Name: 36823-82-2|4-Isopropoxybenzoyl chloride|95%
Brand: Ambeed
SKU: A141535
Rating: 92 (26 reviews)

1
[ 19748-66-4 ]
[ 36823-82-2 ]
4-isopropoxy-benzoic acid-(3-pyrrolidino-propyl ester) [ No CAS ]

Reference： [1]Patent: US2605266,1949,

2
[ 101258-96-2 ]
[ 36823-82-2 ]
4-isopropoxy-benzoic acid-(β-pyrrolidino-isobutyl ester) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzene

Reference： [1]Current Patent Assignee: PFIZER INC - US2605266, 1949, A

3
[ 158261-95-1 ]
[ 36823-82-2 ]
4-isopropoxy-benzoic acid-(3-pyrrolidino-butyl ester) [ No CAS ]

Reference： [1]Patent: US2605266,1949,A

4
[ 13205-46-4 ]
[ 36823-82-2 ]

Yield	Reaction Conditions	Operation in experiment
94%	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 3h;	1D Specifically, to a stirred mixture of 4-isopropoxy-benzoic acid (10.0 g, 55.5 mmol) and DMF (1 drop) in methylene chloride (80 mL) was added dropwise over a period of 15 min a solution of oxalyl chloride (7.40 g, 58.2 mmol) in methylene chloride (20 mL). After stirring for 2.45 h at ambient temperature the reaction mixture was concentrated, taken up into a small amount of methylene chloride, filtered to remove insolubles and again concentrated to afford 8 (10.38 g, 94%) as a yellow liquid: 1H NMR (300 MHz, CDCI3) δ 8.05 (d, 2H), 6.94 (d, 2H), 4.68 (m, 1H)1 1.44 (d, 6H).
	With thionyl chloride
	With phosphorus(V) chloride

	With thionyl chloride In benzene for 11h; Heating;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 0.666667h;
	With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 1h;
	With oxalyl dichloride; N,N-dimethyl-formamide at 20℃; for 1h;
	With thionyl chloride Reflux;	5.1.18. General procedure 2 for preparation of 64-81, 83-91 General procedure: To a solution of organic acids (1.1 eq) in SOCl2, the reaction wasstirred at reflux, then finished, SOCl2 was removed and 5 mL THFwas added and dropwise to compound 26 (1.0 eq). Mixture wasstirred at r.t overnight. Then solvent was removed, H2O and ethylacetate was added, organic layer was dried by anhydrous Na2SO4and concentrated. Next, to a solution of compounds gained above inethyl acetate, HCl gas was added for 0.5 h, filtered the solid to affordproducts.
	With thionyl chloride at 0℃; for 24h; Reflux;	8.1.2.2. Method B, synthesis of amide bond using thionyl chloride. General procedure: The appropriate carboxylic acid (1 eq.) was cooled to 0 C and then thionyl chloride (2 eq.) was added dropwise. The mixture was thenheated under reflux for 2 h, and the excess of thionyl chloride wasevaporated under vacuum. The acid chloride was dissolved in dryTHF and added dropwise to a solution of the appropriate amine (0.9eq.) and DIPEA (3 eq.) in THF. After completion, the reactionmixture was diluted with ethyl acetate and washed with a saturatedaqueous solution of ammonium chloride and brine. Theorganic layerwas dried over anhydrous sodium sulfate, filtered, andconcentrated in vacuo. The residue was purified using columnchromatography (chloroform/methanol as eluents). The yieldswere around 50-70%.
	With sulfuryl dichloride Reflux;
	With thionyl chloride Reflux;

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 142
[2]Rohmann; Scheurle [Archiv der Pharmazie, 1936, vol. 274, p. 110,123]
[3]Pierce; Salsbury; Fredericksen [Journal of the American Chemical Society, 1942, vol. 64, p. 1691,1692]
[4]Muchowski; Unger; Ackrell; Cheung; Cooper; Cook; Gallegra; Halpern; Koehler; Kluge [Journal of Medicinal Chemistry, 1985, vol. 28, # 8, p. 1037 - 1049]
[5]Herron, David K.; Goodson Jr., Theodore; Wiley, Michael R.; Weir, Leonard C.; Kyle, Jeffrey A.; Yee, Ying K.; Tebbe, Ann Louise; Tinsley, Jennifer M.; Mendel, David; Masters, John J.; Franciskovich, Jeffry B.; Sawyer, J. Scott; Beight, Douglas W.; Ratz, Andrew M.; Milot, Guy; Hall, Steven E.; Klimkowski, Valentine J.; Wikel, James H.; Eastwood, Brian J.; Towner, Richard D.; Gifford-Moore, Donetta S.; Craft, Trelia J.; Smith, Gerald F. [Journal of Medicinal Chemistry, 2000, vol. 43, # 5, p. 859 - 872]
[6]Demont, Emmanuel H.; Andrews, Benjamin I.; Bit, Rino A.; Campbell, Colin A.; Cooke, Jason W. B.; Deeks, Nigel; Desai, Sapna; Dowell, Simon J.; Gaskin, Pam; Gray, James R. J.; Haynes, Andrea; Holmes, Duncan S.; Kumar, Umesh; Morse, Mary A.; Osborne, Greg J.; Panchal, Terry; Patel, Bela; Perboni, Alcide; Taylor, Simon; Watson, Robert; Witherington, Jason; Willis, Robert [ACS Medicinal Chemistry Letters, 2011, vol. 2, # 6, p. 444 - 449]
[7]Marighetti, Federico; Steggemann, Kerstin; Hanl, Markus; Wiese, Michael [ChemMedChem, 2013, vol. 8, # 1, p. 125 - 135]
[8]Li, Zezhong; Xin, Weixiang; Wang, Qing; Zhu, Mingyan; Zhou, Huchen [European Journal of Medicinal Chemistry, 2021, vol. 217]
[9]Darwish, Salma; Erdmann, Frank; Ghazy, Ehab; Heimburg, Tino; Jung, Manfred; Lancelot, Julien; Pierce, Raymond; Robaa, Dina; Romier, Christophe; Schmidt, Matthias; Schmidtkunz, Karin; Shaik, Tajith B.; Simoben, Conrad V.; Sippl, Wolfgang; Truhn, Anne; Zeyen, Patrik [European Journal of Medicinal Chemistry, 2021, vol. 225]
[10]Fathalla, Walid; Pazdera, Pavel; Khalifa, Mohamed E.; Ali, Ibrahim A. I.; El Rayes, Samir M. [Journal of Heterocyclic Chemistry, 2022, vol. 59, # 5, p. 933 - 942]
[11]Banoglu, Erden; Ercanlı, Taner; Gür Maz, Tuğçe; Vullo, Daniela; Bonardi, Alessandro; Gratteri, Paola; Supuran, Claudiu T. [ChemMedChem, 2022, vol. 17, # 10]

5
[ 59275-72-8 ]
[ 36823-82-2 ]
[ 113628-62-9 ]

Yield	Reaction Conditions	Operation in experiment
70%	With triethylamine In 1,4-dioxane for 5h; Heating;

Reference： [1]Tarzia, Giorgio; Occelli, Emilio; Toja, Emilio; Barone, Domenico; Corsico, Nerina; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 6, p. 1115 - 1123]

6
[ 36823-82-2 ]
[ 94-09-7 ]
[ 109632-83-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	In 1,4-dioxane at 10℃; for 1h;

Reference： [1]Habib; Issa; Rida; Ashour; Tawil [Pharmazie, 1986, vol. 41, # 11, p. 761 - 764]

7
[ 6052-84-2 ]
[ 36823-82-2 ]
C₃₄H₃₄O₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With pyridine at 0℃; for 7h;

Reference： [1]Kusserow, Joachim; Boberg, Friedrich [Journal fur Praktische Chemie - Chemiker-Zeitung, 1994, vol. 336, # 7, p. 613 - 616]

8
[ 36823-82-2 ]
[ 103517-57-3 ]
N₁-(4-Methoxybenzoyl)-N₂-[4-(1-methylethoxy)benzoyl]-1,2-benzenediamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 0 - 20℃; for 16h;

Reference： [1]Herron, David K.; Goodson Jr., Theodore; Wiley, Michael R.; Weir, Leonard C.; Kyle, Jeffrey A.; Yee, Ying K.; Tebbe, Ann Louise; Tinsley, Jennifer M.; Mendel, David; Masters, John J.; Franciskovich, Jeffry B.; Sawyer, J. Scott; Beight, Douglas W.; Ratz, Andrew M.; Milot, Guy; Hall, Steven E.; Klimkowski, Valentine J.; Wikel, James H.; Eastwood, Brian J.; Towner, Richard D.; Gifford-Moore, Donetta S.; Craft, Trelia J.; Smith, Gerald F. [Journal of Medicinal Chemistry, 2000, vol. 43, # 5, p. 859 - 872]

9
[ 36823-82-2 ]
[ 221876-01-3 ]
C₂₆H₂₉N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In dichloromethane at 20℃;

Reference： [1]Brown, Dearg S.; Belfield, Andrew J.; Brown, George R.; Campbell, Douglas; Foubister, Alan; Masters, David J.; Pike, Kurt G.; Snelson, Wendy L.; Wells, Stuart L. [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 21, p. 5383 - 5387]

10
[ 36823-82-2 ]
[ 113628-71-0 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 70 percent / Et₃N / dioxane / 5 h / Heating 2: 79 percent / KI, HCl / ethanol / 8 h / 100 °C

Reference： [1]Tarzia, Giorgio; Occelli, Emilio; Toja, Emilio; Barone, Domenico; Corsico, Nerina; et al. [Journal of Medicinal Chemistry, 1988, vol. 31, # 6, p. 1115 - 1123]

11
3-amino-6-(4-butylphenyl)-1-(3-chlorobenzyl)indole-2-carboxylic acid ethyl ester [ No CAS ]
[ 36823-82-2 ]
6-(4-butylphenyl)-1-(3-chlorobenzyl)-3-(4-isopropoxybenzoylamino)indole-2-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With dmap; triethylamine In acetonitrile at 20 - 120℃; for 18.4167h;	131.a Example 131 6-(4-Butylphenyl)-1-(3-chlorobenzyl)-3-(4-isopropoxybenzoylamino)- INDOLE-2-CARBOXYLIC acid (a) 6- (4-BUTYLPHENYL)-I- (3-CHLOROBENZVL)-3- (4-ISOPROPOXYBENZOYLAMINO)- INDOLE-2-CARBOXYLIC acid ethyl ester A mixture of 3-AMINO-6-(4-BUTYLPHENYL)-1-(3-CHLOROBENZYL) INDOLE-2- carboxylic acid ethyl ester (250 mg, 540 nmol), 4-isopropoxybenzoyl chloride (162 mg, 810 nmol), DMAP (33 mg, 270 nmol), triethylamine (229 PL, 1.63 mmol) and dry MECN (2 mL) was stirred at room temperature under argon for 18h and then heated at 80°C for 10 min, at 100°C for 5 min and finally at 120°C for 10 min using microwave irradiation. The mixture was poured into HC1 (1M) and extracted with EOAC. The combined extracts were washed with NAHC03, dried with NA2S04 and concentrated. The residue was crystallised from EOAc/benzene to yield the title compound (150 mg, 44%).

Reference： [1]Current Patent Assignee: OREXO AB - WO2005/5415, 2005, A1 Location in patent: Page/Page column 104

12
[ 36823-82-2 ]
[ 216968-87-5 ]

Yield	Reaction Conditions	Operation in experiment
91%		4 N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propoxybenzamide, monohydrochloride EXAMPLE 4 N-(6-Methyl-5,6,7,8-tetrahydro[1,6]naphthyridin-3-yl)-4-iso-propoxybenzamide, monohydrochloride Prepared as described in Example 1 from 4-isopropyloxybenzoyl chloride in 91% yield. 1H NMR [250MHz, (CD3)2SO)] δ: 1.14 (6H, d, J=6 Hz), 2.75 (3H, s), 2.93 (2H, br m), 3.53 (2H, br m), 4.23 and 4.34 (each 1H, 2 br m's), 4.54-4.63 (1H, m), 6.89 (2H, d, J=9 Hz), 7.88 (2H, d, J=9 Hz), 7.94 (1H, d, J=2 Hz), 8.63 (1H, d, J=2 Hz), 10.25 (1H, s, exchangeable), 11.00 (1H, br s, exchangeable); m/z (API): 324.2 (M-H)-

Reference： [1]Current Patent Assignee: GLAXOSMITHKLINE PLC - US6245778, 2001, B1

13
[ 929267-44-7 ]
[ 36823-82-2 ]
[ 929266-12-6 ]

Yield	Reaction Conditions	Operation in experiment
71%	With pyridine In acetone at 0 - 20℃; for 20h;	1M To an ice-cold mixture of 4h (0.50 g, 2.17 mmol) and pyridine (0.18 g, 2.28 mmol) in acetone (35 mL) under N2 was added dropwise a solution of 4-isopropoxybenzoyl chloride 8 (0.45 g, 2.28 mmol) in acetone (5 mL) over 2 min and the resulting solution was stirred at ambient temperature for 20 h. The acetone was removed under reduced pressure and the residue was partitioned between EtOAc (100 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (30 mL) ........... (la-21) (0.62 g, 71%) as a white solid: Rf 0.65 (9:1 CH2CI2/MeOH); mp (DSC) 210.6-211.7 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.25 (d, J = 8.9 Hz, 2H), 7.80 (s, 2H), 7.42- 7.40 (m, 1H), 7.25-7.13 (m, 2H), 7.07 (d, J = 8.9 Hz, 2H), 6.59-6.55 (m, 1H), 5.08 (s, 2H), 4.83-4.75 (m, 1H), 1.33 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ 165.6, 161.0, 157.8, 157.3, 156.8, 142.3, 133.0, 129.5, 123.9, 116.5, 114.3, 111.0, 105.5, 103.5, 69.6, 53.3, 21.5; IR (ATR) 3421 , 3357, 3103, 1676 cm"1; APCI MS m/z 393 [C20H20N6O3 + H]+; HPLC (Method A) 98.8% (AUC), tR - 13.99 min. Anal. Calcd for C20H20N6O3: C, 61.21 ; H, 5.14; N, 21.42. Found: C, 61.17; H, 4.88; N, 21.19.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 160

14
[ 929267-48-1 ]
[ 36823-82-2 ]
[ 929265-74-7 ]

Yield	Reaction Conditions	Operation in experiment
50%	With triethylamine In acetone at 0 - 20℃; for 20h;	1M To an ice-cold mixture of 4i (0.30 g, 0.98 mmol) and Et3N (0.10 g, 1.00 mmol) in acetone (15 mL) under N2 was added dropwise a solution of 4-isopropoxybenzoyl chloride 8 (0.20 g, 0.98 mmol) in acetone (5 mL) over 2 min and the resulting solution was stirred at ambient temperature for 20 h. The acetone was removed under reduced pressure and the residue was partitioned between EtOAc (50 mL) and water (50 mL). The aqueous layer was extracted with EtOAc (50 mL) and the combined organics were washed with brine (50 mL), dried (Na2SO4), and concentrated to give the crude product. Purification by flash chromatography (95:5 CH2CI2/MeOH) afforded 5-amino-1-(4-(iso- propoxy)phenylcarbonyl-3-[3-[2-(morpholin-4-yl)ethoxy]phenylamino]-1H-1,2,4-triazole (la-22) (0.23 g, 50%) as a white solid: Rf 0.50 (9:1 CH2CI2/Me0H); mp (DSC) 152-153.7 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.25 (d, J = 8.9 Hz, 2H), 7.77 (s, 2H)...........106.5, 103.0, 69.9, 66.4, 65.4, 57.5, 54.0, 22.0; IR (ATR) 3664, 1692 cm"1; APCI MS m/z 467 [C24H30N6O4 + H]+; HPLC (Method A) 98.0% (AUC), tR = 9.54 min.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 161

15
[ 929267-52-7 ]
[ 36823-82-2 ]
5-amino-1-(4-(isopropoxy)phenyl)carbonyl-3-(3-(2-(piperidin-1-yl)ethoxy)phenylamino)-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35%	With triethylamine In acetone at 0 - 20℃; for 20h;	1M To an ice-cold mixture of 4j (0.35 g, 1.16 mmol) and Et3N (0.12 g, 1.18 mmol) in acetone (20 mL) under N2 was added dropwise a solution of 4-isopropoxyl benzoylchloride 8 (0.23 g, 1.16 mmol) in acetone (5 mL) over 2 min and the resulting solution was stirred at ambient temperature for 20 h. The acetone was removed under reduced pressure and the residue was partitioned between EtOAc (75 mL) and saturated aqueous NaHCO3. The aqueous layer was separated, extracted with EtOAc (75 mL) and the combined organics were dried (Na2SO4) and concentrated to give the crude product. Purification by flash chromatography (95:5 CH2CI2/MeOH) afforded 5-amino-1- (4-(/so-propoxy)phenyl)carbonyl-3-[3-(piperidin-1-yl)phenylamino]-1 H-1 ,2,4-triazole (Ia- 23) (0.19 g, 35%) as a yellow solid: Rf 0.25 (9:1 CH2CI2/MeOH); mp 121-124 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.25 (d, J = 8.8 Hz, 2H), 7.77 (s, 2H), 7.40 (s, 1 H), H), 3.99 .........124.3, 114.8, 9, 1671 cm-1; APCI MS m/z 465 [C25H32N6O3 + H]+; HPLC (Method A) 97.7% (AUC), tR = 10.19 min.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 162

16
[ 929267-55-0 ]
[ 36823-82-2 ]
[ 929265-76-9 ]

Yield	Reaction Conditions	Operation in experiment
35%	With pyridine In acetone at 0 - 20℃; for 20h;	1M To an ice-cold mixture of 4k (0.50 g, 1.70 mmol) and pyridine (0.16 g, 2.05 mmol) in acetone (35 mL) under N2 was added dropwise a solution of 4-isopropoxybenzoyl chloride 8 (0.37 g, 1.87 mmol) in acetone (5 mL) over 2 min and the resulting solution was stirred at ambient temperature for 20 h. The acetone was removed under reduced pressure and the residue was partitioned between EtOAc (75 mL) and water (75 mL). The aqueous layer was extracted with EtOAc (75 mL) and the combined organics were washed with brine (40 mL), dried (Na2SO4), and concentrated to give the crude product. Purification by trituration with CH3CN afforded 5-amino-3-[3-[2-(1,3-dioxolan-2- yl)ethoxy]phenylamino]~1-(4-(/so~propoxy)phenyl)carbonyl-1 H-1 ,2,4-triazole (la-24) (0.51 g, 35%) as an off-white solid: ftf 0.61 (9:1 CH2CI2/Me0H); mp (DSC) 144.4-145.4 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.31 (s, 1H), 8.25 (d, J = 8.8 Hz, 2H), 7.78 (s, 2H), 7.40 (s, 1H), 7.14-7.03 (m, 3H), 6.95 (dd, J = 8.1, 1.0 Hz, 1H), 6.41 (dd, J = 7.9, 2.1 Hz, 1 H), 4.97 (t, J = 5.1 Hz, 1 H), 4.81-4.73 (m, 1 H), 3.98 (t, J = 6.3 Hz, 2H), 3.93-3.76 (m, 4H), 2.02- 1.96 (m, 2H), 1.32 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ 166.0, 161.4, 1 1 0, 101.5, 70.0.........

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 163

17
[ 929267-15-2 ]
[ 36823-82-2 ]
5-amino-3-(4-(benzyloxy)phenylamino)-1-(4-(isopropoxy)phenyl)carbonyl-1H-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	With pyridine In acetone at 0 - 20℃; for 22.5h;	1D To a stirred mixture of 8 (0.50 g, 1.78 mmol) and pyridine (0.14 g, 1.78 mmol) in acetone (15 ml.) at ice bath temperature was added 31 (0.35 g, 1.78 mmol). After stirring for 1 h at ice bath temperature and an additional 21.5 h at ambient temperature the reaction mixture was poured onto water (150 mL) and stirred vigorously. The aqueous mixture was extracted with ethyl acetate and the organic layer was separated, washed with brine, dried over magnesium sulfate and concentrated to give 0.74 g of a yellow foam. Purification by flash chromatography (97:3 methylene chloride/methanol) afforded 5-amino-3-[4-(benzyloxy)phenylamino]-1 -(4-(/so-propoxy)phenyl)carbonyl-1 H- 1 ,2,4-triazole (la-10) (0.52 g, 51 %) as a yellow solid: Rf 0.51 (95:5 methylene chloride/methanol); mp 79-81 0C; 1H NMR (300 MHz, DMSO-c/6) δ 9.08 (s, 1 H), 8.26 (d, J = 8.9 Hz, 2H), 7.75 (br s, 2H), 7.60-7.20 (m, 7H)1 7.08 (d, J = 9.0 Hz, 2H), 6.93 (d, J = 9.0 Hz1 2H), 5.26 (s, 2H), 4.80 (m, 1 H), 1.33 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ 165.8, 161.4, 158.6, 157.8, 152.5, 137.7, 135.1 , 133.5, 128.7, 128.0, 127.9, 124.4, 118.1 , 115.4, 114.8, 69.9, 69.8. 22.0; IR (ATR) 1669, 1581, 1544, 1506 cm"1; ESI MS m/z 444 [C25H25N5O3 + H]+; HPLC (Method A) >99% (AUC), tR = 16.27 min. Anal. Calcd for C25H25N5O3: C, 67.70; H, 5.68; N, 15.79. Found: C, 67.73; H, 5.63; N, 15.79.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 142-143

18
[ 929267-19-6 ]
[ 36823-82-2 ]
[ 929266-10-4 ]

Yield	Reaction Conditions	Operation in experiment
31%	With pyridine In acetone at 0 - 20℃; for 17h;	1E To a stirred ice-cold mixture of 4c (0.50 g, 2.17 mmol) and pyridine (0.17 g, 2.17 mmol) in acetone (35 mL) was added 4-isopropoxybenzoyl chloride 8 (0.43 g, 2.17 mmol). After stirring for 1 h at ice bath temperature and an additional 16 h at ambient temperature, the reaction mixture was slowly added to a vigorously stirred solution of water (100 mL). The crude product formed a yellow precipitate, which was collected by filtration. Purification by flash chromatography (98:2 methylene chloride/methanol) afforded 5-amino-3-[4-(cyanomethoxy)phenylamino]-1-(4-(/so-propoxy)phenyl)carbonyl- 1H-1 ,2,4-triazole (la-12) (0.27 g, 31%) as a beige solid: Rf 0.72 (97:3 methylene chloride/methanol); mp (DSC) 182.9-186.1 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.22 (s, 1 H), 8.25 (d, J = 9.0 Hz, 2H), 7.77 (br s, 2H), 7.52 (d, J = 9.0 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 7.00 (d, J = 9.0 Hz, 2H), 5.09 (s, 2H), 4.94-4.78 (m, 1H), 1.33 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) 165.5, 161.0, 158.1 , 157.4, 150.0, 136.2, 133.0.....

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 145

19
[ 929267-22-1 ]
[ 36823-82-2 ]
C₂₃H₂₇N₅O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In acetone at 20℃; for 20h;	1F To a ice-cold mixture of 4d (0.50 g, 1.80 mmol) and pyridine (0.14 g, 1.80 mmol) in acetone (25 mL) was added dropwise a solution of 4-isopropoxybenzoyl chloride (8) n was stirred at pressure and w crystals) was ved under reduced pressure and the residue partitioned between EtOAc (100 mL) and water (100 mL). The organic layer was washed with brine (30 mL), dried (Na2SO4), and concentrated to give the crude product. Purification by flash chromatography (95:5 CH2CI2/MeOH) gave 5-amino-3-[3-(hydroxy)phenylamino]-1-(4-(/so- propoxy)phenyl)carbonyl-1 H-1 ,2,4-triazole (la-13) (0.22 g, 35%) as a yellow solid: Rf 0.53 (9:1 CH2CI2/MeOH); mp (DSC) 204.2-211.9 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.17 (s, 1H), 9.13 (s, 1H), 8.26 (d, J = 8.8 Hz, 2H), 7.75 (s, 2H), 7.07-6.96 (m, 5H), 6.29- 6.26 (m, 1H), 4.82-4.74 (m, 1H), 1.32 (d, J = 5.9 Hz, 6H); 13C NMR (75 MHz, DMSO-c/6) EPO δ 165.9, 161.4, 158.4, 158.0, 157.7, 142.4, 133.5, 129.6, 124.3, 114.8, 108.2, 107.8, 104.4, 70.0, 22.0; IR (ATR) 3426, 3305, 1661 cnrf1; APCI MS m/z 354 [C18H19N5O3 + H]+; HPLC (Method A) >99% (AUC), tR = 12.24 min. Anal. Calcd for C18H19N5O3: C, 61.18; H, 5.42; N, 19.82. Found: C, 61.10; H, 5.29; N, 19.69.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 147

20
[ 929267-25-4 ]
[ 36823-82-2 ]
[ 929266-02-4 ]

Yield	Reaction Conditions	Operation in experiment
24%	With pyridine In acetone at 0 - 20℃; for 40h;	1M In a manner similar to that described above in the preparation of (la-21), (la-22), (la-23), and (la-24), a solution of 4-isopropoxybenzoyl chloride 8 (0.37 g, 1.86 mmol) in acetone (5 mL) was added dropwise over 2 min under N2 to an ice-cold mixture of triazole 2i (0.26 g, 0.92 mmol), prepared as described above in Reaction Scheme U, and pyridine (0.08 g, 0.92 mmol) in acetone (15 mL) and the resulting solution was stirred at ambient temperature for 40 h. The solids that formed were collected by filtration and triturated with acetone to afford 5-amino-3-[3-(benzyloxy)phenylamino]-1-(4- (/so-propoxy)phenyl)carbonyl-1 H-1 ,2,4-triazole (la-25) (0.1O g, 24%) as a white solid: Rf0.57 (9:1 CH2CI2/MeOH); mp (DSC) 188.7-189.9 0C; 1H NMR (300 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.27 (d, J = 8.8 Hz, 2H)1 7.78 (s, 2H), 7.58 (s, 1 H), 7.43-7.33 (m, 5H), 7.12 (t, J = 8.1 Hz, 1H), 6.99-6.91 (m, 3H), 6.50-6.47 (m, 1H), 4.98 (s, 2H), 4.52-4.42 (m, 1H), 1.19 (d, J = 6.0 Hz, 6H); 13C NMR (75 MHz, DMSOd6) δ 166.0, 161.4, 159.3, 158.3, 157.7, 142.5, 137.3, 133.4, 129.6, 128.7, 128.3, 128.1 , 124.3, 114.8, 109.8, 106.9, 103.1 , 69.8, 69.3, 21.9; IR (ATR) 3364, 1671 cm-1; APCI MS m/z 444 [C25H25N5O3 + H]+; HPLC (Method A) >99% (AUC), tR = 16.51 min. Anal. Calcd for C25H25N5O3: C, 66.70; H, 5.68; N, 15.79. Found: C, 67.42; H, 5.71; N, 15.63.

Reference： [1]Current Patent Assignee: RIGEL PHARMACEUTICALS INC - WO2007/30680, 2007, A2 Location in patent: Page/Page column 163-164

21
[ 1028485-53-1 ]
[ 36823-82-2 ]
[ 1028485-60-0 ]

Yield	Reaction Conditions	Operation in experiment
50%	With dmap In dichloromethane at 23℃; for 2h;

Reference： [1]Busacca, Carl A.; Lorenz, Jon C.; Grinberg, Nelu; Haddad, Nizar; Lee, Heewon; Li, Zhibin; Liang, Mary; Reeves, Diana; Saha, Anjan; Varsolona, Rich; Senanayake, Chris H. [Organic Letters, 2008, vol. 10, # 2, p. 341 - 344]

22
[ 27025-74-7 ]
[ 36823-82-2 ]
[ 1105633-99-5 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine at 150℃; for 0.5h;	SS1 Table SS: Examples of amides prepared from 3-(2-chlorophenyl)isoxazol-5-amine; In a microwave vial a solution of 3-(2-chlorophenyl)isoxazol-5-amine (25 mg, leq.), dissolved in pyridine was added followed by a solution of the acid chloride monomer (1.5 eq.) dissolved in pyridine. The mixture was heated to 150 0C for 1800 seconds. After cooling the reaction mixture was concentrated to dryness. The residues were dissolved in 1 : 1 DMSO/MeOH and the crude material was purified by HPLC method (n) and the solvents evaporated.

Reference： [1]Current Patent Assignee: ABBVIE INC - WO2009/11850, 2009, A2 Location in patent: Page/Page column 143; 144

23
[ 33421-40-8 ]
[ 36823-82-2 ]
[ 1044239-49-7 ]

Yield	Reaction Conditions	Operation in experiment
32%	With pyridine at 20℃; for 2h; Inert atmosphere;

Reference： [1]Heitman, Laura H.; Van Veldhoven, Jacobus P. D.; Zweemer, Annelien M.; Ye, Kai; Brussee, Johannes; Ijzerrnan, Adriaan P. [Journal of Medicinal Chemistry, 2008, vol. 51, # 15, p. 4724 - 4729]

24
[ 1163141-41-0 ]
[ 36823-82-2 ]
[ 1163142-29-7 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In tetrahydrofuran; N,N-dimethyl-formamide at 100℃;	1.91.A To a solution of (Z)-ethyl 2-(7-(N'-hydroxycarbamimidoyl)-l,2,3,4- tetrahydrocyclopenta[b]indol-3-yl)acetate (0.100 g, 0.332 mmol) and triethylamine (0.046 mL, 0.332 mmol) in THF (1.5 mL) was added 4-isopropoxybenzoyl chloride (0.066 g, 0.332 mmol). After stirring overnight, the solvent was removed under reduced pressure and the residue was dissolved in DMF (1.5 mL). The reaction mixture was stirred for 4 h at 100 0C, then the solvent was removed and the residue was taken up in EtOAc. The organics were washed with IM HCl and bϖne (twice), dried over MgSO4, filtered and concentrated. The residue was purified by silica gel column chromatography to provide the title compound as a yellow solid (0.0435 g). LCMS m/z = 446.3 [M+H]+. 1H NMR (400 MHz, CD3OD) δ ppm 1.24 (t, J = 7.07 Hz, 3H), 1.36 (d, J = 6.06 Hz, 6H), 2.15-2.24 (m, IH), 2.57 (dd, J = 15.92, 7.83 Hz, IH), 2.68-2.92 (m, 4H), 3.60 (dd, J = 6.32, 3.79 Hz, IH), 4.17 (m, 2H), 4.73 (m, IH), 7.07 (d, J = 8.84 Hz, 2H), 7.40 (d, J = 8.59 Hz, IH), 7.74-7.79 (m, IH), 8.06-8.14 (m, 3H).

Reference： [1]Current Patent Assignee: PFIZER INC - WO2009/78983, 2009, A1 Location in patent: Page/Page column 128-129

25
[ 1129401-51-9 ]
[ 36823-82-2 ]
[ 1129401-61-1 ]

Yield	Reaction Conditions	Operation in experiment
96%	In toluene for 4h; Reflux;	15 XIII (71 mg, 0.185 mmol) and aroyl chloride (0.204 mmol) were dissolved in toluene under an inert atmosphere and heated at rx for 4 h. The reaction was quenched by the addition of methanol (5 mL) and stirred for 10 min. Concentration and chromatography of the residue afforded methyl 2-(3,4-difluorophenylamino)-5-(4-(arylamido)benzoyl)benzoate. Hydrolysis according to general method H furnished the free acid (see table 5).

Reference： [1]Current Patent Assignee: OREXO AB - US2010/286215, 2010, A1 Location in patent: Page/Page column 26; 27

26
[ 54802-10-7 ]
[ 36823-82-2 ]
[ 898373-13-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 0 - 20℃;	5 Example 5 Preparation of Compound 95 To a stirred solution of 3-aminobenzofuran-2-carboxamide (3.00 g, 17.03 mmol) in 85 mL of THF were added pyridine (4.10 mL, 51.09 mmol) and 4-isopropoxybenzoyl chloride (4.06 g, 20.44 mmol) at 0° C. and the mixture was stirred at room temperature overnight. The solvent was removed by evaporation and the residue was poured into 200 ml, of water. The mixture was stirred for 1 h. The precipitate was collected by filtration and washed with 200 mL of hexane, washed with 400 mL of methylene chloride/hexane (1/50) and dried under reduced pressure to give 5.34 g of 3-(4-isopropoxybenzamido)benzofuran-2-carboxamide. LC-MS (M+H): 339.1.

Reference： [1]Current Patent Assignee: TAIGEN BIOPHARMACEUTICALS HOLDINGS LTD. - US2011/178107, 2011, A1 Location in patent: Page/Page column 69; 70

27
[ 917504-84-8 ]
[ 36823-82-2 ]
[ 1315326-85-2 ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine In tetrahydrofuran at 0 - 60℃; for 18h;	9 To the solution of 3-aminofuro[3,2-b]pyridine-2-carboxamide (2.0 g, 11.29 mmol) in 56 mL of dry tetrahydrofuran were added pyridine (2.73 mL, 33.87 mmol) and 4-isopropoxybenzoyl chloride (4.46 mL, 22.58 mmol) at 0° C. The mixture was stirred at 60° C. for 18 hours. The solvent was removed by evaporation. The residue was poured into of water and extracted by methylene chloride. The organic layer was separated, washed with brine, dried over MgSO4, and concentrated in vacuo. The solid was combined to give 3.55 g of 3-(4-isopropoxybenzamido)furo[3,2-b]pyridine-2-carboxamide. LC-MS (M+H): 340.1.

Reference： [1]Current Patent Assignee: TAIGEN BIOPHARMACEUTICALS HOLDINGS LTD. - US2011/178107, 2011, A1 Location in patent: Page/Page column 75; 77

28
[ 1165923-94-3 ]
[ 36823-82-2 ]
[ 1286750-84-2 ]

Yield	Reaction Conditions	Operation in experiment
41%	With pyridine In toluene at 20 - 110℃; for 12h; Inert atmosphere;

Reference： [1]Demont, Emmanuel H.; Andrews, Benjamin I.; Bit, Rino A.; Campbell, Colin A.; Cooke, Jason W. B.; Deeks, Nigel; Desai, Sapna; Dowell, Simon J.; Gaskin, Pam; Gray, James R. J.; Haynes, Andrea; Holmes, Duncan S.; Kumar, Umesh; Morse, Mary A.; Osborne, Greg J.; Panchal, Terry; Patel, Bela; Perboni, Alcide; Taylor, Simon; Watson, Robert; Witherington, Jason; Willis, Robert [ACS Medicinal Chemistry Letters, 2011, vol. 2, # 6, p. 444 - 449]

29
[ 36823-82-2 ]
[ 108-94-1 ]
[ 1393713-11-5 ]

Yield	Reaction Conditions	Operation in experiment
25%	Stage #1: cyclohexanone With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.75h; Inert atmosphere; Stage #2: 4-isopropoxybenzoyl chloride In tetrahydrofuran at 20℃; for 2h; Inert atmosphere;

Reference： [1]Van Linden, Oscar P. J.; Wijtmans, Maikel; Roumen, Luc; Rotteveel, Lonneke; Leurs, Rob; De Esch, Iwan. J. P. [Journal of Organic Chemistry, 2012, vol. 77, # 17, p. 7355 - 7363]

30
[ 36823-82-2 ]
[ 203639-63-8 ]
[ 1440967-48-5 ]

Yield	Reaction Conditions	Operation in experiment
65%	With 4-methyl-morpholine In dichloromethane at 0 - 20℃; for 12h;

Reference： [1]Selivanova, Svetlana V.; Stellfeld, Timo; Heinrich, Tobias K.; Müller, Adrienne; Krämer, Stefanie D.; Schubiger, P. August; Schibli, Roger; Ametamey, Simon M.; Vos, Bernhard; Meding, Jörg; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M. [Journal of Medicinal Chemistry, 2013, vol. 56, # 12, p. 4912 - 4920]

31
[ 36823-82-2 ]
[ 6038-49-9 ]
C₂₆H₂₃ClN₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

32
[ 36823-82-2 ]
[ 15987-90-3 ]
C₂₈H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

33
C₁₉H₂₀N₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₉H₃₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

34
C₁₇H₁₄N₂O₃ [ No CAS ]
[ 36823-82-2 ]
C₂₇H₂₄N₂O₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

35
C₁₇H₁₅FN₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₇H₂₅FN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

36
C₁₇H₁₅ClN₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₇H₂₅ClN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

37
C₁₈H₁₈N₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₈H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

38
C₁₇H₁₅FN₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₇H₂₅FN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

39
C₁₇H₁₅ClN₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₇H₂₅ClN₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

40
C₁₈H₁₈N₂O₂ [ No CAS ]
[ 36823-82-2 ]
C₂₈H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 0.5h;	Synthesis of VU6000181 General procedure: Synthesis of VU6000181. To a suspension of Mg (936mg, 38.5mmol) and iodine (5mg) in THF (2mL) was added a part of a solution of 4-bromo-2-methylanisole (7.39g, 36.8mmol) in THF (9mL) at ambient temperature. After initiating the reaction, a solution of 4-bromo-2-methylanisole diluted with THF (19mL) was added dropwise to the mixture diluted with THF (10mL). After the mixture was allowed to stir at ambient temperature for 2h, resulting Grignard reagent was added to a suspension of phthalic anhydride 8 (5.18g, 35.0mmol) in THF (50mL) at -65°C. The mixture was allowed to stir for 2.5h as temperature was elevated up to 0°C. The reaction was quenched with cold water and the aqueous layer was separated. The organic layer was extracted with 1 N NaOH aqueous solution and the combined aqueous layer was acidified with 2N HCl solution. The aqueous layer was extracted with ethyl acetate twice and the combined organic layer was washed with brine and dried over magnesium sulfate. The filtrate was evaporated under reduced pressure. The residue was triturated with ethyl acetate/diethyl ether to give compound 3 as a white powder (5.61g, 59% yield). To a solution of compound 3 (1.0g, 3.7mmol) and para-toluene sulfonic acid monohydrate (10mg) in PhMe (8mL) and 1,4-dioxane (8mL) was added ethylenediamine (0.50mL, 7.4mmol) at ambient temperature. The resulting white suspension was subjected to microwave irradiation at 150°C for 30min. After removing insoluble material, the filtrate was concentrated. The procedure above was repeated twice more and the three portions were combined and purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether to give compound 4 as an off-white powder (1.69g, 52% yield). To a solution of compound 4 (500mg, 1.70mmol) in dichloromethane (8mL) was added DIPEA (0.74mL, 4.25mmol) and 3,4,5-trifluorobenzoyl chloride (0.33mL, 2.55mmol) at ambient temperature. After stirring for 30min, cold NaHCO3-aq was added to the mixture which was extracted with dichloromethane twice. The combined organic layer was concentrated under reduced pressure and the residue was purified on silica gel using hexane/ethyl acetate as an eluent. Crude product was triturated with diethyl ether/hexane to yield compound 7B-6 as a white powder (491mg, 64% yield). Chiral resolution by SFC (Agilent 1260, Column: LUX cellulose-3, Column dimensions: 10×250mm, Co-solvent: MeOH, Modifier: none, Gradient Profile: 10% isocratic, Flow Rate: 15mL/min, Backpressure: 100, Column temperature: 40 degrees, retention time: 2.814min, dated on July 30th) followed by concentration afforded (S)-7B-6 (VU6000181) as a white powder.

Reference： [1]Kurata, Haruto; Gentry, Patrick R.; Kokubo, Masaya; Cho, Hyekyung P.; Bridges, Thomas M.; Niswender, Colleen M.; Byers, Frank W.; Wood, Michael R.; Daniels, J. Scott; Conn, P. Jeffrey; Lindsley, Craig W. [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 3, p. 690 - 694]

41
[ 36823-82-2 ]
4-amino-5-(4-ethoxyphenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]
4-(4-isopropoxybenzamido)-5-(4-ethoxyphenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
81%	With triethylamine In tetrahydrofuran at 0℃; for 12h;
75.6%	With triethylamine In tetrahydrofuran for 6h; Cooling with ice; Molecular sieve;	6 Example 6 A solution of methyl 4-amino-1- (4-phenoxyphenyl) -5- (4-ethoxyphenyl) pyrazole-3-carboxylate129mg(0.3 mmol),Dissolved in 10mL of dried tetrahydrofuran,In an ice bath, 209 μL (1.5 mmol) of triethylamine, which had been dried by molecular sieves,4-isopropoxybenzoyl chloride 100μL, the reaction was stirred in an ice bath 6h.The reaction solution was poured into 100 ml of water,Precipitation white solid, suction filtration, drying.The crude product was separated on a silica gel column with a mobile phase of petroleum ether: ethyl acetate (2: 1 by volume)Got a white solid134 mg of methyl 4- (4-isopropoxybenzamido) -1- (4-phenoxyphenyl) -5- (4-ethoxyphenyl) Rate 75.6%.

Reference： [1]Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao [Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3152 - 3162]
[2]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN105061315, 2017, B Location in patent: Paragraph 0091; 0092; 0093

42
[ 36823-82-2 ]
4-amino-5-(4-isopropoxyphenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]
4-(4-isopropoxybenzamido)-5-(4-isopropoxyphenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With triethylamine In tetrahydrofuran at 0℃; for 12h;
79.8%	With triethylamine In tetrahydrofuran for 6h; Cooling with ice; Molecular sieve;	7 Example 7 A solution of methyl 4-amino-1- (4-phenoxyphenyl) -5- (4-isopropoxyphenyl) pyrazole-3-carboxylate133mg(0.3 mmol),Dissolved in 10mL of dried tetrahydrofuran,In an ice bath, 209 μL (1.5 mmol) of triethylamine, which had been dried by molecular sieves,4-isopropoxybenzoyl chloride 100μL, the reaction was stirred in an ice bath 6h.The reaction solution was poured into 100ml of water, white solid precipitated,Suction filtration,drying. The crude product was isolated on a silica gel column,The mobile phase was petroleum ether: ethyl acetate (2: 1 by volume)Got a white solid145 mg of methyl 4- (4-isopropoxybenzamido) -1- (4-phenoxyphenyl) -5- (4-isopropoxyphenyl) Yield 79.8%.

Reference： [1]Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao [Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3152 - 3162]
[2]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN105061315, 2017, B Location in patent: Paragraph 0096; 0097; 0100

43
[ 36823-82-2 ]
4-amino-5-(4-(benzyloxy)phenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]
4-(4-isopropoxybenzamido)-5-(4-(benzyloxy)phenyl)-1-(4-phenoxyphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
77%	With triethylamine In tetrahydrofuran at 0℃; for 12h;
76.9%	With triethylamine In tetrahydrofuran for 6h; Molecular sieve; Cooling with ice;	8 Example 8 A solution of methyl 4-amino-1- (4-phenoxyphenyl) -5- (4-benzyloxyphenyl) pyrazole-3-carboxylate147 mg (0.3 mmol),Dissolved in 10mL of dried tetrahydrofuran,In an ice bath, 209 μL (1.5 mmol) of triethylamine, which had been dried by molecular sieves,4-isopropoxybenzoyl chloride 100μL, the reaction was stirred in an ice bath 6h.The reaction solution was poured into 100 mlWater, precipitated white solid, suction filtration, drying. The crude product was isolated on a silica gel column,The mobile phase was petroleum ether: ethyl acetate (2: 1 by volume)Got a white solid4- (4-Isopropoxybenzamido) -1- (4-phenoxyphenyl) -5- (4-benzyloxyphenyl) pyrazole-3-carboxylic acid Methyl ester150mg,Yield 76.9%.

Reference： [1]Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao [Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3152 - 3162]
[2]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN105061315, 2017, B Location in patent: Paragraph 0103; 0104; 0107

44
[ 36823-82-2 ]
4-amino-5-(4-(benzyloxy)phenyl)-1-(4-isopropylphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]
4-(4-isopropoxybenzamido)-5-(4-(benzyloxy)phenyl)-1-(4-isopropylphenyl)-1H-pyrazole-3-carboxylate acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triethylamine In tetrahydrofuran at 0℃; for 12h;
86.2%	With triethylamine In tetrahydrofuran for 6h; Cooling with ice; Molecular sieve;	9 Example 9 Methyl 4-amino-1- (4-isopropylphenyl) -5- (4-benzyloxyphenyl) pyrazole-3-carboxylate132mg(0.3mmol) was dissolved in 10mL of dried tetrahydrofuran, respectively, ice bath was successively added molecular sieves dried triethylamine 209μL(1.5mmol), 4-isopropoxybenzoyl chloride 100μL, the reaction was stirred for 6h in ice bath. The reaction solution was poured into 100 mlWater, precipitated white solid, suction filtration, drying. The crude product was separated on a silica gel column with a mobile phase of petroleum ether: ethyl acetate (by volumeThan 2: 1), had a pale yellow solid4- (4-Isopropoxybenzamido) -1- (4-isopropylphenyl)-5- (4-benzyloxyphenyl) pyrazole-3-carboxylate156 mg, 86.2% yield.

Reference： [1]Wang, Ziqian; Song, Ting; Feng, Yingang; Guo, Zongwei; Fan, Yudan; Xu, Wenjie; Liu, Lu; Wang, Anhui; Zhang, Zhichao [Journal of Medicinal Chemistry, 2016, vol. 59, # 7, p. 3152 - 3162]
[2]Current Patent Assignee: DALIAN UNIVERSITY OF TECHNOLOGY - CN105061315, 2017, B Location in patent: Paragraph 0110; 0111; 0114

45
[ 36823-82-2 ]
5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-amine [ No CAS ]
N-(5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
12%	With pyridine at 20℃; for 18h;	5.1.4. *General procedure “A” using a commercially available acylchloride for amide coupling General procedure: 5.1.4.1. N-(5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-yl)benzamide (1). To a vial was added the 4A (0.030 g, 0.14 mmol,1.0 eq.) followed by pyridine (0.6 mL) and 4-benzoyl chloride(0.020 g, 0.14 mmol, 1.0 eq.) at room temperature. The reactionstirred for 18 h then was poured into ice water and a precipitateformed. This precipitate was filtered by vacuum filtration and wasfurther purified by reverse-phase flash chromatography (5-100%MeCN:water). All fractions containing the desired product wereisolated and concentrated to produce 1 (0.028 g, 0.084 mmol, 40%)as a pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 12.21 (br s, 1H),8.26 (d, J 7.7 Hz, 2H), 7.84-7.74 (m, 2H), 7.62 (t, J 7.3 Hz, 1H),7.53 (t, J 7.5 Hz, 2H), 7.19 (d, J 7.8 Hz, 1H), 2.89-2.79 (m, 4H),1.89-1.79 (m, 4H). 13C NMR (200 MHz, DMSO-d6):δ 165.0, 161.5,157.7,141.1,137.9,132.9, 132.2,130.0,128.6, 128.3, 126.5, 123.1, 120.5,28.84, 28.58, 22.35, 22.30. ESI-MS: m/z 319.7 [M H]; HPLCretention time: 12.940 min. HPLC purity 96.5%.

Reference： [1]Kaur, Jatinder; Soto-Velasquez, Monica; Ding, Zhong; Ghanbarpour, Ahmadreza; Lill, Markus A.; van Rijn, Richard M.; Watts, Val J.; Flaherty, Daniel P. [European Journal of Medicinal Chemistry, 2019, vol. 162, p. 568 - 585]

46
[ 36823-82-2 ]
5-(2,3-dihydrobenzo[b] [1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-amine [ No CAS ]
N-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With pyridine at 20℃; for 18h;	5.1.4. *General procedure “A” using a commercially available acylchloride for amide coupling General procedure: 5.1.4.1. N-(5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-yl)benzamide (1). To a vial was added the 4A (0.030 g, 0.14 mmol,1.0 eq.) followed by pyridine (0.6 mL) and 4-benzoyl chloride(0.020 g, 0.14 mmol, 1.0 eq.) at room temperature. The reactionstirred for 18 h then was poured into ice water and a precipitateformed. This precipitate was filtered by vacuum filtration and wasfurther purified by reverse-phase flash chromatography (5-100%MeCN:water). All fractions containing the desired product wereisolated and concentrated to produce 1 (0.028 g, 0.084 mmol, 40%)as a pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 12.21 (br s, 1H),8.26 (d, J 7.7 Hz, 2H), 7.84-7.74 (m, 2H), 7.62 (t, J 7.3 Hz, 1H),7.53 (t, J 7.5 Hz, 2H), 7.19 (d, J 7.8 Hz, 1H), 2.89-2.79 (m, 4H),1.89-1.79 (m, 4H). 13C NMR (200 MHz, DMSO-d6):δ 165.0, 161.5,157.7,141.1,137.9,132.9, 132.2,130.0,128.6, 128.3, 126.5, 123.1, 120.5,28.84, 28.58, 22.35, 22.30. ESI-MS: m/z 319.7 [M H]; HPLCretention time: 12.940 min. HPLC purity 96.5%.

Reference： [1]Kaur, Jatinder; Soto-Velasquez, Monica; Ding, Zhong; Ghanbarpour, Ahmadreza; Lill, Markus A.; van Rijn, Richard M.; Watts, Val J.; Flaherty, Daniel P. [European Journal of Medicinal Chemistry, 2019, vol. 162, p. 568 - 585]

47
[ 98427-18-0 ]
[ 36823-82-2 ]
N-(5-cyclohexyl-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
18%	With pyridine at 20℃; for 18h;	5.1.4. *General procedure “A” using a commercially available acylchloride for amide coupling General procedure: 5.1.4.1. N-(5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-yl)benzamide (1). To a vial was added the 4A (0.030 g, 0.14 mmol,1.0 eq.) followed by pyridine (0.6 mL) and 4-benzoyl chloride(0.020 g, 0.14 mmol, 1.0 eq.) at room temperature. The reactionstirred for 18 h then was poured into ice water and a precipitateformed. This precipitate was filtered by vacuum filtration and wasfurther purified by reverse-phase flash chromatography (5-100%MeCN:water). All fractions containing the desired product wereisolated and concentrated to produce 1 (0.028 g, 0.084 mmol, 40%)as a pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 12.21 (br s, 1H),8.26 (d, J 7.7 Hz, 2H), 7.84-7.74 (m, 2H), 7.62 (t, J 7.3 Hz, 1H),7.53 (t, J 7.5 Hz, 2H), 7.19 (d, J 7.8 Hz, 1H), 2.89-2.79 (m, 4H),1.89-1.79 (m, 4H). 13C NMR (200 MHz, DMSO-d6):δ 165.0, 161.5,157.7,141.1,137.9,132.9, 132.2,130.0,128.6, 128.3, 126.5, 123.1, 120.5,28.84, 28.58, 22.35, 22.30. ESI-MS: m/z 319.7 [M H]; HPLCretention time: 12.940 min. HPLC purity 96.5%.

Reference： [1]Kaur, Jatinder; Soto-Velasquez, Monica; Ding, Zhong; Ghanbarpour, Ahmadreza; Lill, Markus A.; van Rijn, Richard M.; Watts, Val J.; Flaherty, Daniel P. [European Journal of Medicinal Chemistry, 2019, vol. 162, p. 568 - 585]

48
[ 27049-71-4 ]
[ 36823-82-2 ]
N-(5-(thiophen-2-yl)-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
59%	With pyridine; at 20℃; for 18.0h;	General procedure: 5.1.4.1. N-(5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,3,4-oxadiazol-2-yl)benzamide (1). To a vial was added the 4A (0.030 g, 0.14 mmol,1.0 eq.) followed by pyridine (0.6 mL) and 4-benzoyl chloride(0.020 g, 0.14 mmol, 1.0 eq.) at room temperature. The reactionstirred for 18 h then was poured into ice water and a precipitateformed. This precipitate was filtered by vacuum filtration and wasfurther purified by reverse-phase flash chromatography (5-100%MeCN:water). All fractions containing the desired product wereisolated and concentrated to produce 1 (0.028 g, 0.084 mmol, 40%)as a pale yellow solid. 1H NMR (500 MHz, CDCl3): delta 12.21 (br s, 1H),8.26 (d, J 7.7 Hz, 2H), 7.84-7.74 (m, 2H), 7.62 (t, J 7.3 Hz, 1H),7.53 (t, J 7.5 Hz, 2H), 7.19 (d, J 7.8 Hz, 1H), 2.89-2.79 (m, 4H),1.89-1.79 (m, 4H). 13C NMR (200 MHz, DMSO-d6):delta 165.0, 161.5,157.7,141.1,137.9,132.9, 132.2,130.0,128.6, 128.3, 126.5, 123.1, 120.5,28.84, 28.58, 22.35, 22.30. ESI-MS: m/z 319.7 [M H]; HPLCretention time: 12.940 min. HPLC purity 96.5%.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 162,p. 568 - 585

49
[ 36823-82-2 ]
[ 1612-76-6 ]
N-(5-phenyl-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	With pyridine at 20℃; for 18h;	N-(5-phenyl-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide (67). To a vial was added the 5-phenyl-1,3,4-oxadiazol-2-amine (0.040 g, 0.25 mmol, 1.0 eq.) followed bypyridine (0.6 mL) and 4-isopropoxybenzoyl chloride (0.054 g, 0.27 mmol, 1.2 eq.) at room temperature. Thereaction stirred for 18 hours then was poured into ice water and a precipitate formed. This precipitate was filteredby vacuum filtration and was further purified by reverse-phase flash chromatography (5 - 100% MeCN:water).All fractions containing the desired product were isolated and concentrated to produce 67 (0.028 g, 0.084 mmol,40%) as a pale yellow solid. (0.010 g, 0.031 mmol, 12%).

Reference： [1]Kaur, Jatinder; Soto-Velasquez, Monica; Ding, Zhong; Ghanbarpour, Ahmadreza; Lill, Markus A.; van Rijn, Richard M.; Watts, Val J.; Flaherty, Daniel P. [European Journal of Medicinal Chemistry, 2019, vol. 162, p. 568 - 585]

50
[ 7659-06-5 ]
[ 36823-82-2 ]
N-(5-(furan-2-yl)-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
26%	With pyridine at 20℃; for 18h;	N-(5-phenyl-1,3,4-oxadiazol-2-yl)-4-(isopropoxy)benzamide (67). General procedure: To a vial was added the 5-phenyl-1,3,4-oxadiazol-2-amine (0.040 g, 0.25 mmol, 1.0 eq.) followed bypyridine (0.6 mL) and 4-isopropoxybenzoyl chloride (0.054 g, 0.27 mmol, 1.2 eq.) at room temperature. Thereaction stirred for 18 hours then was poured into ice water and a precipitate formed. This precipitate was filteredby vacuum filtration and was further purified by reverse-phase flash chromatography (5 - 100% MeCN:water).All fractions containing the desired product were isolated and concentrated to produce 67 (0.028 g, 0.084 mmol,40%) as a pale yellow solid. (0.010 g, 0.031 mmol, 12%).

Reference： [1]Kaur, Jatinder; Soto-Velasquez, Monica; Ding, Zhong; Ghanbarpour, Ahmadreza; Lill, Markus A.; van Rijn, Richard M.; Watts, Val J.; Flaherty, Daniel P. [European Journal of Medicinal Chemistry, 2019, vol. 162, p. 568 - 585]

51
[ 36823-82-2 ]
6-amino-1-(4-chlorobenzyl)-3-isopropyl-1,3,5-triazine-2,4(1H,3H)-dione [ No CAS ]
N-(1-(4-chlorobenzyl)-5-isopropyl-4,6-dioxo-1,4,5,6-tetrahydro-1,3,5-triazin-2-yl)-4-isopropoxybenzamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48.6%	With triethylamine In N,N-dimethyl-formamide for 6h;	Preparation of N-(1-(4-chlorobenzyl)-5-isopropyl-4,6-dioxo-1,4,5,6-tetrahydro-1,3,5-triazin-2-yl)-4-isopropoxybenzamide (9) To a solution of 6-amino-1-(4-chlorobenzyl)-3-isopropyl-1,3,5-triazine-2,4(1H, 3H)-dione 8 (60 mg, 0.204 mmol) in DMF (2 ml) were added Et3N (0.037 ml, 0.265 mmol) and 4-Isopropoxy-benzoyl chloride (42.5 mg, 0.214 mmol) to give yellow suspension. After being stirred for 6h, water (2 ml) was added to give white suspension. The suspension was filtered to give a solid, which was suspended in EtOAc. The mixture was washed with sat.NaHCO3 aq, and brine, producing emulsion. The emulsion was filtered and dried to give 9 (45.2 mg, Yield: 48.6 %) as a white solid. 1H-NMR (DMSO-D6) δ: 1.27 (6H, d, J = 5.9 Hz), 1.38 (6H, d, J = 6.9 Hz), 4.66-4.74 (H1, m), 4.80-4.89 (1H, m), 5.20 (2H, s), 6.94 (2H, d, J = 8.8 Hz), 7.38 (2H, d, J = 8.5 Hz), 7.47 (2H, d, J = 8.5 Hz), 7.97 (2H, d, J = 8.78 Hz), 12.48 (1H, s); MS-ESI (m/z) = 457 [M+H]+.

Reference： [1]Kai, Hiroyuki; Horiguchi, Tohru; Kameyama, Takayuki; Asahi, Kentaro; Endoh, Takeshi; Jikihara, Sae; Hasegawa, Tsuyoshi; Tanaka, Satoru; Nozu, Azusa; Takeyama, Chie; Tomari, Maki; Takahashi, Fumiyo; Tamura, Naomi; Yagi, Shigenori; Itoh, Tetsuji; Isou, Yasuyoshi [Bioorganic and Medicinal Chemistry Letters, 2021, vol. 37]

52
N-(N-tert-butoxycarbonyl-L-leucyl)-3-aminobenzenesulfonamide [ No CAS ]
[ 36823-82-2 ]
C₂₇H₃₇N₃O₇S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran at 20℃;	5.1.18. General procedure 2 for preparation of 64-81, 83-91 General procedure: To a solution of organic acids (1.1 eq) in SOCl2, the reaction wasstirred at reflux, then finished, SOCl2 was removed and 5 mL THFwas added and dropwise to compound 26 (1.0 eq). Mixture wasstirred at r.t overnight. Then solvent was removed, H2O and ethylacetate was added, organic layer was dried by anhydrous Na2SO4and concentrated. Next, to a solution of compounds gained above inethyl acetate, HCl gas was added for 0.5 h, filtered the solid to affordproducts.

Reference： [1]Li, Zezhong; Xin, Weixiang; Wang, Qing; Zhu, Mingyan; Zhou, Huchen [European Journal of Medicinal Chemistry, 2021, vol. 217]

53
[ 36823-82-2 ]
[ 24812-90-6 ]
C₁₉H₂₁NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine In tetrahydrofuran	8.1.2.2. Method B, synthesis of amide bond using thionyl chloride. General procedure: The appropriate carboxylic acid (1 eq.) was cooled to 0 C and then thionyl chloride (2 eq.) was added dropwise. The mixture was thenheated under reflux for 2 h, and the excess of thionyl chloride wasevaporated under vacuum. The acid chloride was dissolved in dryTHF and added dropwise to a solution of the appropriate amine (0.9eq.) and DIPEA (3 eq.) in THF. After completion, the reactionmixture was diluted with ethyl acetate and washed with a saturatedaqueous solution of ammonium chloride and brine. Theorganic layerwas dried over anhydrous sodium sulfate, filtered, andconcentrated in vacuo. The residue was purified using columnchromatography (chloroform/methanol as eluents). The yieldswere around 50-70%.

Reference： [1]Darwish, Salma; Erdmann, Frank; Ghazy, Ehab; Heimburg, Tino; Jung, Manfred; Lancelot, Julien; Pierce, Raymond; Robaa, Dina; Romier, Christophe; Schmidt, Matthias; Schmidtkunz, Karin; Shaik, Tajith B.; Simoben, Conrad V.; Sippl, Wolfgang; Truhn, Anne; Zeyen, Patrik [European Journal of Medicinal Chemistry, 2021, vol. 225]

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
{[ item.p_purity ]}	{[ item.pr_size ]}	{[ getRatePrice(item.pr_usd, 1,1) ]} {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]}	{[ getRatePrice(item.pr_usd, 1,1) ]}	Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate) ]} {[ getRatePrice(item.pr_usd,1,item.mem_rate) ]}	{[ item.pr_usastock ]}	Inquiry -	{[ item.pr_chinastock ]}	Inquiry -

CAS No. :	36823-82-2	MDL No. :	MFCD00044898
Formula :	C₁₀H₁₁ClO₂	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	USRKDQLKRQMYKX-UHFFFAOYSA-N
M.W :	198.64	Pubchem ID :	2724465
Synonyms :

Num. heavy atoms :	13
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.3
Num. rotatable bonds :	3
Num. H-bond acceptors :	2.0
Num. H-bond donors :	0.0
Molar Refractivity :	52.73
TPSA :	26.3 Å²

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) :	-5.24 cm/s

[ CAS No. 36823-82-2 ] {[proInfo.proName]}

Quality Control of [ 36823-82-2 ]

Related Doc. of [ 36823-82-2 ]

Product Details of [ 36823-82-2 ]

Calculated chemistry of [ 36823-82-2 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 36823-82-2 ]

Application In Synthesis of [ 36823-82-2 ]

[ 36823-82-2 ] Synthesis Path-Downstream 1~53

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Log Po/w (iLOGP) :	2.52
Log Po/w (XLOGP3) :	3.2
Log Po/w (WLOGP) :	2.85
Log Po/w (MLOGP) :	2.3
Log Po/w (SILICOS-IT) :	2.85
Consensus Log Po/w :	2.75

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

Log S (ESOL) :	-3.23
Solubility :	0.117 mg/ml ; 0.000587 mol/l
Class :	Soluble
Log S (Ali) :	-3.42
Solubility :	0.0748 mg/ml ; 0.000377 mol/l
Class :	Soluble
Log S (SILICOS-IT) :	-3.53
Solubility :	0.0586 mg/ml ; 0.000295 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.24

Signal Word:	Danger	Class:	8
Precautionary Statements:	P260-P264-P280-P301+P330+P331-P303+P361+P353-P304+P340-P305+P351+P338-P310-P321-P363-P405-P501	UN#:	3265
Hazard Statements:	H314	Packing Group:	Ⅲ
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
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Prevention
Code	Phrase
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P285	In case of inadequate ventilation wear respiratory protection.
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Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
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P307	IF exposed:
P308	IF exposed or concerned:
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P321
P322
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P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
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P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
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P411
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P413
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P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
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P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling