[ CAS No. 1007882-23-6 ] HCV-IN-30

Cat. No.: A203689

2D 3D

Structure of 1007882-23-6 * Storage: Sealed in dry,2-8°C

Purity	Size	Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
95%	1g	$12.00	Inquiry	Inquiry
95%	5g	$24.00	Inquiry	Inquiry
95%	10g	$38.00	Inquiry	Inquiry
95%	25g	$71.00	Inquiry	Inquiry

Search after Editing

* Storage: Sealed in dry,2-8°C

For Research Only 120K+ Compounds Competitive Price 1-2 Day Shipping

Quality Control of [ 1007882-23-6 ]

COA NMR CNMR HPLC LC-MS

Related Doc. of [ 1007882-23-6 ]

Specification

Alternatived Products of [ 1007882-23-6 ]

Product Details of [ 1007882-23-6 ]

CAS No. :	1007882-23-6	MDL No. :	MFCD28404669
Formula :	C₃₆H₄₄N₆O₄	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WPMTYMFNINZZHE-KYJUHHDHSA-N
M.W :	624.77	Pubchem ID :	24898407
Synonyms :		Chemical Name :	BIs(2-methyl-2-propanyl) (2S,2'S)-2,2'-[4,4'-biphenyldiylbis(1H-imidazole-4,2-diyl)]di(1-pyrrolidinecarboxylate)

Calculated chemistry of [ 1007882-23-6 ] Expand+

Safety of [ 1007882-23-6 ]

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 [ 1007882-23-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1007882-23-6 ]

[ 1007882-23-6 ] Synthesis Path-Downstream 1~22

1
[ 14221-01-3 ]
[ 1007882-04-3 ]
[ 1007882-12-3 ]
[ 1007882-23-6 ]
[ 791-28-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate; In 1,2-dimethoxyethane; water; at 80℃; for 5.75h;	Example 1, Step d di-tert-butyl (2S,2'S)-2,2'-(4,4'-biphenyldiylbis(]H-imidazole-5,2-diyl))di(1-pyrrolidinecarboxylate) Pd(Ph3P)4 (59.9 mg, 0.0518 mmol) was added to a mixture of bromide 1b (576.1 mg, 1.469 mmol), boronate 1c (621.8 mg, 1.415 mmol), NaHCO3 (400.4 mg, 4.766 mmol) in 1,2-dimethoxyethane (12 mL) and water (4 mL). The reaction mixture was flushed with nitrogen, heated with an oil bath at 80 C. for 5.75 hours, and then the volatile component was removed in vacuo. The residue was partitioned between 20% methanol/CHCl3 (60 mL) and water (30 mL), and the aqueous phase was extracted with 20% methanol/CHCl3 (30 mL). The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. A silica gel mesh was prepared from the resulting crude material and submitted to flash chromatography (ethyl acetate) to provide dimer id, contaminated with Ph3PO, as an off-white solid (563 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): 6 12.21-12-16/11.95-11.78 (m, 2H), 7.85-7.48/7.32-7.25 (m, 10H), 4.90-4.71 (m, 2H), 3.60-3.32 (m, 4H), 2.30-1.79 (m, 8H), 1.46-1.10 (m, 18H). LC (Cond. 1b): RT=1.77 min; LC/MS: Anal. Calcd. for [M+H]+C36H45BN6O4: 625.35; found 625.48.

Reference： [1]Patent: US2008/44380,2008,A1 .Location in patent: Page/Page column 73

2
[ 1007882-23-6 ]
[ 1007882-27-0 ]

Yield	Reaction Conditions	Operation in experiment
87%	With hydrogenchloride; In methanol; water; at 50℃; for 4h;	Compound 4 (1.3 g, 2.08mmol) was treated with 6M aqueous hydrogen chloride (2 ml) in methanol (30 ml) and stirred at ambient temperature overnight. The resulting solid was filtered and washed with petroleum ether to give 5 (0.9 g, 87 %) as a yellow solid.
104.5 g	With hydrogenchloride; In water; toluene; at 60 - 65℃;	Step 3: Preparation of 5,5'-biphenyl-4,4'-diylbis{2-[(2S)-pyrrolidin-2-yl]-lH- imidazole}: The reaction mixture obtained in step 2 was cooled to 60C to 65 C and concentrated hydrochloric acid (400 mL) was added slowly over a period of 2.5 hours. The reaction mixture was stirred for 3 hours to 4 hours at 60C to 65C. On completion of reaction, the reaction mixture was cooled to 25C and de-ionized water (200 mL) was added. The organic layer was discarded, and carbon (5 g) was added to the aqueous layer. The mixture was stirred for an hour at 25C, then filtered through a Hyflo bed, and then washed with water (2 chi 150 mL). The aqueous filtrate was added slowly over a period of 60 minutes to an aqueous ammonia solution (25%, 800 mL) at 10C to 30C. The reaction mixture was stirred for 3 hours at 25 C, then filtered, and then washed with water (3 x 500 mL) to obtain a solid residue. The solid residue was dried under vacuum (5 mmHg - 20 mmHg) at 25 C for 2 hours to 3 hours, followed by drying under vacuum (5 mmHg - 20 mmHg) at 45C to 50C for about 15 hours to about 20 hours to obtain the title product. Dry weight: 104.5g Yield (w/w): 97.2%
	With trifluoroacetic acid; In dichloromethane; at 20℃; for 3.2h;	A mixture of carbamate 1d (560 mg) and 25% TFA/CH2Cl2 (9.0 mL) was stirred at ambient condition for 3.2 hours. The volatile component was removed in vacuo, and the resulting material was free based using an MCX column (methanol wash; 2.0 M NH3/methanol elution) to provide pyrrolidine 1e as a dull yellow solid (340 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): delta11.83 (br s, 2H), 7.80 (d, J=8.1, 4H), 7.66 (d, J=8.3, 4H), 7.46 (br s, 2H), 4.16 (app t, J=7.2, 2H), 2.99-2.69 (m, 6H), 2.09-2.00 (m, 2H), 1.94-1.66 (m, 6H). LC (Cond. 1): RT=1.27 min; >98% homogeneity index; LC/MS: Anal. Calcd. for [M+H]- C26H29N6: 425.25; found 425.25; HRMS: Anal. Calcd. for [M+H]- C26H29N6: 425.2454; found 425.2448

		Example 1, Step e 5,5'-(4,4'-biphenyldiyl)bis(2-((2S)-2-pyrrolidinyl)-1H-imidazole) A mixture of carbamate 1d (560 mg) and 25% TFA/CH2Cl2 (9.0 mL) was stirred at ambient condition for 3.2 hours. The volatile component was removed in vacuo, and the resulting material was free based using an MCX column (methanol wash; 2.0 M NH3/methanol elution) to provide pyrrolidine 1e as a dull yellow solid (340 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): delta 11.83 (br s, 2H), 7.80 (d, J=8.1, 4H), 7.66 (d, J=8.3, 4H), 7.46 (br s, 2H), 4.16 (app t, J=7.2, 2H), 2.99-2.69 (m, 6H), 2.09-2.00 (m, 2H), 1.94-1.66 (m, 6H). LC (Cond. 1): RT=1.27 min; >98% homogeneity index; LC/MS: Anal. Calcd. for [M+H]- C26H29N6: 425.25; found 425.25; HRMS: Anal. Calcd. for [M+H]-C26H29N6: 425.2454; found 425.2448
		A mixture of carbamate 1d (560 mg) and 25% TFA/CH2Cl2 (9.0 mL) was stirred at ambient condition for 3.2 hours. The volatile component was removed in vacuo, and the resulting material was free based using an MCX column (methanol wash; 2.0 M NH3/methanol elution) to provide pyrrolidine 1e as a dull yellow solid (340 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): delta 11.83 (br s, 2H), 7.80 (d, J=8.1, 4H), 7.66 (d, J=8.3, 4H), 7.46 (br s, 2H), 4.16 (app t, J=7.2, 2H), 2.99-2.69 (m, 6H), 2.09-2.00 (m, 2H), 1.94-1.66 (m, 6H). LC (Cond. 1): RT=1.27 min; >98% homogeneity index; LC/MS: Anal. Calcd. for [M+H]+ C26H29N6: 425.25; found 425.25; HRMS: Anal. Calcd. for [M+H]+ C26H29N6: 425.2454; found 425.2448
	With trifluoroacetic acid; In dichloromethane; at 20℃; for 3.2h;	Example 1, Step e5,5'-(4,4'-biphenyldiyl)bis(2-((2S)-2-pyrrolidinyl)-lH-imidazole)A mixture of carbamate Id (560 mg) and 25% TFA/CH2C12 (9.0 mL) was stirred at ambient condition for 3.2 hours. The volatile component was removed in vacuo, and the resulting material was free based using an MCX column (methanol wash; 2.0 M NH3/methanol elution) to provide pyrrolidine Ie as a dull yellow solid (340 mg). 1H NMR (DMSO-d6, delta= 2.5 ppm, 400 MHz): delta 11.83 (br s, 2H), 7.80 (d, <n="121"/>J = 8.1, 4H), 7.66 (d, J = 8.3, 4H), 7.46 (br s, 2H), 4.16 (app t, J = 7.2, 2H), 2.99- 2.69 (m, 6H), 2.09-2.00 (m, 2H), 1.94-1.66 (m, 6H). LC (Cond. 1): RT = 1.27 min; > 98% homogeneity index; LC/MS: Anal. Calcd. for [M+H]+ C26H29N6: 425.25; found 425.25; HRMS: Anal. Calcd. for [M+H]+ C26H29N6: 425.2454; found 425.2448

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150
[2]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012
[3]Patent: WO2016/79697,2016,A1 .Location in patent: Page/Page column 9
[4]Patent: US2008/44379,2008,A1 .Location in patent: Page/Page column 71
[5]Patent: US2008/44380,2008,A1 .Location in patent: Page/Page column 74
[6]Patent: US2008/50336,2008,A1 .Location in patent: Page/Page column 70
[7]Patent: WO2009/102318,2009,A1 .Location in patent: Page/Page column 119-120

3
[ 1007882-04-3 ]
[ 1007882-12-3 ]
[ 1007882-23-6 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 5.75h;	Pd(Ph3P)4 (59.9 mg, 0.0518 mmol) was added to a mixture of bromide 1b (576.1 mg, 1.469 mmol), boronate 1c (621.8 mg, 1.415 mmol), NaHCO3 (400.4 mg, 4.766 mmol) in 1,2-dimethoxyethane (12 mL) and water (4 mL). The reaction mixture was flushed with nitrogen, heated with an oil bath at 80 C. for 5.75 hours, and then the volatile component was removed in vacuo. The residue was partitioned between 20% methanol/CHCl3 (60 mL) and water (30 mL), and the aqueous phase was extracted with 20% methanol/CHCl3 (30 mL). The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. A silica gel mesh was prepared from the resulting crude material and submitted to flash chromatography (ethyl acetate) to provide dimer 1d, contaminated with Ph3PO, as an off-white solid (563 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): delta 12.21-12-16/11.95-11.78 (m, 2H), 7.85-7.48/7.32-7.25 (m, 10H), 4.90-4.71 (m, 2H), 3.60-3.32 (m, 4H), 2.30-1.79 (m, 8H), 1.46-1.10 (m, 18H). LC (Cond. 1b): RT=1.77 min; LC/MS: Anal. Calcd. for [M+H]+ C36H45BN6O4: 625.35; found 625.48.
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 5.75h;Product distribution / selectivity;	Pd(Ph3P)4 (59.9 mg, 0.0518 mmol) was added to a mixture of bromide 1b (576.1 mg, 1.469 mmol), boronate 1c (621.8 mg, 1.415 mmol), NaHCO3 (400.4 mg, 4.766 mmol) in 1,2-dimethoxyethane (12 mL) and water (4 mL). The reaction mixture was flushed with nitrogen, heated with an oil bath at 80 C. for 5.75 hours, and then the volatile component was removed in vacuo. The residue was partitioned between 20% methanol/CHCl3 (60 mL) and water (30 mL), and the aqueous phase was extracted with 20% methanol/CHCl3 (30 mL). The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. A silica gel mesh was prepared from the resulting crude material and submitted to flash chromatography (ethyl acetate) to provide dimer 1d, contaminated with Ph3PO, as an off-white solid (563 mg). 1H NMR (DMSO-d6, delta=2.5 ppm, 400 MHz): delta 12.21-12-16/11.95-11.78 (m, 2H), 7.85-7.48/7.32-7.25 (m, 10H), 4.90-4.71 (m, 2H), 3.60-3.32 (m, 4H), 2.30-1.79 (m, 8H), 1.46-1.10 (m, 18H). LC (Cond. 1b): RT=1.77 min; LC/MS: Anal. Calcd. for [M+H]+ C36H45BN6O4: 625.35; found 625.48.
	With sodium hydrogencarbonate;tetrakis(triphenylphosphine) palladium(0); In 1,2-dimethoxyethane; water; at 80℃; for 5.75h;	Example 1, Step d di-tert-butyl (2S, 2 'S)-2, 2 '-(4,4'-biphenyldiylbis(lH-imidazole-5, 2-diyl))di(l- pyrrolidinecarboxylate)Pd(Ph3P)4 (59.9 mg, 0.0518 mmol) was added to a mixture of bromide Ib (576.1 mg, 1.469 mmol), boronate Ic (621.8 mg, 1.415 mmol), NaHCO3 (400.4 mg, 4.766 mmol) in 1,2-dimethoxyethane (12 mL) and water (4 mL). The reaction mixture was flushed with nitrogen, heated with an oil bath at 80 0C for 5.75 hours, and then the volatile component was removed in vacuo. The residue was partitioned <n="119"/>between 20% methanol/ CHCI3 (60 mL) and water (30 mL), and the aqueous phase was extracted with 20% methanol/CHCl3 (30 mL). The combined organic phase was washed with brine, dried (MgSO4), filtered, and concentrated in vacuo. A silica gel mesh was prepared from the resulting crude material and submitted to flash chromatography (ethyl acetate) to provide dimer Id, contaminated with Ph3PO, as an off-white solid (563 mg). 1H NMR (DMSO-d6, delta = 2.5 ppm, 400 MHz): delta 12.21-12- 16/11.95-11.78 (m, 2H), 7.85-7.48/ 7.32-7.25 (m, 10H), 4.90-4.71 (m, 2H), 3.60-3.32 (m, 4H), 2.30-1.79 (m, 8H), 1.46-1.10 (m, 18H). LC (Cond. Ib): RT = 1.77 min; LC/MS: Anal. Calcd. for [M+H]+ C36H45BN6O4: 625.35; found 625.48.

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012
[2]Patent: US2008/44379,2008,A1 .Location in patent: Page/Page column 70
[3]Patent: US2008/50336,2008,A1 .Location in patent: Page/Page column 68
[4]Patent: WO2009/102318,2009,A1 .Location in patent: Page/Page column 117-118

4
[ 1009119-82-7 ]
[ 1007882-23-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	With ammonium acetate; In toluene; at 130℃; for 15h;	A mixture of 3 (2 g, 3.01 mmol) and NH4OAc (4.65 g, 60.3 mmol) in methylbenzene (30 mL) was heated at 130 C for 15 h. The volatile component was removed in vacuo, and the residue was partitioned between CH2Cl2 and H2O, where enough satd. aq NaHCO3 solution was added to neutralize the aqueous medium. The aqueous phase was extracted with CH2Cl2, and the combined organic phase was dried (MgSO4), filtered, and concentrated in vacuo. The residue was puried by flash chromatography (silica gel; 50% EtOAc/hexanes) to afford 4 as white solid (1.6 g, 85 %).
63%		Preparation of Compound (6); The toluene solution of Compound 5 was charged with 78 g (1.011 moles, 20 equiv) ammonium acetate and heated to 95-100 C. The mixture was allowed to stir at 95-100 C. for 15 hours. After reaction completion, the mixture was cooled to 70-80 C. and charged with 7 mL acetic acid, 40 mL n-butanol, and 80 mL of 5 vol % aqueous acetic acid. The resulting biphasic solution was split while maintaining a temperature >50 C. The rich organic phase was charged with 80 mL of 5 vol % aqueous acetic acid, 30 mL acetic acid and 20 mL n-butanol while maintaining a temperature >50 C. The resulting biphasic solution was split while maintaining a temperature >50 C. and the rich organic phase was washed with an additional 80 mL of 5 vol % aqueous acetic acid. The rich organic phase was then solvent exchanged into toluene to a target volume of 215 mL by vacuum distillation. While maintaining a temperature >60 C., 64 mL methanol was charged. The resulting slurry was heated to 70-75 C. and aged for 1 hour. The slurry was cooled to 20-25 C. over 1 hour and aged at that temperature for an additional hour. The slurry was filtered and the cake was washed with 200 mL 10:3 toluene:methanol. The product was dried under vacuum at 70 C., resulting in 19.8 g (31.7 mmol, 63%) of the desired product: 1H NMR (400 MHz, DMSO-d6) delta 13.00-11.00 (s, 2H), 7.90-7.75 (m, 4H), 7.75-7.60 (m, 4H), 7.60-7.30 (s, 2H), 4.92-4.72 (m, 2H), 3.65-3.49 (m, 2H), 3.49-3.28 (m, 2H), 2.39-2.1 (m, 2H), 2.10-1.87 (m, 6H), 1.60-1.33 (s, 8H), 1.33-1.07 (s, 10H); 13 C NMR (100 MHz, DMSO-d6) delta 154.1, 153.8, 137.5, 126.6, 125.0, 78.9, 78.5, 55.6, 55.0, 47.0, 46.7, 33.7, 32.2, 28.5, 28.2, 24.2, 23.5; IR (KBr, cm-1) 2975, 2876, 1663, 1407, 1156, 1125; HRMS calcd for C36H45N6O4 (M+H; ESI+): 625.3502. Found: 625.3502. mp 190-195 C. (decomposed).
63%	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;	The above toluene solution of Example CQ-Ib was charged with 78 g (1.011 moles, 20 equiv) ammonium acetate and heated to 95-100 0C. The mixture was allowed to stir at 95-100 0C for 15h. After reaction completion, the mixture was cooled to 70-80 0C and charged with 7 mL acetic acid, 40 mL n-butanol, and 80 mL of 5 vol% aqueous acetic acid. The resulting biphasic solution was split while maintaining a temperature >; 50 0C. The rich organic phase was charged with 80 mL of 5 vol% aqueous acetic acid, 30 mL acetic acid and 20 mL n-butanol while maintaining a temperature >; 50 C. The resulting biphasic solution was split while maintaining a temperature >; 50 0C and the rich organic phase was washed with an additional 80 mL of 5 vol% aqueous acetic acid. The rich organic phase was then solvent exchanged into toluene to a target volume of 215 mL by vacuum distillation. While maintaining a temperature >; 60 0C, 64 mL MeOH was charged. The resulting slurry was heated to 70-75 0C and aged for Ih. The slurry was cooled to 20-25 0C over Ih and aged at that temperature for an additional hour. The slurry was filtered and the cake was washed with 200 mL 10:3 toiuene:MeOH. The product was dried under vacuum at 70 0C, resulting in 19.8 g (31.7 mmol, 63%) of the desired product: 1H NMR (400 MHz, OMSO-d6) delta 13.0041.00 (s, 2H), 7.90-7.75 (m, 4H), 7.75-7.60 (m, 4H), 7.60-7.30 (s, 2H), 4.92-4.72 (m, 2H), 3.65-3.49 (m, 2H), 3.49-3.28 (m, 2H), 2.39-2.1 (m, 2H), 2.10-1.87 (m, 6H)1 1.60-1.33 (s, 8H), 1.33-1.07 (s, 10H); 13c NMR (100 MHz, OMSO-d6) 5 154.1, 153.8, 137.5, 126.6, 125.0, 78.9, 78.5, 55.6, 55.0, 47.0, 46.7, 33.7, 32.2, 28.5, 28.2, 24.2, 23.5; IR (KBr, cm-1) 2975, 2876, 1663, 1407, 1156, 1125; HRMS calcd for C36H45N6O4 (M + H; ESI+): 625.3502. Found: 625.3502. mp 190-195 0C (decomposed).

63%	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;	To the toluene solution of compound 3 was added 78 g (1.011 mole, 20 eq.) Of ammonium acetate and heated to 95-100 . The mixture was stirred at 95-100 & lt; 0 & gt; C for 15 h. After completion of the reaction, the mixture was cooled to 70-80 , and 7 mL acetic acid, 40 mL n-butanol, and 80 mL of 5 vol% aqueous acetic acid were added. The resulting biphasic solution was separated while maintaining the temperature above 50 & lt; 0 & gt; C. 80 mL of 5 vol% aqueous acetic acid, 30 mL acetic acid and 20 mL n-butanol were added to the rich organic phase while maintaining the temperature above 50 & lt; 0 & gt; C. The resulting biphasic solution was separated while maintaining the temperature above 50 & lt; 0 & gt; C, The rich organic phase was washed with an additional 80 mL of 5 vol% aqueous acetic acid. The rich organic phase was then solvent exchanged to toluene with a target volume of 215 mL by vacuum distillation. 64 mL of methanol was added while maintaining the temperature above 60 & lt; 0 & gt; C. The resulting slurry was heated to 70-75 & lt; 0 & gt; C and aged for 1 hour. The slurry was cooled to 20-25 [deg.] C over 1 hour and aged at this temperature for an additional hour. The slurry was filtered and the cake was washed with 200 mL 10: 3 toluene: methanol. The product was dried under vacuum at 70 & lt; 0 & gt; C to give 19.8 g (31.7 mmol, 63%) of the desired product:
63.5%	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;Large scale;	To a solution of dakatatvein IV (8.5 kg) in toluene (45.5 kg) (51 liters), ammonium acetate (14.59 kg) was added and the temperature was raised to 95 to 100 C. After stirring for 15 hours, the temperature was lowered to 20-25 C, 1.75 Kg of glacial acetic acid, 8.14 Kg of n-butanol and 20.1 Kg of 13% by mass sodium chloride aqueous solution (The mass percentage refers to the percentage of the mass of sodium chloride as a percentage of the total mass of sodium chloride aqueous solution) to form a mixed solution, and the mixture is stirred and left to stand for delamination. The organic phase was further added with 20.1 Kg of 13% by mass sodium chloride aqueous solution (Said mass percentage refers to the percentage of the mass of sodium chloride as a percentage of the total mass of sodium chloride aqueous solution), and the mixture is stirred for standing and stratification. The organic phase was decompressed and swirled with 30 liters of solvent, and 4.74 Kg of methanol was added at a temperature higher than 50 C. The mixture was heated to 60 C.-65 C. for 1 hour, cooled to 10 C.-15 C., stirred for 2 hours, filtered, Washed with 4.26Kg mixed solvent of toluene and methanol (the mass ratio of toluene and methanol in the mixed solvent is 10: 3), and dried at 50 C under vacuum for 16 hours to obtain 5.00 kg of intermediate product of daclatasvir with a yield of 63.5%. HPLC : 97.46%.
63%	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;Product distribution / selectivity;	The above toluene solution of Example A-1e-2 was charged with 78 g (1.011 moles, 20 equiv) ammonium acetate and heated to 95-100 C. The mixture was allowed to stir at 95-100 C. for 15 h. After reaction completion, the mixture was cooled to 70-80 C. and charged with 7 mL acetic acid, 40 mL n-butanol, and 80 mL of 5 vol % aqueous acetic acid. The resulting biphasic solution was split while maintaining a temperature>50 C. The rich organic phase was charged with 80 mL of 5 vol % aqueous acetic acid, 30 mL acetic acid and 20 mL n-butanol while maintaining a temperature>50 C. The resulting biphasic solution was split while maintaining a temperature>50 C. and the rich organic phase was washed with an additional 80 mL of 5 vol % aqueous acetic acid. The rich organic phase was then solvent exchanged into toluene to a target volume of 215 mL by vacuum distillation. While maintaining a temperature>60 C., 64 mL MeOH was charged. The resulting slurry was heated to 70-75 C. and aged for 1 h. The slurry was cooled to 20-25 C. over 1 h and aged at that temperature for an additional hour. The slurry was filtered and the cake was washed with 200 mL 10:3 toluene:MeOH. The product was dried under vacuum at 70 C., resulting in 19.8 g (31.7 mmol, 63%) of the desired product: 1H NMR (400 MHz, DMSO-d6) delta 13.00-11.00 (s, 2H), 7.90-7.75 (m, 4H), 7.75-7.60 (m, 4H), 7.60-7.30 (s, 2H), 4.92-4.72 (m, 2H), 3.65-3.49 (m, 2H), 3.49-3.28 (m, 2H), 2.39-2.1 (m, 2H), 2.10-1.87 (m, 6H), 1.60-1.33 (s, 8H), 1.33-1.07 (s, 10H); 13C NMR (100 MHz, DMSO-d6) delta 154.1, 153.8, 137.5, 126.6, 125.0, 78.9, 78.5, 55.6, 55.0, 47.0, 46.7, 33.7, 32.2, 28.5, 28.2, 24.2, 23.5; IR (KBr, cm-1) 2975, 2876, 1663, 1407, 1156, 1125; HRMS calcd for C36H45N6O4 (M+H; ESI+): 625.3502. Found: 625.3502. mp 190-195 C. (decomposed).
62%		Alternative Preparation of Compound (6); The toluene solution of Compound 5 was charged with 78 g (1.011 moles, 20 equiv) ammonium acetate and heated to 95-100 C. The mixture was allowed to stir at 95-100 C. for 15 hours. After reaction completion, the mixture was cooled to 50-60 C. and charged with 140 mL of 2:1 acetic acid:water. The resulting biphasic solution was split while maintaining a temperature >50 C. The organic layer was washed with 70 mL 1:1 acetic acid:water. The rich aqueous layers were combined and the residual toluene removed via vacuum distillation. While maintaining a temperature of 50-60 C., 50 mL methanol was charged followed by 68 mL 10 N NaOH. The resulting slurry was cooled to 20-25 C. over 1 hour and aged at that temperature for an additional hour. The slurry was filtered and the cake was washed with 200 mL water followed by 75 mL MeOH. The product was dried under vacuum at 70 C., resulting in 27.4 g of crude product. A 1 L jacketed flask, equipped with a nitrogen line, overhead stirrer and thermocouple was charged with 63 mL NMP and 25 g of the above crude product. The mixture was heated to 50-60 C. and charged with 83 mL MeOH. The resulting slurry was allowed to stir at 50-60 C. for 18 hours. The slurry was then charged with 208 mL MeOH while maintaining a temperature >50 C. The slurry was cooled to ambient temperature over 1.5 hours and stirred for an additional 2 hours. The solids were filtered, washed with 75 mL MeOH and dried under vacuum (at)70 C. to give 18.0 g (28.8 mmol, 62% adjusted) of the desired product.
62%	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;	Ester (15.6 g, 23.5 mmol) and 95 mL of toluene were added into the reaction flask,then ammonium acetate (30 g, 389 mmol) was added and the temperature was raised to 98 C (temperature range 95 to 100 C) for 15 hours; ] Cooled to 60 C, slowly add saturated aqueous sodium bicarbonate solution to adjust the pH to 8 (PH range of 7-8); at about 60 C carried out stratification , then add 10 g of methanol into to the toluene layer, slowly drop temperature to 14 C (temperature range 10 to 15 C), precipitate the solid and filter to give 9. 1g imidazole product (33. 1g, yield 62 %)
19.8 g	With ammonium acetate; In toluene; at 95 - 100℃; for 15h;	To the above toluene solution was added 78g of ammonium acetate and heated to 95-100 C and kept at this temperature for 15 hours. When the reaction is complete, the reaction system was cooled to 70-80 degrees, added to the system 7mL of acetic acid, 40mL of n-butanol and 80mL 5% aqueous acetic acid. 50 degrees phase. The organic phase was washed with 5% acetic acid solution, the organic phase was poured into a methanol solution, filtered, the cake washed with a volume ratio of 10: 3 methanol - toluene solution, and dried under 70 degrees, to give 19.8g product, 63% yield.
100 g	With ammonium acetate; In toluene; for 18h;Reflux;	A reaction vessel was charged with 2,2'-[biphenyl-4,4'-diylbis(2-oxoethane-2,l-diyl)] 1, l'-di- tert-butyl dipyrrolidine- 1 ,2-dicarboxylate (formula IVa, 50.0 g), ammonium acetate (115.9 g), and toluene (750 mL). The reaction mass was stirred and the temperature was raised to reflux and stirring continued for about 18 hours. Upon completion of the reaction (as monitored by TLC), the reaction mass was cooled to below about 60 C and toluene (-400 mL) was distilled off under vacuum. After distillation, ethyl acetate (600 mL) and 5% aqueous acetic acid (600 mL) were added. Stirring was continued for an additional 3 hours. The solution was filtered and the resulting solid washed with ethyl acetate (200 mL) to afford di-tert-butyl (2S,2'S)-2,2'-[biphenyl-4,4'-diylbis(lH-imidazole-5,2-diyl)]dipyrrolidine-l-carboxylate. Yield: 100 g
70.2 g	With ammonium acetate; In toluene; at 95℃; for 20h;	In 2 lit three necked round bottom flask equipped with mechanical stiner, 50 g of 1,1- biphenyl-4,4-diylbis(2-chloroethanone) of Formula V, 400 ml toluene, 80.51 g of N-bocproline and 63 g diisopropylethylamine were added at 25-30C and stined for 15 mm at same temperature. Reaction mass was heated to 70-75C and stined for 4 hr. After completion of the reaction, filtered the reaction mass and washed with 100 ml toluene. To the filterate, 250.5 g ammonium acetate was added and heated to 95C and stined for about 2Ohr at same temperature. After completion of the reaction, reaction mass was allowed to cool to 60C and 500 ml 10% methanol in water was added slowly at 50-55C. The precipitated solids was filtered and washed with water. The obtained solid compound was stined in 250 ml methanol at 60-65C for 1 hr and the reaction mass was allowed to cool to 25-30C, filtered the solids and washed with 50 ml methanol followed by dried at 60-65C to get title compound. Yield: 70.2 g.
	With ammonium acetate; In toluene; at 55℃; for 18h;	To 1-1 was added 600 g of toluene and 32 g of ammonium acetate,Heated to 55 C and stirred for 18h,A solid precipitation.The solid was filtered to dry at 70 C to a moisture of less than 1.0%Intermediate N-3 was obtained
130 g	With ammonium acetate; In toluene; at 0.105 - 0.95℃;	Ammonium acetate (390g) was added to the toluene solution of example 1 and the reaction mixture was stirred, heated to about 95C to about 105C and maintained for about 1 Oh to about 1 5h. The reaction mixture was cooled to about 75C to about 80C and water (400mL) was added to it while maintaining the temperature at about above75C. The reaction mixture was stirred and the two layers were separated at about the same temperature. The organic layer was cooled to about room temperature and stirred for about 2h to about 3h. The solid obtained was filtered, washed with toluene and dried under vacuum at about 45C to about 55C. Yield: 130g

5
[ 1007882-23-6 ]
methyl N-[(2S)-1-[(2S)-2-[5-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With hydrogenchloride; water; isopropyl alcohol; at 20 - 50℃; for 3h;Product distribution / selectivity;	Alternative Preparation of Compound (7); A jacketed reactor equipped with a mechanical stirrer, thermocouple and a nitrogen inlet was charged with 2.8 L isopropyl alcohol, 1.32 L water, and 1 kg of Compound 6 (1.6 moles, 1 equiv). The slurry was then charged with 1.31 L (1.58 kg, 16.0 moles, 10 equiv) concentrated hydrogen chloride at ambient temperature in 30 min. The resulting solution was heated to 50 C. and allowed to stir for 2.5 hours. The product was crystallized by the addition of 7.2 L isopropyl alcohol and the slurry was cooled to ambient temperature. The product was collected by filtration and washed with 3.7 L 20% water/isopropyl alcohol followed by 7.4 L isopropyl alcohol. The wet cake was dried in a vacuum oven at 50 C. to give 0.84 kg (1.44 moles, 90%) of the desired product.
85.4%	With hydrogenchloride; In 2-methyltetrahydrofuran; methanol; water; at 15 - 20℃; for 6h;	To 40mL of methanol, 60mL 2- methyltetrahydrofuran added 20g of dakatamivir intermediate II, rapid stirring was added dropwise 9% by mass of hydrochloric acid 200mL (The mass percentage refers to the percentage of the mass of hydrogen chloride as a percentage of the total mass of hydrochloric acid), stirred at room temperature (15-20 C) for 6 hours, and the reaction solution was filtered and washed. The resulting wet product was added 80mL of methanol, warmed to 50 C ~ 55 C and stirred for 4 hours, cooled to 15 C ~ 20 C, stirred for 1 hour, filtered, washed at 50 C ~ 55 C under vacuum (-0.08MPa ~ -0.1MPa) for 6 hours to 10 hours to obtain 15.6g of dakatavir intermediate I with a yield of 85.4% and an HPLC purity of 99.42%.
82.6%	With hydrogenchloride; In methanol; water; at 50℃; for 5h;Inert atmosphere;	To a 250 mL reactor equipped with a nitrogen line and overhead stirrer was added 25.0 g of compound 4 (40.01 mmol, 1 equiv.) Followed by 250 mL methanol and 32.85 mL (400.1 mmol, 10 eq.) Of 6M aqueous HCl. The temperature was increased by 50 and stirred at 50 for 5 hours. The resulting slurry was cooled to 20-25 & lt; 0 & gt; C and left to stir for about 18 hours. The slurry was filtered to give a solid which was washed successively with 100 mL of 90% methanol / water (v / v) and 2 x 100 mL of methanol. The wet cake was dried in a vacuum oven at 50 & lt; 0 & gt; C overnight to give 18.12 g (31.8 mmol, 79.4%) of the desired product Respectively

80%	With hydrogenchloride; In methanol; at 20 - 50℃; for 18h;	Imidazole (9.1 g, 14.6 mmol) and 45 mL of methanol were added into the reaction flask,then 6 M hydrochloric acid (24 mL, 146 mmol) was added and the temperature was raised to 50 C for 5 hours , cooled to 20 C, stirred for 18 hours, and filtered to give the hydrochloride salt (6.7 g, yield 80%). (6.7 g, yield 80%).
79.4%	With hydrogenchloride; methanol; water; at 20 - 50℃; for 23h;Product distribution / selectivity;	Preparation of Compound (7); To a 250 mL reactor equipped with a nitrogen line and overhead stirrer, 25.0 g of Compound 6 (40.01 mmol, 1 equiv) was charged followed by 250 mL methanol and 32.85 mL (400.1 mmol, 10 equiv) 6M aqueous HCl. The temperature was increased to 50 C. and agitated at 50 C. for 5 hours. The resulting slurry was cooled to 20-25 C. and held with agitation for about 18 hours. Filtration of the slurry afforded a solid which was washed successively with 100 mL 90% methanol/water (V/V) and 2×100 mL of methanol. The wet cake was dried in a vacuum oven at 50 C. overnight to give 18.12 g (31.8 mmol, 79.4%) of the desired product.
79.4%	With hydrogenchloride; In water; at 20 - 50℃; for 23h;Inert atmosphere;	To a 250 ml reactor equipped with a nitrogen line and overhead stirrer, 25.O g of Example CQ-Ic (40.01 mmol, 1 equiv) was charged followed by 250 mL methanol and (400.1 mmol, 10 equiv) concentrated hydrogen chloride. The temperature was increased to 50 0C and agitated at 50 0C for 5h. The resulting slurry was cooled to 20- 25 0C and held with agitation for ca. 18h. Filtration of the slurry afforded a solid which was washed successively with 100 ml 90% methanol/water (V/V) and 2x100 ml of methanol. The wet cake was dried in a vacuum oven at 50 0C overnight to give 18.12 g (31.8 mmol, 79.4%) of the desired product.
79.4%	With hydrogenchloride; at 20 - 50℃; for 23h;	To a 250mL reaction flask 25g <strong>[1007882-23-6]methyl N-[(2S)-1-[(2S)-2-[5-[4-[4-[2-[(2S)-1-[(2S)-2-(methoxycarbonylamino)-3-methylbutanoyl]pyrrolidin-2-yl]-1H-imidazol-5-yl]phenyl]phenyl]-1H-imidazol-2-yl]pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl]carbamate</strong> dissolved 250mL methanol, 32.85mL 6M hydrochloric acid solution was added. Stirred at 50 degrees for 5 hours. Cooled to room temperature, and stirred at room temperature for 18 hours. Filtered, the filter cake was washed once 100mL 90% aqueous methanol and washed twice with 100mL of methanol. Dried at 50 deg. C to give 18.12g product yield of 79.4%. Recrystallized from methanol, 82.6% recovery.
79.4%	With hydrogenchloride; In methanol; at 20 - 50℃; for 23h;	To a 250 ml reactor equipped with a nitrogen line and overhead stirrer, 25.0 g of Example A-1e-3 (40.01 mmol, 1 equiv) was charged followed by 250 mL methanol and 32.85 mL (400.1 mmol, 10 equiv) 6M aqueous hydrogen chloride. The temperature was increased to 50 C. and agitated at 50 C. for 5 h. The resulting slurry was cooled to 20-25 C. and held with agitation for ca. 18 h. Filtration of the slurry afforded a solid which was washed successively with 100 ml 90% methanol/water (V/V) and 2×100 ml of methanol. The wet cake was dried in a vacuum oven at 50 C. overnight to give 18.12 g (31.8 mmol, 79.4%) of the desired product.Recrystallization of Example A-1e-4To a 250 ml reactor equipped with a nitrogen line and an overhead stirrer, 17.8 g of crude Example A-1e-4 was charged followed by 72 mL methanol. The resulting slurry was agitated at 50 C. for 4 h, cooled to 20-25 C. and held with agitation at 20-25 C. for 1 h. Filtration of the slurry afforded a crystalline solid which was washed with 60 ml methanol. The resulting wet cake was dried in a vacuum oven at 50 C. for 4 days to yield 14.7 g (25.7 mmol, 82.6%) of the desired product: 1H NMR (400 MHz, DMSO-d6) delta 10.5-10.25 (br, 2H), 10.1-9.75 (br, 2H), 8.19 (s, 2H), 7.05 (d, J=8.4, 4H), 7.92 (d, J=8.5, 4H), 5.06 (m, 2H), 3.5-3.35 (m, 4H), 2.6-2.3 (m, 4H), 2.25-2.15 (m, 2H), 2.18-1.96 (m, 2H); 13C NMR (100 MHz, DMSO-d6) delta 156.6, 142.5, 139.3, 128.1, 127.5, 126.1, 116.9, 53.2, 45.8, 29.8, 24.3; IR (KBr, cm-1) 3429, 2627, 1636, 1567, 1493, 1428, 1028. Anal calcd for C26H32N6Cl4: C, 54.75; H, 5.65; Cl, 24.86; Adjusted for 1.9% water: C, 53.71; H, 5.76; N, 14.46; Cl, 24.39. Found: C, 53.74; H, 5.72; N, 14.50; Cl, 24.49; KF=1.9. mp 240 C. (decomposed)
120 g	With hydrogenchloride; In methanol; at 25 - 60℃; for 6h;	A reaction vessel was charged with di-tert-butyl (2S,2'S)-2,2'-[biphenyl-4,4'-diylbis(lH- imidazole-5,2-diyl)]dipyrrolidine-l-carboxylate (formula Ilia, 220.0 g), methanol (660 mL), and methanolic HC1 (on 100% assay of HC1) (82.25 g) at 25 - 35 C. The internal temperature of the reaction mixture was raised to about 60 C and stirring continued for 6 hours. Upon completion of the reaction, as monitored by TLC, -300 mL of methanol was distilled off from the reaction mass which was subsequently cooled to 25 - 35 C. The solution was stirred for an additional 5 hours at 25 - 35 C and filtered to yield 5,5'-biphenyl-4,4'-diylbis{2-[(2S)-pyrrolidin-2-yl]-lH- imidazole} tetrahydrochlonde (tetrahydrochlonde salt of formula II) as a solid. Yield: 120.0 g
70 g	With hydrogenchloride; In water; isopropyl alcohol; at 25 - 55℃; for 4.25h;	In 1 lit three necked round bottom flask equipped with mechanical stiner, 100 g of ditert-butyl (2S,2? S)-2,2? -(4,4? -biphenyldiylbis( 1 H-imidazole-5 ,2-diyl)di( 1 -pynolidin carboxylate) of formula VIII and 300 ml isopropyl alcohol and 130 ml water were added and stirred for 5 mm at 25-30C. To this, 130 ml concentrated HC1 was added slowlyover 60 mm at 25 -30C and stined for 15 mm. Reaction mass was heated to 50-55C and stined for 3 hrs at same temperature. After completion of the reaction, 700 ml isopropyl alcohol was added to the reaction mass at 50-55C. Reaction mass was allowed to cool to 25-35C and stirred for 1 hr at same temperature, filtered the solids and washed with 100 ml isopropyl alcohol. The obtained solid was dissolved in 400 ml methanol at 50-55Cand stined for 3 hrs at same temperature. Reaction mass was allowed to cool to 25-35Cand stined for 1 hr at same temperature. Precipitated solid was filtered and washed with100 ml methanol and 150 ml acetone and dried at 60-65C to get title compound. Yield:70 g; Purity by HPLC: 99.9%.
130g	With hydrogenchloride; In water; isopropyl alcohol; at 0.5 - 0.55℃;	To a stirred mixture of 1 -pyrrolidinecarboxylic acid, 2,2?-( [1,1 ?-biphenyl] -4,4?-diyldi- 1H- imidazole-5,2-diyl)bis-, 1,1 ?-bis( 1,1 -dimethylethyl) ester, (2S,2?5)- (60g) in isopropyl alcohol (1 8OmL) was added water (9OmL) followed by hydrochloric acid (9OmL). The reaction mixture was heated to about 50C to about 55C and maintained at about thesame temperature for about 3h to Sh. Isopropyl alcohol (720mL) was added to the reaction mixture which was cooled to about 20C to about 30C and stirred for about 2h to about 3h. The solid obtained was filtered and washed with isopropyl alcohol. The wet cake was added into methanol and the reaction mixture was heated to about 50C to about 55C under stirring and maintained for about lh at about the same temperature.The reaction mixture was cooled to about 20C to about 30C and stirred for about 2h to about 3h. The solid was filtered, washed with methanol and dried under vacuum at about 45C to about 55C. Yield: 130g

6
[ 1007882-23-6 ]
[ 74-88-4 ]
[ 1007883-24-0 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydride; In dichloromethane; at 20℃; for 5h;	Example 151(IR, 1 'R)-2, 2 '-(4,4'-biphenyldiylbis((l-methyl-lH-imidazole-4, 2-diyl) (2S)-2, 1- pyrrolidinediyl))bis(N,N-dimethyl-2-oxo-l-phenylethanamine)Example 151, Step aTo a stirred solution of 1 d, (2S,2'S)-tert-butyl 2,2'-(4,4'-(biphenyl-4,4'- diyl)bis(lH-imidazole-4,2-diyl))dipyrrolidine-l-carboxylate (100 mg, 0.16 mmole) and iodomethane (40 muL, 0.16 mmole) in CH2Cl2 ( 2 mL) was added sodium hydride <n="169"/>( 40%) (21.2 mg, 0.352 mmole). After five hours at ambient temperature, it was concentrated under reduced pressure. The crude reaction product 151a, (2S,2'S)-tert- butyl 2,2'-(4,4'-(biphenyl-4,4'-diyl)bis(l-methyl-lH-imidazole-4,2- diyl))dipyrrolidine- 1 -carboxylate (~ 90 mg) was moved onto next step without further purification ( purity ~ 85%) LCMS: Anal. Calcd. for: C38H48N6O4 652.83; Found: 653.51 (M+H)+. It should be recognized that multiple methylation isomers are possible in this reaction and no attempt to assign these was made.

Reference： [1]Patent: WO2009/102318,2009,A1 .Location in patent: Page/Page column 167-168

7
[ 1007882-23-6 ]
[ 1312336-87-0 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868

8
[ 1007882-23-6 ]
[ 1388224-19-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868

9
[ 1007882-23-6 ]
[ 1312338-86-5 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868

10
[ 1007882-23-6 ]
[ 1388224-20-1 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868

11
[ 1007882-23-6 ]
[ 1373165-16-2 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868

12
[ 15761-39-4 ]
[ 4072-67-7 ]
[ 1007882-23-6 ]

Yield	Reaction Conditions	Operation in experiment
60.0 g		4,4?-Bis(2-bromoacetyl)biphenyl bOg was added to methylene dichloride (l000ml) andstirred to get solution. Boc-L-Proline (120g) was added to it. Diisopropylethylamine68.5g was added to the reaction mass at 15-25C. The reaction mass was stirred for about4 to 5h. The reaction mass was quenched by adding water. The aqueous layer was separated and organic layer was washed with aqueous acetic acid solution (Conc HC1 also can be used instead of acetic acid) till pH of aqueous layer was between 4-6. Theorganic layer was washed with water and distilled under vacuum to get a residue. The residue was dissolved in toluene and toluene solution was used further. Ammonium acetate 390g was added to the toluene solution and the reaction mass was stirred. The reaction mass heated to 95-105C and maintained till completion of reaction. After completion of the reaction, the reaction mass was cooled to 50-60C, methanol wasadded and the reaction mass cooled to 20-30C and stirred for 2 to 3 hours. The solid was filtered and washed with toluene. Purity of crude:- 93.92%.Crude wet cake was stirred in mixture of toluene, methanol and acetic acid and the reaction mass was heated to 60- 70C, water was added to reaction mass at 60-70C and the reaction mass cooled to 20-30C and stirred. The solid obtained was filtered and washed with toluene and then withwater. Wet solid was dried. Purity - 97.04%. The above purification was repeated to obtain 60.Og of the title compound in a purity of 98.97%.

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2012,vol. 22,p. 4864 - 4868
[2]Patent: WO2018/15847,2018,A1 .Location in patent: Paragraph 0132

13
[ 1007882-23-6 ]
2-phenyl-1-[(2S)-2-{5-[4-(4-{2-[(2S)-1-(2-phenylacetyl)-pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]ethan-1-one trifluoroacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012

14
[ 1007882-23-6 ]
methyl N-[(1R)-2-[(2S)-2-{5-[4-(4-{2-[(2S)-1-[(2R)-2-[(methoxycarbonyl)amino]-2-phenylacetyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-2-oxo-1-phenylethyl]carbamate trifluoroacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012

15
[ 1007882-23-6 ]
(2R)-2-(dimethylamino)-1-[(2S)-2-{5-[4-(4-{2-[(2S)-1-[(2R)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-2-phenylethan-1-one trifluoroacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012
[2]Patent: US2008/44379,2008,A1

16
[ 1007882-23-6 ]
(2S)-2-(dimethylamino)-1-[(2S)-2-{5-[4-(4-{2-[(2S)-1-[(2S)-2-(dimethylamino)-2-phenylacetyl]pyrrolidin-2-yl]-1H-imidazol-5-yl}phenyl)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-2-phenylethan-1-one trifluoroacetate [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012

17
[ 1007881-98-2 ]
[ 1007882-23-6 ]

Reference： [1]Journal of Medicinal Chemistry,2014,vol. 57,p. 1995 - 2012
[2]Patent: US2008/44379,2008,A1
[3]Patent: US2008/44379,2008,A1
[4]Patent: US2008/50336,2008,A1
[5]Patent: WO2009/102318,2009,A1
[6]Patent: WO2009/102318,2009,A1

18
[ 1007882-23-6 ]
daclatasvir [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150
[2]Patent: WO2017/21904,2017,A1
[3]Patent: CN107501243,2017,A

19
[ 1007882-23-6 ]
dimethyl ((2S,2'S)-((2S,2'S)-2,2'-(5,5'-([1,1'-biphenyl]-4,4'-diyl)bis(1-acetyl-1H-imidazole-5,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl))dicarbamate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150

20
[ 1007882-23-6 ]
dimethyl ((2S,2'S)-((2S,2'S)-2,2'-(5,5'-([1,1'-biphenyl]-4,4'-diyl)bis(1-propionyl-1H-imidazole-5,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl))dicarbamate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150

21
[ 1007882-23-6 ]
dimethyl ((2S,2'S)-((2S,2'S)-2,2'-(5,5'-([1,1'-biphenyl]-4,4'-diyl)bis(1-butyryl-1H-imidazole-5,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl))dicarbamate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150

22
[ 1007882-23-6 ]
dimethyl ((2S,2'S)-((2S,2'S)-2,2'-(5,5'-([1,1'-biphenyl]-4,4'-diyl)bis(1-isobutyryl-1H-imidazole-5,2-diyl))bis(pyrrolidine-2,1-diyl))bis(3-methyl-1-oxobutane-2,1-diyl))dicarbamate [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2015,vol. 25,p. 3147 - 3150

Recommend Products

Same Skeleton Products

Related Products

Isomers

Technical Information

• Acyl Group Substitution • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • Hydride Reductions • Lawesson's Reagent • Preparation of Amines • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes

Historical Records

Related Functional Groups of
[ 1007882-23-6 ]

Aryls

[ 1441670-89-8 ]

(S)-tert-Butyl 6-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)-5-azaspiro[2.4]heptane-5-carboxylate

Similarity: 0.73

[ 1377049-84-7 ]

Methyl ((2S)-1-((2S,5S)-2-(9-(2-((2S,4S)-1-((2R)-2-((methoxycarbonyl)amino)-2-phenylacetyl)-4-(methoxymethyl)pyrrolidin-2-yl)-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4',3':6,7]naphtho[1,2-d]imidazol-2-yl)-5-methylpyrrolidin-1-yl)-3-methyl-1-oxobutan-2-yl)carbamate

Similarity: 0.72

[ 864825-23-0 ]

(S)-1-(4-Phenyl-1H-imidazol-2-yl)ethanamine

Similarity: 0.68

[ 1009119-83-8 ]

4,4'-Bis(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-1,1'-biphenyl tetrahydrochloride

Similarity: 0.67

[ 870281-85-9 ]

(S)-tert-Butyl (1-(5-fluoro-4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)propyl)carbamate

Similarity: 0.64

Amides

[ 1441670-89-8 ]

(S)-tert-Butyl 6-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)-5-azaspiro[2.4]heptane-5-carboxylate

Similarity: 0.73

[ 1229000-10-5 ]

tert-Butyl 3-(1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate

Similarity: 0.73

[ 1377049-84-7 ]

Similarity: 0.72

[ 205264-33-1 ]

1-Boc-4-Isoquinolin-1-yl-piperazine

Similarity: 0.72

[ 1250996-70-3 ]

tert-Butyl 2-(hydroxymethyl)-5,6-dihydroimidazo[1,2-a]pyrazine-7(8H)-carboxylate

Similarity: 0.67

Related Parent Nucleus of
[ 1007882-23-6 ]

Pyrrolidines

[ 1441670-89-8 ]

(S)-tert-Butyl 6-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)-5-azaspiro[2.4]heptane-5-carboxylate

Similarity: 0.73

[ 1377049-84-7 ]

Similarity: 0.72

[ 1009119-83-8 ]

4,4'-Bis(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-1,1'-biphenyl tetrahydrochloride

Similarity: 0.67

[ 1352534-35-0 ]

tert-Butyl 2-(6-chloropyridin-3-yl)pyrrolidine-1-carboxylate

Similarity: 0.61

[ 646055-62-1 ]

tert-Butyl 1-benzyl-1,7-diazaspiro[4.4]nonane-7-carboxylate

Similarity: 0.57

Imidazoles

[ 1441670-89-8 ]

(S)-tert-Butyl 6-(5-(7-bromo-9,9-difluoro-9H-fluoren-2-yl)-1H-imidazol-2-yl)-5-azaspiro[2.4]heptane-5-carboxylate

Similarity: 0.73

[ 1377049-84-7 ]

Similarity: 0.72

[ 864825-23-0 ]

(S)-1-(4-Phenyl-1H-imidazol-2-yl)ethanamine

Similarity: 0.68

[ 1009119-83-8 ]

4,4'-Bis(2-((S)-pyrrolidin-2-yl)-1H-imidazol-5-yl)-1,1'-biphenyl tetrahydrochloride

Similarity: 0.67

[ 670-83-7 ]

2,5-Diphenyl-1H-imidazole

Similarity: 0.61

Num. heavy atoms :	46
Num. arom. heavy atoms :	22
Fraction Csp3 :	0.44
Num. rotatable bonds :	11
Num. H-bond acceptors :	6.0
Num. H-bond donors :	2.0
Molar Refractivity :	186.7
TPSA :	116.44 Å²

GI absorption :	Low
BBB permeant :	No
P-gp substrate :	Yes
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	Yes
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.11 cm/s

Log Po/w (iLOGP) :	5.21
Log Po/w (XLOGP3) :	5.64
Log Po/w (WLOGP) :	6.87
Log Po/w (MLOGP) :	2.86
Log Po/w (SILICOS-IT) :	6.02
Consensus Log Po/w :	5.32

Lipinski :	1.0
Ghose :	None
Veber :	1.0
Egan :	1.0
Muegge :	2.0
Bioavailability Score :	0.55

Log S (ESOL) :	-6.89
Solubility :	0.0000796 mg/ml ; 0.000000127 mol/l
Class :	Poorly soluble
Log S (Ali) :	-7.85
Solubility :	0.00000884 mg/ml ; 0.0000000142 mol/l
Class :	Poorly soluble
Log S (SILICOS-IT) :	-9.52
Solubility :	0.00000019 mg/ml ; 0.0000000003 mol/l
Class :	Poorly soluble

[ CAS No. 1007882-23-6 ] HCV-IN-30

Quality Control of [ 1007882-23-6 ]

Related Doc. of [ 1007882-23-6 ]

Product Details of [ 1007882-23-6 ]

Calculated chemistry of [ 1007882-23-6 ] Expand+

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1007882-23-6 ]

Application In Synthesis of [ 1007882-23-6 ]

[ 1007882-23-6 ] Synthesis Path-Downstream 1~22

Technical Information