[ CAS No. 1316216-05-3 ] {[proInfo.proName]}

Name: 1316216-05-3|Ethyl 2-(diphenylamino)pyrimidine-5-carboxylate|97%
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SKU: A203124
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Quality Control of [ 1316216-05-3 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1316216-05-3 ]

SDS Specification

Alternatived Products of [ 1316216-05-3 ]

Product Details of [ 1316216-05-3 ]

CAS No. :	1316216-05-3	MDL No. :	MFCD24539407
Formula :	C₁₉H₁₇N₃O₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	ZUKQDXJKYIIHBW-UHFFFAOYSA-N
M.W :	319.36	Pubchem ID :	58536986
Synonyms :

Calculated chemistry of [ 1316216-05-3 ]

Physicochemical Properties

Num. heavy atoms :	24
Num. arom. heavy atoms :	18
Fraction Csp3 :	0.11
Num. rotatable bonds :	6
Num. H-bond acceptors :	4.0
Num. H-bond donors :	0.0
Molar Refractivity :	92.8
TPSA :	55.32 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	Yes
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.42 cm/s

Lipophilicity

Log Po/w (iLOGP) :	3.4
Log Po/w (XLOGP3) :	3.99
Log Po/w (WLOGP) :	4.12
Log Po/w (MLOGP) :	3.07
Log Po/w (SILICOS-IT) :	2.91
Consensus Log Po/w :	3.5

Druglikeness

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

Water Solubility

Log S (ESOL) :	-4.49
Solubility :	0.0103 mg/ml ; 0.0000322 mol/l
Class :	Moderately soluble
Log S (Ali) :	-4.85
Solubility :	0.00448 mg/ml ; 0.000014 mol/l
Class :	Moderately soluble
Log S (SILICOS-IT) :	-6.48
Solubility :	0.000105 mg/ml ; 0.000000329 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.55

Safety of [ 1316216-05-3 ]

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 [ 1316216-05-3 ]

* 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 [ 1316216-05-3 ]
Downstream synthetic route of [ 1316216-05-3 ]

[ 1316216-05-3 ] Synthesis Path-Upstream 1~5

1
[ 591-50-4 ]
[ 864172-93-0 ]
[ 1316216-05-3 ]

Yield	Reaction Conditions	Operation in experiment
38%	With caesium carbonate In tetraethoxy orthosilicate at 140℃; for 14 h;	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), CS₂CO₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95percentEtOH (200 ml), NH₄F-H₂0 on silica gel [50g, pre- prepared by the addition of NH₄F (lOOg) in water (1500 ml) to silica gel (500g, 100- 200mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 percent).
38%	at 140℃; for 14 h; Inert atmosphere	Synthesis of Intermediate 3A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂C0₃ (16.3 g, 50 mmol) in tetraethyl orthosilicate (TEOS) (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and95percentEtOH (200 ml), NH₄F-H₂0 on silica gel [50g, pre-prepared by the addition of NH₄F (lOOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resulting mixture was kept at room temperature for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 percent).
38%	at 140℃; for 14 h; Inert atmosphere	[0234] A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).

38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 3Ommol), Cul (955 mg, 5.Ommol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140°C. for 14 hrs. Afier cooling to tt., the residue was diluted with EtOAc (200 ml). 95percent EtOR (200 ml) and NH4F—H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at tt. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	Synthesis of Intermediate 3 A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95percent EtOH (200 ml), NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	Synthesis of Intermediate 3 [0155] A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 h. After cooling to r.t., the residue was diluted with EtOAc (200 ml) and 95percent EtOH (200 ml), NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	Synthesis of Intermediate 3 [0248] [0249] A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95percent EtOH (200 ml), NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	Synthesis of Intermediate 3: A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene(6.12 g, 3Ommol), Cul (955 mg, 5.Omrnol), Cs2CO3(16.3 g, SOmmol) inTEOS (200m1)was degassed and purged with nitrogen. The resulting mixture was stirred at 140°C for 14hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml)and NH4F-H20 on silica gel [50g, pre-prepared by the addition ofNH4F (bOg) in water(1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography(petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of the compound 2 (6.2 g, 25 mmol),iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) inTEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at140 °C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and95percentEtOH (200 ml), NH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F(bOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resultingmixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc.The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 hrs. Afier cooling to tt., the residue was diluted with EtOAc (200 ml). 95percent EtOR (200 ml) and NH4F—H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at tt. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12g, 30 mmol), CuT (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) andNH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (bOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate wasevaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 3 8percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs₂CO₃(16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140° C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95percent EtOH (200 ml), NH₄F—H₂O on silica gel [50 g, pre-prepared by the addition of NH₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	0127] A mixture of intermediate 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 mL) was degassed and purged with nitrogen. The resulting mixture was stirred at 140°C for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 mL) and 95percent EtOH (200 mL), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 mL) to silica gel (500 g, 100-200 mesh)] was added and the resulting mixture was kept at rt for 2h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂C0₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95percentEtOH (200 ml), H₄F-H₂0 on silica gel [50g, pre-prepared by the addition of H₄F (lOOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 ° C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and H₄F-H₂0 on silica gel [50g, pre-prepared by the addition of H₄F (lOOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent)
38%	at 140℃; for 14 h;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂CO₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and H₄F-H₂0 on silica gel [50 g, pre-prepared by the addition of H₄F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ether/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	10282] A mixture of compound 2 (6.2 g, 25 mmol),iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol),Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassedand purged with nitrogen. The resulting mixture was stirredat 1400 C. for 14 hrs. After cooling to r.t., the residue wasdiluted with EtOAc (200 ml). 95percent EtOH (200 ml) andNH4F—H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture waskept at r.t. for 2 hrs. The solidified materials were filtered andwashed with EtOAc. The filtrate was evaporated to drynessand the residue was purified by silica gel chromatography(petroleum ethers/EtOAc10/1) to give a yellow solid (3 g,38percent).
38%	at 140℃; for 14 h;	Synthesis of Intermediate 3: A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂C0₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t. , the residue was diluted with EtOAc (200 ml) . 95percent EtOH (200 ml) and NH₄F-H₂0 on silica gel [50g, pre-prepared by the addition of NH₄F (1 OOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂C0₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH₄F- H₂0 on silica gel [50g, pre-prepared by the addition of NH₄F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH4F- H20 on silica gel [50g, pre-prepared by the addition of NH4F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs₂C0₃ (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 °C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtOH (200 ml) and NH₄F- H₂0 on silica gel [50g, pre-prepared by the addition of NH₄F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).
38%	at 140℃; for 14 h; Inert atmosphere	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmcl), Cs2CO3 (16.3 g, 50 mmcl) in TEOS (200 ml) wasdegassed and purged with nitrogen. The resulting mixture was stirred at 140 9C for 14 hrs.After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95percent EtCH (200 ml) andNH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (1 OOg) in water (1500 ml)to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38percent).

Reference： [1] Patent: WO2011/91213, 2011, A2, . Location in patent: Page/Page column 73-74
[2] Patent: WO2013/13113, 2013, A2, . Location in patent: Page/Page column 69
[3] Patent: US2015/99744, 2015, A1, . Location in patent: Paragraph 0234
[4] Patent: US2015/105384, 2015, A1, . Location in patent: Paragraph 0400; 0401
[5] Patent: US2015/105358, 2015, A1, . Location in patent: Paragraph 0390-0391
[6] Patent: US2015/119413, 2015, A1, . Location in patent: Paragraph 0154-0155
[7] Patent: US2015/105409, 2015, A1, . Location in patent: Paragraph 0200
[8] Patent: US2015/105383, 2015, A1, . Location in patent: Paragraph 0214
[9] Patent: US2015/150871, 2015, A1, . Location in patent: Paragraph 0248-0249
[10] Patent: WO2016/7423, 2016, A1, . Location in patent: Page/Page column 38
[11] Patent: WO2016/87950, 2016, A1, . Location in patent: Page/Page column 27
[12] Patent: US2016/355486, 2016, A1, . Location in patent: Paragraph 0138; 0140
[13] Patent: WO2016/200919, 2016, A1, . Location in patent: Page/Page column 20; 21
[14] Patent: US9663825, 2017, B2, . Location in patent: Paragraph 155; 156
[15] Patent: US2017/114023, 2017, A1, . Location in patent: Paragraph 0125; 0127
[16] Patent: WO2017/143237, 2017, A1, . Location in patent: Page/Page column 48; 49
[17] Patent: WO2017/184774, 2017, A1, . Location in patent: Page/Page column 44
[18] Patent: WO2017/214565, 2017, A1, . Location in patent: Page/Page column 34; 35
[19] Patent: US2018/36306, 2018, A1, . Location in patent: Paragraph 0278; 0281; 0282
[20] Patent: WO2018/81556, 2018, A1, . Location in patent: Page/Page column 28-29
[21] Patent: WO2018/98168, 2018, A1, . Location in patent: Page/Page column 30; 31
[22] Patent: WO2018/85652, 2018, A1, . Location in patent: Page/Page column 29; 30
[23] Patent: WO2018/81585, 2018, A1, . Location in patent: Page/Page column 33
[24] Patent: WO2018/98348, 2018, A1, . Location in patent: Page/Page column 28; 29

2
[ 89793-12-4 ]
[ 1316216-05-3 ]

Reference： [1] Patent: WO2011/91213, 2011, A2,
[2] Patent: WO2013/13113, 2013, A2,
[3] Patent: WO2018/98348, 2018, A1,
[4] Patent: US2015/99744, 2015, A1,
[5] Patent: US2015/105409, 2015, A1,
[6] Patent: US2015/119413, 2015, A1,
[7] Patent: US2015/150871, 2015, A1,
[8] Patent: WO2016/87950, 2016, A1,
[9] Patent: US2016/355486, 2016, A1,
[10] Patent: US2018/36306, 2018, A1,
[11] Patent: US2015/105384, 2015, A1,
[12] Patent: US2015/105383, 2015, A1,
[13] Patent: US2015/105358, 2015, A1,
[14] Patent: WO2016/7423, 2016, A1,
[15] Patent: WO2016/200919, 2016, A1,
[16] Patent: US2017/114023, 2017, A1,
[17] Patent: US9663825, 2017, B2,
[18] Patent: WO2017/143237, 2017, A1,
[19] Patent: WO2017/184774, 2017, A1,
[20] Patent: WO2017/214565, 2017, A1,
[21] Patent: WO2018/81556, 2018, A1,
[22] Patent: WO2018/98168, 2018, A1,
[23] Patent: WO2018/85652, 2018, A1,
[24] Patent: WO2018/81585, 2018, A1,

3
[ 62-53-3 ]
[ 1316216-05-3 ]

Reference： [1] Patent: WO2011/91213, 2011, A2,
[2] Patent: WO2013/13113, 2013, A2,
[3] Patent: WO2018/98348, 2018, A1,
[4] Patent: US2015/99744, 2015, A1,
[5] Patent: US2015/105409, 2015, A1,
[6] Patent: US2015/119413, 2015, A1,
[7] Patent: US2015/150871, 2015, A1,
[8] Patent: WO2016/87950, 2016, A1,
[9] Patent: US2016/355486, 2016, A1,
[10] Patent: US2018/36306, 2018, A1,
[11] Patent: US2015/105384, 2015, A1,
[12] Patent: US2015/105383, 2015, A1,
[13] Patent: US2015/105358, 2015, A1,
[14] Patent: WO2016/7423, 2016, A1,
[15] Patent: WO2016/200919, 2016, A1,
[16] Patent: US2017/114023, 2017, A1,
[17] Patent: WO2017/143237, 2017, A1,
[18] Patent: WO2017/184774, 2017, A1,
[19] Patent: WO2017/214565, 2017, A1,
[20] Patent: WO2018/81556, 2018, A1,
[21] Patent: WO2018/98168, 2018, A1,
[22] Patent: WO2018/85652, 2018, A1,
[23] Patent: WO2018/81585, 2018, A1,

4
[ 95928-49-7 ]
[ 1316216-05-3 ]

Reference： [1] Patent: WO2011/91213, 2011, A2,
[2] Patent: WO2013/13113, 2013, A2,

5
[ 1316216-05-3 ]
[ 1316214-52-4 ]

Reference： [1] Patent: WO2011/91213, 2011, A2,
[2] Patent: WO2013/13113, 2013, A2,
[3] Patent: US2015/99744, 2015, A1,
[4] Patent: US2015/105384, 2015, A1,
[5] Patent: US2015/105358, 2015, A1,
[6] Patent: US2015/119413, 2015, A1,
[7] Patent: US2015/105409, 2015, A1,
[8] Patent: US2015/105383, 2015, A1,
[9] Patent: US2015/150871, 2015, A1,
[10] Patent: WO2016/7423, 2016, A1,
[11] Patent: WO2016/87950, 2016, A1,
[12] Patent: US2016/355486, 2016, A1,
[13] Patent: WO2016/200919, 2016, A1,
[14] Patent: US9663825, 2017, B2,
[15] Patent: US2017/114023, 2017, A1,
[16] Patent: WO2017/143237, 2017, A1,
[17] Patent: WO2017/184774, 2017, A1,
[18] Patent: WO2017/214565, 2017, A1,
[19] Patent: WO2018/81556, 2018, A1,
[20] Patent: WO2018/98168, 2018, A1,
[21] Patent: WO2018/85652, 2018, A1,
[22] Patent: WO2018/81585, 2018, A1,
[23] Patent: WO2018/98348, 2018, A1,

[ 1316216-05-3 ] Synthesis Path-Downstream 1~48

1
[ 89793-12-4 ]
[ 1316216-05-3 ]

Reference： [1]Patent: WO2011/91213,2011,A2
[2]Patent: WO2013/13113,2013,A2
[3]Patent: US2015/99744,2015,A1
[4]Patent: US2015/105384,2015,A1
[5]Patent: US2015/105383,2015,A1
[6]Patent: WO2016/7423,2016,A1
[7]Patent: WO2016/200919,2016,A1
[8]Patent: US2017/114023,2017,A1
[9]Patent: US9663825,2017,B2
[10]Patent: WO2017/143237,2017,A1
[11]Patent: WO2017/184774,2017,A1
[12]Patent: WO2017/214565,2017,A1
[13]Patent: WO2018/81556,2018,A1
[14]Patent: WO2018/98168,2018,A1
[15]Patent: WO2018/85652,2018,A1
[16]Patent: WO2018/81585,2018,A1
[17]Patent: WO2018/39581,2018,A1
[18]Patent: CN110885316,2020,A

2
[ 62-53-3 ]
[ 1316216-05-3 ]

Reference： [1]Patent: WO2011/91213,2011,A2
[2]Patent: WO2013/13113,2013,A2
[3]Patent: US2015/99744,2015,A1
[4]Patent: US2015/105384,2015,A1
[5]Patent: US2015/105383,2015,A1
[6]Patent: WO2016/7423,2016,A1
[7]Patent: WO2016/200919,2016,A1
[8]Patent: US2017/114023,2017,A1
[9]Patent: WO2017/143237,2017,A1
[10]Patent: WO2017/184774,2017,A1
[11]Patent: WO2017/214565,2017,A1
[12]Patent: WO2018/81556,2018,A1
[13]Patent: WO2018/98168,2018,A1
[14]Patent: WO2018/85652,2018,A1
[15]Patent: WO2018/81585,2018,A1
[16]Patent: WO2018/39581,2018,A1
[17]Patent: CN110885316,2020,A

3
[ 1316216-05-3 ]
[ 1310-73-2 ]
[ 1316216-06-4 ]

Yield	Reaction Conditions	Operation in experiment
92%		2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layer was separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2S04. Removal of solvent gave a brown solid (2.5 g, 92 %).

Reference： [1]Patent: WO2011/91213,2011,A2 .Location in patent: Page/Page column 73-75

4
[ 591-50-4 ]
[ 864172-93-0 ]
[ 1316216-05-3 ]

Yield	Reaction Conditions	Operation in experiment
69.9%	With copper(l) iodide; caesium carbonate; In N,N-dimethyl-formamide; at 140.0℃; for 12.0h;Inert atmosphere;	In a 500ml three-necked flask, add compound 2 (17.00g, 70mmol),Iodobenzene (17.11g, 84mmol), cesium carbonate (45.54g, 140mmol),Cuprous iodide (6.65g, 35mmol), DMF 200ml, under nitrogen protection at 140 for 12h.Cool to room temperature, add 200 ml of ethyl acetate to dilute, filter to remove copper salt, add 200 ml of water to the filtrate, stir at room temperature for 20 min, separate the liquid, and extract the aqueous phase twice with 100 ml of ethyl acetate.Combine the organic phases, add 200ml of EDTA saturated solution, stir for 30min, and separate the organic layer.Wash with 100ml of saturated saline, concentrate to dryness under reduced pressureObtained brown oil, recrystallized by adding 50ml of ethanol,15.6g light yellow solid was obtained,The yield was 69.90%.
38%	With caesium carbonate;copper(l) iodide; In tetraethoxy orthosilicate; at 140.0℃; for 14.0h;	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), CS2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95%EtOH (200 ml), NH4F-H20 on silica gel [50g, pre- prepared by the addition of NH4F (lOOg) in water (1500 ml) to silica gel (500g, 100- 200mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 %).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	Synthesis of Intermediate 3A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in tetraethyl orthosilicate (TEOS) (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and95%EtOH (200 ml), NH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (lOOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resulting mixture was kept at room temperature for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 %).

38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	[0234] A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 3Ommol), Cul (955 mg, 5.Ommol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140C. for 14 hrs. Afier cooling to tt., the residue was diluted with EtOAc (200 ml). 95% EtOR (200 ml) and NH4F-H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at tt. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	Synthesis of Intermediate 3 A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95% EtOH (200 ml), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	Synthesis of Intermediate 3 [0155] A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 h. After cooling to r.t., the residue was diluted with EtOAc (200 ml) and 95% EtOH (200 ml), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	Synthesis of Intermediate 3 [0248] [0249] A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95% EtOH (200 ml), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	Synthesis of Intermediate 3: A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene(6.12 g, 3Ommol), Cul (955 mg, 5.Omrnol), Cs2CO3(16.3 g, SOmmol) inTEOS (200m1)was degassed and purged with nitrogen. The resulting mixture was stirred at 140C for 14hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml)and NH4F-H20 on silica gel [50g, pre-prepared by the addition ofNH4F (bOg) in water(1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography(petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of the compound 2 (6.2 g, 25 mmol),iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) inTEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at140 C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and95%EtOH (200 ml), NH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F(bOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resultingmixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc.The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 %).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 hrs. Afier cooling to tt., the residue was diluted with EtOAc (200 ml). 95% EtOR (200 ml) and NH4F-H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at tt. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12g, 30 mmol), CuT (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) andNH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (bOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate wasevaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 3 8%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), CuI (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C. for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95% EtOH (200 ml), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	0127] A mixture of intermediate 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 mL) was degassed and purged with nitrogen. The resulting mixture was stirred at 140C for 14 h. After cooling to rt, the residue was diluted with EtOAc (200 mL) and 95% EtOH (200 mL), NH4F-H2O on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 mL) to silica gel (500 g, 100-200 mesh)] was added and the resulting mixture was kept at rt for 2h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc=10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of the compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14h. After cooling to rt, the residue was diluted with EtOAc (200 ml) and 95%EtOH (200 ml), H4F-H20 on silica gel [50g, pre-prepared by the addition of H4F (lOOg) in water (1500 ml) to silica gel (500g, 100-200mesh)] was added, and the resulting mixture was kept at rt for 2 h, the solidified materials was filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38 %).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and H4F-H20 on silica gel [50g, pre-prepared by the addition of H4F (lOOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%)
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and H4F-H20 on silica gel [50 g, pre-prepared by the addition of H4F (100 g) in water (1500 ml) to silica gel (500 g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ether/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	10282] A mixture of compound 2 (6.2 g, 25 mmol),iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol),Cs2CO3 (16.3 g, 50 mmol) in TEOS (200 ml) was degassedand purged with nitrogen. The resulting mixture was stirredat 1400 C. for 14 hrs. After cooling to r.t., the residue wasdiluted with EtOAc (200 ml). 95% EtOH (200 ml) andNH4F-H20 on silica gel [50 g, pre-prepared by the addition of NH4F (100 g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture waskept at r.t. for 2 hrs. The solidified materials were filtered andwashed with EtOAc. The filtrate was evaporated to drynessand the residue was purified by silica gel chromatography(petroleum ethers/EtOAc10/1) to give a yellow solid (3 g,38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;	Synthesis of Intermediate 3: A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t. , the residue was diluted with EtOAc (200 ml) . 95% EtOH (200 ml) and NH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (1 OOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F- H20 on silica gel [50g, pre-prepared by the addition of NH4F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F- H20 on silica gel [50g, pre-prepared by the addition of NH4F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and NH4F- H20 on silica gel [50g, pre-prepared by the addition of NH4F (100g) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; tetraethoxy orthosilicate; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmcl), Cs2CO3 (16.3 g, 50 mmcl) in TEOS (200 ml) wasdegassed and purged with nitrogen. The resulting mixture was stirred at 140 9C for 14 hrs.After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtCH (200 ml) andNH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (1 OOg) in water (1500 ml)to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) in TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to room temperature, the residue was diluted with EtOAc (200 ml). 95% EtOH (200 ml) and H4F-H20 on silica gel [50g, pre- prepared by the addition of H4F (lOOg) in water (1500 ml) to silica gel (500g, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).
38%	With copper(l) iodide; caesium carbonate; at 140.0℃; for 14.0h;Inert atmosphere;	A mixture of compound 2 (6.2 g, 25 mmol), iodobenzene (6.12 g, 30 mmol), Cul (955 mg, 5.0 mmol), Cs2C03 (16.3 g, 50 mmol) In TEOS (200 ml) was degassed and purged with nitrogen. The resulting mixture was stirred at 140 C for 14 hrs. After cooling to r.t., the residue was diluted with EtOAc (200 ml). 95% EtOH (200 mi) and NH4F-H20 on silica gel [50g, pre-prepared by the addition of NH4F (10Gg) in water (1500 ml) to silica gel (5GQg, 100-200 mesh)] was added, and the resulting mixture was kept at r.t. for 2 hrs. The solidified materials were filtered and washed with EtOAc. The filtrate was evaporated to dryness and the residue was purified by silica gel chromatography (petroleum ethers/EtOAc = 10/1) to give a yellow solid (3 g, 38%).

Reference： [1]Patent: CN110885316,2020,A .Location in patent: Paragraph 0095; 0102-0104; 0127-0130
[2]Patent: WO2011/91213,2011,A2 .Location in patent: Page/Page column 73-74
[3]Patent: WO2013/13113,2013,A2 .Location in patent: Page/Page column 69
[4]Patent: US2015/99744,2015,A1 .Location in patent: Paragraph 0234
[5]Patent: US2015/105384,2015,A1 .Location in patent: Paragraph 0400; 0401
[6]Patent: US2015/105358,2015,A1 .Location in patent: Paragraph 0390-0391
[7]Patent: US2015/119413,2015,A1 .Location in patent: Paragraph 0154-0155
[8]Patent: US2015/105409,2015,A1 .Location in patent: Paragraph 0200
[9]Patent: US2015/105383,2015,A1 .Location in patent: Paragraph 0214
[10]Patent: US2015/150871,2015,A1 .Location in patent: Paragraph 0248-0249
[11]Patent: WO2016/7423,2016,A1 .Location in patent: Page/Page column 38
[12]Patent: WO2016/87950,2016,A1 .Location in patent: Page/Page column 27
[13]Patent: US2016/355486,2016,A1 .Location in patent: Paragraph 0138; 0140
[14]Patent: WO2016/200919,2016,A1 .Location in patent: Page/Page column 20; 21
[15]Patent: US9663825,2017,B2 .Location in patent: Paragraph 155; 156
[16]Patent: US2017/114023,2017,A1 .Location in patent: Paragraph 0125; 0127
[17]Patent: WO2017/143237,2017,A1 .Location in patent: Page/Page column 48; 49
[18]Patent: WO2017/184774,2017,A1 .Location in patent: Page/Page column 44
[19]Patent: WO2017/214565,2017,A1 .Location in patent: Page/Page column 34; 35
[20]Patent: US2018/36306,2018,A1 .Location in patent: Paragraph 0278; 0281; 0282
[21]Patent: WO2018/81556,2018,A1 .Location in patent: Page/Page column 28-29
[22]Patent: WO2018/98168,2018,A1 .Location in patent: Page/Page column 30; 31
[23]Patent: WO2018/85652,2018,A1 .Location in patent: Page/Page column 29; 30
[24]Patent: WO2018/81585,2018,A1 .Location in patent: Page/Page column 33
[25]Patent: WO2018/98348,2018,A1 .Location in patent: Page/Page column 28; 29
[26]Patent: WO2018/39581,2018,A1 .Location in patent: Page/Page column 30-31
[27]Patent: WO2019/106633,2019,A1 .Location in patent: Page/Page column 29

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[ 1316216-07-5 ]

Reference： [1]Patent: WO2011/91213,2011,A2
[2]Patent: WO2013/13113,2013,A2
[3]Patent: US2015/99744,2015,A1
[4]Patent: US2015/105384,2015,A1
[5]Patent: US2015/105358,2015,A1
[6]Patent: US2015/119413,2015,A1
[7]Patent: US2015/105383,2015,A1
[8]Patent: US2015/150871,2015,A1
[9]Patent: WO2016/7423,2016,A1
[10]Patent: WO2016/87950,2016,A1
[11]Patent: US2016/355486,2016,A1
[12]Patent: US9663825,2017,B2
[13]Patent: US2017/114023,2017,A1
[14]Patent: WO2017/214565,2017,A1
[15]Patent: WO2018/98168,2018,A1
[16]Patent: WO2018/85652,2018,A1
[17]Patent: WO2018/81585,2018,A1
[18]Patent: WO2018/98348,2018,A1

6
[ 1316216-05-3 ]
[ 1316214-52-4 ]

Reference： [1]Patent: WO2011/91213,2011,A2
[2]Patent: WO2013/13113,2013,A2
[3]Patent: US2015/99744,2015,A1
[4]Patent: US2015/105384,2015,A1
[5]Patent: US2015/105358,2015,A1
[6]Patent: US2015/119413,2015,A1
[7]Patent: US2015/105409,2015,A1
[8]Patent: US2015/105383,2015,A1
[9]Patent: US2015/150871,2015,A1
[10]Patent: WO2016/7423,2016,A1
[11]Patent: WO2016/87950,2016,A1
[12]Patent: US2016/355486,2016,A1
[13]Patent: US9663825,2017,B2
[14]Patent: US2017/114023,2017,A1
[15]Patent: WO2017/143237,2017,A1
[16]Patent: WO2017/184774,2017,A1
[17]Patent: WO2017/214565,2017,A1
[18]Patent: WO2018/98168,2018,A1
[19]Patent: WO2018/85652,2018,A1
[20]Patent: WO2018/81585,2018,A1
[21]Patent: WO2018/98348,2018,A1
[22]Patent: WO2018/39581,2018,A1

7
[ 95928-49-7 ]
[ 1316216-05-3 ]

Reference： [1]Patent: WO2011/91213,2011,A2
[2]Patent: WO2013/13113,2013,A2

8
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[ 1316216-06-4 ]

Yield	Reaction Conditions	Operation in experiment
93.97%	With lithium hydroxide monohydrate; In tetrahydrofuran; water; at 20.0℃; for 12.0h;	In a 250ml three-necked flask, add compound 3 (4.2g, 13mmol),Lithium hydroxide monohydrate (2.20g, 53mmol), 50ml THF, 50ml water.Stir at room temperature for 12h,Adjust the pH to 3 with 2N hydrochloric acid, extract 3 times with 50ml of ethyl acetate, combine the organic layers,Wash with 100ml of saturated saline and dry with anhydrous sodium sulfate,Concentrate to dryness under reduced pressure3.60g light yellow solid was obtained,The yield was 93.97%.
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	Synthesi f Intermediate 42N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layer was separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2S04. Removal of solvent gave a brown solid (2.5 g, 92 %).
92%		[0235] 2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layers were separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92%).

92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	10403] 2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOR (200 ml). The mixture was stirred at 60 C. for 30 mm. After evaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2x200 ml), and the organic layers were separated, washed with water (2x100 ml), brine (2x100 ml), and dried over Na2504. Removal of the solvent gave a brown solid (2.5 g, 92%).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	Synthesis of Intermediate 4 2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layer was separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of solvent gave a brown solid (2.5 g, 92%).
92%	With water; sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	Synthesis of Intermediate 4 [0157] 2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layer was separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of solvent gave a brown solid (2.5 g, 92%).
92%	With water; sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layers were separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92%).
92%	With water; sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layers were separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92%).
92%	With water; sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	Synthesis of Intermediate 4 [0250] [0251] 2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layer was separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of solvent gave a brown solid (2.5 g, 92%).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	Synthesis of Intermediate 4: 2N NaOH (200 ml) was added to a solution of compound(3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60C for 30mm. Afterevaporation of the solvent, the solution was neutralized with 2N HC1 to give a whiteprecipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layers were separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60C for30mm. After evaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layer was separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2504. Removal of solvent gave a brown solid (2.5 g, 92 %).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 mi Afier evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2x200 ml), and the organic layers were separated, washed with water (2x100 ml), brine (2x100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid(2.5 g, 92%).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60C for 30mm. Afterevaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layers were separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C. for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2×200 ml), and the organic layer was separated, washed with water (2×100 ml), brine (2×100 ml), and dried over Na2SO4. Removal of solvent gave a brown solid (2.5 g, 92%).
92%	With sodium hydroxide; In ethanol; water; at 60.0℃; for 0.5h;	0128] 2N NaOH (200 mL) was added to a solution of intermediate 3 (3.0 g, 9.4 mmol) in EtOH (200 mL). The mixture was stirred at 60C for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 mL) and the organic layer was separated, washed with water (2 x 100 mL), brine (2 x 100 mL) and dried over Na2SO4. Removal of solvent gave a brown solid (2.5 g, 92%).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of the compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layer was separated, washed with water (2 x 100 ml), brine (2 x 100 ml), and dried over Na2S04. Removal of solvent gave a brown solid (2.5 g, 92 %).
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HC1 to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %)
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	Synthesis of Intermediate 4: 2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCI to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCI to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCI to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30min. After evaporation of the solvent, the solution was neutralized with 2N HCI to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With sodium hydroxide; In ethanol; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution ofcompound 3 (3.0 g, 9.4 mmol) in EtCH (200 ml). The mixture was stirred at 60 C for 30mm. After evaporation of the solvent, the solution was neutralized with 2N HCI to give a white precipitate. The suspension was extracted with EtOAc (2 x 200 ml), and the organic layers were separated, washed with water (2 x 100 ml), brine (2 x 1 00 ml), and dried over Na2SO4. Removal of the solvent gave a brown solid (2.5 g, 92 %).
92%	With ethanol; sodium hydroxide; at 60.0℃; for 0.5h;	2N NaOH (200 ml) was added to a solution of compound 3 (3.0 g, 9.4 mmol) in EtOH (200 ml). The mixture was stirred at 60 C for 30 min. After evaporation of the solvent, the solution was neutralized with 2N HCl to give a white precipitate. The suspension was extracted with EtOAc (2 chi 200 ml), and the organic layers were separated, washed with water (2 chi 100 ml), brine (2 chi 100 ml), and dried over Na2S04. Removal of the solvent gave a brown solid (2.5 g, 92 %).

Reference： [1]Patent: CN110885316,2020,A .Location in patent: Paragraph 0095; 0105-0107; 0127-0130
[2]Patent: WO2013/13113,2013,A2 .Location in patent: Page/Page column 69
[3]Patent: US2015/99744,2015,A1 .Location in patent: Paragraph 0235
[4]Patent: US2015/105384,2015,A1 .Location in patent: Paragraph 0402; 0403
[5]Patent: US2015/105358,2015,A1 .Location in patent: Paragraph 0392-0393
[6]Patent: US2015/119413,2015,A1 .Location in patent: Paragraph 0156-0157
[7]Patent: US2015/105409,2015,A1 .Location in patent: Paragraph 0201
[8]Patent: US2015/105383,2015,A1 .Location in patent: Paragraph 0215
[9]Patent: US2015/150871,2015,A1 .Location in patent: Paragraph 0250-0251
[10]Patent: WO2016/7423,2016,A1 .Location in patent: Page/Page column 38; 39
[11]Patent: WO2016/87950,2016,A1 .Location in patent: Page/Page column 27; 28
[12]Patent: US2016/355486,2016,A1 .Location in patent: Paragraph 0138; 0141
[13]Patent: WO2016/200919,2016,A1 .Location in patent: Page/Page column 20; 21
[14]Patent: US9663825,2017,B2 .Location in patent: Page/Page column 156
[15]Patent: US2017/114023,2017,A1 .Location in patent: Paragraph 0125; 0128
[16]Patent: WO2017/143237,2017,A1 .Location in patent: Page/Page column 48; 49
[17]Patent: WO2017/184774,2017,A1 .Location in patent: Page/Page column 44; 45
[18]Patent: WO2017/214565,2017,A1 .Location in patent: Page/Page column 34; 35
[19]Patent: WO2018/81556,2018,A1 .Location in patent: Page/Page column 28; 29
[20]Patent: WO2018/98168,2018,A1 .Location in patent: Page/Page column 31
[21]Patent: WO2018/85652,2018,A1 .Location in patent: Page/Page column 30
[22]Patent: WO2018/81585,2018,A1 .Location in patent: Page/Page column 33
[23]Patent: WO2018/98348,2018,A1 .Location in patent: Page/Page column 28; 29
[24]Patent: WO2018/39581,2018,A1 .Location in patent: Page/Page column 31; 30

9
[ 1316216-05-3 ]
C₂₇H₃₃N₅O₃ [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

10
[ 1316216-05-3 ]
2-(diphenylamino)-N-(5-(2-mercaptoacetamido)pentyl)pyrimidine-5-carboxamide [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

11
[ 1316216-05-3 ]
C₂₂H₂₅N₅O*ClH [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

12
[ 1316216-05-3 ]
C₂₄H₂₇N₅O₂S*ClH [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

13
[ 1316216-05-3 ]
2-(diphenylamino)-N-(6-mercaptohexyl)pyrimidine-5-carboxamide [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

14
[ 1316216-05-3 ]
C₂₄H₂₇N₅O₂S*CH₄O₃S [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

15
[ 1316216-05-3 ]
C₂₄H₂₇N₅O₂S*BrH [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

16
[ 1316216-05-3 ]
C₂₄H₂₇N₅O₂S*C₂H₂O₄ [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

17
[ 1316216-05-3 ]
C₂₃H₂₅BrN₄O [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

18
[ 1316216-05-3 ]
C₂₅H₂₈N₄O₂S [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

19
[ 1316216-05-3 ]
C₂₃H₂₆N₄OS*BrH [ No CAS ]

Reference： [1]Patent: CN110885316,2020,A

20
[ 1316216-05-3 ]
2-(diphenylamino)-N-(5-mercaptopentyl)pyrimidine-5-carboxamide [ No CAS ]