39539-66-7|4-Methylpiperazine-1-carbonyl chloride| Ambeed

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Quality Control of [ 39539-66-7 ] Purity: 98% SDS Specification

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Product Details of [ 39539-66-7 ]

CAS No. :	39539-66-7
Formula :	C₆H₁₁ClN₂O
M.W :	162.62
SMILES Code :	O=C(Cl)N1CCN(C)CC1
MDL No. :	MFCD01320509

Safety of [ 39539-66-7 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H314
Precautionary Statements:	P280-P305+P351+P338-P310
Class:	8
UN#:	3265
Packing Group:	Ⅱ

Application In Synthesis of [ 39539-66-7 ]

* 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 [ 39539-66-7 ]

[ 39539-66-7 ] Synthesis Path-Downstream 1~55

1
[ 109-01-3 ]
[ 75-44-5 ]
[ 67-66-3 ]
[ 39539-66-7 ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1956,vol. 76,p. 605.
Chem.Abstr.,1957,p. 434.

2
[ 109-01-3 ]
[ 75-44-5 ]
[ 39539-66-7 ]

References: [1]Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan,1956,vol. 76,p. 605.
Chem.Abstr.,1957,p. 434.
[2]Bulletin des Societes Chimiques Belges,1949,vol. 58,p. 103,104.

3
[ 109-01-3 ]
[ 75-44-5 ]
[ 108-88-3 ]
[ 71-43-2 ]
[ 39539-66-7 ]

References: [1]Bulletin des Societes Chimiques Belges,1949,vol. 58,p. 103,104.

4
[ 39539-66-7 ]
[ 109-89-7 ]
[ 90-89-1 ]

References: [1]Bulletin des Societes Chimiques Belges,1949,vol. 58,p. 103,104.

5
[ 39539-66-7 ]
[ 63397-92-2 ]
[ 94961-58-7 ]

References: [1]Monatshefte fur Chemie,1962,vol. 93,p. 807 - 813.

6
[ 39539-66-7 ]
[ 97205-34-0 ]
1-benzyl-4-<(4-methylpiperazin-1-yl)carbonylaminomethyl>-2-oxopyrrolidine [ No CAS ]

References: [1]Collection of Czechoslovak Chemical Communications,1994,vol. 59,p. 1126 - 1136.

7
[ 39539-66-7 ]
[ 108199-05-9 ]
[ 108199-13-9 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1986,vol. 25,p. 828 - 831.

8
[ 39539-66-7 ]
[ 105492-78-2 ]
[ 105492-90-8 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1985,vol. 24,p. 1154 - 1157.

9
[ 39539-66-7 ]
[ 181579-66-8 ]
4-Methyl-piperazine-1-carboxylic acid (2-{4-[ethyl-(3-ethylamino-pyridin-2-yl)-amino]-piperidine-1-carbonyl}-1H-indol-5-yl)-amide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3769 - 3789.

10
[ 39539-66-7 ]
[ 179557-45-0 ]
4-Methyl-piperazine-1-carboxylic acid (2-{4-[ethyl-(3-isopropylamino-pyridin-2-yl)-amino]-piperidine-1-carbonyl}-1H-indol-5-yl)-amide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3769 - 3789.

11
[ 39539-66-7 ]
[ 179557-50-7 ]
4-Methyl-piperazine-1-carboxylic acid (2-{4-[(3-tert-butylamino-pyridin-2-yl)-ethyl-amino]-piperidine-1-carbonyl}-1H-indol-5-yl)-amide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3769 - 3789.

12
[ 39539-66-7 ]
[ 181579-65-7 ]
4-Methyl-piperazine-1-carboxylic acid (2-{4-[(3-tert-butylamino-6-fluoro-pyridin-2-yl)-ethyl-amino]-piperidine-1-carbonyl}-1H-indol-5-yl)-amide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1996,vol. 39,p. 3769 - 3789.

13
[ 62226-74-8 ]
[ 32315-10-9 ]
[ 39539-66-7 ]

References: [1]Synthetic Communications,1998,vol. 28,p. 1189 - 1195.

14
[ 39539-66-7 ]
[ 156055-46-8 ]
1-[(2-Dimethylaminoethyl)aminocarbonyl]-5,6-dimethyl-9-(4-methylpiperazino-carbonyloxy)-6H-pyrido[4,3-b]carbazole [ No CAS ]

References: [1]Journal of Medicinal Chemistry,1999,vol. 42,p. 2191 - 2203.

15
[ 476314-26-8 ]
[ 39539-66-7 ]
4-(4-Fluorophenyl)-2-(4-methylpiperazine-1-carbonyl)-3-pyridin-4-yl-2H-isoxazol-5-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 2399 - 2403.

16
[ 39539-66-7 ]
[ 346656-39-1 ]
[ 20929-25-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5342 - 5343.

17
[ 476629-38-6 ]
[ 39539-66-7 ]
C₂₁H₃₃N₃O₄ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2006,vol. 16,p. 5542 - 5545.

18
[ 39539-66-7 ]
[ 103343-47-1 ]
4-methyl-piperazine-1-carboxylic acid-(2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)-amide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2006,vol. 49,p. 2311 - 2319.

19
[ 144553-76-4 ]
[ 39539-66-7 ]
7-isopropoxy-5,6-dimethoxy-2-{{4-[(4-methyl-1-piperazinyl)carbonyl]oxy}phenyl}thio}-4H-chromen-4-one [ No CAS ]

References: [1]Chemical and Pharmaceutical Bulletin,2007,vol. 55,p. 328 - 333.

20
[ 39539-66-7 ]
[ 909300-27-2 ]
2-(2-difluoromethylbenzimidazol-1-yl)-4-[4-(4-methylpiperazin-1-ylcarbonyl)piperazin-1-yl]-6-morpholinopyrimidine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 1h;	Example 8; 2-(2-difluoromethylbenzimidazoH-yI)-4-[4-(4-methylpiperaziii-l-ylcarbonyl)piperazin- 1 -y 1] -6-morpholinopy rimidine; Diisopropylethylamine (0.261 ml) was added to a stirred mixture of2-(2-difluoromethylbenzimidazol- 1 -yl)-6-morpholino-4-piperazin- 1 -ylpyrimidine (0.208 g), 4-methylpiperazin-l-ylcarbonyl chloride (0.122 g) and methylene chloride (20 ml) and the resultant mixture was stirred at ambient temperature for 1 hour. The reaction mixture was evaporated and the reaction product was purified using a Waters 'Sunfre' preparative reversed-phase column (5 microns silica, 19 mm diameter, 100 mm length) and decreasingly polar mixtures of a 0.1% solution of trifluoroacetic acid in water and a 0.1% solution of trifluoroacetic acid in acetonitrile as eluent. There was thus obtained the title compound (0.085 g); NMR Spectrum: (CDCl3) 2.85 (s, 3H), 3.35-3.43 (m, 2H), 3.45-3.5 (m, 4H), 3.5-3.62 (m, 4H), 3.63-3.73 (m, 8H), 3.75-3.88 (m, 6H), 5.53 (s, IH), 7.35-7.5 (m, 3H), 7.9-7.94 (d, IH), 8.18-8.22 (d, IH); Mass Spectrum: MH-H+ 542.

References: [1]Patent: WO2008/32064,2008,A1 .Location in patent: Page/Page column 112.

21
[ 956901-01-2 ]
[ 39539-66-7 ]
C₂₂H₂₃N₃O₅ [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 5423 - 5427.

22
[ 39539-66-7 ]
[ 645418-54-8 ]
[ 645418-58-2 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 65℃;	Example 8 N- [3,3-Dimethyl -1- (4-methyl-piperazine-1-carbonyl) -2, 3- [ DIHYDRO-LH-INDOL-6-YL]-2- (4-FLUORO-BENZYLAMINO)-BENZAMIDE] Step A: Preparation of [N- [3, 3-DIMETHYL-L- (4-METHYL-] [PIPERAZINE-1-CARBONYL)-2, 3-DIHYDRO-LH-INDOL-6-YL]-2-NITRO-] benzamide [N- (3,] 3-dimethyl-2, [3-DIHYDRO-LH-INDOL-6-YL)-2-NITRO-] benzamide (Example 7, Step A) (300 mg, 0.96 mmol) was treated with [4-METHYL-PIPERAZINE-1-CARBONYL] chloride (200 mg, 1 mmol) in the presence of DIEA (40 mL) in THF overnight at 65 [C.] The mixture was partitioned between EtOAc and saturated aqueous [NAHC03.] The organic layer was washed with [H2O] and brine, then dried over [NA2SO4.] The organic solution was concentrated in vacuo to yield the desired compound.

References: [1]Patent: WO2004/5279,2004,A2 .Location in patent: Page 127.

23
[ 39539-66-7 ]
5,6-dimethyl-2-(3-fluorophenyl)-3-(4-methyl-1-piperazinyl)-carbonyloxyisoindolin-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 5,6-dimethyl-2-(3-fluorophenyl)-3-hydroxyisoindolin-1-one (83 mg, 0.31 mmol) in anhydrous dimethylformamide (3 ml) was added to a suspension of 65% sodium hydride (13 mg, 0.34 mmol) in anhydrous dimethylformamide (3 ml), and stirred at 25C for 35 minutes. Then, a solution of 1-chlorocarbonyl-4-methylpiperazine (50 mg, 0.31 mmol) in anhydrous dimethylformamide was added thereto, and stirred with heating at 70C for 5 hrs. The reaction solution was concentrated under reduced pressure, and water was added to the residue, followed by extracting with chloroform. The extract was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (chloroform: methanol = 20: 1). The resulting crystals were washed with petroleum ether to give 21 mg of the title compound. melting point: 146-148C 1H-NMR (CDCl3) delta: 2.38 (3H, s, CH3), 2.40 (3H, s, CH3), 2.73 (3H, s, NCH3), 3.01-3.14 (6H, m, piperazine), 3.18-3.24 (1H, m, piperazine), 3.32-3.38 (1H, m, piperazine), 6.43 (1H, s, CH), 6.85-6.91 (1H, m, PhH), 7.33-7.39 (1H, m, PhH), 7.36 (1H, s, C4-H), 7.66 (1H, s, C7-H), 7.66-7.76 (2H, m, PhH)

References: [1]Patent: EP1566378,2005,A1 .Location in patent: Page/Page column 45.

24
[ 596845-98-6 ]
[ 39539-66-7 ]
[ 596846-09-2 ]

Yield	Reaction Conditions	Operation in experiment
45%	With triethylamine; In dichloromethane; at 18 - 25℃; for 2h;	Example 18 : 2,3-Dichloro-N-((1S,2S)-1-[(4-methylpiperazin-1-yl)carbonyl]amino}-2,3- dihydro-lH-inden-2-yl)-4H-thienof3, 2-blpyrrole-5-carboxamide; To a solution of N-[(1S,2S)-1-amino-2,3-dihydro-1H-inden-2-yl]-2,3-dichloro-4H- thieno [3, 2-b] pyrrole-5-carboxamide (Method 9, 240 mg, 0. 5 mmol) and Et3N (101 mg, 1. 0 mmol) in DCM (4 mL) was added a solution of 4-methyl-1-piperazine carbonyl chloride (100 mg, 0. 5 mmol) in DCM (1 mL). The reaction was stirred at ambient temperature for 2 hours, washed with saturated Narc03 (1 mL), water (1 mL), brine (1 mL) and dried (MgS04). The volatiles were removed by evaporation under reduced pressure to give the title compound (110 mg, 45%) as a foam. MS m/z (M-H)-491.

References: [1]Patent: WO2003/74531,2003,A1 .Location in patent: Page/Page column 82-83.

25
[ 39539-66-7 ]
N-[9-chloro-7-(2,6-difluoro-phenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-yl]-benzene-1,4-diamine [ No CAS ]
4-Methyl-piperazine-1-carboxylic acid {4-[9-chloro-7-(2,6-difluoro-phenyl)-5H-benzo[c]pyrimido[4,5-e]azepin-2-ylamino]-phenyl}-amide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
10%	With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 160℃; for 1h;	A solution of this product (50 mg, 0.1 mmol), 4-methylpiperazine-1-carbonylchloride (89 mg, 0.6 mmol), diisopropylethylamine (142 mg, 1.1 mmol), in dioxane (0.5 mL) was submitted to microwave irradiation (300 W) for 60 minutes at 160 C. The reaction solution was cooled to room temperature and slowly poured into a stirring saline solution (10 mL). The resulting precipitate was collected by filtration, washed with water and purified by RP-HPLC (C18, 0 to 100% CH3CN in 0.1% aqueous HCO2H) to yield 1-280 as a pale yellow solid (6 mg, 10%) MS m/z=574 (M+H).

References: [1]Patent: US2005/256102,2005,A1 .Location in patent: Page/Page column 148.

26
[ 39539-66-7 ]
[ 477207-95-7 ]
[ 477208-13-2 ]

References: [1]Patent: WO2005/112919,2005,A2 .Location in patent: Page/Page column 134-135.

27
[ 39539-66-7 ]
[ 870487-40-4 ]
[ 870487-41-5 ]

Yield	Reaction Conditions	Operation in experiment
73%	With allyl alcohol; In pyridine; dichloromethane; at 20℃; for 5h;	To a solution of the bromo methyl seco compound (0.074 mMoles) in 3 mL DMF was added the 5-actyl indole-2-carboxylate (30 mg, 0.15 mMoles) and EDC (28 mg, 0.15 mMoles) and the resulting mixture was stirred overnight. The reaction mixture was concentrated and purified by silica gel chromatography using 5% MeOH in DCM Tt give 29 mg (74 % yield) of product which was confirmed by mass spec M+1 = 523. To a solution of the compound synthesized in step C in 5 mL DCM and 300 muL allyl alcohol was added methyl piperazine carbonyl chloride (22 mg, 0.11 m Moles) and pyridine 44 muL. The reaction mixture was stirred at room temperature for 5 hours. Concentration followed by purification by silica gel chromatography using 5 % MeOH/DCM as eluant gave 48 mg of the desired product (73 % yield). The product was confirmed by Mass Spec. M+1 = 650. A solution of the above compound (8.2 mg , 0.012 mmoles) and Mal-PEG4-hydrazine in 5 % acetic acid in anhydrous DCM was stirred at room temperature for 20 minutes followed by evaporation of Solvents and Reverse phase Prep HPLC using acetonitrile and ammonium formate buffered aqueous phase gave 2.5 mg of the desired final product which was confirmed by mass Spec, M+1 = 1063

References: [1]Patent: WO2005/112919,2005,A2 .Location in patent: Page/Page column 140-141.

28
[ 39539-66-7 ]
[ 870487-27-7 ]
[ 870487-28-8 ]

Yield	Reaction Conditions	Operation in experiment
	With allyl alcohol; In pyridine; dichloromethane; for 2h;	The 4'-OH was protected using methyl pipirazine carbonyl chloride (11 mg, 0.054 mMoles) in 2mL DCM, 200 muL Allyl alcohol and pyridine (21 muL) for 2 hours. The product was purified by silica gel column chromatography and Identified by Mass Spec, MS+1 = 654

References: [1]Patent: WO2005/112919,2005,A2 .Location in patent: Page/Page column 131.

29
[ 39539-66-7 ]
[ 869720-24-1 ]
[4S-(3,5-bistrifluoromethylbenzyloxy)-3R-2-tolylpiperidine-1-yl]-(4-methylpiperazine-1-yl)methanone hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		A solution of 4S-(3,5-bis-trifluoromethyl-benzloxy)-3R-2-tolyl-piperidine (Example 1) 100 mg (0.220 mmol) was dissolved in CH2Cl2 under nitrogen. 4-methyl-piperazine carbonyl chloride (purchased from Aldrich Chemical Company or Aztec Chemical Company) 46 mg (0.231 mmol), and diisopropylethylamine 0.4 mL (2.20 mmol) were added, and the reaction mixture was stirred at room temperature under nitrogen. The reaction mixture was diluted with EtOAc (100 ml) and washed with water three times. The organic layer was dried with MgSO4. Evaporation of most of the solvent gave 120 mg of oil. This oil was dissolved in about 10 mL of ether and a solution of HCl gas in ether was added drop by drop. The HCl salt was dried under nitrogen on high vacuum for one hour to give 125 mg of [4S-(3,5-bis-trifluoromethyl-benzyloxy)-3R-2-tolyl-piperidine-1-yl]-(4-methyl-piperazine-1-yl)-methanone. Fab/MS m/e 544 (M+1)

References: [1]Patent: US2005/256164,2005,A1 .Location in patent: Page/Page column 38.

30
[ 39539-66-7 ]
4-(5-chloropyridin-2-yl)-5-hydroxy-3-methyl-1,2,4-triazole [ No CAS ]
[ 110-17-8 ]
4-(5-Chloropyridin-2-yl)-3-methyl-5-[(4-methylpiperazinyl)carbonyl]oxy-1,2,4-triazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In tetrahydrofuran; methanol; water; toluene;	EXAMPLE 1 4-(5-Chloropyridin-2-yl)-3-methyl-5-[(4-methylpiperazin-1-yl)carbonyl]oxy-1,2,4-triazole 50 g (0.24 mol) of 4-(5-chloropyridin-2-yl)-5-hydroxy-3-methyl-1,2,4-triazole are dissolved or suspended in 1 litre of absolute tetrahydrofuran. The sodium hydride, degreased with toluene, is added thereto from 10.8 g of a 55% sodium hydride dispersion and the mixture is stirred for 1 hour at ambient temperature. Then 39 g (0.24 mol) of freshly distilled 1-chlorocarbonyl-4-methyl-piperazine (Bp17: 120-124 C.) are added dropwise thereto and the mixture is stirred for a further 5 hours whilst moisture is excluded. The resulting suspension is concentrated by evaporation in vacuo and the residue is carefully mixed with water and neutralised. The solution containing the carbamate is extracted several times with methylene chloride and the organic phase is washed with water, dried and concentrated. The residue is triturated with ether and 55 g (68% of theory) of the title compound are obtained in the form of crystals, m.p. 121-122 C. 12.5 g of this base are dissolved in 100 ml of methanol and 4.3 g of fumaric acid are added hot. On cooling, the hemifumarate crystallises out, m.p. 173-175 C. (yield: 17 g). The compound is highly water-soluble; pH of the solution 3.5. The starting compound, 4-(5-chloropyridin-2-yl)-5-hydroxy-3-methyl-1,2,4-triazole, is obtained as follows:

References: [1]Patent: US4732900,1988,A .

31
[ 39539-66-7 ]
[ 24313-88-0 ]
1-Methyl-4-[N-(3,4,5-trimethoxyphenyl)-carbamoyl]piperazine (hydrochloride) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	In diethyl ether; ethanol; dichloromethane;	EXAMPLE 2 1-Methyl-4-[N-(3,4,5-trimethoxyphenyl)-carbamoyl]piperazine (hydrochloride) A solution of 10 g (0.061 mole) 1-methyl-4-chloroformyl-piperazine in 100 ml dry methylene chloride is added to a solution of 11.2 g (0.061 mole) 3,4,5-trimethoxy-aniline in a 100 ml methylenechloride. After stirring at ambient temperature for 24 hours, the solvent is evaporated off in vacuo; the residue is dissolved in the minimum of ethanol and then the crude hydrochloride precipated by the addition of diethyl ether, and dried. Purification by recrystallisation from an acetone 3-ethanol 1 mixture gives the pure product (9.4 g; 44% yield) which melts at 184-86 C.

References: [1]Patent: US4252804,1981,A .

32
[ 123-75-1 ]
[ 39539-66-7 ]
[ 81363-72-6 ]

Yield	Reaction Conditions	Operation in experiment
66.9%	In toluene;	EXAMPLE 1 [1-methyl-4-(N-pyrrolidinocarbonyl)piperazine] In 50 ml of toluene was dissolved 8.1 g (0.05 mole) of 1-methyl-4-chlorocarbonylpiperazine at room temperature and a solution of 10.7 g (0.15 mole) of pyrrolidine in 50 ml of toluene was dropped to the above solution at 0 C. over a period of 30 minutes. The mixture was refluxed for 1 hour to complete the reaction. The reaction mixture was cooled, and the precipitated yellow crystal (pyrrolidine hydrochloride) was removed by filtration. The filtrate was dried with anhydrous sodium sulfate and toluene as the solvent was removed by distillation under reduced pressure to obtain crude 1-methyl-4-(pyrrolidinocarbonyl)piperazine as the distillation residue. The crude product was purified by distillation under reduced pressure to obtain 6.6 g of a pure product having a boiling point of 109.5 to 110.0 C. at 0.5-0.6 mm Hg obs. The yield was 66.9%. The elementary analysis values are as follows: Found: C=61.07%, H=9.89%, N=21.20% Anal. Calcd for C10 H19 N3 O: C=60.87%, H=9.73%, N=21.30%

References: [1]Patent: US4420481,1983,A .

33
[ 680-31-9 ]
[ 39539-66-7 ]
[ 55112-46-4 ]
[ 55112-47-5 ]
[ 53788-34-4 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; mineral oil;	EXAMPLE 4 Sodium hydride (50% dispersion in mineral oil) (0.8 g.) is added to a suspension of 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one (4.63 g.) in anhydrous dimethylformamide (45 cc.), whilst keeping the temperature between 18-20 C. The reaction mixture is stirred for a further 4 hours 30 minutes. A solution of 1-chlorocarbonyl-4-methylpiperazine (2.7 g.) in anhydrous dimethylformamide (25 cc.) is then added over the course of 15 minutes and at a temperature of 20 C. The suspension is stirred for 17 hours at a temperature of about 20 C., and then anhydrous hexamethylphosphotriamide (7 cc.) is added. After 15 minutes, the reaction mixture is poured into ice-water (500 g.). The precipitate is filtered off and washed with water (45 cc.). A product (6.1 g.) is obtained and is recrystallized from diisopropyl ether (1,500 cc.). 2-(7-Methoxy-1,8 -naphthyridin-2-yl)-3-(4-methylpiperazin-1-yl)carbonyloxy-isoindolin-1-one (3 g.), melting at 191 C., is thus obtained. The 2-(7-methoxy-1,8-naphthyridin-2-yl)-3-hydroxy-isoindolin-1-one can be prepared in the following way: Preparation of 2-acetylamino-7-chloro-1,8-naphthyridine, m.p. 251-253 C., according to S.

References: [1]Patent: US4016274,1977,A .

34
[ 39539-66-7 ]
[ 55112-43-1 ]
[ 55112-44-2 ]

Yield	Reaction Conditions	Operation in experiment
	In N-methyl-acetamide; mineral oil;	EXAMPLE 3 A suspension of sodium hydride (50% dispersion in mineral oil) (1.46 g.) in anhydrous dimethylformamide (80 cc.) is added to a suspension of 3-hydroxy-2-(1,5-naphthyridin-2-yl)isoindolin-1-one (7 g.) in anhydrous dimethylformamide (410 cc.). When the evolution of gas has ceased, a solution of 1-chlorocarbonyl-4-methyl-piperazine (4.6 g.) in anhydrous dimethylformamide (25 cc.) is added dropwise. After stirring for 4 hours, the reaction mixture is poured into water (3,000 cc.) cooled to 13 C. The precipitate is filtered off, washed with water (75 cc.) and then dried to yield 3-(4-methylpiperazin-1-yl)carbonyloxy-2-(1,5-naphthyridin-2-yl)isoindolin-1-one (5.7 g.) melting at 170-171 C. After recrystallisation from acetonitrile (50 cc.), the products melts at 173 C.

References: [1]Patent: US4016274,1977,A .

35
[ 39539-66-7 ]
2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-hydroxy-1-isoindolinone [ No CAS ]
[ 55112-42-0 ]
2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-(4-methyl-piperazinyl)-carbonyloxy-1-isoindolinone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; triethylamine; In dichloromethane; water;	EXAMPLE 28 Triethylamine (3.4 cc. equivalent to 2.44 g.), followed by pyridine (15 cc.) are added to a suspension of 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-hydroxy-1-isoindolinone (2 g.) and 4-chlorocarbonyl-1-methyl-piperazine hydrochloride (3.6 g.) in methylene chloride (30 cc.). The suspension obtained is heated to the reflux temperature (55 C) for 1 hour and further 4-chlorocarbonyl-1-methylpiperazine (3.6 g.) and triethylamine (3.4 cc.) are then added. The mixture is further heated to the reflux temperature for 45 minutes. After cooling, methylene chloride (30 cc.) and water (60 cc.) are added. After phase separation, the aqueous layer is extracted with methylene chloride (60 cc.). The organic extracts are dried over anhydrous sodium sulphate. After filtration and concentration, the residue is triturated in water (30 cc.). The precipitate is filtered off and dried in air. The crude product is recrystallized from acetonitrile (64 cc.). The product is filtered off and then washed with isopropyl ether (60 cc.). This gives 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-(4-methylpiperazinyl)-carbonyloxy-1-isoindolinone (0.8 g.) melting at 247-248 C. 2-(7-chloro-1,8-naphthyridin-2-yl)-5-fluoro-3-hydroxy-1-isoindolinone can be prepared in the following manner:

References: [1]Patent: US4016274,1977,A .

36
[ 39539-66-7 ]
6-(2-chloro-4-methyl-1,8-naphthyridin-7-vl)-5-(4-methylpiperazin-1-yl)carbonyloxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole [ No CAS ]
6-(2-chloro-4-methyl-1,8-naphthyridin-7-yl)-5-hydroxy-7-oxo-2,3,6,7-tetrahydro-1,4-dithiino[2,3-c]pyrrole [ No CAS ]
[ 1569-15-9 ]