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Chemical Structure| 22162-53-4
Chemical Structure| 22162-53-4
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Product Details of [ 22162-53-4 ]

CAS No. :22162-53-4 MDL No. :MFCD02093091
Formula : C12H12N2 Boiling Point : -
Linear Structure Formula :- InChI Key :-
M.W : 184.24 Pubchem ID :-
Synonyms :

Safety of [ 22162-53-4 ]

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Application In Synthesis of [ 22162-53-4 ]

* 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 [ 22162-53-4 ]

[ 22162-53-4 ] Synthesis Path-Downstream   1~21

  • 1
  • [ 22162-53-4 ]
  • [ 168080-80-6 ]
  • [ 168079-32-1 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In dichloromethane; N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)ylcarbonyl)-3-chlorophenyl]-5-fluoro-2-methylbenzamide To a solution of 1.84 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is added 1.30 g of N,N-diisopropylethylamine. While cooling in an ice bath, a solution of 3.45 g of [4-[(2-methyl-5-fluorobenzoyl)amino]-2-chlorobenzoyl chloride in 50 ml of methylene chloride is added. The reaction mixture becomes homogeneous after 5 minutes and is stirred at room temperature for 18 hours. Water is added and the separated organic layer washed with saturated sodium bicarbonate, dried with Na2 SO4 and passed through a short pad of hydrous magnesium silicate. The methylene chloride is removed in vacuo to give 4.60 g of the desired product as a glass. A sample is crystallized from ethyl acetate to give crystalline solid, m.p. 191-195 C.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; water; N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl]-5-fluoro-2-methylbenzamide To a solution of 1.84 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is added 1.30 g of N,N-diisopropylethylamine. While cooling in an ice bath, a solution of 3.45 g of ?4-[(2-methyl-5-fluorobenzoyl)amino]-2-chlorobenzoyl chloride in 50 ml of methylene chloride is added. The reaction mixture becomes homogeneous after 5 minutes and is stirred at room temperature for 18 hours. Water is added and the separated organic layer washed with saturated sodium bicarbonate, dried with Na2 SO4 and passed through a short pad of hydrous magnesium silicate. The methylene chloride is removed in vacuo to give 4.60 g of the desired product as a glass. A sample is crystallized from ethyl acetate to give crystalline solid, m.p. 191-195 C.
With N-ethyl-N,N-diisopropylamine; In dichloromethane; N-[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)ylcarbonyl)-3-chlorophenyl]-5-fluoro-2-methylbenzamide To a solution of 1.84 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is added 1.30 g of N,N-diisopropylethylamine. While cooling in an ice bath, a solution of 3.45 g of ?4-[(2-methyl-5-fluorobenzoyl)amino]-2-chlorobenzoyl chloride in 50 ml of methylene chloride is added. The reaction mixture becomes homogeneous after 5 minutes and is stirred at room temperature for 18 hours. Water is added and the separated organic layer washed with saturated sodium bicarbonate, dried with Na2 SO4 and passed through a short pad of hydrous magnesium silicate. The methylene chloride is removed in vacuo to give 4.60 g of the desired product as a glass. A sample is crystallized from ethyl acetate to give crystalline solid, m.p. 191-195 C.
  • 2
  • [ 181074-22-6 ]
  • [ 79-37-8 ]
  • [ 117738-77-9 ]
  • [ 22162-53-4 ]
  • [ 220461-91-6 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; hexane; dichloromethane; ethyl acetate; EXAMPLE 77 3-Chloro-4-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-benzonitrile To a cooled suspension of <strong>[117738-77-9]2-chloro-4-cyanobenzoic acid</strong> (9.1 g) in a mixture of dichloromethane (40 ml) and dimethylformamide (3.88 ml) was added dropwise a solution of oxalyl chloride (4.6 ml) in dichloromethane (10 ml) at 0 C. The stirred reaction was allowed to warm to room temperature over a one hour period. A cloudy solution of 2-chloro-4-cyanobenzoyl chloride was utilized without further purification. To a stirred suspension of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (7.32 g) and diisopropylethylamine (13.6 ml) in dichloromethane (35 ml) was added under nitrogen the cloudy solution of 2-chloro-4-cyanobenzoyl chloride. After one hour at room temperature, the mixture was diluted with dichloromethane and washed sequentially with water, 5% sodium bicarbonate, and 50% saturated brine, After drying over anhydrous sodium sulfate, the solvent was removed in vacuo to afford a crude product (18.0 g). Purification by column chromatography on silica gel (250 g), eluding with 20% ethyl acetate/hexane, followed by 25% ethyl acetate/hexane, yielded the title compound (13.56 g) as a straw yellow foam, MS (EI), m/z: 347 (M)+.
  • 3
  • [ 22162-53-4 ]
  • [ 33863-86-4 ]
  • [ 180416-79-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; triethylamine In dichloromethane 10,11-Dihydro-10-(4-(4-butyloxy)benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine 10,11-Dihydro-10-(4-(4-butyloxy)benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine To a solution of 92 mg of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 2 ml of methylene chloride is added 100 mg of triethylamine followed by 130 mg of 4-(n-butyloxy)benzoyl chloride. The reaction mixture is stirred at room temperature for 24 hours and then treated with 4 ml of 1N sodium hydroxide. The mixture is extracted with 10 ml of ethyl acetate and the extract washed with 1N sodium hydroxide and 5 ml of brine. The organic layer is dried over anhydrous sodium sulfate and filtered through hydrous magnesium silicate. The filtrate is concentrate in vacuo to a residue which is stirred with ether-hexanes to give 160 mg of the desired product as a white solid:mass spectrum(CI), 361 (MH+).
With sodium hydroxide; triethylamine In dichloromethane 10,11-Dihydro-10-(4-(4-butyloxy)benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine 10,11-Dihydro-10-(4-(4-butyloxy)benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine To a solution of 92 mg of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 2 ml of methylene chloride is added 100 mg of triethylamine followed by 130 mg of 4-(n-butyloxy)benzoyl chloride. The reaction mixture is stirred at room temperature for 24 hours and then treated with 4 ml of 1N sodium hydroxide. The mixture is extracted with 10 ml of ethyl acetate and the extract washed with 1N sodium hydroxide and 5 ml of brine. The organic layer is dried over anhydrous sodium sulfate and filtered through hydrous magnesium silicate. The filtrate is concentrate in vacuo to a residue which is stirred with ether-hexanes to give 160 mg of the desired product as a white solid: mass spectrum(CI), 361(MH+).
  • 4
  • [ 31076-84-3 ]
  • [ 22162-53-4 ]
  • [ 220461-03-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h; 22 EXAMPLE 22; 1-[4-(5H,11H-Pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-phenyl]-ethanone EXAMPLE 22 1-[4-(5H,11H-Pyrrolo[2,1-c][1,4]benzodiazepine-10-carbonyl)-phenyl]-ethanone 4-Acetylbenzoic acid (5.0 g) and thionyl chloride (10 ml) were heated on a steam bath under argon for 0.75 hour, and the volatile material was removed under reduced pressure.. toluene was added and the volatiles were removed again to give the crude acid chloride as a red-orange oil.. This compound tended to solidify and was used as such for further transformations. The acid chloride (4.56 g) in dichloromethane (25 ml) was added portionwise to an ice-cooled solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (3.68 g) and diisopropylethylamine (3.25 g) in dichloromethane (100 ml).. After stirring at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate.. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate eluding with several volumes of dichloromethane.. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred.. After cooling, the crystals were collected by filtration to yield the title compound (1.75 g), m.p. 135-137 °C.
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 18h; 22 The acid chloride (4.56 g) in dichloromethane (25 ml) was added portionwise to an ice-cooled solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (3.68 g) and diisopropylethylamine (3.25 g) in dichloromethane (100 ml). After stirring at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate eluting with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (1.75 g), m.p. 135-137° C.
  • 5
  • [ 22162-53-4 ]
  • [ 95383-36-1 ]
  • (4-fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c] [1,4]benzodiazepin-10-yl)-methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine In dichloromethane 90.b [2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5H,11H,)-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone Step b) (4-Fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzo-diazepin-10-yl)-methanone: A solution of 4-fluoro-2-bromobenzoyl chloride (5.32 g) from step a), in dichloromethane (35 ml), was added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4)-benzodiazepine (3.44 g) and triethylamine (2.27 g) in dichloromethane (80 ml) and cooled in an ice bath. The cooling bath was removed and after stirring for 16 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The dichloromethane solution was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a pale purple foam. Purification by flash chromatography on silica gel eluding with hexane-ethyl acetate (1:1) resulted in the intermediate (4-fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone as a tan foam (6.91 g), MS m/z: 384 (M)+. This material was used without further purification in the next step.
With triethylamine In dichloromethane for 16h; 90.b EXAMPLE 90; [2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5H,11H)-pyrrolo[2,1-c] ; Step b) (4-Fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzo-diazepin-10-yl)-methanone: EXAMPLE 90; [2-Bromo-4-(3-methyl-pyrazol-1-yl)-phenyl]-(5H,11H)-pyrrolo[2,1-c] ; Step b) (4-Fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzo-diazepin-10-yl)-methanone: A solution of 4-fluoro-2-bromobenzoyl chloride (5.32 g) from step a), in dichloromethane (35 ml), was added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (3.44 g) and triethylamine (2.27 g) in dichloromethane (80 ml) and cooled in an ice bath.. The cooling bath was removed and after stirring for 16 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride.. The dichloromethane solution was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a pale purple foam.. Purification by flash chromatography on silica gel eluding with hexane-ethyl acetate (1:1) resulted in the intermediate (4-fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c] [1,4]benzodiazepin-10-yl)-methanone as a tan foam (6.91 g), MS m/z: 384 (M)+.. This material was used without further purification in the next step.
With triethylamine In dichloromethane at 0 - 20℃; for 16h; 90.b Step b) (4-Fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzo-diazepin-10-yl)-methanone: A solution of 4-fluoro-2-bromobenzoyl chloride (5.32 g) from step a), in dichloromethane (35 ml), was added dropwise to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (3.44 g) and triethylamine (2.27 g) in dichloromethane (80 ml) and cooled in an ice bath. The cooling bath was removed and after stirring for 16 hours, the reaction mixture was washed sequentially with water, saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride. The dichloromethane solution was dried over anhydrous magnesium sulfate, filtered and evaporated in vacuo to give a pale purple foam. Purification by flash chromatography on silica gel eluting with hexane-ethyl acetate (1:1) resulted in the intermediate (4-fluoro-2-bromophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone as a tan foam (6.91 g), MS m/z: 384 (M)+. This material was used without further purification in the next step.
  • 6
  • [ 22162-53-4 ]
  • [ 189807-21-4 ]
  • [ 220461-64-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In hexane; dichloromethane at 20℃; for 18h; 1 REFERENCE EXAMPLE 1; (4-Fluoro-2-trifluoromethyl-phenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone REFERENCE EXAMPLE 1 (4-Fluoro-2-trifluoromethyl-phenyl)-(5H,11H-pyrrolo[2,1-c] [1,4]benzodiazepin-10-yl)-methanone oxalyl chloride (2.0 g) was added to a suspension of 4-fluoro-2-trifluoromethylbenzoic acid (2.0 g) in dichloromethane (25 ml).. Two drops of dimethylformamide were added and the mixture was stirred for 18 hours at room temperature.. The resultant solution was evaporated to dryness to give the crude acid chloride.. This was redissolved in dichloromethane and filtered.. Evaporation of this material gave a liquid which was then redissolved in hexane, filtered, and evaporated to yield the acid chloride as a pale yellow viscous liquid, which was used without further purification. The acid chloride (2.26 g) in dichloromethane (25 ml) was added portionwise to a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.66 g), dichloromethane (10 ml), and diisopropylethylamine (1.30 g), cooled in an ice bath.. After remaining at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate.. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane.. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred.. After cooling, the crystals were collected by filtration to yield 2.57 g of the title compound, m.p. 154-155 °C.
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 18h; 1 The acid chloride (2.26 g) in dichloromethane (25 ml) was added portionwise to a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.66 g), dichloromethane (10 ml), and diisopropylethylamine (1.30 g), cooled in an ice bath. After remaining at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield 2.57 g of the title compound, m.p. 154-155° C.
  • 7
  • [ 21900-54-9 ]
  • [ 22162-53-4 ]
  • [ 220461-65-4 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In hexane; dichloromethane 8 (2-Chloro-4-fluorophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone The crude 2-chloro-4-fluorobenzoyl chloride (3.68 g) in dichloromethane (25 ml) was added portionwise to a stirred, ice cooled solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.76 g), diisopropylethylamine (2.47 g) and dichloromethane (50 ml). After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried with anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (3.85 g), m.p. 110-112° C.
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h; 8 REFERENCE EXAMPLE 8; (2-Chloro-4-fluorophenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone The crude 2-chloro-4-fluorobenzoyl chloride (3.68 g) in dichloromethane (25 ml) was added portionwise to a stirred, ice cooled solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.76 g), diisopropylethylamine (2.47 g) and dichloromethane (50 ml).. After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate.. The dichloromethane solution was dried with anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane.. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred.. After cooling, the crystals were collected by filtration to yield the title compound (3.85 g), m.p. 110-112 °C.
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h; 8 The crude 2-chloro-4-fluorobenzoyl chloride (3.68 g) in dichloromethane (25 ml) was added portionwise to a stirred, ice cooled solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (2.76 g), diisopropylethylamine (2.47 g) and dichloromethane (50 ml). After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried with anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (3.85 g), m.p. 110-112° C.
  • 8
  • [ 22162-53-4 ]
  • [ 189807-21-4 ]
  • [ 220461-29-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 18h; 55 The acid chloride was added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (0.37 g) and diisopropylethylamine (0.58 g) in dichloromethane (50 ml). After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (0.38 g), m.p. 200-201° C.; MS m/z: 368 (M)+.
  • 9
  • [ 544-00-3 ]
  • [ 5728-33-6 ]
  • [ 22162-53-4 ]
  • [ 473717-55-4 ]
YieldReaction ConditionsOperation in experiment
82.8% In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene 2.C Step C. Step C. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(3'-methyl-[1,1'-biphenyl]-4-yl)-methanone A suspension of 3'-methyl-[1,1'-biphenyl]-4-carboxylic acid of Step B (0.50 g, 2.36 mmol) in thionyl chloride (3 mL) was heated at reflux for 30 minutes. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a yellow oil. The acid chloride was then dissolved in dichloromethane (5 mL) and slowly added to a solution of the 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (0.65 g, 3.53 mmol) and N,N-diisopropylethyl amine (0.90 mL, 5.17 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to give a white foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 25% of ethyl acetate in hexane gave a white foam which was crystallized by sonication from ethyl acetate/hexane to provide the title compound (0.74 g, 82.8%) as a white solid, m.p. 128-130° C. 1H-NMR (DMSO-d6, 400 MHz): δ 2.35 (s, 3H), 4.80-5.40 (broad s, 4H), 5.93-5.95 (m, 1H), 5.97 (s, 1H), 6.85 (t, 1H), 6.96-6.98 (m, 1H), 7.12 (t, 1H), 7.17-7.21 (m, 2H), 7.30-7.44 (m, 5H), 7.48-7.54 (m, 3H). MS [EI, m/z]: 378 [M]+. Anal. Calcd. for C26H22N2O+0.10C4H8O2: C, 81.88; H, 5.93; N, 7.23. Found: C, 81.54; H, 5.99; N, 7.29.
  • 10
  • [ 544-00-3 ]
  • [ 20029-52-1 ]
  • [ 22162-53-4 ]
  • [ 473545-95-8 ]
YieldReaction ConditionsOperation in experiment
In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene 4 10-(4-Cyclohexyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine EXAMPLE 4 10-(4-Cyclohexyl-benzoyl)-10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine 4-Cyclohexylbenzoic acid (0.50 g, 2.45 mmol) was suspended in thionyl chloride (3 mL) and heated at reflux for 30 minutes. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a yellow oil which was then dissolved in dichloromethane (5 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4] benzodiazepine (0.67 g, 3.64 mmol) and N,N-diisopropylethyl amine (0.94 mL, 5.4 mmol) in dichloromethane (15 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. Purification by flash chromatography using a solvent system of 50% dichloromethane in hexane followed by 25% ethyl acetate in hexane gave a white foam which crystallized upon sonication from hexane/ethyl acetate to provide the title compound (0.60 g) as a white solid, m.p. 127-129° C. NMR (DMSO-d6, 400 MHz): δ 1.15-1.32 (m, 5H), 1.64-1.74 (m, 5H), 2.39-2.42 (m, 1H), 4.80-5.40 (broad s, 4H), 5.91-5.94 (m, 2H), 6.81 (t, 1H), 6.90 (d, 1H), 7.05-7.11 (m, 3H), 7.15-7.19 (m, 3H), 7.45-7.47 (m, 1H). Anal. Calcd. for C25H26N2O +0.05 C4H8O2: C 80.74, H 7.10, N 7.47. Found: C 80.36, H 7.11, N 7.53. MS [EI, m/z]: 370 [M]+. Calcd. for C25H26N20: 370.4868.
  • 11
  • [ 544-00-3 ]
  • [ 725-14-4 ]
  • [ 22162-53-4 ]
  • [ 473717-56-5 ]
YieldReaction ConditionsOperation in experiment
86.8% In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene; Step C. (10,11-Dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-(4'-methoxy-[1,1'-biphenyl]-4-yl)-methanone A suspension of the carboxylic acid of Step B (1.0 g, 4.38 mmol) in thionyl chloride (6 mL) was heated at reflux for 1 hour. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a light brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (1.2 g, 6.52 mmol) and N,N-diisopropylethyl amine (1.7 mL, 9.76 mmol) in dichloromethane (25 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 50% of ethyl acetate in hexane provided the title compound (1.5 g, 86.8%) as a white solid, m.p. 187-189 C. 1H-NMR (DMSO-d6, 400 MHz): δ 3.76 (s, 3H), 4.80-5.40 (broad s, 4H), 5.92-5.94 (m, 1H), 5.96 (s, 1H), 6.83 (t, 1H), 6.94-6.99 (m, 3H), 7.10 (t, 1H), 7.15-7.19 (m, 1H), 7.32 (d, 2H), 7.47-7.49 (m, 3H), 7.55-7.58 (m, 2H). MS [(+)ESI, m/z]: 395 [M+H]+. Anal. Calcd. for C26H99N2O2+0.20CH2Cl2: C, 76.48; H, 5.49; N, 6.81. Found: C, 76.10; H, 5.68; N, 6.87.
  • 12
  • 4-lodo-2-methoxybenzoic acid [ No CAS ]
  • [ 544-00-3 ]
  • [ 89942-34-7 ]
  • [ 22162-53-4 ]
  • [ 473264-08-3 ]
YieldReaction ConditionsOperation in experiment
In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene; Step C. 10-(4-Iodo-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine A suspension of <strong>[89942-34-7]4-iodo-2-methoxybenzoic acid</strong> of Step B (2.5 g, 9.0 mmol) in thionyl chloride (10 mL) was heated at reflux for 1 hour. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.75 g, 9.5 mmol) and N,N-diisopropylethyl amine (3.4 mL, 19.5 mmol) in dichloromethane (20 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane provided 3.6 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness prior to use in the next step. 1H NMR (DMSO-d6, 400 MHz): delta 3.55 (br, 3H), 4.80-5.32 (br, 4H), 5.88-5.90 (m, 1H), 5.94 (s, 1H), 6.79 (s, 1H), 6.94 (s, 1H), 7.03 (t, 1H), 7.09-7.13 (m, 3H), 7.20-7.22 (m, 1H), 7.36-7.38 (m, 1H). MS [(+)ESI, m/z]: 445 [M+H]+. Anal. Calcd. for C20H171N2O2+0.10 C4H8O2+0.13 CH2Cl2: C 53.13, H 3.92, N 6.04. Found: C 53.03, H 3.65, N 6.03.
  • 13
  • [ 544-00-3 ]
  • [ 5728-32-5 ]
  • [ 22162-53-4 ]
  • [ 473717-54-3 ]
YieldReaction ConditionsOperation in experiment
In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene 1.C Step C. Step C. (2'-Methoxy-[1,1'-biphenyl]-4-yl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone A suspension of 2'-methoxy-[1,1'-biphenyl]-4-carboxylic acid of Step B (1.0 g, 4.38 mmol) in thionyl chloride (6 mL) was heated at reflux for 30 min. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a yellow solid. The latter was then dissolved in dichloromethane (10 mL) and the solution was slowly added to a solution of 10,11-dihydro-5H-pyrrolo [2,1-c][1,4]benzodiazepine (0.97 g, 5.27 mmol) and N,N-diisopropylethyl amine (1.6 mL, 9.19 mmol) in dichloromethane (30 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification of the residue by flash chromatography using a solvent gradient from 15% to 25% of ethyl acetate in hexane provided the title compound as a white foam which was crystallized by sonication from ethyl acetate/hexane (1.4 g, 81.0%) to give a white solid m.p. 145-147° C. 1H-NMR (DMSO-d6, 400 MHz): δ 3.71 (s, 3H), 4.80-5.40 (broad s, 4H), 5.92-5.93 (m, 1H), 5.95 (s, 1H), 6.82 (t, 1H), 6.96-7.00 (m, 2H), 7.08 (d, 1H), 7.12-7.21 (m, 3H), 7.29-7.35 (m, 5H), 7.47-7.49 (m, 1H) MS [(+)ESI, m/z]: 395 [M+H]+. Anal. Calcd. for C26H22N2O2+0.08C4H8O2: C, 78.73; H, 5.68; N 6.98. Found: C, 78.47; H, 5.77; N, 7.00.
  • 14
  • [ 544-00-3 ]
  • [ 89942-34-7 ]
  • [ 22162-53-4 ]
  • [ 473264-08-3 ]
YieldReaction ConditionsOperation in experiment
In thionyl chloride; hexane; dichloromethane; ethyl acetate; toluene; Step C. 10-(4-Iodo-2-methoxybenzoyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4] benzodiazepine A suspension of <strong>[89942-34-7]4-iodo-2-methoxybenzoic acid</strong> of Step B (2.5 g, 9.0 mmol) in thionyl chloride (10 mL) was heated at reflux for 1 hour. After cooling, the thionyl chloride was removed in vacuo. The residue was dissolved in toluene and concentrated in vacuo to give the crude acid chloride as a brown solid. The acid chloride was then dissolved in dichloromethane (10 mL) and slowly added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.75 g, 9.5 mmol) and N,N-diisopropylethyl amine (3.4 mL, 19.5 mmol) in dichloromethane (20 mL). After stirring for 2 hours, the reaction was quenched with water. The organic layer was washed with 1 N hydrochloric acid, 1 N sodium hydroxide and brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give a yellow foam. Purification by flash chromatography on silica gel using a solvent gradient of 15 to 25% ethyl acetate in hexane provided 3.6 g of title product as a white foam, which was redissolved in dichloromethane and evaporated to dryness prior to use in the next step. 1H NMR (DMSO-d6, 400 MHz): delta3.55 (br, 3H), 4.80-5.32 (br, 4H), 5.88-5.90 (m, 1H), 5.94 (s, 1H), 6.79 (s, 1H), 6.94 (s, 1H), 7.03 (t, 1H), 7.09-7.13 (m, 3H), 7.20-7.22 (m, 1H), 7.36-7.38 (m, 1H). MS [(+)ESI, m/z]: 445 [M+H]+. Anal. Calcd. for C20H17IN2O2+0.10 C4H8O2+0.13 CH2Cl2: C, 53.13; H, 3.92; N, 6.04. Found: C, 53.03; H, 3.65; N, 6.03.
  • 15
  • [ 79-37-8 ]
  • [ 141179-72-8 ]
  • [ 22162-53-4 ]
  • [ 220461-64-3 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; hexane; dichloromethane; EXAMPLE 1 (4-Fluoro-2-trifluoromethyl-phenyl)-(5H,11H-pyrrolo[2,1-c][1,4]benzodiazepin-10-yl)-methanone Oxalyl chloride (2.0 g) was added to a suspension of <strong>[141179-72-8]4-fluoro-2-trifluoromethylbenzoic acid</strong> (2.0 g) in dichloromethane (25 ml). Two drops of dimethylformamide were added and the mixture was stirred for 18 hours at room temperature. The resultant solution was evaporated to dryness to give the crude acid chloride. This was redissolved in dichloromethane and filtered. Evaporation of this material gave a liquid which was then redissolved in hexane, filtered, and evaporated to yield the acid chloride as a pale yellow viscous liquid, which was used without further purification. The acid chloride (2.26 g) in dichloromethane (25 ml) was added portionwise to a mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (1.66 g), dichloromethane (10 ml), and diisopropylethylamine (1.30 g), cooled in an ice bath. After remaining at room temperature for 18 hours, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield 2.57 g of the title compound, m.p. 154-155 C.
  • 16
  • [ 199678-06-3 ]
  • [ 79-37-8 ]
  • [ 22162-53-4 ]
  • [ 220461-29-0 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In N-methyl-acetamide; hexane; dichloromethane; EXAMPLE 55 [4-(1-Methyl-1H-pyrazol-4-yl)-phenyl]-(5H,11H-pyrrolo[2,1-c][1,4]-benzodiazepin-10-yl)-methanone Oxalyl chloride (0.30 g) was added to a suspension of 4-(1-methyl-1H-pyrazol-4-yl)-benzoic acid (0.46 g) in dichloromethane (25 ml). Two drops of dimethylformamide were added and the mixture was stirred for 18 hours at room temperature. The resultant solution was evaporated to dryness to yield the crude acid chloride (0.57 g), which was utilized without further purification. The acid chloride was added to a solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]-benzodiazepine (0.37 g) and diisopropylethylamine (0.58 g) in dichloromethane (50 ml). After 18 hours at room temperature, the reaction mixture was washed with water and saturated aqueous sodium bicarbonate. The dichloromethane solution was dried over anhydrous sodium sulfate and filtered through a short column of hydrous sodium magnesium silicate and further eluted with several volumes of dichloromethane. The combined organic phase was concentrated on a hot plate with the gradual addition of hexane until crystallization occurred. After cooling, the crystals were collected by filtration to yield the title compound (0.38 g), m.p. 200-201 C.; MS m/z: 368 (M)+.
  • 17
  • [ 3113-71-1 ]
  • [ 22162-53-4 ]
  • [ 168078-68-0 ]
YieldReaction ConditionsOperation in experiment
With thionyl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane; chloroform 94 10,11-Dihydro-10-(3-methyl-4-nitro-benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine EXAMPLE 94 10,11-Dihydro-10-(3-methyl-4-nitro-benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine A mixture of 1.81 g of 3-methyl-4-nitrobenzoic acid and 1.25 g of thionyl chloride in 75 ml of chloroform is heated at reflux under argon for 48 hours. The volatiles are removed in vacuo to a residue which is evaporated with toluene several times in vacuo. The residue is partially dissolved in methylene chloride and filtered free of solids and the filtrate evaporated in vacuo to give 1.47 g of the desired acid chloride. A 1.36 g sample of the acid chloride, 0.90 g of N,N-diisopropylethylamine and 1.25 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is allowed to stand at room temperature for 8 hours. Water is added to the reaction mixture, the organic layer is separated and dried over Na2 SO4, filtered and hexane added to the filtrate at the boil to give 1.4 g of the desired product as crystals, m.p. 246°-248° C.
With thionyl chloride; N-ethyl-N,N-diisopropylamine In dichloromethane; chloroform; toluene 94 10,11-Dihydro-10-(3-methyl-4-nitro-benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine EXAMPLE 94 10,11-Dihydro-10-(3-methyl-4-nitro-benzoyl)-5H-pyrrolo[2,1-c][1,4]benzodiazepine A mixture of 1.81 g of 3-methyl-4-nitrobenzoic acid and 1.25 g of thionyl chloride in 75 ml of chloroform is heated at reflux under argon for 48 hours. The volatiles are removed in vacuo to a residue which is evaporated with toluene several times in vacuo. The residue is partially dissolved in methylene chloride and filtered free of solids and the filtrate evaporated in vacuo to give 1.47 g of the desired acid chloride. A 1.36 g sample of the acid chloride, 0.90 g of N,N-diisopropylethylamine and 1.25 g of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine in 25 ml of methylene chloride is allowed to stand at room temperature for 8 hours. Water is added to the reaction mixture, the organic layer is separated and dried over Na2 SO4, filtered and hexane added to the filtrate at the boil to give 1.4 g of the desired product as crystals, m.p. 246°-248° C.
  • 18
  • [ 2567-29-5 ]
  • [ 22162-53-4 ]
  • 10-(1,1'-biphenyl-4-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine [ No CAS ]
YieldReaction ConditionsOperation in experiment
68% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 24h; Example 73 10-(1,1'-BIPHENYL-4-YLMETHYL)-N-(PYRIDIN-3-YLMETHYL)-10,11-DIHYDRO-5H-PYRROLO[2,1-C][1,4]BENZODIAZEPINE-3-CARBOXAMIDE Step A. 10-(1,1'-Biphenyl-4-ylmethyl)-10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine; A mixture of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.200 g, 1.09 mmol), 4-bromomethyl-biphenyl (0.322 g, 1.303 mmol) and potassium carbonate (0.300 g, 2.17 mol) in dry N, N-dimethyl formamide (6 mL) was stirred at room temperature under nitrogen for 24 hours. The reaction mixture was then partitioned between ethyl acetate (50 mL) and 2 M sodium hydroxide (50 mL). The separated organic phase was washed with 2 M sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous magnesium sulfate, and concentrated in vacuo to afford a colorless syrup (0.42 g). Purification by flash chromatography using a solvent gradient of 0 to 5% ethyl acetate in hexane afforded a white foam that was crystallized from ethyl acetate/hexane to afford the title compound (0.261 g, 68%) as a white crystalline solid, m.p. 135-137 C. MS [(-)ESI, m/z]: 349 [M-H]-. Anal. Calcd for C25H22N2: C, 85.68; H, 6.33; N, 7.99. Found: C, 85.89; H, 6.24; N, 7.83.
  • 19
  • [ 70049-77-3 ]
  • [ 22162-53-4 ]
  • [ 917374-93-7 ]
YieldReaction ConditionsOperation in experiment
With <i>N</i>,<i>N</i>-dimethyl-aniline In 1,4-dioxane at 20℃; for 2h; 114.A Example 114 10-[3-(AMINOSULFONYL)-4-MORPHOLIN-4-YLBENZOYL]-N-(PYRIDIN-3-YLMETHYL)-10,11-DIHYDRO-5H-PYRROLO[2,1-C][1,4]BENZODIAZEPINE-3-CARBOXAMIDE HEMIHYDRATE Step A. 2-Chloro-5-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)benzenesulfonamide; A solution containing 1.02 g (0.004 mol) of 4-chloro-3-sulfamoylbenzoyl chloride, 0.74 g (0.004 mol) of 10,11-dihydro-5H-pyrolo[2,1-c][1,4]benzodiazepine and 0.48 g (0.004 mol) of N,N-dimethylaniline in 50 ml of 1,4-dioxane was allowed to stand at room temperature for 2 hours. The reaction mixture was then poured into 500 mL of water with stirring. The precipitate was collected, washed and dried to provide the title compound (0.7 g), m.p. 137° C. dec. MS [(+)ESI, m/z]: 402 [M+H]+. MS [(-)ESI, m/z]: 400 [M-H]-
  • 20
  • [ 69535-85-9 ]
  • [ 22162-53-4 ]
  • [ 909040-95-5 ]
YieldReaction ConditionsOperation in experiment
A solution of 0.45 g (0.002 mole) of <strong>[69535-85-9]2,2'-dimethyl-1,1'-biphenyl-4-carboxylic acid</strong> in 50 mL of thionyl chloride was heated under reflux overnight. The excess thionyl chloride was stripped off in vacuo. To the residue was added 0.37 g (0.002 mole) of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine and 50 mL of 1,4-dioxane followed by 0.24 g (0.002 mole) of N,N-dimethylaniline. After standing for three hours, the reaction solution was poured into 300 mL of water to provide 0.6 g of title compound which was used directly in the next step after drying. MS [(+)ESI, m/z]: 393 [M+H]+.
  • 21
  • [ 22162-53-4 ]
  • [ 168079-32-1 ]
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