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[ CAS No. 99614-02-5 ]

{[proInfo.proName]} (Synonyms:GR 3832; SN-37; NSC665799) ,{[proInfo.pro_purity]}
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Chemical Structure| 99614-02-5
Chemical Structure| 99614-02-5
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CAS No. :99614-02-5 MDL No. :MFCD00833882
Formula : C18H19N3O Boiling Point : 546°C at 760 mmHg
Linear Structure Formula :- InChI Key :-
M.W :293.36 g/mol Pubchem ID :4595
Synonyms :

1. Ondansetron

Safety of [ 99614-02-5 ]

Signal Word:Danger Class:6.1
Precautionary Statements:P301+P310 UN#:2811
Hazard Statements:H301 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 99614-02-5 ]

  • Upstream synthesis route of [ 99614-02-5 ]
  • Downstream synthetic route of [ 99614-02-5 ]

[ 99614-02-5 ] Synthesis Path-Upstream   1~16

  • 1
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YieldReaction ConditionsOperation in experiment
92% With sodium hydroxide In ethanol; waterHeating / reflux 680 g of ondansetron hydrochloride dihydrate was dissolved in 4000 ml of ethanol at reflux. A solution of 82 g of NAOH in 1000ML of water was added. A solid was formed. 3000 ml of water was added and the mixture was cooled to ambient temperature. The solid was filtered off and washed with 2*500 ml of water. The solid was dried at 50°C under vacuum for 2 days. The product exhibited the DSC curve shown in fig. 1 and the XRPD pattern of fig. 2. Yield : 527 g (96percent)80 g of ondansetron hydrochloride dihydrate was suspended in 500 ml of ethanol and heated to reflux until a clear solution was obtained. To this solution, 250 ml of a 1 M NAOH solution was added. During addition a solid started to form. 250 ml of water was added and the mixture was slowly cooled to room temperature. The mixture was cooled to 10- 15°C and the solid was filtered off. The solid was washed with 2X200 ml of water. After drying in a vacuumoven at 40°C for 3 days. 59.3 g of a white solid was obtained. The product exhibited the DSC curve shown in fig. 3 and the XRPD pattern of fig. 4. Yield : 59.3 g (92percent)
Reference: [1] Patent: WO2004/63189, 2004, A1, . Location in patent: Page 20-21
[2] Patent: WO2005/80381, 2005, A1, . Location in patent: Page/Page column 17-18
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YieldReaction ConditionsOperation in experiment
98% for 2.16667 h; Heating / reflux Example 17 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one prepared in any one of Examples 1 to 7 and 11 g of 2-methyl-l-trimethylsilyl imidazole were suspended in 35 ml of acetonitrile. The solution of 6.2 g of tetra-n- butylammonium fluoride hydrate in 15 ml of acetonitrile was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to ambient temperature, the reaction solvent was distilled off. 100 ml of water was added to the residue, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 6.61 g of the title compound as a white solid (yield 98percent).; Example 20 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one prepared in any one of Examples 1 to 7 and 22 g of 2-methyl-l-trimethylsilyl imidazole were suspended in 35 ml of acetonitrile. The solution of 6.2 g of tetra-n- butylammonium fluoride hydrate in 15 ml of acetonitrile was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to ambient temperature, the reaction solvent was distilled off. 100 ml of water was added to the residue, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 6.75 g of the title compound as a white solid (yield 100percent).
96.7% for 2.16667 h; Heating / reflux Example 19 The same procedures as described in Example 17 were repeated, except that ethyl acetate was employed instead of acetonitrile, to give 6.72 g of the title compound (yield 96.7percent).
96.1% at 80℃; for 2 h; Example 21 To the mixture of 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H- carbazol-4-one prepared in any one of Examples 1 to 7 and 22 g of 2-methyl-1- trimethylsilyl imidazole was added 6.2 g of tetra-n-butylammonium fluoride hydrate at 80 °C, and then the reaction mixture was stirred for 2 hours. After cooling to ambient temperature, 100 ml of water was added to the reaction mixture, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 6.48 g of the title compound as a white solid (yield 96. 1percent).
94.5% for 2.16667 h; Heating / reflux Example 18 The same procedures as described in Example 17 were repeated, except that tetrahydrofuran was employed instead of acetonitrile, to give 6.57 g of the title compound (yield 94.5percent).
92% at 80℃; for 2.16667 h; Heating / reflux Example 15 The mixture of 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H- carbazol-4-one prepared in any one of Examples 1 to 7 and 11 g of 2-methyl-1- trimethylsilyl imidazole was heated to 80 °C. 23.7 ml of IN tetra-n- butylammonium fluoride solution was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to room temperature, 100 ml of water was added to the reaction mixture, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 6.2 g of the title compound as a white solid (yield 92percent). Example 16 The mixture of 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H- carbazol-4-one prepared in any one of Examples 1 to 7 and 22 g of 2-methyl-1- trimethylsilyl imidazole was heated to 80°C. 2. 37ml of IN tetra-n-butylammonium fluoride solution was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to ambient temperature, 100 ml of water was added to the reaction mixture, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 6.61 g of the title compound as a white solid (yield 98percent).
87% for 2.16667 h; Heating / reflux Example 14 5g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one prepared in any one of Examples 1 to 7 and llg of 2-methyl-l-trimethylsilyl imidazole were suspended in 25 ml of acetonitrile. 1. 9ml of IN tetra-n- butylammonium fluoride solution was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to room temperature, 100 ml of water was added to the reaction mixture, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 5.85 g of the title compound as a white solid (yield 87percent).

Reference: [1] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 14-15
[2] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 14
[3] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 15
[4] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 14
[5] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 13-14
[6] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 13
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YieldReaction ConditionsOperation in experiment
81.5% With acetyl chloride In toluene; acetonitrileHeating / reflux Example 11: Synthesis of ls239-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one To the solution of 36 ml of acetyl chloride in 50 ml of actonitrile and 750 ml of toluene, was slowly added 51 ml of N, N, N', N'- tetramethyldiaminomethane at 0°C, which was then stirred for 10min. 50 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 100 g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 150 ml of water was added to the resulting residue. The resulting solid was filtered and washed, and then dried under a reduced pressure. The resulting solid was suspended in 350 ml of methanol, and then 0.7g of active carbon was added to thereto, which was then stirred for 1 hour under reflux. The resulting mixture was filtered and washed with methanol, which was then stirred for 3 hours at room temperature. The resulting solid was filtered and dried to give 60 g of pure white title compound (yield 81.5percent).
75%
Stage #1: at 120 - 130℃; for 8 h;
Stage #2: With sodium hydroxide In water
Example 8: Synthesis of 12s3 " 9-tetrahydro-9-methyl-3-[(2-methel-lH- imidazole-1-vl) methyl]-4H-carbazol-4-one At-10°C, 4 ml of N, N, N', N'-tetramethyldiaminomethane was slowly added to 46 ml of trifluoroacetic acid, which was then stirred for 30 min. 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one and 8 g of 2-methyl imidazole was added to the reaction mixture, which was then stirred for about 8 hours at 120-130°C. After completion of reaction, the reaction mixture was cooled at room temperature, and then IN aq. sodium hydroxide was added thereto. The resulting solid was filtered and washed with water, and then dried. The resulting solid was suspended in 80 ml of methanol, and then 0.28 g of active carbon was added thereto, which was then stirred under reflux for 1 hour. The resulting mixture was filtered and washed with methanol, and then evaporated to give 2.2 g of 1, 2,3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazol-1-yl) methyl]- 4H-carbazol-4-one (yield 75percent).
66% With chloro-trimethyl-silane In DMF (N,N-dimethyl-formamide) at 90℃; for 10 h; Example 2: Synthesis of 1, 23*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 20 ml of N, N-dimethylformamide, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred at 90 °C for 10 hours. 100ml of water was added to the reaction mixture. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.93 g of title compound (yield 66percent).
60% With chloro-trimethyl-silane In acetonitrile for 10 h; Heating / reflux Example 1 : Synthesis of 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl) methyll-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 40 ml of water was added to the resulting residue. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.76 g of title compound (yield 60percent).
58% With acetyl chloride In toluene for 10 h; Heating / reflux Example 7: Synthesis of 123*9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yl methyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 2 ml of N, N, N', N'-tetramethyl- diaminomethane were suspended in 30 ml of toluene, and then 1.4 ml of acetyl chloride was slowly added thereto, which was then stirred for 10 min. 1.65g of 2-methyl imidazole was added to the reaction mixture, which was then stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 150ml dichloromethane and 50ml of IN aq. sodium hydroxide were added to the resulting residue. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone, which was then stirred for 3 hours, and then filtered and dried to give 1.70 g of title compound (yield 58percent).
55% With aluminum (III) chloride In acetonitrile for 10 h; Heating / reflux Example 4: Synthesis of 123, 9-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-1-yDmethyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2 ml of N, N, N', N'-tetramethyldiaminomethane were suspended in 30 ml of acetonitrile, and then 1.4 g of aluminum chloride was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. 150 ml dichloromethane and 50 ml of IN aq. sodium hydroxide were added to the reaction mixture. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.61 g of title compound (yield 55percent).

Reference: [1] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 11
[2] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 10
[3] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 7
[4] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 7
[5] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 9-10
[6] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 8
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YieldReaction ConditionsOperation in experiment
83% at 5 - 103℃; for 5.5 - 6.5 h; Preparation of 1, 23*9-Tetrahydro-9-methYl-3- [ (2-methyl-1 H-imidazol-1-yPmethyl]-4H-carbazol-4-onc; Example 1; 3- [ (Dimethylamino) methyl]-1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride (10 g, 34 mmol) and 2-methylimidazole (16.8 g, 205 mmol, 6.0 eq. ) were suspended in mixture of water (75 ml) and dimethyl formamide (37.5 ml). The reaction mixture was heated to reflux (102-103°C) and stirred for a further 6 hours at this temperature. The reaction mixture was cooled to 5-10°C and stirred for half an hour at this temperature. The precipitated crude ondansetron base was filtered and washed with cold water (3x 90 ml) and dried under vacuum at 60 °C to give ondansetron base (9.68 g, 96.4 percent yield) in 98.9percent HPLC purity. Example 2; 3- [(Dimethylamino) methyl]-1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one hydrochloride (12 kg, 41 mol) and 2-methylimidazole (20.2 kg, 246 mol, 6 eq. ) were suspended in mixture of water (120 L) and DMF (30 L). The reaction mixture was heated to reflux (100-102°C) and stirred for 5 hours at this temperature. The reaction mixture was cooled to 5-10 °C and stirred for half an hour. The precipitated crude ondansetron base was filtered and washed with cold water (2x110 L) and dried under vacuum at 60 °C to give ondansetron base (10 kg, 83percent yield) in 97.3percent HPLC purity. The major impurity was the exomethylene carbazolone which amounted to 2.6percent of the crude ondansetron mixture.
Reference: [1] Patent: WO2003/93281, 2003, A1, . Location in patent: Page/Page column 15; 16
[2] Patent: US6544550, 2003, B1,
[3] Patent: US4753789, 1988, A,
[4] Patent: US4835173, 1989, A,
[5] Patent: US4983621, 1991, A,
[6] Patent: US4847281, 1989, A,
[7] Patent: EP411900, 1991, A2,
[8] Patent: EP269452, 1989, A3,
[9] Patent: US4695578, 1987, A,
[10] Patent: EP269452, , A2, [10] Patent: , 1988, ,
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  • [ 99614-02-5 ]
YieldReaction ConditionsOperation in experiment
99% for 6 h; Heating / reflux Example 8 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one prepared in any one of Examples 1 to 7,5. 89 g of 2-methyl imidazole and 1 g of montmorillonite K10 were added to 100ml of toluene, and then the reaction mixture was stirred under reflux for 6 hours. After completion of reaction, the solvent was distilled off, and then chloroform was added to the resulting residue and the catalyst was filtered off. The filtrate was washed with water, dried over anhydrous magnesium sulfate, and evaporated. The resulting solid was purified with ethyl acetate to give 6.94 g of the title compound as white solid (yield 99percent).
94% for 3 - 4 h; Heating / reflux Example 4
Synthesis of Ondansetron Without Using Alumina
In this reaction, we examined the feasibility of producing ondansetron from 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one without alumina as a catalyst.
The crude 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one from Example 3 (145 grams, 0.69 mol) and 2-methylimidazole (71 grams; 0.86 mol) were added to toluene (800 mL), and the mixture was heated to reflux temperature.
After about 3-4 hours (TLC indicated that 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one had been substantially consumed), the reaction was cooled to room temperature.
The resulting precipitate was isolated by filtration to provide 190 grams (0.65 mol; 94percent yield) of crude ondansetron.
Accordingly, ondansetron was prepared from 1,2,3,9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one in a yield of about 94percent after heating for about 3-4 hours.
Note that alumina was not used as a catalyst.
In addition, the ondansetron was isolated from the reaction mixture quickly and efficiently by filtering the reaction mixture.
91% for 2 h; Heating / reflux Example 13 The same procedures as described in Example 10 were repeated, except that toluene was employed instead of acetonitrile, to give 6.32 g of the title compound (yield 91percent).
90% for 6 h; Heating / reflux Example 9 The suspension of 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H- carbazol-4-one prepared in any one of Examples 1 to 7,5. 89 g of 2-methyl imidazole and 1 g of montmorillonite KSF in 100ml of toluene was stirred under reflux for 6 hours. After completion of reaction, the reaction solvent was distilled off, and then chloroform was added to the resulting residue, and then the catalyst was filtered off. The filtrate was washed with water, dried over anhydrous magnesium sulfate, and evaporated to dryness. The resulting solid was purified with ethyl acetate to give 6.3 g of the title compound as white solid (yield 90percent).
88.3% for 2 h; Heating / reflux Example 11 The same procedures as described in Example 10 were repeated, except that tetrahydrofuran was employed instead of acetonitrile, to give 6.14 g of the title compound (yield 88.3percent).
84.2% for 2 h; Heating / reflux Example 10 5 g of 1, 2,3, 9-tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one prepared in any one of Examples 1 to 7 and 11 g of 2-methyl-1-trimethylsilyl imidazole was suspended in 25 ml of acetonitrile. 23. 7ml of 1N tetra-n- butylammonium fluoride solution was added dropwise for 10 min under reflux, and then the reaction mixture was stirred for 2 hours. After cooling to room temperature, 100 ml of water was added to the reaction mixture, and then stirred for 30 min. The resulting solid was filtered and washed with 100 ml of water to give 5.85 g of the title compound as a white solid (yield 84.2percent).
80% for 2 h; Heating / reflux Example 12 The same procedures as described in Example 10 were repeated, except that 1.4-dioxane was employed instead of acetonitrile, to give 5.56 g of the title compound (yield 80percent).

Reference: [1] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 11
[2] Patent: US2006/41004, 2006, A1, . Location in patent: Page/Page column 8
[3] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 13
[4] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 12
[5] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 12
[6] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 12
[7] Patent: WO2005/37823, 2005, A1, . Location in patent: Page/Page column 12
[8] Heterocycles, 1997, vol. 45, # 10, p. 2041 - 2043
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Reference: [1] Patent: WO2004/46116, 2004, A1, . Location in patent: Page 13
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  • [ 99614-02-5 ]
Reference: [1] Patent: WO2004/46116, 2004, A1, . Location in patent: Page 12
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Reference: [1] Patent: WO2004/46116, 2004, A1, . Location in patent: Page 12-13
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YieldReaction ConditionsOperation in experiment
70% With aluminum (III) chloride In acetonitrile for 10 h; Heating / reflux Example 6: Synthesis of 123s9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl) methvl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 274 g of dipiperidinomethane were suspended in 30 ml of acetonitrile, and then 2 g of aluminum chloride was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. 150 ml dichloromethane and 50 ml of IN aq. sodium hydroxide were added to the reaction mixture. The resulting organic layer was separated and dried over MgS04, and then evaporated. The resulting solid was suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 2.05 g of title compound (yield 70percent).
68% With chloro-trimethyl-silane In DMF (N,N-dimethyl-formamide) at 90℃; for 8 h; Example 5: Synthesis of 1239-tetrahydro-9-methyl-3-r (2-methyl-lH- imidazole-l-yl . methyl]-4H-carbazol-4-one 2.0 g of 1, 2,3, 9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2- methyl imidazole and 2.74 g of dipiperidinomethane were suspended in 20 ml of N, N-dimethylformamide, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred for 8 hours at 90 °C. 100 ml of water was added to the reaction mixture. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours, and then filtered and dried under a reduced pressure to give 1.99 g of title compound (yield 68percent).
Reference: [1] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 9
[2] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 9
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YieldReaction ConditionsOperation in experiment
32% With methanesulfonic acid In methanol Step 1
9-Methyl-3- (2-methyl-imidazol-1ylmethyl)-1,2,3,9-tetrahydro-carbazol-4-one:
At about 70° C., a solution of 2-(oxazolidin-3-yl)ethanol (372 mg, 3.18 mmol, 1.50 equiv) and n-butanol (50 mL) was added to a mixture of 9-methyl-2,3-dihydro-1H-carbazol-4(9H)-one (420 mg, 2.11 mmol, 1.00 equiv), methanesulfonic acid (324 mg, 3.38 mmol, 1.60 equiv) and n-butanol (50 mL).
The resulting mixture was stirred at about 80° C. for about 30 minutes, and then stirred at about 120° C. for about 2.5 hours. 2-Methyl-1H-imidazole (870 mg, 10.6 mmol, 5.00 equiv) was then added to the mixture.
After stifling the mixture at about 120° C. for about 6 hours, the mixture was concentrated in vacuo and the resulting residue was resuspended in methanol.
The resulting solids were collected by filtration and washed with water and methanol.
The solids were then purified by silica gel column chromotagraphy (ethyl acetate/petroleum ether (1:1)), to give the title product as a light yellow solid (200 mg, yield=32percent).
Reference: [1] Patent: US2010/119623, 2010, A1,
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Reference: [1] Patent: US4695578, 1987, A,
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  • [ 99614-02-5 ]
YieldReaction ConditionsOperation in experiment
54% With chloro-trimethyl-silane In toluene; acetonitrileHeating / reflux Example 10: Synthesis of 1*23*9-tetrahydro-9-methyl-3-[(2-methyl-lH- imidazole-1-yl) methel]-4H-carbazol-4-one To the solution 19.5 g of 1, 3, 5-trimethylhexahydro-1, 3,5-triazine in 20 ml of actonitrile and 150 ml of toluene, was slowly added 19 ml of chlorotrimethylsilane, which was then stirred for lOmin. lOg of 1,2, 3,9- tetrahydro-9-methyl-4H-carbazol-4-one and 8.2g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 200 ml of water was added to the resulting residue, which was then stirred for 2 hours at room temperature. The resulting solid was filtered and washed with water to give 7.95 g of light yellow title compound (yield 54percent).
51% Heating / reflux Example 9: Synthesis of 12s39-tetrahydro-9-methel-3-[(2-methyl-lH- imidazole-1-yl) methyll-4H-carbazol-4-one To the solution of 7.1 ml of 1, 3, 5-trimethylhexahydro-1, 3,5-triazine in 150ml of toluene, was slowly added 4 ml of trifluoroacetic acid, which was then stirred for 10min. lOg of 1,2, 3,9-tetrahydro-9-methyl-4H-carbazol-4-one and 20 g of 2-methyl imidazole were subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 200 ml of water was added to the resulting residue, which was then stirred for 2 hours at room temperature. The resulting solid was filtered and washed with excess water to give 7.5 g of light yellow title compound (yield 51percent).
Reference: [1] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 11
[2] Patent: WO2005/37822, 2005, A1, . Location in patent: Page/Page column 10-11
  • 13
  • [ 123-91-1 ]
  • [ 27387-31-1 ]
  • [ 18162-48-6 ]
  • [ 99614-02-5 ]
Reference: [1] Patent: US6388091, 2002, B1,
[2] Patent: EP1207160, 2002, A1,
  • 14
  • [ 77-78-1 ]
  • [ 99614-14-9 ]
  • [ 99614-02-5 ]
Reference: [1] Patent: US4695578, 1987, A,
  • 15
  • [ 693-98-1 ]
  • [ 99614-64-9 ]
  • [ 99614-02-5 ]
Reference: [1] Patent: WO2006/46253, 2006, A1, . Location in patent: Page/Page column 18-19
[2] Patent: WO2006/46253, 2006, A1, . Location in patent: Page/Page column 19
  • 16
  • [ 27387-31-1 ]
  • [ 99614-02-5 ]
  • [ 132666-57-0 ]
Reference: [1] Patent: EP1207160, 2002, A1,
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