title compound.
	In acetonitrile; at 84℃; for 12h;	The synthetic route is shown in flow diagram 1: The detailed preparation process is as follows: 165mL acetonitrile, 30.7g (R)-3-[[(1,1-dimethyl ethyl)dimethyl silyl]oxo]-5-oxo-6-(triphenyl phosphoranylidene)-methyl hexanoate and 20.2g N-[4-(4-flurophenyl)-5-formyl-6-(1-methylethyl)-2-pyrimidyl]-N-methyl-methanesulfonamide were added to a 200mL reaction flask. Subsequently, the mixture was heated to 84C and refluxed until TLC indicated that the content of N-[4-(4-flurophenyl)-5-formyl-6-(1-methylethyl)-2-pyrimidyl]-N-methyl-methanesulfonamide in the reaction solution did not change any more. This reaction took around 12 hours, then the reaction mixture was cooled and vacuum distilled at 50C to remove acetonitrile. In this way oily product was obtained. The oily product was immediately transferred to a 500mL reaction flask, subsequently, 345mL cyclohexane was added, the mixture was heated and refluxed for 20 minutes, and then the reaction mixture was cooled to 5C and stirred for 5 hours until solid precipitated. The obtained product was filtered to remove the solid, the filter cake was washed twice with cyclohexane (40mL each time), and then the washing solution was combined with filtrate. The obtained filtrate was vacuum distilled to remove the organic solvent cyclohexane at 45C. As a result, 46g oily (3R,6E)-3-[[(1,1-dimethyl ethyl) dimethyl silyl]-oxo]-7-[4-(4-flurophenyl)-6-(1-methyl ethyl)-2-[methyl (methyl sulfonyl) amino]-5-pyrimidyl]-5-oxo-6-methyl heptenoate was obtained.
	In cyclohexane; at 25 - 85℃;	Example 1Preparation of methyl 7-[4-(4-fluorophenyl)-6-isopropyl-2-(N-methyl-N- methylsulfonyIamino)pyrimidin-5-yI]-(3R)-3-(ter^butyldimethylsilyloxy)-5-oxo-( - 6-heptenate (IV)4-(4-Fluorophenyl)-6-isopropyl-2-(N-methyl-N-methylsulfonylamino)-5- pyrimidinecarbaldehyde (lOOg) was taken in cyclohexane (500 ml) and to this methyl (3 ?)-3-(tert-butyldimethylsilyloxy)-5-oxo-6-triphenylphosphoranylidene hexanoate (160g) was added at 25-30C. The reaction mixture was refluxed under azeotropic condition at 80-85 C for 48-60 hours under stirring. After completion of reaction, the reaction mixture was cooled and stirred for 2.0 hours. The reaction mass was filtered and washed with cyclohexane. The organic layer was concentrated under reduced pressure to obtain the title compound as thick oily mass.
	In acetonitrile; for 30h;Reflux;	A 500 ml four-necked flask was charged with 4- (4-fluorophenyl) -6-isopropyl-2 (N-methyl-N-methanesulfonamido) pyrimidin- 5-yl] -carbaldehyde (Z9, 10 g, 28.5 mmol),(3R) -3-tert-butyldimethylsilyloxy-5- carbonyl-6- (triphenylphosphinoethenyl) -hexanoic acid methyl ester (J6, 16.76 g, 31.3 mmol) and acetonitrile ,Reflux reaction for about 30h, HPLC monitoring, until the reaction is complete, concentrated to dryness under reduced pressure, were added cyclohexane 60ml spin-dry strip twice,Then 200 ml of cyclohexane was added and the reaction was refluxed for 1 hour. The mixture was cooled to 10-15 C for 2 hours and filtered. The filtrate was concentrated to dryness under reduced pressure and directly used for the next reaction.

References: [1]Patent: WO2003/97614,2003,A2 .Location in patent: Page/Page column 8; 12.
[2]Patent: WO2008/93205,2008,A2 .Location in patent: Page/Page column 7.
[3]Patent: WO2008/93205,2008,A2 .Location in patent: Page/Page column 7-8.
[4]Patent: CN104910078,2017,B .Location in patent: Paragraph 0009; 0034-0036; 0044; 0050; 0056; 0062.
[5]Organic Process Research and Development,2015,vol. 19,p. 635 - 638.
[6]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.
[7]Patent: WO2006/17357,2006,A1 .Location in patent: Page/Page column 15.
[8]Patent: WO2006/91771,2006,A2 .Location in patent: Page/Page column 23.
[9]Patent: WO2008/67440,2008,A2 .Location in patent: Page/Page column 13.
[10]Patent: WO2008/67440,2008,A2 .Location in patent: Page/Page column 14.
[11]Patent: EP2298745,2011,A1 .Location in patent: Page/Page column 14-15.
[12]Patent: WO2012/63115,2012,A2 .Location in patent: Page/Page column 16-17.
[13]Patent: CN104844525,2017,B .Location in patent: Paragraph 0033; 0035; 0036.

9
[ 147118-35-2 ]
C₁₇H₂₁FN₄O₃S [ No CAS ]
C₃₀H₄₅FN₄O₆SSi [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

10
[ 147118-35-2 ]
C₁₆H₁₉FN₄O₃S [ No CAS ]
C₂₉H₄₃FN₄O₆SSi [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,1997,vol. 5,p. 437 - 444.

11
[ 949524-33-8 ]
[ 147118-35-2 ]
[ 950598-98-8 ]

References: [1]Tetrahedron,2007,vol. 63,p. 8124 - 8134.

12
[ 950598-75-1 ]
[ 147118-35-2 ]
[ 950598-99-9 ]