[ CAS No. 607742-69-8 ] {[proInfo.proName]}

Name: 607742-69-8|3-(Phenylsulfonyl)-8-(piperazin-1-yl)quinoline|98+%
Brand: Ambeed
SKU: A879799
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Quality Control of [ 607742-69-8 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 607742-69-8 ]

SDS Specification

Alternatived Products of [ 607742-69-8 ]

Product Details of [ 607742-69-8 ]

CAS No. :	607742-69-8	MDL No. :	MFCD12828872
Formula :	C₁₉H₁₉N₃O₂S	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	JJZFWROHYSMCMU-UHFFFAOYSA-N
M.W :	353.44	Pubchem ID :	11256720
Synonyms :	SB-742457;GSK-742457;RVT101. intepirdine.;RVT-101	Chemical Name :	3-(Phenylsulfonyl)-8-(piperazin-1-yl)quinoline

Calculated chemistry of [ 607742-69-8 ]

Physicochemical Properties

Num. heavy atoms :	25
Num. arom. heavy atoms :	16
Fraction Csp3 :	0.21
Num. rotatable bonds :	3
Num. H-bond acceptors :	4.0
Num. H-bond donors :	1.0
Molar Refractivity :	105.04
TPSA :	70.68 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	Yes
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	Yes
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.72 cm/s

Lipophilicity

Log Po/w (iLOGP) :	2.72
Log Po/w (XLOGP3) :	2.45
Log Po/w (WLOGP) :	2.8
Log Po/w (MLOGP) :	2.22
Log Po/w (SILICOS-IT) :	2.37
Consensus Log Po/w :	2.51

Druglikeness

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

Water Solubility

Log S (ESOL) :	-3.85
Solubility :	0.0499 mg/ml ; 0.000141 mol/l
Class :	Soluble
Log S (Ali) :	-3.58
Solubility :	0.0934 mg/ml ; 0.000264 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-6.6
Solubility :	0.0000892 mg/ml ; 0.000000252 mol/l
Class :	Poorly soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	0.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.98

Safety of [ 607742-69-8 ]

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 [ 607742-69-8 ]

* 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 [ 607742-69-8 ]
Downstream synthetic route of [ 607742-69-8 ]

[ 607742-69-8 ] Synthesis Path-Upstream 1~7

1
[ 110-85-0 ]
[ 607743-09-9 ]
[ 607742-69-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium t-butanolate In 1,4-dioxane at 40℃; for 16.5 h;	A 100 mi three necked flask was charged with Pd2 (dba) 3 (174 mg, 0.19 mmol, 0.03eq), 8-lodo-3-phenylsulfonylquinoline (D4) (2.5g, 6.33 mmol), 1,1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 mmol), sodium tetibutoxide (851 mg, 8.86 mmol, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1,4-dioxane (17.5 ml, 7vol) was added. The mixture was stirred and heated to 40°C for 16 Y2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ml) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2x12. 5 ml). The combined aqueous layers were washed with (dichloromethane 2.5 ml) then transferred to a conical flask, dichloromethane (12.5 ml) was added and the flask was cooled in an ice/water bath. 1 ohm Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with dichloromethane (7.5 ml), the combined organic layers were concentrated under reduce pressure to.-5 mi. Isooctane (2.5 mi) was added to the dark brown solution resulting in crystallisation, the mixture was stirred at room temp for 5 min then isooctane (22.5 ml) was added over 5 min. The mixture was aged at room temp for 11/2 hrs before being cooled in an ice/water bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ml). The cake was dried under reduced pressure to give the title compound D5; yield 1.67g, 75percent. No.H (CDCl3) : 1.6 (1H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9.21 (1H, d).
75%	With sodium t-butanolate In 1,4-dioxane at 40℃; for 16.5 h;	A 100 ml three necked flask was charged with Pd2 (dba) 3 (174 mg, 0. 19 mmol, 0.03eq), 8-iodo-3-phenylsulfonyfquinoline (D6) (2.5g, 6.33 MMOL), 1,1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 MMOL), sodium TERTBUTOXIDE (851 mg, 8.86 MMOL, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1,4-dioxane (17. 5 MI, 7VOL) was added. The mixture was stirred and heated to 40°C for 16 1/2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ML) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2X12. 5 ml), The combined aqueous layers were washed with (DICHLOROMETHANE 2, 5 ml) then transferred to a conical flask, dichloromethane (12.5 ML) was added and the flask was cooled in an ice/water bath. 10M Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with DICHLOROMETHANE (7.5 ml), the combined organic layers were concentrated under reduce pressure TO-5 ML. ISOOCTANE (2.5 ML) was added to the dark brown solution resulting in CRYSTALLISATION, the mixture was stirred at room temp for 5 min then isooctane (22.5 ML) was added over 5 min. The mixture was aged at room temp for 15/2 hrs before being cooled in an ICE/WATER bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ML). The cake was dried under reduced pressure to give the title compound (D12) YIELD 1.67g, 75percent. RECRYSTALLISATION from isopropanol (12 vols) gives material of mp 164°C in 80percent recovery; 8H (CDC) G) : 1. 6 (1 H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9. 21 (1H, d).

Reference： [1] Patent: WO2005/40124, 2005, A1, . Location in patent: Page/Page column 6-7
[2] Patent: WO2005/26125, 2005, A1, . Location in patent: Page/Page column 21-22

2
[ 110-85-0 ]
[ 866782-60-7 ]
[ 607742-69-8 ]

Yield	Reaction Conditions	Operation in experiment
82.8%	With potassium carbonate In propan-1-ol at 100℃; for 17.25 - 23 h;	Example 3aPreparation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline EPO <DP n="16"/>A flask was charged with 8-fluoro-3-phenylsulfonylquinoline (50.00 g, 174.03 mmol, 1.00 wt, 1.00 eq), piperazine (74.95g, 870.14mmol, 1.50wt, 5.00 eq), potassium carbonate (24.05 g, 174.03 mmol, 0.48 wt, 1.00 eq) and n-propanol (100 ml, 2 vol). The mixture was stirred and heated under nitrogen at circa 1000C. After 17.25 h water (400 ml, 8 vol) was added over 1.25 h at 93-980C. The slurry was allowed to cool to ambient temperature. After 1.5 h the product was collected by vacuum filtration. The bed was washed with 4:1 water / n-propanol (2 x 100 ml, 2 x 2 vol) and water (2 x 100 ml, 2 x 2 vol). The bed was briefly pulled dry and then the product was dried in vacuo at 50-550C to give the title compound, 50.92 g, 82.8percent yield. 1H NMR1 CDCI3, 400 MHz3.17ppm (4H, t, J 4.5 Hz), 3.34 ppm (4H, t, J 4.5 Hz), 7.27 ppm (1 H, dd, J 2.0 7.0 Hz), 7.49-7.60 ppm (5H, m), 8.00-8.02 ppm (2H, m), 8.76 ppm (1H, d, J 2.5 Hz), 9.22 ppm (1H1 d, J 2.5 Hz).; Example 3bPreparation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline Form IIIA vessel was charged with 8-fluoro-3-phenylsulfonylquinoline (20.0 g, 1.00 wt, 1.00 eq), piperazine (30.0 g, 1.50 wt, 5.00 eq), potassium carbonate (9.60 g, 0.48 wt, 1.00 eq) and n-propanol (40 ml, 2 vol). The mixture was stirred and heated under nitrogen at 100°C. After 23 h the reaction mixture was cooled to 95°C and seeded with Form III 3- phenylsulfonyl-8-piperazin-1-yl-quinoline (20 mg, 0.001 wt, 0.001 eq) slurried in n- propanol (2 x 0.1 ml, 2 x 0.005 vol). (See WO 05/040124 for a process for making EPO <DP n="17"/>Form III 3-phenylsulfonyl-8-piperazin-1-yl-quinoline). The reaction mixture was aged at 950C for 15 min then cooled to 3O0C over 1 hr. Water (160 ml, 8 vol) was added over 1 hr maintaining contents at 30-340C. The slurry was aged at 3O0C for 16 hrs then the product was collected by vacuum filtration. The bed was washed with 4:1 water / n- propanol (2 x 40 ml, 2 x 2 vol) and pulled dry. The product was dried in vacuo at 5O0C to give the title compound, 21.25 g, 86percent yield. 1H NMR, CDCI3, 400 MHz3.17ppm (4H, t, J 4.5 Hz), 3.34 ppm (4H, t, J 4.5 Hz), 7.27 ppm (1H, dd, J 2.0 7.0 Hz), 7.49-7.60 ppm (5H, m), 8.00-8.02 ppm (2H, m), 8.76 ppm (1 H, d, J 2.5 Hz), 9.22 ppm (1 H, d, J 2.5 Hz).

Reference： [1] Journal of Organic Chemistry, 2018, vol. 83, # 12, p. 6589 - 6599
[2] Patent: WO2007/39238, 2007, A1, . Location in patent: Page/Page column 14-16

3
[ 110-85-0 ]
[ 1429304-29-9 ]
[ 607742-69-8 ]

Reference： [1] Angewandte Chemie - International Edition, 2013, vol. 52, # 48, p. 12679 - 12683[2] Angew. Chem., 2013, vol. 125, # 48, p. 12911 - 12915,5

4
[ 847727-21-3 ]
[ 607742-69-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 9, p. 3884 - 3890

5
[ 1429304-29-9 ]
[ 607742-69-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 9, p. 3884 - 3890

6
[ 611-33-6 ]
[ 607742-69-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 9, p. 3884 - 3890

7
[ 607743-10-2 ]
[ 607742-69-8 ]

Reference： [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 9, p. 3884 - 3890

[ 607742-69-8 ] Synthesis Path-Downstream 1~13

Yield	Reaction Conditions	Operation in experiment
	Purification / work up;	Example 1; Crystallisation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline (Form lil); 3-Phenylsulfonyl-8-piperazin-1-yl-quinoline (D5) (5g) was dissolved in isopropanol (60ml) with warming to reflux. The resultant solution was then treated with charcoal (1.25g), filtered, then the solution was allowed to cool to ambient, crystallisation initiating at ~60C. The product was collected by filtration, washed with isopropanol (1 Oml ; ) and dried in vacuo at 45C to give the title compound, 3.1g, 62%. Melting point 188C.; Example 2; Crystallisation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline (Form lil) (Alternative Procedure); 3-Phenylsulfonyl-8-piperazin-1-yl-quinoline (D5) (10g) was dissolved in ethanol (80ml) with warming to 70C. The resultant solution was then treated with charcoal (1g), filtered, and the filter bed rinsed with ethanol (20moi). The combined filtrate was adjusted to 54C, then cooled to 50 C over 15 minutes. The solution was seeded with 3- phenylsulfonyl-8-piperazin-1-yl-quinoline (Form iii) (10mg), cooled to 35C over 30 minutes, held for 1 hour, then cooled to 20 C over 30 minutes, and stirred for a further 1 hour 15 minutes. The product was collected by filtration, washed with cold ethanol, (2 x 10ml ; ) and dried in vacuo at 40C to give the title compound, 6.64g, 66.4%. Melting point 188C. Example 3; Crystallisation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline (Form Ht) (Alternative Procedure); 3-Phenylsulfonyl-8-piperazin-1-yl-quinoline (D5) (10g) was dissolved in ethanol (80mut) with warming to 72C. The resultant solution was then pumped through a Cuno R55SP filter into a second vessel (pre-heated to 55C) via a sinter funnel. The original flask and the Cuno filter were washed with ethanol (20ml). The combined filtrate was heated to 72C to redissolve the material, then adjusted to 50C. The solution was seeded with 3- phenylsulfonyl-8-piperazin-1-yl-quinoline (Form III) (10mg), cooled to 35C over 30 minutes, held for 1 hour, then cooled to 20C over 30 minutes, and stirred for a further 48 hours. The product was collected by filtration, washed with ethanol (20ml) and dried in vacuo at 50C to give the title compound, 5.64g, 56.4%. Melting point 188C.

2
[ 110-85-0 ]
[ 607743-09-9 ]
[ 607742-69-8 ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium t-butanolate;1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 40℃; for 16.5h;	A 100 mi three necked flask was charged with Pd2 (dba) 3 (174 mg, 0.19 mmol, 0.03eq), 8-lodo-3-phenylsulfonylquinoline (D4) (2.5g, 6.33 mmol), 1,1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 mmol), sodium tetibutoxide (851 mg, 8.86 mmol, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1,4-dioxane (17.5 ml, 7vol) was added. The mixture was stirred and heated to 40C for 16 Y2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ml) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2x12. 5 ml). The combined aqueous layers were washed with (dichloromethane 2.5 ml) then transferred to a conical flask, dichloromethane (12.5 ml) was added and the flask was cooled in an ice/water bath. 1 ohm Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with dichloromethane (7.5 ml), the combined organic layers were concentrated under reduce pressure to.-5 mi. Isooctane (2.5 mi) was added to the dark brown solution resulting in crystallisation, the mixture was stirred at room temp for 5 min then isooctane (22.5 ml) was added over 5 min. The mixture was aged at room temp for 11/2 hrs before being cooled in an ice/water bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ml). The cake was dried under reduced pressure to give the title compound D5; yield 1.67g, 75%. No.H (CDCl3) : 1.6 (1H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9.21 (1H, d).
75%	With sodium t-butanolate;1,1'-bis-(diphenylphosphino)ferrocene; tris-(dibenzylideneacetone)dipalladium(0); In 1,4-dioxane; at 40℃; for 16.5h;	A 100 ml three necked flask was charged with Pd2 (dba) 3 (174 mg, 0. 19 mmol, 0.03eq), 8-iodo-3-phenylsulfonyfquinoline (D6) (2.5g, 6.33 MMOL), 1,1'-bis- diphenylphosphenoferrocene (316 mg, 0.57 MMOL), sodium TERTBUTOXIDE (851 mg, 8.86 MMOL, 1.4eq) and piperazine (2.72g, 31.6 mmol, 5eq). The flask was evacuated and filled with nitrogen 4 times then anhydrous 1,4-dioxane (17. 5 MI, 7VOL) was added. The mixture was stirred and heated to 40C for 16 1/2 hrs. The dark solution was allowed to cool to room temperature, dichloromethane (12.5 ML) was added and the solution was washed with H20 (12.5 ml). The aqueous wash was extracted with dichloromethane and the combined organic layers were extracted with 5M HCI (2X12. 5 ml), The combined aqueous layers were washed with (DICHLOROMETHANE 2, 5 ml) then transferred to a conical flask, dichloromethane (12.5 ML) was added and the flask was cooled in an ice/water bath. 10M Aqueous sodium hydroxide (13 ml) was added whilst stirring, the mixture was then stirred at room temperature until all the solids were dissolved. The lower organic layer was removed and the aqueous layer was extracted with DICHLOROMETHANE (7.5 ml), the combined organic layers were concentrated under reduce pressure TO-5 ML. ISOOCTANE (2.5 ML) was added to the dark brown solution resulting in CRYSTALLISATION, the mixture was stirred at room temp for 5 min then isooctane (22.5 ML) was added over 5 min. The mixture was aged at room temp for 15/2 hrs before being cooled in an ICE/WATER bath for 30 min, the mixture was filtered and the cake washed with isooctane (5 ML). The cake was dried under reduced pressure to give the title compound (D12) YIELD 1.67g, 75%. RECRYSTALLISATION from isopropanol (12 vols) gives material of mp 164C in 80% recovery; 8H (CDC) G) : 1. 6 (1 H, bs), 3.18 (4H, m), 3.34 (4H, m), 7.27 (1H, m), 7.49-7. 60 (5H, m), 8.01 (2H, dd), 8.75, (1H, d), 9. 21 (1H, d).

Reference： [1]Patent: WO2005/40124,2005,A1 .Location in patent: Page/Page column 6-7
[2]Patent: WO2005/26125,2005,A1 .Location in patent: Page/Page column 21-22

3
[ 607742-69-8 ]
[ 421-06-7 ]
8-(4-(2,2,2-trifluoroethyl)-piperazin-1-yl)-3-phenylsulfonylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In tetrahydrofuran; at 100℃; for 96h;	A solution of 3-PHENYLSULFONYL-8-PIPERAZIN-1-YL-QUINOLINE (D12) (200 mg, 0.55 MMOL) in dry THF (2 ML) was treated with sodium hydride (24mg, 0.6 mmol, 60% oil dispersion), and 1-BROM-2, 2, 2-trifluoroethane (815 mg, 5 MMOL). The mixture was heated to 100 C for 4 days then cooled, evaporated and the residue subjected to purification by flash chromatography on silica gel (eluting with dichloromethane-methanol-aq. NH3) to give the free base form of the title compound. This was treated with 1 M HCI in ether then crystallised from isopropanol to give the title compound (E8) as a yellow solid : Mass Spectrum: C21H20F3N302S requires 435; found 436 (MH+).

Reference： [1]Patent: WO2005/26125,2005,A1 .Location in patent: Page/Page column 25

4
[ 607742-69-8 ]
[ 459-57-4 ]
8-(4-(4-fluorobenzyl)-piperazin-1-yl)-3-phenylsulfonylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid; In ethanol; at 20℃; for 18h;	Example 1 8- (4- (4-FLUOROBENZYL)-PIPERAZIN-1-YL)-3-PHENYLSUTFONYLQUINOLINE HYDROCHLORIDE (E1) A suspension of <strong>[607742-69-8]3-phenylsulfonyl-8-piperazin-1-yl-quinoline</strong> (D12) (200 mg, 0.55 MMOL) in ethanol (4 ml) was treated successively with acetic acid (100P1), 4-FLUOROBENZALDEHYDE (124 mg, 1 MMOL) and RESIN BOUND AMBERLYST CYANOBOROHYDRIDE (~3 MMOL/G, 0.5g). The mixture was stirred at ambient temperature for 18 hours then filtered and the filtrate absorbed onto an SCX cartridge. This was washed with ethanol then eluted with a solution of 3% ammonia in 7% aqueous methanol. The solution was evaporated and the residue subjected to purification by flash chromatography on silica gel (eluting with dichloromethane-methanol-aq. NH3) to give the free base of the title compound: 6H (CDCl3) : 2.73-2. 77 (4H, m), 3.40 (4H, br. s), 3.59 (2H, s), 7.02 (2H, t), 7.23-7. 36 (3H, m), 7.47-7. 47 (5H, m), 8.01 (2H, dd), 8.75 (1 H, d), 9.20 (1h, d). This was treated with 1 M HCI in ether then CRYSTALLISED from isopropanol to give the title compound (E1) as a yellow solid : Mass Spectrum: C26H24FN3O2S requires 461 ; found 462 (MH+).

Reference： [1]Patent: WO2005/26125,2005,A1 .Location in patent: Page/Page column 22-23

5
[ 110-85-0 ]
[ 866782-60-7 ]
[ 607742-69-8 ]

Yield	Reaction Conditions	Operation in experiment
82.8%	With potassium carbonate; In propan-1-ol; at 100℃; for 17.25 - 23h;Product distribution / selectivity;	Example 3aPreparation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline EPO <DP n="16"/>A flask was charged with 8-fluoro-3-phenylsulfonylquinoline (50.00 g, 174.03 mmol, 1.00 wt, 1.00 eq), piperazine (74.95g, 870.14mmol, 1.50wt, 5.00 eq), potassium carbonate (24.05 g, 174.03 mmol, 0.48 wt, 1.00 eq) and n-propanol (100 ml, 2 vol). The mixture was stirred and heated under nitrogen at circa 1000C. After 17.25 h water (400 ml, 8 vol) was added over 1.25 h at 93-980C. The slurry was allowed to cool to ambient temperature. After 1.5 h the product was collected by vacuum filtration. The bed was washed with 4:1 water / n-propanol (2 x 100 ml, 2 x 2 vol) and water (2 x 100 ml, 2 x 2 vol). The bed was briefly pulled dry and then the product was dried in vacuo at 50-550C to give the title compound, 50.92 g, 82.8% yield. 1H NMR1 CDCI3, 400 MHz3.17ppm (4H, t, J 4.5 Hz), 3.34 ppm (4H, t, J 4.5 Hz), 7.27 ppm (1 H, dd, J 2.0 & 7.0 Hz), 7.49-7.60 ppm (5H, m), 8.00-8.02 ppm (2H, m), 8.76 ppm (1H, d, J 2.5 Hz), 9.22 ppm (1H1 d, J 2.5 Hz).; Example 3bPreparation of 3-phenylsulfonyl-8-piperazin-1-yl-quinoline Form IIIA vessel was charged with 8-fluoro-3-phenylsulfonylquinoline (20.0 g, 1.00 wt, 1.00 eq), piperazine (30.0 g, 1.50 wt, 5.00 eq), potassium carbonate (9.60 g, 0.48 wt, 1.00 eq) and n-propanol (40 ml, 2 vol). The mixture was stirred and heated under nitrogen at 100C. After 23 h the reaction mixture was cooled to 95C and seeded with Form III 3- phenylsulfonyl-8-piperazin-1-yl-quinoline (20 mg, 0.001 wt, 0.001 eq) slurried in n- propanol (2 x 0.1 ml, 2 x 0.005 vol). (See WO 05/040124 for a process for making EPO <DP n="17"/>Form III 3-phenylsulfonyl-8-piperazin-1-yl-quinoline). The reaction mixture was aged at 950C for 15 min then cooled to 3O0C over 1 hr. Water (160 ml, 8 vol) was added over 1 hr maintaining contents at 30-340C. The slurry was aged at 3O0C for 16 hrs then the product was collected by vacuum filtration. The bed was washed with 4:1 water / n- propanol (2 x 40 ml, 2 x 2 vol) and pulled dry. The product was dried in vacuo at 5O0C to give the title compound, 21.25 g, 86% yield. 1H NMR, CDCI3, 400 MHz3.17ppm (4H, t, J 4.5 Hz), 3.34 ppm (4H, t, J 4.5 Hz), 7.27 ppm (1H, dd, J 2.0 & 7.0 Hz), 7.49-7.60 ppm (5H, m), 8.00-8.02 ppm (2H, m), 8.76 ppm (1 H, d, J 2.5 Hz), 9.22 ppm (1 H, d, J 2.5 Hz).

Reference： [1]Journal of Organic Chemistry,2018,vol. 83,p. 6589 - 6599
[2]Patent: WO2007/39238,2007,A1 .Location in patent: Page/Page column 14-16

6
[ 110-85-0 ]
[ 1429304-29-9 ]
[ 607742-69-8 ]

Reference： [1]Angewandte Chemie - International Edition,2013,vol. 52,p. 12679 - 12683
Angew. Chem.,2013,vol. 125,p. 12911 - 12915,5

7
[ 607742-69-8 ]
[ 54245-42-0 ]
[ 1578264-76-2 ]

Yield	Reaction Conditions	Operation in experiment
	In acetonitrile; at 20℃;	The precursor is <strong>[607742-69-8]3-phenylsulfonyl-8-(piperazin-1-yl)quinoline</strong> (C19H19N3O2S; MW: 353.4) and is known and publically disclosed compound. The precursor was dissolved in acetonitrile and transferred to a BioScan Autoloop System and reacted with [11C]-Iodomethane prepared as follows. 11CO2 prepared from bombardment of high purity nitrogen gas containing 0.5 to 1.0% oxygen with accelerated protons was reacted with hydrogen on a molecular sieve:nickel catalyst column at 380 C. to produce 11CH4, which was reacted with iodine vapor heated to 740 C. to form 11CH3I. [11C]-Iodomethane was swept through a furnace containing silver triflate to convert the radiolabeled iodomethane to [11C]-methyl triflate. [11C]-methyl triflate was swept into the loop methylation system using helium gas at a flow rate of about 20 mL/min at ambient temperature. The accumulation of [11C]-radioactivity in the loop was monitored with a local radiation monitor until the radioactivity reaches a plateau. The reaction mixture in the loop was allowed to remain at room temperature for 4.5 minutes. Crude [11C]LuPET was purified by preparative high-pressure liquid chromatography (HPLC) using Waters XBridge Prep OBD C18 10 mum 10×150 mm column with 30% acetonitrile: 70% aqueous buffer (57 mM TEA adjusted to pH 7.2 with o-phosphoric acid) using a 10 mL/min flow rate. The [11C]LuPET fraction as determined with an in-line radiometric detector was collected in a reservoir of water. The reservoir was pressurized to load the [11C]LuPET onto the C18 Sep-Pak. The C18 Sep-Pak was then washed with 10 mL 0.9% Sodium Chloride for Injection. The [11C]LuPET is eluted from the C18 Sep-Pak with 1 mL of Ethanol followed by 10 mL of 0.9% Sodium Chloride Injection, through a sterilizing 0.22mu filter in a sterile, pyrogen-free vial that has been preloaded with 4 mL Sodium Chloride Injection.

Reference： [1]Patent: US2014/73681,2014,A1 .Location in patent: Paragraph 0111

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[ 847727-21-3 ]
[ 607742-69-8 ]