[ CAS No. 56456-49-6 ] {[proInfo.proName]}

Name: 56456-49-6|4-Chloro-2-fluorobenzyl alcohol|98%
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Quality Control of [ 56456-49-6 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

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Product Details of [ 56456-49-6 ]

CAS No. :	56456-49-6	MDL No. :	MFCD00143285
Formula :	C₇H₆ClFO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	XUZRWKWJKDCQNA-UHFFFAOYSA-N
M.W :	160.57	Pubchem ID :	2773609
Synonyms :

Calculated chemistry of [ 56456-49-6 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	1
Num. H-bond acceptors :	2.0
Num. H-bond donors :	1.0
Molar Refractivity :	37.54
TPSA :	20.23 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.03 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.94
Log Po/w (XLOGP3) :	1.76
Log Po/w (WLOGP) :	2.24
Log Po/w (MLOGP) :	2.57
Log Po/w (SILICOS-IT) :	2.74
Consensus Log Po/w :	2.25

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.32
Solubility :	0.764 mg/ml ; 0.00476 mol/l
Class :	Soluble
Log S (Ali) :	-1.8
Solubility :	2.53 mg/ml ; 0.0158 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-3.11
Solubility :	0.124 mg/ml ; 0.000774 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.36

Safety of [ 56456-49-6 ]

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H319-H335	Packing Group:	N/A
GHS Pictogram:

Application In Synthesis of [ 56456-49-6 ]

* 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 [ 56456-49-6 ]
Downstream synthetic route of [ 56456-49-6 ]

[ 56456-49-6 ] Synthesis Path-Upstream 1~4

1
[ 56456-49-6 ]
[ 61072-56-8 ]

Reference： [1] Patent: WO2015/75025, 2015, A1, . Location in patent: Page/Page column 81
[2] Patent: WO2015/75023, 2015, A1, . Location in patent: Page/Page column 111-112
[3] Patent: WO2016/177690, 2016, A1, . Location in patent: Page/Page column 75

2
[ 61072-56-8 ]
[ 56456-49-6 ]

Yield	Reaction Conditions	Operation in experiment
78.7%	at 0 - 20℃; for 1 h;	Example 1 1-(5-(4-Chloro-2-fluorobenzyloxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (1)1-(Bromomethyl)-4-chloro-2-fluorobenzene was prepared using the following two-step procedure. To a stirred solution of 4-chloro-2-fluorobenzaldehyde (1.0 g, 6.31 mmol) in methyl alcohol (CH₃OH; 15 mL) was added sodium borohydride (NaBH₄; 0.47 g, 12.6 mmol) at 0° C. The reaction mixture was stirred at RT for 1 h. After consumption of the starting material (by TLC), the reaction mixture was quenched with ice pieces, and the volatiles were evaporated under reduced pressure. The residue was diluted with H₂O (25 mL) and extracted with EtOAc (2.x.50 mL). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure. The obtained crude material was purified by column chromatography (SiO₂, 100-200 mesh) to afford the corresponding alcohol (0.8 g, 5.0 mmol, 78.7percent) as a semi solid. ¹H NMR (200 MHz, CDCl₃): δ 7.41 (q, J=8.0, 15.6 Hz, 1H), 7.17-7.05 (m, 2H), 4.73 (d, J=6.2 Hz, 2H), 1.83 (t, J=6.2 Hz, 1H).

Reference： [1] Patent: US2012/329788, 2012, A1, . Location in patent: Page/Page column 22
[2] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 13, p. 3463 - 3468
[3] Patent: US6100257, 2000, A,
[4] Patent: EP1577290, 2005, A1, . Location in patent: Page/Page column 107

3
[ 446-30-0 ]
[ 56456-49-6 ]

Yield	Reaction Conditions	Operation in experiment
224 mg	With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 16 h;	To a solution of 4-chloro-2-fluorobenzoic acid (300mg) in THF (15m1) was added at 0°CLiAIH4 (130mg). The suspension was stirred at 0°C for 16h. The reaction mixture wasdiluted with EA and aq. solution of potassium sodium tartrate and stirred for lh at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgSO4, filtrated off and evaporated in vacuo. The crude was purified by CC (Büchi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in percentB: 0 to 5, flow rate: 6.0 mI/mm) to afford 224mg of colourless oil. LCMS: (A) tR = 0.68 mm; [M+H]: not visible.
224 mg	With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 16 h; Inert atmosphere	To a solution of 4-chloro-2-fluorobenzoic acid (300 mg) in THF (15 ml_) was added at 0°C UAIH₄ (130 mg). The suspension was stirred at 0°C for 16h. The reaction mixture was diluted with EA and aq. solution of potassium sodium tartrat and stirred for 1 h at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgS0₄, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in percentB: 0 to 5, flow rate: 6.0 imL/min) to afford 224 mg of colourless oil. LC-MS (A) t_R = 0.68 min; [M+H]⁺: not visible.
224 mg	With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 16 h;	To a solution of 4-chloro-2-fluorobenzoic acid (300mg) in THF (15ml) was added at 0°C UAIH4 (130mg). The suspension was stirred at 0°C for 16h. The reaction mixture was diluted with EA and aq. solution of potassium sodium tartrat and stirred for 1 h at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in percentB: 0 to 5, flow rate: 6.0 ml/min) to afford 224mg of colourless oil. LC-MS (A) tR = 0.68min; [M+H]+: not visible.

Reference： [1] Helvetica Chimica Acta, 1985, vol. 68, p. 1444 - 1452
[2] Patent: WO2015/75025, 2015, A1, . Location in patent: Page/Page column 80; 81
[3] Patent: WO2015/75023, 2015, A1, . Location in patent: Page/Page column 111
[4] Patent: WO2016/177690, 2016, A1, . Location in patent: Page/Page column 74

4
[ 452-75-5 ]
[ 56456-49-6 ]

Reference： [1] Helvetica Chimica Acta, 1985, vol. 68, p. 1444 - 1452

[ 56456-49-6 ] Synthesis Path-Downstream 1~76

1
[ 56456-49-6 ]
[ 71916-82-0 ]

Yield	Reaction Conditions	Operation in experiment
54%	With phosphorus tribromide; In diethyl ether; at 0 - 20℃; for 3h;	To a stirred solution of alcohol (0.8 g, 5.0 mol) in dry Et2O (10 mL) was added phosphorus tribromide (PBr3; 0.33 mL, 3.5 mmol) at 0 C. The reaction mixture was stirred at RT for 3 h. After consumption of the starting material (by TLC), the reaction mixture was quenched with ice pieces, and the aqueous layer was extracted with EtOAc (2×75 mL). The combined organic layers were washed with satd NaHCO3 solution, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford 1-(bromomethyl)-4-chloro-2-fluorobenzene (0.6 g, 2.7 mmol, 54%) as a light yellow liquid. 1H NMR (200 MHz, CDCl3): delta 7.41 (q, J=14.5, 16.6 Hz, 1H), 7.15-7.07 (m, 2H), 4.46 (s, 2H).

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452
[2]Patent: US2012/329788,2012,A1 .Location in patent: Page/Page column 22

2
[ 446-30-0 ]
[ 56456-49-6 ]

Yield	Reaction Conditions	Operation in experiment
224 mg	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 16h;	To a solution of 4-chloro-2-fluorobenzoic acid (300mg) in THF (15m1) was added at 0CLiAIH4 (130mg). The suspension was stirred at 0C for 16h. The reaction mixture wasdiluted with EA and aq. solution of potassium sodium tartrate and stirred for lh at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgSO4, filtrated off and evaporated in vacuo. The crude was purified by CC (Buechi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in %B: 0 to 5, flow rate: 6.0 mI/mm) to afford 224mg of colourless oil. LCMS: (A) tR = 0.68 mm; [M+H]: not visible.
224 mg	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 16h;Inert atmosphere;	To a solution of 4-chloro-2-fluorobenzoic acid (300 mg) in THF (15 ml_) was added at 0C UAIH4 (130 mg). The suspension was stirred at 0C for 16h. The reaction mixture was diluted with EA and aq. solution of potassium sodium tartrat and stirred for 1 h at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in %B: 0 to 5, flow rate: 6.0 imL/min) to afford 224 mg of colourless oil. LC-MS (A) tR = 0.68 min; [M+H]+: not visible.
224 mg	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 16h;	To a solution of 4-chloro-2-fluorobenzoic acid (300mg) in THF (15ml) was added at 0C UAIH4 (130mg). The suspension was stirred at 0C for 16h. The reaction mixture was diluted with EA and aq. solution of potassium sodium tartrat and stirred for 1 h at rt. The layers were separated and the org. phase was further washed with water. The combined org. layers were dried over MgS04, filtrated off and evaporated in vacuo. The crude was purified by CC (Buchi Sepacore, 5g cartridge, solvent A: DCM, solvent B: 3N ammonia in MeOH, gradient in %B: 0 to 5, flow rate: 6.0 ml/min) to afford 224mg of colourless oil. LC-MS (A) tR = 0.68min; [M+H]+: not visible.

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452
[2]Patent: WO2015/75025,2015,A1 .Location in patent: Page/Page column 80; 81
[3]Patent: WO2015/75023,2015,A1 .Location in patent: Page/Page column 111
[4]Patent: WO2016/177690,2016,A1 .Location in patent: Page/Page column 74

3
[ 136918-14-4 ]
[ 56456-49-6 ]
[ 536761-10-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468

4
[ 61072-56-8 ]
[ 56456-49-6 ]

Yield	Reaction Conditions	Operation in experiment
78.7%	With methanol; sodium tetrahydroborate; at 0 - 20℃; for 1h;	Example 1 1-(5-(4-Chloro-2-fluorobenzyloxy)pyridin-2-yl)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-tetrazol-1-yl)propan-2-ol (1)1-(Bromomethyl)-4-chloro-2-fluorobenzene was prepared using the following two-step procedure. To a stirred solution of 4-chloro-2-fluorobenzaldehyde (1.0 g, 6.31 mmol) in methyl alcohol (CH3OH; 15 mL) was added sodium borohydride (NaBH4; 0.47 g, 12.6 mmol) at 0 C. The reaction mixture was stirred at RT for 1 h. After consumption of the starting material (by TLC), the reaction mixture was quenched with ice pieces, and the volatiles were evaporated under reduced pressure. The residue was diluted with H2O (25 mL) and extracted with EtOAc (2×50 mL). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The obtained crude material was purified by column chromatography (SiO2, 100-200 mesh) to afford the corresponding alcohol (0.8 g, 5.0 mmol, 78.7%) as a semi solid. 1H NMR (200 MHz, CDCl3): delta 7.41 (q, J=8.0, 15.6 Hz, 1H), 7.17-7.05 (m, 2H), 4.73 (d, J=6.2 Hz, 2H), 1.83 (t, J=6.2 Hz, 1H).
	With hydrogenchloride; sodium borohydrid; In 1,4-dioxane; methanol;	(1) First, 25 g of 4-chloro-2-fluorobenzaldehyde was dissolved in a mixed solvent consisting of 250 ml of 1,4-dioxane and 25 ml of methanol, to which 2.4 g of sodium borohydride was added under ice cooling, and the mixture was stirred for 30 minutes. After completion of the reaction, a small amount of diluted aqueous hydrochloric acid was added, and the reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 25 g of 4-chloro-2-fluorobenzyl alcohol. 1 H--NMR (300 MHz, CDCl3): delta (ppm) 1.82 (1 H, t, J=6.1 Hz), 4.72 (2 H, d, J=6.1 Hz), 7.08 (1 H, dd, J=2.1, 9.8 Hz), 7.15 (1 H, dd, J=2.1, 8.2 Hz), 7.37 (1 H, dd, J=8.2, 8.2 Hz)
	With sodium tetrahydroborate; In methanol; at 0 - 20℃; for 1.5h;	4.75 g of 4-chloro-2-fluorobanzaldehyde and 30 ml of methanol were mixed. It was cooled to 0 C, and 0.57 g of sodium borohydride was added to it, and stirred at 0 C for 30 minutes and at room temperature for 1 hour. Water was added to the reaction mixture, and concentrated under reduced pressure. The obtained residue was extracted with chloroform. The organic layer was washed successively with 5 % hydrochloric acid, saturated aqueous solution of sodium chloride, dried by magnesium salfate, and concentrated under reduced pressure to obtain 4.57 g of (4-chloro-2-fluorophenyl)methanol.1H-NMR (CDCl3, TMS) delta (ppm): 7.37 (1H, t, J=8.0 Hz), 7.12-7.17 (1H, m), 7.08 (1H, dd, J=9.7 Hz, 1.9 Hz), 4.73 (2H, s), 2.04 (1H, br.s)

Reference： [1]Patent: US2012/329788,2012,A1 .Location in patent: Page/Page column 22
[2]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468
[3]Patent: US6100257,2000,A
[4]Patent: EP1577290,2005,A1 .Location in patent: Page/Page column 107

5
[ 56456-49-6 ]
[ 900505-17-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468

6
[ 56456-49-6 ]
4-(4-chloro-2-fluoro-benzyl)-3-(4-chloro-phenyl)-7-iodo-1-(2-morpholin-4-yl-ethyl)-3,4-dihydro-1H-benzo[e][1,4]diazepine-2,5-dione [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468

7
[ 56456-49-6 ]
(2-{(4-chloro-2-fluoro-benzyl)-[(4-chloro-phenyl)-(cyclohex-1-enylcarbamoyl)-methyl]-carbamoyl}-4-iodo-phenyl)-carbamic acid tert-butyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468

8
[ 56456-49-6 ]
[ 72235-57-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 3463 - 3468

9
[ 452-75-5 ]
[ 56456-49-6 ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

10
[ 56456-49-6 ]
4-Chloro-2-fluoro-1-[(E)-2-(4-pentyl-cyclohexyl)-vinyl]-benzene [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

11
[ 56456-49-6 ]
4-Chloro-2-fluoro-1-[2-(4-pentyl-cyclohexyl)-ethyl]-benzene [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

12
[ 56456-49-6 ]
4-Chloro-2-fluoro-1-[(E)-2-(4-heptyl-cyclohexyl)-vinyl]-benzene [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

13
[ 56456-49-6 ]
4-Chloro-2-fluoro-1-[2-(4-heptyl-cyclohexyl)-ethyl]-benzene [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

14
[ 56456-49-6 ]
3-Fluoro-4-[2-(4-pentyl-cyclohexyl)-ethyl]-benzonitrile [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

15
[ 56456-49-6 ]
3-Fluoro-4-[2-(4-heptyl-cyclohexyl)-ethyl]-benzonitrile [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

16
[ 56456-49-6 ]
4-[2-(4-Chloro-2-fluoro-phenyl)-ethyl]-4'-pentyl-bicyclohexyl [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

17
[ 56456-49-6 ]
3-Fluoro-4-[2-(4'-pentyl-bicyclohexyl-4-yl)-ethyl]-benzonitrile [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

18
[ 56456-49-6 ]
4-[(E)-2-(4-Chloro-2-fluoro-phenyl)-vinyl]-4'-pentyl-bicyclohexyl [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

19
[ 56456-49-6 ]
(4-chloro-2-fluorobenzyl)triphenylphosphonium bromide [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

20
[ 56456-49-6 ]
[ 101160-87-6 ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

21
[ 56456-49-6 ]
3-Fluoro-4-{2-[4-(4-pentyl-cyclohexyl)-phenyl]-ethyl}-benzonitrile [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

22
[ 56456-49-6 ]
1-(4-chloro-2-fluorophenyl)-2-<4-(trans-4-pentylcyclohexyl)phenyl>ethylene [ No CAS ]

Reference： [1]Helvetica Chimica Acta,1985,vol. 68,p. 1444 - 1452

23
[ 56456-49-6 ]
[ 478373-33-0 ]

Reference： [1]Patent: EP1394147,2004,A1 .Location in patent: Page 161

24
[ 56456-49-6 ]
[ 478373-83-0 ]

Reference： [1]Patent: EP1394147,2004,A1 .Location in patent: Page 175

25
[ 56456-49-6 ]
[ 478373-53-4 ]

Reference： [1]Patent: EP1394147,2004,A1 .Location in patent: Page 167

26
[ 18162-48-6 ]
[ 56456-49-6 ]
[ 909186-19-2 ]

Yield	Reaction Conditions	Operation in experiment
	With 1H-imidazole; In tetrahydrofuran; at 20℃; for 12h;	To a stirred solution of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (4.60 g, 28.6 mmol) in THF (100 mL) was added 1H-imidazole (1.95 g, 28.6 mmol) and tert-butylchlorodimethylsilane (4.32 g, 28.6 mmol) at room temperature. The reaction mixture was stirred for 12 h at RT. The white precipitate was filtered and the filtrate was washed with 0.1 N aqueous HCl. The separated aqueous phase was extracted with diethyl ether (2×40 mL). The combined organic phases were washed with saturated aqueous solution of sodium bicarbonate, and brine. The resulting organic solution was dried over magnesium sulfate and concentrated under reduced pressure. Flash chromatography on silica (hexanes) gave (4-chloro-2-fluorobenzyloxy)(tert-butyl)dimethylsilane as colorless oil. 1H NMR (300 MHz, CHLOROFORM-d) 6 ppm 7.31 (1H, t, J=8.1 Hz), 7.01 (1H, d, J=8.3 Hz), 6.91 (1 H, dd, J=9.9, 1.8 Hz), 4.64 (2H, s), 0.73-0.86 (9H, m), -0.06 (6H, s)

Reference： [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 6280 - 6292
[2]Patent: US2006/199817,2006,A1 .Location in patent: Page/Page column 30

27
[ 56456-49-6 ]
4-chloro-1-chloromethyl-2-fluoro-benzene [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; thionyl chloride; In tetrahydrofuran;	(2) Then, 16.5 g of 4-chloro-2-fluorobenzylalcohol was dissolved in 150 ml of tetrahydrofuran and 1 ml of pyridine, to which 10 ml of thionyl chloride was added dropwise at 5 C., and the mixture was stirred for 2.5/6 hours. After cormpletion of the reaction, the reaction mixture was concentrated, and the precipitated crystals were collected by filtration. The filtrate was subjected to silica gel column chromatography, which afforded 18.5 g of 4-chloro-2-fluorobenzyl chloride. 1 H--NMR (250 MHz, CDCl3): delta (ppm) 4.59 (2 H, s), 7.09-7.17 (2 H, m), 7.36 (1 H, dd, J=7.9, 7.9 Hz)

Reference： [1]Patent: US6100257,2000,A

28
[ 170923-67-8 ]
[ 56456-49-6 ]
1-(2-butenyl)-7-(4-chloro-2-fluorobenzyloxy)-2,3-dimethylpyrrolo[2,3-d]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63.8%		EXAMPLE 48 1-(2-Butenyl)-7-(4-chloro-2-fluorobenzyloxy)-2,3-dimethylpyrrolo[2,3-d]pyridazine The title compound (cis/trans=24:76) was prepared as a white powder in 63.8% yield in a similar procedure to that described in Example 1 by using using 1-(2-butenyl)-7-chloro-2,3-dimethylpyrrolo[2,3-d]pyridazine (cis/trans=24/76) and <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong>. m.p.: 106-109 C. Mass spectrum (CI, m/z): 360 (M+ +1), 362 (M+ +3). NMR spectrum (CDCl3, deltappm): 1.59 (d;J=6 Hz, 2.28H), 1.65 (d;J=6 Hz, 0.72H), 2.24 (s, 3H), 2.30 (s, 3H), 4.82 (d;J=6 Hz, 1.52H), 4.99 (d;J=6 Hz, 0.48 Hz), 5.12-5.60 (m, 2H), 5.73 (s, 2H), 7.12 (d;J=9 Hz, 2H), 7.51 (t;J=9 Hz, 1H), 8.97 (s, 1H). Elementary analysis (%): Calc'd for C19 H19 ClFN3 O: C, 63.42; H, 5.32; N, 11.68, Found: C, 63.41; H, 5.17; N, 11.54.

Reference： [1]Patent: US6063782,2000,A

29
4,5-dibromo-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone [ No CAS ]
[ 56456-49-6 ]
4-bromo-5-(4-chloro-2-fluorobenzyloxy)-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium hydroxide; In N,N-dimethyl-formamide;	SYNTHESIS EXAMPLE 10 Synthesis of 4-bromo-5-(4-chloro-2-fluorobenzyloxy)-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone (Compound No. 522) To a mixture of 2.0 g (5.0 m mol) of 4,5-dibromo-2-(3,4-dichlorophenyl)-3(2H)-pyridazinone and 0.84 g (5.2 m mol) of <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong> was added 80 ml of N,N-dimethylformamide. The resulting mixture was cooled with ice, incorporated with 0.4 g of potassium hydroxide and then stirred for one day. Then, the procedures in Synthesis Example 2 were repeated to give a crude product. The crude product was recrystallized from benzene to give 1.3 g of the intended compound. m.p. 172.0-173.0 C. 1 H-NMR (CDCl3, delta, TMS); 5.57 (2H, s), 7.25-7.95 (6H, m), 8.43 (1H, s).

Reference： [1]Patent: US4910201,1990,A

30
[ 478930-01-7 ]
[ 32315-10-9 ]
[ 56456-49-6 ]
C₂₂H₂₅ClFNO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		25 mg of Triphosgene was dissolved in 0.5 ml of dichloromethane, 5 mul of pyridine was added, and a solution of 20 mg of ethyl-3-(3-aminophenyl)-2-isopropoxypropanoate in dichloromethane and 50 mul of triethylamine were added under ice-cooling. After the insoluble substances had been removed by cotton plug filtration, 15 mg of <strong>[56456-49-6]2-fluoro-4-chlorobenzyl alcohol</strong> was added. The solvent was removed under a stream of nitrogen, and the residue was dissolved in 0.6 ml of ethanol. 0.12 ml of 5N sodium hydroxide was added, followed by stirring at room temperature for 1 hour. The reaction solution was treated with 1 ml of water and 0.14 ml of 5N hydrochloric acid, then extracted with ethyl acetate. The organic layers were collected, and the solvent was removed under a stream of nitrogen. The residue was purified by reverse-phase HPLC using a water-acetonitrile-trifluoroacetic acid solvent system, to give 1.4 mg of the title compound. MS m/e(ESI) 438 (MNa+)

Reference： [1]Patent: EP1380562,2004,A1 .Location in patent: Page 236

31
[ 124-63-0 ]
[ 56456-49-6 ]
[ 721968-74-7 ]

Yield	Reaction Conditions	Operation in experiment
		4.75 g of (4-chloro-2-fluoro-phenyl)methanol, 4.31 g of triethylamine and 60 ml of tetrahydrofuran were mixed. It was cooled to 0 C, then 4.24 g of methanesulfonyl chloride was added to it, and stirred at 0 C for 30 minutes, at room temperature for 2 hours. Water was added to the reaction mixture, and concentrated under reduced pressure. The obtained residue was extracted with chloroform. The organic layer was washed successively with 5 % hydrochloric acid, saturated aqueous solution of sodium chloride, dried by magnesium sulfate, concentrated under reduced pressure to obtain (4-chloro-2-fluorobenzyl) methanesulfonate.1H-NMR (CDCl3, TMS) delta (ppm): 7.37-7.43 (1H, m), 7.14-7.22 (2H, m), 5.25 (2H, s), 3.01 (3H, s)

Reference： [1]Patent: EP1577290,2005,A1 .Location in patent: Page/Page column 108

32
[ 153034-86-7 ]
[ 56456-49-6 ]
[ 1260240-58-1 ]

Yield	Reaction Conditions	Operation in experiment
28%		A suspension of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (3.24 g, 20.1 mmol), 2-chloro-4-iodopyridine (4.40 g, 18.3 mmol), Cs2CO3 (7.76 g, 23.8 mmol), CuI (3.48 g, 18.7 mmol) and 1,10-phenanthroline (659 mg, 3.66 mmol) in toluene (20 mL) was degassed by bubbling N2 through the suspension for 15 min. The suspension was put under N2 and heated at 105 C. for 18 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was passed through a plug of SiO2. The resulting solution was concentrated under reduced pressure. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. A suspension of the white solid and NH4OAc (2.66 g, 34.6 mmol) in 1:1 HCO2H/H2O (20 mL) was heated at reflux with stirring for 4 d. The solution was cooled and concentrated under reduced pressure. The resulting residue was made basic with saturated NaHCO3 solution, and the resulting suspension was filtered. The solid was washed with H2O and CH2Cl2, and dried under reduced pressure to afford 1.28 g (28%) of the title compound as a white solid: 1H NMR (300 MHz, DMSO-d6) delta 11.14 (br s, 1H), 7.59 (dd, J=8.1, 8.1 Hz, 1H), 7.52 (dd, J=10.2, 1.8 Hz, 1H), 7.36 (dd, J=8.1, 1.8 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 5.89 (d, J=7.2, 2.4 Hz, 1H), 5.83 (d, J=2.4 Hz, 1H), 5.06 (s, 2H).
28%		a) 4-(4-Chloro-2-fluorobenzyloxy)pyridin-2(1H)-one A suspension of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (3.24 g, 20.1 mmol), 2-chloro-4-iodopyridine (4.40 g, 18.3 mmol), Cs2CO3 (7.76 g, 23.8 mmol), CuI (3.48 g, 18.7 mmol) and 1,10-phenanthroline (659 mg, 3.66 mmol) in toluene (20 mL) was degassed by bubbling N2 through the suspension for 15 min. The suspension was put under N2 and heated at 105 C. for 18 h. The suspension was cooled, 9:0.9:0.1 CH2Cl2/MeOH/NH4OH (10 mL) was added, and the resulting suspension was passed through a plug of SiO2. The resulting solution was concentrated under reduced pressure. Flash chromatography on silica gel (hexanes/(1:1 EtOAc/hexanes), 100:0 to 0:100) afforded a white solid. A suspension of the white solid and NH4OAc (2.66 g, 34.6 mmol) in 1:1 HCO2H/H2O (20 mL) was heated at reflux with stirring for 4 d. The solution was cooled and concentrated under reduced pressure. The resulting residue was made basic with saturated NaHCO3 solution, and the resulting suspension was filtered. The solid was washed with H2O and CH2Cl2, and dried under reduced pressure to afford 1.28 g (28%) of the title compound as a white solid: 1H NMR (300 MHz, DMSO-d6) delta 11.14 (br s, 1H), 7.59 (dd, J=8.1, 8.1 Hz, 1H), 7.52 (dd, J=10.2, 1.8 Hz, 1H), 7.36 (dd, J=8.1, 1.8 Hz, 1H), 7.25 (d, J=7.2 Hz, 1H), 5.89 (d, J=7.2, 2.4 Hz, 1H), 5.83 (d, J=2.4 Hz, 1H), 5.06 (s, 2H).

Reference： [1]Patent: US2011/3738,2011,A1 .Location in patent: Page/Page column 44-45
[2]Patent: US2011/3793,2011,A1 .Location in patent: Page/Page column 78

33
[ 153034-86-7 ]
[ 56456-49-6 ]
[ 1260492-49-6 ]

Reference： [1]Patent: US2011/3793,2011,A1

34
[ 56456-49-6 ]
[ 1416859-68-1 ]

Reference： [1]Patent: US2012/329788,2012,A1

35
[ 56456-49-6 ]
[ 1416860-93-9 ]

Reference： [1]Patent: US2012/329788,2012,A1

36
[ 1373150-91-4 ]
[ 56456-49-6 ]
[ 1373145-47-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 0 - 20℃;	(4) Sodium hydride (60%: 44 mg) was added at 0 C. to a suspension of N-{5-methyl-6-[4-(morpholin-4-yl)cyclohex-1-en-1-yl]pyridin-3-yl}-1H-pyrrole-3-carboxamide (200 mg) in N,N-dimethylformamide (2.7 ml), then 2-chloro-5-(trifluoromethyl)pyridine (120 mg) was added and stirred at room temperature for 3.5 hours. Water was added to the reaction solution at 0 C., and the precipitated solid was filtered and washed with water. The resulting solid (276 mg) was dissolved in methanol (8 ml), methanesulfonic acid (35 mul) was added and stirred at room temperature. The solvent was evaporated in vacuo, ethanol and ethyl acetate were added to the resulting residue and the precipitated solid was washed with ethanol and ethyl acetate to give the titled compound (207 mg) as an orange solid. [1213] MS (ESI) m/z: 512 (M+H)+. The next compounds (Examples H2 to H17) were prepared from the corresponding starting material in a similar manner as Example H1. Conversion into mesylate or hydrochloride salt was carried out in a similar manner as Examples D1, D5 etc.

Reference： [1]Patent: US2013/211075,2013,A1 .Location in patent: Paragraph 1212-1214

37
[ 56456-49-6 ]
[ 61072-56-8 ]

Yield	Reaction Conditions	Operation in experiment
	With manganese(IV) oxide; In acetonitrile; for 24h;	To a solution of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (222mg) in MeCN (20m1) was addedMnO (480mg). The mixture was stirred for 24h. The mixture was filtered over celite, theorg. layer was dried over MgSO4 and evaporated in vacuo. The crude aldehyde was used without purification in the next step. LC-MS (A): tR = 0.76 mm; [M+H]: not visible.
	With manganese(IV) oxide; In acetonitrile; at 20℃; for 24h;Inert atmosphere;	To a solution of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (222 mg) in MeCN (20 mL) was added MnC>2 (480 mg). The mixture was stirred for 24h. The mixture was filtered over celite, the org. layer was dried over MgS04 and evaporated in vacuo. The crude aldehyde was used without purification in the next step. LC-MS (A): tR = 0.76 min; [M+H]+: not visible.
	With manganese(IV) oxide; In acetonitrile; for 24h;	To a solution of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (222mg) in MeCN (20ml) was added Mn02 (480mg). The mixture was stirred for 24h. The mixture was filtered over celite, the org. layer was dried over MgS04 and evaporated in vacuo. The crude aldehyde was used without purification in the next step. LC-MS (A): tR = 0.76min; [M+H]+: not visible.

Reference： [1]Patent: WO2015/75025,2015,A1 .Location in patent: Page/Page column 81
[2]Patent: WO2015/75023,2015,A1 .Location in patent: Page/Page column 111-112
[3]Patent: WO2016/177690,2016,A1 .Location in patent: Page/Page column 75

38
[ 56456-49-6 ]
1-(4-chloro-2-fluorophenyl)-1,2,3,4,6,7,8,9-octahydroimidazo[1,2-a:5,4-c']dipyridine [ No CAS ]

Reference： [1]Patent: WO2015/75025,2015,A1

39
[ 56456-49-6 ]
6-chloro-5-(2-(1-(4-chloro-2-fluorophenyl)-3,4,6,7,8,9-hexahydroimidazo[1,2-a:5,4-c’]dipyridin-2(1H)-yl)-2-oxoethoxy)-N,N-dimethylpicolinamide [ No CAS ]

Reference： [1]Patent: WO2015/75025,2015,A1

40
N-(((3S,4R)-3-fluoropiperidin-4-yl)methyl)-[1,2,4]triazolo[4,3-a]pyrazin-5-amine dihydrochloride [ No CAS ]
[ 56456-49-6 ]
[ 530-62-1 ]
(3S,4R)-4-chloro-2-fluorobenzyl 4-(([1,2,4]triazolo[4,3-a]pyrazin-5-ylamino)methyl)-3-fluoropiperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%		Step 2: (3S,4 ?)-4-chloro-2-fluorobenzyl 4-(([l,2,4]triazolo[4,3-o]pyrazin-5-ylamino)-methyl)-3- fluoropiperidine-l-carboxylate [0239] To a solution of <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (136 mg, 0.85 mmol) in dried DMSO (5 mL) was added CDI (145 mg, 0.93 mmol) at room temperature. After stirring for 1.5 hrs, A/-(((3S,4 ?)-3- fluoropiperidin-4-yl)methyl)-[l,2,4]triazolo[4,3-o]pyrazin-5-amine dihydrochloride salt (250 mg, 0.77 mmol) was added. The reaction mixture was heated to 50 C under N2 atmosphere, overnight. The mixture was allowed to cool to room temperature and diluted with EtOAc. The organic layer was washed with water, brine, dried over Na2S04 and concentrated. The concentrate was purified by column chromatography over silica gel (DCM/MeOH = 30/1) to afford the title compound as a pale- yellow powder (140 mg, 42%). MS (ESI) calcd for C19H19CIF2N602: 436.1 ; found: 437.2 [M+H]. *H NMR (400 MHz, CD3OD) delta 9.09 (s, 1H), 7.69 (d, J = 4.8 Hz, 1H), 7.43 (t, J = 8.0 Hz, 1H), 7.30 (d, J = 4.8 Hz, 1H), 7.26-7.20 (m, 2H), 5.21-5.12 (m, 2H), 4.88-4.73 (m, 1H), 4.48-4.39 (m, 1H), 4.26-4.29 (m, 1H), 3.67-3.62 (m, 1H), 3.59-3.54 (m, 1H), 3.14-2.81 (m, 2H), 2.31-2.15 (m, 1H), 1.72-1.54 (m, 2H).

Reference： [1]Patent: WO2016/100349,2016,A2 .Location in patent: Paragraph 0239

41
N-(((3S,4R)-3-fluoropiperidin-4-yl)methyl)-[1,2,4]triazolo[4,3-a]pyrazin-5-amine dihydrochloride [ No CAS ]
[ 56456-49-6 ]
(3S,4R)-4-chloro-2-fluorobenzyl 4-(([1,2,4]triazolo[4,3-a]pyrazin-5-ylamino)methyl)-3-fluoropiperidine-1-carboxylate methanesulfonate [ No CAS ]

Reference： [1]Patent: WO2016/100349,2016,A2

42
4-chloro-2-fluorobenzoic acid methyl ester [ No CAS ]
[ 56456-49-6 ]

Yield	Reaction Conditions	Operation in experiment
82%	With lithium aluminium tetrahydride; In tetrahydrofuran; at 0℃; for 1h;Inert atmosphere;	Step 1: (4-chloro-2-fluorophenyl)methanol [0238] To a stirred suspension of LiAIH4 (110 mg, 2.88 mmol) in dried THF (10 mL) was added dropwise a solution of methyl 4-chloro-2-fluoromethylbenzoate (500 mg, 2.88 mmol) in dried THF (10 mL) at 0 C under N2 atmosphere. After stirring for 1 h, the mixture was quenched by addition of Na2S04 10H2O at 0 C. The mixture was stirred at r.t for30 min and subsequently filtered through celite. The filter pad was extracted with ethyl acetate, and the total filtrate was concentrated. The concentrate was purified by column chromatography over silica gel (Hex/EtOAc = 20/1) to afford the title compound as a yellow oil (378mg, 82%). *H NM (400 MHz, CDCI3) delta 7.38 (t, J = 8.0 Hz, 1H), 7.15 (dd, J = 8.0 and 2.0 Hz, 1H), 7.09 (dd, J = 10.0, 2.0 Hz, 1H), 4.73 (d, J = 6.0 Hz, 2H), 1.82 (t, J = 6.0 Hz, 1H).

Reference： [1]Patent: WO2016/100349,2016,A2 .Location in patent: Paragraph 0238

43
[ 1613412-22-8 ]
[ 56456-49-6 ]
[ 1613412-52-4 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 1490 - 1494

44
tert-butyl (S)-4-(3,6-difluoropyridin-2-yl)-2-methylpiperazine-1-carboxylate [ No CAS ]
[ 56456-49-6 ]
tert-butyl (S)-4-(6-((4-chloro-2-fluorobenzyl)oxy)-3-fluoropyridin-2-yl)-2-methylpiperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
47%		To a solution of <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong> (102 mg, 0.638 mmol) in DMF (2 mL) was added NaH (44.7 mg, 1.12 mmol, 60% in mineral oil). The yellow mixture was stirred at 30 C. for 15 min. Then a solution of tert-butyl (S)-4-(3,6-difluoropyridin-2-yl)-2-methylpiperazine-1-carboxylate (100 mg, 0.319 mmol) in DMF (2 mL) was added at RT. The reaction mixture was stirred at 90 C. for 18 h. The reaction mixture were poured into water (30 mL) and then extracted with EtOAc (330 mL). The combined organic extracts were washed with brine (320 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by Prep-TLC (EtOAc:PE 5:1) to give tert-butyl (S)-4-(6-((4-chloro-2-fluorobenzyl)oxy)-3-fluoropyridin-2-yl)-2-methylpiperazine-1-carboxylate (136 mg, 47%) as a colorless oil. LC-MS(ES+): 397.9 (M+H-tBu).

Reference： [1]Patent: US2018/170908,2018,A1 .Location in patent: Paragraph 0413

45
[ 2402-78-0 ]
[ 56456-49-6 ]
2-chloro-6-((4-chloro-2-fluorobenzyl)oxy)pyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%		To a solution of <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong> (15.0 g, 93.4 mmol) in DMF (250 mL) was added NaH (4.48 g, 112 mmol, 60% susp.) at 0 C. After stirring at 15 C. for 40 min, 2,6-dichloropyridine (16.6 g, 112 mmol) was added. The resulting mixture was stirred at 15 C. for 3 h. The mixture was poured into water (1 L) and extracted with EtOAc (2*200 mL). The combined organic layers were washed with sat. NH4Cl (500 mL), brine (500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (PE) to give 2-chloro-6-((4-chloro-2-fluorobenzyl)oxy)pyridine (19.2 g, 75%) as a solid. 1H NMR (CDCl3) delta 7.55 (t, 1H), 7.47 (t, 1H), 7.15 (t, 2H), 6.94 (d, 1H), 6.71 (d, 1H), 5.40 (s, 2H).

Reference： [1]Patent: US2018/170908,2018,A1 .Location in patent: Paragraph 0502

46
[ 3512-18-3 ]
[ 56456-49-6 ]
2-((4-chloro-2-fluorobenzyl)oxy)-3,6-difluoropyridine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With potassium carbonate; In 1-methyl-pyrrolidin-2-one; at 25 - 100℃; for 16h;	To a solution of 2,3,5-trifluoropyridine (1.5 g, 11 mmol) and <strong>[56456-49-6]4-chloro-2-fluorobenzyl alcohol</strong> (1.81 g, 11.3 mmol) in NMP (20 mL) was added K2CO3 (4.67 g, 33.8 mmol) at 25 C. and the mixture was stirred at 100 C. for 16 h. The mixture was poured into water (30 mL) and then extracted with EtOAc (350 mL). The combined organic extracts were washed with brine (340 mL), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by flash chromatography (0 to 5% EtOAc/PE gradient) to give 2-((4-chloro-2-fluorobenzyl)oxy)-3,6-difluoropyridine (2.45 g, 80%) as a colorless oil. 1H NMR (CDCl3) delta 7.41-7.54 (m, 2H), 7.11-7.20 (m, 2H), 6.47 (ddd, 1H), 5.44 (s, 2H).

Reference： [1]Patent: US2018/170908,2018,A1 .Location in patent: Paragraph 0409

47
tert-butyl 4-(6-chloropyridin-2-yl)piperidine-1-carboxylate [ No CAS ]
[ 56456-49-6 ]
tert-butyl 4-(6-((4-chloro-2-fluorobenzyl)oxy)pyridin-2-yl)piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
82%	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 100℃; for 16h;	A reaction vessel equipped with a reflux condenser was charged with Intermediate 2 (6.5 g, 22 mmol), <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (3.5 g, 22 mmol), Pd2(dba)3 (1.0 g, 1.1 mmol), BINAP (1.4 g, 2.2 mmol) and cesium carbonate (14 g, 44 mmol). Toluene (73 mL) was added and the mixture was heated to 100 C. After 16 h, the mixture was allowed to cool to RT, filtered through Celite with EtOAc (100 mL) and concentrated under reduced pressure. The crude material was purified using column chromatography eluting with 10% EtOAc in PE to obtain tert-butyl 4-(6-((4-chloro-2-fluorobenzyl)oxy)pyridin-2-yl)piperidine-1-carboxylate as a yellow oil (7.6 g, 82%). 1H NMR (CDCl3) delta: 7.51 (dd, 1H), 7.39-7.47 (m, 1H), 7.06-7.18 (m, 2H), 6.73 (d, 1H), 6.62 (d, 1H), 5.40 (s, 2H), 4.22 (br s, 2H), 2.83 (m, 2H), 2.73 (tt, 1H), 1.81-1.94 (m, 2H), 1.64-1.79 (m, 2H), 1.50 (s, 9H).

Reference： [1]Patent: US2018/170908,2018,A1 .Location in patent: Paragraph 0378

48
[ 56456-49-6 ]
tert-butyl (S)-4-(6-((4-chloro-2-fluorobenzyl)oxy)-5-fluoropyridin-2-yl)-2-methylpiperazine-1-carboxylate [ No CAS ]

Reference： [1]Patent: US2018/170908,2018,A1

49
[ 56456-49-6 ]
(S)-1-(6-((4-chloro-2-fluorobenzyl)oxy)-5-fluoropyridin-2-yl)-2-methylpiperazine hydrochloride [ No CAS ]

Reference： [1]Patent: US2018/170908,2018,A1

50
[ 2402-78-0 ]
[ 56456-49-6 ]
methyl 2-((4-(6-((4-chloro-2-fluorobenzyl)oxy)pyridin-2-yl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-(2-methoxyethyl)-1H-benzo[d]imidazole-6-carboxylic acid [ No CAS ]
methyl 2-((4-(6-((4-chloro-2-fluorobenzyl)oxy)pyridin-2-yl)-2-(trifluoromethyl)piperazin-1-yl)methyl)-1-(2-methoxyethyl)-1H-benzo[d]imidazole-6-carboxylic acid [ No CAS ]

Reference： [1]Patent: US2018/170908,2018,A1

51
[ 1349184-43-5 ]
[ 56456-49-6 ]
tert-butyl 4-{3-[(4-chloro-2-fluorobenzyl)oxy]pyrazin-2-yl}piperidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With palladium diacetate; caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In 1,4-dioxane; at 90℃; for 18h;Inert atmosphere;	Palladium(ll) acetate (271 mg, 1 .21 mmol), 1 ,T-binaphthalene-2,2'- diylbis(diphenylphosphane) (BINAP; 1 .51 g, 2.42 mmol), and cesium carbonate (13.1 mg, 40.3 mmol) were added to a solution of C7 (6.00 g, 20.1 mmol) and <strong>[56456-49-6](4-chloro-2-fluorophenyl)methanol</strong> (3.56 g, 22.2 mmol) in 1 ,4-dioxane (60 ml_). Nitrogen was bubbled through the suspension, after which the reaction mixture was stirred at 90 C for 18 hours and filtered. The filtrate was concentrated in vacuo and purified using chromatography on silica gel (Gradient: 3% to 20% EtOAc in petroleum ether) to afford C8 as a yellow gum. Yield: 7.96 g, 18.9 mmol, 94%.

Reference： [1]Patent: WO2019/239371,2019,A1 .Location in patent: Page/Page column 53

52
[ 36178-05-9 ]
[ 56456-49-6 ]
3-bromo-2-[(4-chloro-2-fluorobenzyl)oxy]pyridine [ No CAS ]