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Chemical Structure| 57616-74-7 Chemical Structure| 57616-74-7

Structure of 57616-74-7

Chemical Structure| 57616-74-7

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Product Details of [ 57616-74-7 ]

CAS No. :57616-74-7
Formula : C7H15Cl2NO
M.W : 200.11
SMILES Code : ClCCCN1CCOCC1.[H]Cl
MDL No. :MFCD00035333
InChI Key :PQECODMSWJOUAT-UHFFFAOYSA-N
Pubchem ID :12296283

Safety of [ 57616-74-7 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H312-H314-H317
Precautionary Statements:P280-P305+P351+P338-P310
Class:8(6.1)
UN#:2923
Packing Group:

Application In Synthesis of [ 57616-74-7 ]

* 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 [ 57616-74-7 ]

[ 57616-74-7 ] Synthesis Path-Downstream   1~41

  • 1
  • [ 6320-03-2 ]
  • [ 57616-74-7 ]
  • 4-[3-(2-chloro-phenylsulfanyl)-propyl]-morpholine [ No CAS ]
  • 2
  • [ 5470-75-7 ]
  • [ 57616-74-7 ]
  • (6-chloro-[8]quinolyl)-(3-morpholino-propyl)-amine [ No CAS ]
  • 3
  • [ 90-52-8 ]
  • [ 57616-74-7 ]
  • (6-methoxy-[8]quinolyl)-(3-morpholino-propyl)-amine [ No CAS ]
  • 4
  • [ 857551-22-5 ]
  • [ 57616-74-7 ]
  • benzo[4,5]furo[2,3-<i>f</i>]quinolin-5-yl-(3-morpholino-propyl)-amine [ No CAS ]
  • 5
  • [ 57616-74-7 ]
  • 8-methoxy-[6]quinolylamine; hydrochloride [ No CAS ]
  • [ 107419-20-5 ]
  • 6
  • [ 57616-74-7 ]
  • [ 108-24-7 ]
  • [ 1193-02-8 ]
  • acetic acid-[4-(3-morpholino-propylmercapto)-anilide] [ No CAS ]
  • 8
  • [ 57616-74-7 ]
  • [ 137-07-5 ]
  • [ 69967-26-6 ]
  • 9
  • [ 57616-74-7 ]
  • [ 118-41-2 ]
  • [ 60439-46-5 ]
  • 10
  • [ 13327-27-0 ]
  • [ 57616-74-7 ]
  • [ 93085-64-4 ]
  • 11
  • [ 2166-31-6 ]
  • [ 57616-74-7 ]
  • [ 21741-66-2 ]
  • 12
  • [ 26413-18-3 ]
  • [ 57616-74-7 ]
  • 4-[3-(1,1,3,3-Tetraoxo-1λ6,3λ6-[1,3]dithian-2-yl)-propyl]-morpholine [ No CAS ]
  • 13
  • [ 57616-74-7 ]
  • [ 2894-71-5 ]
  • [ 57616-75-8 ]
  • 14
  • [ 57616-74-7 ]
  • [ 135385-31-8 ]
  • 3-butyryl-4-(2-methylphenylamino)-8-(3-morpholinopropylamino)quinoline [ No CAS ]
  • 15
  • [ 57616-74-7 ]
  • [ 125500-46-1 ]
  • 3-butyryl-4-(2-methylphenylamino)-8-(3-morpholinopropoxy)quinoline [ No CAS ]
  • 16
  • [ 57616-74-7 ]
  • (3-Bromo-phenyl)-(8H-pyrrolo[3,2-g]quinazolin-4-yl)-amine [ No CAS ]
  • 5-[(3-bromophenyl)amino]-1-[3-(4-morpholino)propyl]pyrrolo[3,2-g]quinazoline [ No CAS ]
  • 17
  • [ 29865-90-5 ]
  • [ 57616-74-7 ]
  • 3,4-dimethoxy-5-(3-morpholin-4-yl-propoxy)-benzaldehyde [ No CAS ]
  • 18
  • [ 57616-74-7 ]
  • [ 100-83-4 ]
  • 3-(3-morpholin-4-yl-propoxy)-benzaldehyde [ No CAS ]
  • 19
  • [ 57616-74-7 ]
  • [ 193001-59-1 ]
  • 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-morpholinopropoxy)quinazoline [ No CAS ]
  • 20
  • [ 57616-74-7 ]
  • [ 311819-88-2 ]
  • 1-<i>tert</i>-butyl-3-[3-(3,5-dimethoxy-phenyl)-7-(3-morpholin-4-yl-propylamino)-[1,6]naphthyridin-2-yl]-urea [ No CAS ]
  • N-[7-amino-3-(3,5-dimethoxyphenyl)-1-[3-(4-morpholinyl)propyl]-1,6-naphthyridin-2(1H)-ylidene]N'-tert-butylurea [ No CAS ]
  • 21
  • [ 57616-74-7 ]
  • [ 311819-90-6 ]
  • 1-<i>tert</i>-butyl-3-[3-(3,5-dimethoxy-phenyl)-7-(3-morpholin-4-yl-propylamino)-[1,6]naphthyridin-2-yl]-urea [ No CAS ]
  • 22
  • [ 57616-74-7 ]
  • [ 311819-90-6 ]
  • 1-<i>tert</i>-butyl-3-[3-(3,5-dimethoxy-phenyl)-7-(3-morpholin-4-yl-propylamino)-[1,6]naphthyridin-2-yl]-urea [ No CAS ]
  • N-[7-[bis[3-(4-morpholinyl)propyl]amino]-3-(3,5-dimethoxyphenyl)-1,6-naphthyridin-2-yl]-N'-tert-butylurea [ No CAS ]
  • 23
  • [ 57616-74-7 ]
  • 3-Benzo[1,3]dioxol-5-yl-5-hydroxy-5-(4-methoxy-phenyl)-4-[3-(3-morpholin-4-yl-propoxy)-benzyl]-5H-furan-2-one [ No CAS ]
  • 24
  • [ 57616-74-7 ]
  • 3-Benzo[1,3]dioxol-5-yl-4-[3,4-dimethoxy-5-(3-morpholin-4-yl-propoxy)-benzyl]-5-hydroxy-5-(4-methoxy-phenyl)-5H-furan-2-one [ No CAS ]
  • 25
  • [ 57616-74-7 ]
  • [ 67974-82-7 ]
  • 26
  • [ 57616-74-7 ]
  • 4-amino-thiobenzoic acid <i>S</i>-(3-morpholino-propyl ester) [ No CAS ]
  • 27
  • [ 57616-74-7 ]
  • 4-butylamino-thiobenzoic acid <i>S</i>-(3-morpholino-propyl ester) [ No CAS ]
  • 28
  • [ 57616-74-7 ]
  • 4-nitro-thiobenzoic acid <i>S</i>-(3-morpholino-propyl ester) [ No CAS ]
  • 29
  • [ 668-94-0 ]
  • [ 57616-74-7 ]
  • [ 473826-15-2 ]
YieldReaction ConditionsOperation in experiment
68% With potassium carbonate; In acetonitrile; for 24h;Heating / reflux; EXAMPLE 1 Synthesis of 4-[3-(4,5-diphenylimidazol-1-yl)-propyl]morpholine of the Following Formula [0236] [CHEMMOL-00002] [0237] 200 ml of acetonitrile, 8 g of 4,5-diphenylimidazole (36 mmol) sold by the company Acros, 10 g of K2CO3 (72 mmol) and then 11 g of morpholinepropyl chloride in hydrochloride form (1.5 equivalents) are placed in a three-necked flask. The mixture is refluxed for 24 hours. After cooling, the mixture is evaporated to dryness under vacuum. The mixture is dissolved in 100 ml of water and then extracted with ethyl acetate. The organic phase is washed with water and then dried over sodium sulphate. After evaporation to dryness, the oil obtained is precipitated by adding diethyl ether. The precipitate is filtered off and then recrystallized from a water/ethyl alcohol mixture (20/80). [0238] 8.6 g of product are obtained in a yield of 68%. Analysis [0239] 1H NMR (400 MHz, in DMSO-d6): delta (ppm)=1.6 (m, 2H); 2.1 (m, 6H); 3.4 (m, 4H); 3.8 (t, 2H); 7.1-7.5 (4m, 10H); 7.8 (s, 1H)
  • 30
  • [ 205448-27-7 ]
  • [ 57616-74-7 ]
  • [ 205448-37-9 ]
YieldReaction ConditionsOperation in experiment
51% With potassium carbonate; potassium iodide; In DMF (N,N-dimethyl-formamide); at 60℃; for 2h; The starting material was prepared as follows: A solution of 5-((3-hydroxy-4-methoxyanilino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione, (prepared as described for the starting material in Example 3), <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong> (680 mg, 3.57 mmol), (J. Amer. Chem. Soc. 1945, 67, 736), in DMF (25 ml) containing potassium carbonate (940 mg, 7.48 mmol) and potassium iodide (56 mg, 0.34 mmol) was stirred at 60 C. for 2 hours.. The mixture was partitioned between ethyl acetate and water.. The organic layer was separated, washed with brine, dried (MgSO4), the insoluble materials were removed by filtration and the volatiles were removed by evaporation.. The residue was triturated with ether, collected by filtration and dried under vacuum to give 5-((3-(3-morpholinopropoxy)-4-methoxyanilino)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione 2735 mg, 5 1%).
  • 31
  • [ 873450-59-0 ]
  • [ 57616-74-7 ]
  • 3-(1-cyano-1-methylethyl)-5-(2-morpholin-4-ylethoxy)benzoic acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; sodium iodide; In acetone; for 5h;Heating / reflux; Method 90; 3-d-Cvano-l-methylethvl)-5-('2-morpholm-4-vlethoxv')benzoic acid methyl ester; A suspension of 3-(cyano-dimethyl-methyl)-5-hydroxy-benzoic acid methyl ester(Method 89; 500 mg, 2.283 mmol), morpholinopropylchloride hydrochloride (594 mg, 2.97mol,-1.3 eq), potassium carbonate (3.15 g, 22.8 mmol, 10 eq) and sodium iodide (35 mg, 0.23mmol, 0.1 eq) in acetone was heated to reflux for 5 hours. The salt was filtered off, the filtratewas concentrated to provide the desired product.
  • 32
  • [ 69445-45-0 ]
  • [ 57616-74-7 ]
  • 5-<3-(4-morpholino)propoxy>-1-phenylbenzimidazole dihydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
Example 39 5-[3-(4-Morpholino)propoxy]-1-phenylbenzimidazole Dihydrochloride by the Method of Scheme 3 Similar reaction of 5-hydroxy-1-phenylbenzimidazole (Example 14) with sodium hydride followed by <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong> gave Example 39 (52%). DiHCl salt: mp (MeOH/Et2 O) dec. above 84 C. (hygroscopic solid). 1 H NMR (D2 O): delta9.42 (s, 1 H, H-2), 7.81-7.74 (m, 5 H, Ph), 7.72 (d, J=9.2 Hz, 1 H, H-7), 7.47 (d, J=2.2 Hz, 1 H, H-4), 7.34 (dd, J=9.2, 2.2 Hz, 1 H, H-6), 4.33 (t, J=5.6 Hz, 2 H, CH2 N+), 4.23 (br d, J=12.9 Hz, 2 H, morpholino CH2 N+), 3.92 (br t, J=12.9 Hz, 2 H, morpholino CH2 N+), 3.70 (br d, J=12.6 Hz, 2 H, morpholino CH2 O), 3.52 (t, J=5.6 Hz, 2 H, CH2 O), 3.36-3.28 (m, 2 H, morpholino CH2 O), 2.42-2.36 (m, 2 H, CH2 CH2 CH2). 13 C NMR: delta160.39 (s), 142.00 (d), 135.93 (s), 134.61 (s), 133.35 (d), 133.14 (d), 128.94 (s), 127.43 (d), 120.08 (d), 116.89 (d), 100.79 (d), 68.65 (t), 66.58 (t), 57.58 (t), 54.62 (t), 25.86 (t). Analysis calculated for C20 H23 N3 O2.2HCl.3.5H2 O requires: C, 50.7; H, 6.7; N, 8.9%. Found: C, 51.1; H, 7.0; N, 8.8%.
  • 33
  • [ 57616-74-7 ]
  • [ 584-08-7 ]
  • [ 118-61-6 ]
  • 2-(3-morpholino-propoxy)-benzoic acid ethyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N,N-dimethyl-formamide; (a) To a mixture of ethyl 2-hydroxybenzoate (2.4 ml, 16.38 mmol), K2 CO3 (4.98 g), and DMF (30 ml) was added <strong>[57616-74-7]N-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong> (3.93 g). The mixture was stirred at room temperature for 30 minutes, then was warmed on a steam bath overnight. The reaction mixture was cooled, filtered and stripped to afford a liquid which was partitioned between EtOAc (350 ml) and water. The organic layer was separated, washed with water (2*200 ml), dried over MgSO4 and stripped to afford ethyl 2-[3-(4-morpholinyl)propoxy]benzoate.
  • 34
  • [ 184475-74-9 ]
  • [ 57616-74-7 ]
  • 4-[(2,4-difluorophenyl)amino]-6-[3-(morpholin-4-yl)propyloxy]-7-methoxyquinazoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
30% With potassium carbonate; In N,N-dimethyl-formamide; EXAMPLE 14 A mixture of 4-(2',4'-difluoroanilino)-6-hydroxy-7methoxyquinazoline (2.5 g), 3-morpholinopropyl chloride hydrochloride (1.6 g), potassium carbonate (6 g) and DMF (100 ml) was stirred and heated to 60 C. for 1 hour. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic phase was washed with water and with brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography using a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained 4-(2',4'-difluoroanilino)-7-methoxy-6-(3-morpholinopropoxy)quinazoline (1.05 g, 30%), m.p. 151-153 C.; NMR Spectrum: 2.0 (m, 2H), 2.35-2.67 (m, 6H), 3.58 (t, 2H), 3.94 (s, 3H), 4.16 (t, 2H), 7.13 (m, 1H), 7.16 (s, 1H), 7.33 (m, 1H), 7.54 (m, 1H), 7.78 (s, 1H), 8.1 (s, 1H), 9.4 (board s, 1H); Elemental Analysis: Found C, 61.4; H, 5.5; N, 12.8; C22 H24 F2 N4 O3 requires C, 61.4; H, 5.6; N, 13.0%.
  • 35
  • [ 110-91-8 ]
  • [ 6940-76-7 ]
  • [ 57616-74-7 ]
YieldReaction ConditionsOperation in experiment
32% A solution of morpholine (2 mL, 23.0 mmol) in /V,A/-dimethylformamide (15 mL) was treated with potassium carbonate (4.75g, 34.4 mmol) and1-chloro-3-iodopropane (3.7 mL, 34.4 mmol). After 16h, the reaction mixture was partitioned between EtOAc and H20. The aqueous layer was washed with EtOAc(15x). The combined organic layers were dried (Na2S04) and concentrated. 1H NMR indicated a very large amount of DMF still remaining, so the product was taken up in EtOAc and washed with H20. The organic layer was washed with brine, dried (Na2S04) and concentrated. The resulting pale yellow oil was taken up in Et20 and treated with 4N HCI in dioxane to precipitate the product, affording 1.45g (32%) of the hydrochloride salt of 4-(3-chloropropyl)morpholine as a white solid. 1H NMR (D20): 8 3.94 (br m, 2H), 3.70 (brm, 2H), 3.53 (m, 2H), 3.15 (brm, 2H), 3.19 (m, 2H), 3.10 (brm, 2H), 2.08 (m, 2H).
  • 36
  • N-{3-fluoro-4-[(7-hydroxy-6-methoxyquinolin-4-yl)oxy]phenyl}-N'-(2-phenylethyl)ethanediamide [ No CAS ]
  • [ 57616-74-7 ]
  • N-(3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxy}phenyl)-N'-(2-phenylethyl)ethanediamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
74% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; A solution of N-{3-fluoro-4-[(7- hydroxy-6-methoxyquinolin-4-yl)oxy]phenyl}-N'-(2-phenylethyl)ethanediamide (25.6 g, 54 mmol), JV-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong> (11.7 g, 592 mmol) and EPO <DP n="95"/>potassium carbonate (16.6 g, 120 mmol) in DMF (300 mL) was heated to 80 C overnight. Upon cooling, a majority of the DMF (250 mL) was removed on a rotary evaporator, 5% aqueous LiCl (300 mL) was added and the mixture was sonicated at room temperature. The solid was filtered, suspended in IN HCl and washed with ethyl acetate (2 x 300 mL). The solution was adjusted to pH 14 using 2N sodium hydroxide and subsequently extracted with dichloromethane (3 x 200 mL). The organic layer was dried over sodium sulfate, filtered and evaporated to give N-(3-fluoro-4-[6-methoxy-7-(3-morpholin-4- ylpropoxy)quinolin-4-yl]oxy}phenyl)-iV'-(2-phenylethyl)ethanediamide as a yellow solid (24 g, 74 %). 1H NMR (400 MHz, CDCl3): delta 9.37 (s, IH), 8.46 (d, IH), 7.81 (dd, IH), 7.57 (t, IH), 7.53 (s, IH), 7.42 (s, 2H), 7.34-7.20 (m, 6H), 6.39 (d, IH), 4.27 (t, 2H), 4.03 (s, 3H), 3.71 (m, 4H), 3.65 (q, 2H), 2.91 (t, 2H), 2.56 (br s, 4H), 2.13 (m, 2H); 13C NMR (100 MHz, ^-DMSO): delta 160.1, 160.0, 159.5, 155.2, 152.7, 152.6, 150.2, 149.5, 147.1, 139.7, 137.3, 137.1, 129.3, 129.1, 126.9, 124.8, 117.9, 115.1, 109.2, 102.7, 99.6, 67.4, 66.9, 56.5, 55.5, 54.1, 41.3, 35.2, 26.4; IR (cm"1): 1655, 1506, 1483, 1431, 1350, 1302, 1248, 1221, 1176, 1119, 864, 843, 804, 741, 700; LC/MS (M+H = 603).
74% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; A solution of N- {3-FLUORO-4- [ (7- hydroxy-6-methoxyquinolin-4-yl) OXY] PHENYL}-N- (2-PHENYLETHYL) ethanediamide (25.6 g, 54 mmol), N- (3-chloropropyl) morpholine hydrochloride (11.7 g, 592 mmol) and potassium carbonate (16.6 g, 120 mmol) in DMF (300 mL) was heated to 80 C overnight. Upon cooling, a majority of the DMF (250 ML) was removed on a rotary evaporator, 5% aqueous LiCI (300 mL) was added and the mixture was sonicated at room temperature. The solid was filtered, suspended in 1N HC1 and washed with ethyl acetate (2 x 300 mL). The solution was adjusted to pH 14 using 2N sodium hydroxide and subsequently extracted with dichloromethane (3 x 200 mL). The organic layer was dried over sodium sulfate, filtered and evaporated to give N- (3-FLUORO-4-1 [6-METHOXY-7- (3-MORPHOLIN-4- ylpropoxy) quinolin-4-yl] oxy}phenyl)-N'-(2-phenylethyl) ethanediamide as a yellow solid (24 g, 74 %).
  • 37
  • [ 83166-07-8 ]
  • [ 108-20-3 ]
  • [ 57616-74-7 ]
  • [ 110-17-8 ]
  • 11-[3-(4-morpholinyl)propyl]-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine fumarate [ No CAS ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; water; mineral oil; EXAMPLE 11 11-[3-(4-Morpholinyl)propyl]-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine fumarate [1:1] To a stirred suspension of 1.10 g (0.046 mole) of sodium hydride (in mineral oil) in 25 ml of anhydrous dimethylformamide under nitrogen pressure was added, portionwise, 5.0 g (0.0184 mole) of 6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine. The reaction mixture was stirred at room temperature for 15 min, warmed at 65-70 C. for 10 min and allowed to cool to room temperature. To the mixture was added, portionwise, 4.1 g (0.02 mole) of <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong>. The reaction mixture was stirred at room temperature for 16 hr and then poured into 800 ml of water. This mixture was extracted twice with 200 ml portions of methylene chloride. The combined methylene chloride extracts were extracted with 150 ml and 75 ml portions of 3 N hydrochloric acid and the combined aqueous extracts were basified with 3 N sodium hydroxide. The resulting suspension was extracted with two 150 ml portions of methylene chloride and these latter two extracts combined, dried over magnesium sulfate and evaporated under reduced pressure. The residue, the free base of the title compound, was reacted with an equal molar amount of fumaric acid in warm isopropyl alcohol and the mixture treated with isopropyl ether. The fumarate salt was collected by filtration and recrystallized from ethanol-ethyl acetate to give 5.6 g, m.p. 154-7 C. Drying conditions prior to analyses were: 4 hr at 97-98 C./0.1 mm Hg; overnight at room temperature/0.1 mm Hg. Analysis: Calculated for C29 H30 N4 O5: C,67.69; H,5.88; N,10.88. Found: C,67.52; H,5.84; N,10.90.
In N-methyl-acetamide; water; mineral oil; EXAMPLE 11 11-[3-(4-Morpholinyl)propyl]-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine fumarate [1:1] To a stirred suspension of 1.10 g (0.046 mole) of sodium hydride (in mineral oil) in 25 ml of anhydrous dimethylformamide under nitrogen pressure was added, portionwise, 5.0 g (0.0184 mole) of 6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine. The reaction mixture was stirred at room temperature for 15 min, warmed at 65-70 C. for 10 min and allowed to cool to room temperature. To the mixture was added, portionwise, 4.1 g (0.02 mole) of <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong>. The reaction mixture was stirred at room temperature for 16 hr and then poured into 800 ml of water. This mixture was extracted twice with 200 ml portions of methylene chloride. The combined methylene chloride extracts were extracted with 150 ml and 75 ml portions of 3N hydrochloric acid and the combined aqueous extracts were basified with 3N sodium hydroxide. The resulting suspension was extracted with two 150 ml portions of methylene chloride and these latter two extracts combined, dried over magnesium sulfate and evaporated under reduced pressure. The residue, the free base of the title compound, was reacted with an equal molar amount of fumaric acid in warm isopropyl alcohol and the mixture treated with isopropyl ether. The fumarate salt was collected by filtration and recrystallized from ethanol-ethyl acetate to give 5.6 g, m.p. 154-7 C. Drying conditions prior to analyses were: 4 hr at 97-98 C./0.1 mm Hg; overnight at room temperature/0.1 mm Hg. Analysis: Calculated for C29 H30 N4 O5: C, 67.69; H,5.88; N,10.88. Found: C,67.52; H,5.84; N,10.90.
In N-methyl-acetamide; water; mineral oil; EXAMPLE 11 11-[3-(4-Morpholinyl)propyl]-6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine fumarate [1:1] To a stirred suspension of 1.10 g (0.046 mole) of sodium hydride (in mineral oil) in 25 ml of anhydrous dimethylformamide under nitrogen presssure was added, portionwise, 5.0 g (0.0184 mole) of 6-phenyl-11H-pyrido[2,3-b][1,4]benzodiazepine. The reaction mixture was stirred at room temperature for 15 min, warmed at 65-70 C., for 10 min and allowed to cool to room temperature. To the mixture was added, portionwise, 4.1 g (0.02 mole) of <strong>[57616-74-7]4-<strong>[57616-74-7](3-chloropropyl)morpholine hydrochloride</strong></strong>. The reaction mixture was stirred at room temperature for 16 hr and then poured into 800 ml of water. This mixture was extracted twice with 200 ml portions of methylene chloride. The combined methylene chloride extracts were extracted with 150 ml and 75 ml portions of 3N hydrochloric acid and the combined aqueous extracts were basified with 3N sodium hydroxide. The resulting suspension was extracted with two 150 ml portions of methylene chloride and these latter two extracts combined, dried over magnesium sulfate and evaporated under reduced pressure. The residue, the free base of the title compound, was reacted with an equal molar amount of fumaric acid in warm isopropyl alcohol and the mixture treated with isopropyl ether. The fumarate salt was collected by filtration and recrystallized from ethanol-ethyl acetate to give 5.6 g, m.p. 154-7 C. Drying conditions prior to analyses were: 4 hr at 97-98 C./0.1 mm Hg; overnight at room temperature/0.1 mm Hg. Analysis: Calculated for C29 H30 N4 O5: C,67.69; H,5.88; N,10.88. Found: C,67.52; H,5.84; N,10.90.
YieldReaction ConditionsOperation in experiment
When in the procedure of Example 8a the following are substituted for 3-dimethylaminopropyl chloride hydrochloride, 4-(3-chloropropyl)-morpholine hydrochloride, N-(3-chloropropyl)-piperidine hydrochloride, N-(3-chloropropyl)-pyrrolidine hydrochloride, and N-(3-chloropropyl)-4-methyl-1-piperazinyl hydrochloride,
When in the procedure of example 8, equal molar amounts of the following are substituted for 3-dimethylaminopropyl chloride: 4-(3-chloropropyl)morpholine hydrochloride, N-(3-chloropropyl)piperidine hydrochloride, N-(3-chloropropyl)pyrrolidine hydrochloride, and 1-(3-chloropropyl)-4-methylpiperazine dihydrochloride,
A. n-(3-chloropropyl)morpholine, hydrochloride Trimethylene chlorobromide (180 g; 1.15 moles) and 150 g (1.72 moles) of morpholine are reacted in 450 ml of benzene by the method of Adams and Whitmore, JACS, 67, 736 (1945). However, instead of extracting with HCl as in the reference, the solvents are evaporated and the residue distilled to give 76.8 g of colorless oil; b.p. 112-117 /25 mm. Lit. b.p., 113-115 /25 mm. The product is dissolved in 1.2 1. of ether, cooled, stirred, and treated with 58 ml. of 8.2 N alcoholic HCl to precipitate the solid HCl salt; yield, 81.6 g (36%); m.p. 164-166.
  • 39
  • aqueous potassium hydroxide [ No CAS ]
  • [ 57616-74-7 ]
  • [ 110-17-8 ]
  • [ 2894-71-5 ]
  • [ 57616-76-9 ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; EXAMPLE 18 To a solution of 6.4 g of 1,3-dihydro-5-(2-chlorophenyl)-7-chloro-2H-1,4-benzodiazepine-2-thione in a solvent mixture comprising 34 ml of a 10% aqueous potassium hydroxide solution and 5 ml of tetrahydrofuran is added at room temperature with stirring 5.2 g of 1-chloro-3-morpholinopropane hydrochloride and the resulting mixture is then stirred at 50 C for 2.5 hours. The reaction mixture is diluted with a saturated aqueous sodium chloride solution and then extracted with ethyl acetate. The extract is washed with water and dried over magnesium sulfate, and the solvent is removed by distillation under reduced pressure. Resulting oily product is converted into the fumarate with 2.38 g of fumaric acid. Recrystallization from isopropyl alcohol gives 6.8 g of 2-(3-morpholinopropylthio)-5-(2-chlorophenyl)-7-chloro-3H-1,4-benzodiazepine fumarate, m.p. 169-171 C. Elementary analysis: for C22 H23 N3 OSCl2.C4 H4 O4 = 564.51: Calculated: C: 55.32, H: 4.82, N: 7.45; Found: C: 55.08, H: 4.79, N: 7.28.
  • 40
  • [ 1786-05-6 ]
  • [ 57616-74-7 ]
  • [ 64555-45-9 ]
YieldReaction ConditionsOperation in experiment
71% EXAMPLE 16 4-(3'-Morpholinopropoxy)-3-phenyl-coumarin This compound is obtained by the method indicated in Example 8, from 14.3 g. (0.06 mol) of 4-hydroxy-3-phenyl-coumarin and 15.6 g. (0.078 mol) of 3-morpholino-1-chloropropane hydrochloride. 15.6 g. of a white solid are isolated. Yield 71% (theoretical yield 21.9 g.); M.P. 82 C. (isopropanol).
  • 41
  • (cis)-1-(1H-benzimidazol-2-ylmethyl)-1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline [ No CAS ]
  • [ 57616-74-7 ]
  • (cis)-1-({1-[3-(4-morpholinyl)propyl]-1H-benzimidazol-2-yl}methyl)-1,2,3,4,4a,5,6,10b-octahydro-1,10-phenanthroline [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With potassium carbonate;potassium iodide; In N,N-dimethyl-formamide; at 80℃; for 16h; To a solution of (cis) 1 -(1 H-benzimidazol-2-ylmethyl)-1 ,2,3,4,4a,5,6,1 Ob-octahydro-1 ,10-phenanthroline (0.032 g, 0.10 mmol) in 5 mL of N,N-dimethylformamide was added potassium carbonate (0.14 g, 1.0 mmol), 4-(3-chioropropyl)morpholine hydrochloride (0.050 g, 0.25 mmol), and potassium iodide (10 mg). The reaction mixture was heated to 80 9C in a sealed tube for 16 hours. After being allowed to cool, the mixture was diluted with 10 mL of water and extracted 3 times with 10 mL of dichloromethane. The combined organic layers were concentrated and the residue purified by silica chromatography eluting with a 0% to 10% gradient of 30% aqueous ammonium hydroxide in acetonitrile to yield 0.025 g (56%) of (cis) 1-({1-[3-(4- morpholinyl)propyl]-1 H-benzimidazol-2-yl}methyl)-1 ,2,3,4,4a,5,6,10b-octahydro-1 ,10- phenanthroline. 1 H NMR (400 MHz, METHANOL-D4) delta ppm 1.5 (m, 2 H), 1.7 (m, 4H), 1.9 (t, J=7.2 Hz, 2 H), 2.1 (m, 1 H), 2.2 (m, 2 H), 2.3 (m, 1 H), 2.4 (m, 1 H), 2.4 (m, 1 H), 2.6 (m, 1 H), 2.8 (d, J=12.1 Hz, 1 H), 2.9 (m, 1 H), 3.1 (m, 1 H), 3.5 (m, 5 H), 3.7 (m, 2 H), 4.0 (m, 1 H)1 4.2 (m, 2 H), 7.2 (m, 2 H), 7.3 (dd, J=7.9, 4.8 Hz, 1 H), 7.4 (d, J=6.8 Hz, 1 H)1 7.6 (m, 1 H), 7.7 (d, J=9.0 Hz, 1 H), 8.4 (d, J=6.4 Hz, 1 H); MS m/z 446 (M+1).
 

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