Name: 2996-58-9|4-Methylpyrrolidin-2-one|98%
Brand: Ambeed
SKU: A119744
Rating: 98 (30 reviews)

1
[ 2996-58-9 ]
[ 368-39-8 ]
[ 69295-18-7 ]

Yield	Reaction Conditions	Operation in experiment
81%	In dichloromethane for 24h; Ambient temperature;

Reference： [1]Dunn, A. D.; Kinnear, K. I. [Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 53 - 57]

2
[ 16507-06-5 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
57%	With iron; acetic acid In water at 100℃; for 2h;
	Multi-step reaction with 2 steps 1: acetic acid; palladium 10% on activated carbon; hydrogen / 12 h / 20 °C / 760.05 Torr 2: triethylamine / ethanol / 12 h / Reflux
	Multi-step reaction with 2 steps 1: acetic acid; palladium 10% on activated carbon; hydrogen / 12 h / 20 °C 2: triethylamine / ethanol / 12 h / Reflux

	With hydrogen In ethanol
10 g	With hydrogen In methanol at 50℃; for 4h;	Step 2: 4-methylpyrrolidin-2-one To a solution of methyl 3-methyl-4-nitrobutanoate (20 g, 124.10 mmol) in MeOH (200 mL) was added Raney Ni (728.41 mg, 12.41 mmol). The mixture was stirred at 50°C for 4 hours under H 2 atmosphere. TLC indicated the reaction was complete. The reaction mixture was filtered and concentrated under reduced pressure to give 4-methylpyrrolidin-2-one (10 g) as a yellow solid, which was used in next step without further purification.

Reference： [1]Dunn, A. D.; Kinnear, K. I. [Journal of Heterocyclic Chemistry, 1986, vol. 23, p. 53 - 57]
[2]Current Patent Assignee: UNIVERSITY OF STRASBOURG - US2014/45910, 2014, A1
[3]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]
[4]Shankaran; Donnelly, Karla L.; Shah, Shrenik K.; Guthikonda, Ravindra N.; MacCoss, Malcolm; Humes, John L.; Pacholok, Stephen G.; Grant, Stephan K.; Kelly; Wong [Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 17, p. 4539 - 4544]
[5]Current Patent Assignee: BEIGENE LTD. - WO2019/210828, 2019, A1 Location in patent: Paragraph 0328; 0329

3
[ 91989-83-2 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
61%	With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride at 140℃; for 8h;
	With 2,2'-azobis(isobutyronitrile); tri-n-butyl-tin hydride at 140℃; for 3h;

Reference： [1]Hagen, Timothy J.; Bergmanis, Arija A.; Kramer, Steven W.; Fok, Kam F.; Schmelzer, Albert E.; Pitzele, Barnett S.; Swenton, Lydia; Jerome, Gina M.; Kornmeier, Christine M.; Moore, William M.; Branson, Linda F.; Connor, Jane R.; Manning, Pamela T.; Currie, Mark G.; Hallinan, E. Ann [Journal of Medicinal Chemistry, 1998, vol. 41, # 19, p. 3675 - 3683]
[2]Nagashima, Hideo; Wakamatsu, Hidetoshi; Itoh, Kenji [Journal of the Chemical Society. Chemical communications, 1984, # 10, p. 652 - 653]

4
[ 2996-58-9 ]
[ 37517-81-0 ]
[ 196882-09-4 ]

Yield	Reaction Conditions	Operation in experiment
84%	In benzene for 2.5h; Heating;

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

5
[ 2996-58-9 ]
[ 420-37-1 ]
[ 107805-49-2 ]

Yield	Reaction Conditions	Operation in experiment
	In dichloromethane for 12h;
		181 3,4-dihydro-5-methoxy-3-methyl-2H-pyrrole STR187 EXAMPLE 181 3,4-dihydro-5-methoxy-3-methyl-2H-pyrrole STR187 The product of EXAMPLE 180 (500 mg, 5 mmol) was reacted with trimethyloxonium tetrafluoroborate (890 mg, 6 mmol) by the method of EXAMPLE 26 to yield, after chromatography 610 mg of the title material containing traces of solvent.

Reference： [1]Hagen, Timothy J.; Bergmanis, Arija A.; Kramer, Steven W.; Fok, Kam F.; Schmelzer, Albert E.; Pitzele, Barnett S.; Swenton, Lydia; Jerome, Gina M.; Kornmeier, Christine M.; Moore, William M.; Branson, Linda F.; Connor, Jane R.; Manning, Pamela T.; Currie, Mark G.; Hallinan, E. Ann [Journal of Medicinal Chemistry, 1998, vol. 41, # 19, p. 3675 - 3683]
[2]Current Patent Assignee: PFIZER INC - US6046211, 2000, A

6
[ 303108-53-4 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
96%	In ethanol at 110℃; for 21h;

Reference： [1]Ghelfi, Franco; Parsons, Andrew F. [Journal of Organic Chemistry, 2000, vol. 65, # 19, p. 6249 - 6253]

7
[ 2996-58-9 ]
[ 77-78-1 ]
[ 107805-49-2 ]

Yield	Reaction Conditions	Operation in experiment
15%	at 60℃; for 16h;

Reference： [1]Schann; Bruban; Pompermayer; Feldman; Pfeiffer; Renard; Scalbert; Bousquet; Ehrhardt [Journal of Medicinal Chemistry, 2001, vol. 44, # 10, p. 1588 - 1593]

8
[ 303108-47-6 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 94 percent / [Cu(TMEDA)2]Cl / ethyl acetate / 20 h / 60 °C 2: 96 percent / Ra-Ni / ethanol / 21 h / 110 °C

Reference： [1]Ghelfi, Franco; Parsons, Andrew F. [Journal of Organic Chemistry, 2000, vol. 65, # 19, p. 6249 - 6253]

9
[ 2996-58-9 ]
4-methylpyrrolidin-2-imine, monohydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: CH₂Cl₂ / 12 h 2: NH₄Cl / methanol / Heating

Reference： [1]Hagen, Timothy J.; Bergmanis, Arija A.; Kramer, Steven W.; Fok, Kam F.; Schmelzer, Albert E.; Pitzele, Barnett S.; Swenton, Lydia; Jerome, Gina M.; Kornmeier, Christine M.; Moore, William M.; Branson, Linda F.; Connor, Jane R.; Manning, Pamela T.; Currie, Mark G.; Hallinan, E. Ann [Journal of Medicinal Chemistry, 1998, vol. 41, # 19, p. 3675 - 3683]

10
[ 2996-58-9 ]
[ 196882-10-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 84 percent / benzene / 2.5 h / Heating 2: 87 percent / mesyl azide, Et₃N / CH₂Cl₂ / 18 h / Ambient temperature

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

11
[ 2996-58-9 ]
tetrahydro-2,8-dimethyl-1,3,5-trioxo-7H-4,9a-epoxy-1H-pyrrolo[3,4-g]indolizine-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 84 percent / benzene / 2.5 h / Heating 2: 87 percent / mesyl azide, Et₃N / CH₂Cl₂ / 18 h / Ambient temperature 3: 30 percent / Rh₂(pfm)4 / benzene / Heating

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

12
[ 2996-58-9 ]
tetrahydro-2,8-dimethyl-1,3,5-trioxo-7H-4,9a-epoxy-1H-pyrrolo[3,4-g]indolizine-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 84 percent / benzene / 2.5 h / Heating 2: 87 percent / mesyl azide, Et₃N / CH₂Cl₂ / 18 h / Ambient temperature 3: 61 percent / Rh₂(pfm)4 / benzene / Heating

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

13
[ 2996-58-9 ]
tetrahydro-8-methyl-1,3,5-trioxo-2-phenyl-7H-4,9a-epoxy-1H-pyrrolo[3,4-g]indolizine-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 84 percent / benzene / 2.5 h / Heating 2: 87 percent / mesyl azide, Et₃N / CH₂Cl₂ / 18 h / Ambient temperature 3: 32 percent / Rh₂(pfm)4 / benzene / Heating

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

14
[ 2996-58-9 ]
tetrahydro-8-methyl-1,3,5-trioxo-2-phenyl-7H-4,9a-epoxy-1H-pyrrolo[3,4-g]indolizine-4-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 84 percent / benzene / 2.5 h / Heating 2: 87 percent / mesyl azide, Et₃N / CH₂Cl₂ / 18 h / Ambient temperature 3: 56 percent / Rh₂(pfm)4 / benzene / Heating

Reference： [1]Padwa, Albert; Prein, Michael [Journal of Organic Chemistry, 1997, vol. 62, # 20, p. 6842 - 6854]

15
(4R)-2-(2-cyanopropyl)-4-phenyl-4,5-dihydrooxazole [ No CAS ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: 100 percent / LiAlH₄ / tetrahydrofuran / 0.08 h / 18 °C 2: 6N HCl / Heating 3: SOCl₂ 4: base

Reference： [1]Langlois; Dahuron [Tetrahedron Letters, 1996, vol. 37, # 23, p. 3993 - 3996]

16
[ 2996-58-9 ]
[ 420-37-1 ]
[ 1027892-99-4 ]

Yield	Reaction Conditions	Operation in experiment
		211 3-ethyl-3,4-dihydro-5-methoxy-2H-pyrrole STR217 EXAMPLE 211 3-ethyl-3,4-dihydro-5-methoxy-2H-pyrrole STR217 The product of EXAMPLE 180 is reacted with trimethyloxonium tetrafluoroborate by the method of EXAMPLE 26 to produce the title material.

Reference： [1]Current Patent Assignee: PFIZER INC - US5854234, 1998, A Current Patent Assignee: PFIZER INC - US6046211, 2000, A

17
[ 2996-58-9 ]
[ 76-05-1 ]
4-methylpyrrolidonium trifluoroacetate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97.7%	In benzene at 20℃; for 6.66h;	6 To a 100 ml flask containing 9.91 g of 4-methylpyrrolidone (0.1 mol), 30 ml benzene was added and stirred for dissolution. 11.40 g of trifluoroacetic acid (0.1 mol) was added dropwise into the flask over 40 min at room temperature. Then the reaction was stirred for another 6 hours. Desired product was formed after benzene was removed under reduced pressure and dried at 110° C. under 1-5 mmHg for 1 hour. The brown viscous, moisture- and water-stable liquid of 4-methylpyrrolidonium trifluoroacetate was obtained with a yield of 97.7%, which has a glass transition temperature of -85.0° C., a density of 1.33 g/ml, a viscosity of 22 cP, an electrochemical window of 2.4 V, an ionic conductivity of 5.63×10-4 S/cm, and a Hammett acidic scale H0 of 4.82 using methyl yellow as indicator. No melting point was observed. IR (cm-1): 3251, 2956, 2887, 1687, 1292. 1H-NMR (400 MHz, CDCl3): 1.52 (d, 3H), 2.11-2.19 (m, 2H), 2.45 (q, 1H), 3.49 (t, 2H), 7.72(s, 1H). 13C-NMR (100 MHz, CDCl3): 18.74, 25.63, 30.42, 37.05, 115.16 (q, CF3), 163.74, 181.41. FAB-MS for cation: m/z 100.1. C7H10F3NO3 (162.1): calcd: C, 51.82; H 6.17. Found: C, 51.74; H 6.05.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES - US2007/21604, 2007, A1 Location in patent: Page/Page column 4

18
[ 2996-58-9 ]
[ 51934-41-9 ]
[ 1346123-48-5 ]

Yield	Reaction Conditions	Operation in experiment
377 mg	With copper(l) iodide; potassium carbonate; N,N`-dimethylethylenediamine In toluene for 8h; Reflux;	48 [0282] Preparation Example 48: Preparation of ethyl 4-(4-methyl-2-oxopyrrolidin-1-yl)benzoate [0282] Preparation Example 48: Preparation of ethyl 4-(4-methyl-2-oxopyrrolidin-1-yl)benzoate[0283][0284] To a mixture of ethyl 4-iodobenzoate (552 mg), 4-methylpyrrolidin-2-one (198 mg), potassium carbonate (536mg) and copper(I) iodide (190 mg) were added toluene (2 mL) and N,N’-dimethylethylenediamine (215 mL), and themixture was stirred with heating under reflux for 8 hr. The reaction mixture was cooled, water was added, and the mixturewas extracted with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated.The obtained residue was purified by column chromatography (hexane:ethyl acetate) to give the title compound (377mg). MS (ESI) m/z:248(M+H)+.

Reference： [1]Current Patent Assignee: MITSUBISHI CHEMICAL HOLDINGS CORPORATION - EP2565182, 2013, A1 Location in patent: Paragraph 0282; 0283; 0284

19
[ 2996-58-9 ]
[ 1613-37-2 ]
4-methyl-1-(quinolin-N-oxide-2-yl)pyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With copper diacetate; silver carbonate In benzene at 90℃; for 24h; Sealed tube;

Reference： [1]Li, Gang; Jia, Chunqi; Sun, Kai [Organic Letters, 2013, vol. 15, # 20, p. 5198 - 5201]

20
[ 2996-58-9 ]
[ 87-60-5 ]
N-(3-chloro-2-methylphenyl)-(4-methyl-4,5-dihydro-3H-pyrrol-2-yl)amine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methyl-2-pyrrolidinone; 3-chloro-2-methylbenzenamine With trichlorophosphate In 1,2-dichloro-ethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol; 1,2-dichloro-ethane Inert atmosphere;	A.1.4 Preparation of Aminopyrrolines 1-27 General procedure: [0205] A solution of suitable lactame 28-33 (5 mmol) andof the chosen aniline derivative was prepared in dichioroethane (10 ml) in an argon atmosphere. POCl3 (1 eq) was addeddrop-wise to the mixture which was then heated to 60° C. for 6 h. The mixture was cooled and hydrolyzed with 5 ml of asaturated aqueous solution of Na2CO3. The aqueous phasewas extracted twice with dichloromethane. The organic phasewas dried over anhydrous sodium sulfate and the solvent wasevaporated under reduced pressure.[0206] The product was purified by flash chromatography(3% TEA in AcOEt) leading to one of the aminopyrrolines1-27. (3-Chloro-2-methyl-phenyl)-(4-methyl-4,5-dihydro- 3H-pyrrol-2-yl)-amine hydrochloride (1) [0208] 1H NMR (D2O) δ 7.45 (d, 1H, Har, J=7.9); 7.25 (d,1H, Har, J=7.9); 7.20 (t, 1H, Har, J=7.8); 3.73-3.68 (m, 1H,CH2); 3.22-3.16 (m, 2H, CH2+CH); 2.77-2.71 (m, 2H,CH2); 2.22 (s, 3H, CH3); 1.10 (d, 3H, CH3, J=6.5). ‘3C NMR(D20) δ 169.1; 135.5; 133.4; 132.3; 130.1; 128.1; 125.3;54.2; 37.9; 29.5; 18.1; 14.2. Anal. (C12H15ClN2,HCl) C, H,N.

Reference： [1]Current Patent Assignee: UNIVERSITY OF STRASBOURG - US2014/45910, 2014, A1 Location in patent: Paragraph 0172; 0204-0208

21
[ 752154-41-9 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine In ethanol for 12h; Reflux;	A.1.2 Preparation of the Lactames L 30-33: General procedure: [0184] The nitroester 34-38 (100 mmol) was dissolved in250 ml glacial acetic acid and 500 mg of 10% Pd-C were added. The mixture was hydrogenated at ambient temperature and atmospheric pressure for 12 h. The mixture was filtered and the solvent evaporated. The product was then dissolved in 100 ml of absolute ethanol and alkalinized with triethylamine (TEA). The mixture was heated under reflux for 12 h. The solvents were evaporated under reduced pressure; the residue was diluted in Et20 and iN HC1 was added. The aqueous phase was extracted twice with Et20. The organic phases were dried over Na2504 and the solvent was evaporated. The product was purified by distillation under reduced pressure which led to obtaining of the lactames 30-33.Pyrrolidin-2-one (28) commercial product 4-Methyl-pyrrolidin-2-one (30). Yield 83%, colourless oil (subsequently crystallized), bp 103° C. (6 mmHg); ‘H NMR (CDC13) ö 6.75 (br s, 1H, NH); 3.46 (dd, 1H, -CH2, J=7.6, J=9.3); 2.93 (dd, 1H, -CH2, J=6.0, J=9.5); 2.53-2.44 (m, 1H, CH); 2.46 (dd, 1H, -CH2, J=6.9, J=1 6.3); 1.94 (dd, 1H, -CH2, J7.0, J=16.2); 1.10 (d, 3H, CH3, J=6.9).5,5-Dimethyl-pyrrolidin-2-one (31). Yield 61%, colourless oil (subsequently crystallized), bp 85-88° C. (2 mmHg); ‘H NMR (CDC13) ö 6.52 (br s, 1H, NH): 2.42 (t, 2H, CH2, J=8.0); 1.92 (t, 2H, CH2, J=8.0); 1.28 (s, 6H, 2xCH3).4,4-Dimethyl-pyrrolidin-2-on (32). Yield 73%, colourless oil (subsequently crystallized), bp 94-95° C. (2 mmHg); ‘H NMR (CDC13) ö 6.68 (br s, 1H, NH); 3.06 (s, 2H, CH2); 2.11 (s, 2H, CH2); 1.16 (s, 6H, 2xCH3).5-(2-methyl-propyl)-pyrrolidin-2-one (33). Yield 67%, viscous oil. [0185] 1H NMR (CDCl3) δ 6.68 (m, 1H); 3.75-3.70 (m, 1H); 2.38-2.19 (m, 3H); 1.72-1.60 (m, 2H); 1.68 (m, 1H),1.52-1.42 (m, 1H); 1.36-1.26 (m, 1H) 0.93 (d, J=8 Hz, 6H).
	With triethylamine In ethanol for 12h; Reflux;

Reference： [1]Current Patent Assignee: UNIVERSITY OF STRASBOURG - US2014/45910, 2014, A1 Location in patent: Paragraph 0183; 0184
[2]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

22
[ 2996-58-9 ]
[ 1403902-55-5 ]
[ 1605311-65-6 ]

Yield	Reaction Conditions	Operation in experiment
87%	Stage #1: 4-methyl-2-pyrrolidinone With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 0.5h; Stage #2: (2R,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1-carboxylic acid tert-butyl ester In N,N-dimethyl-formamide; mineral oil at 80℃; for 4h;	8 Preparation 8: (2R,5S)-4-Benzyl-2-methyl-5-(4-methyl-2-oxo-pyrrol idi n-I -ylmethyl)pi perazi ne-I -carboxyl ic acid tert-butyl ester Preparation 8: (2R,5S)-4-Benzyl-2-methyl-5-(4-methyl-2-oxo-pyrrol idi n-I -ylmethyl)pi perazi ne-I -carboxyl ic acid tert-butyl ester4-Methyl-pyrrolidin-2-one (0.2 g, 2.2 mmol) was dissolved in DMF (8 mL) to this was added NaH (60% dispersed in mineral oil) (77 mg, 2.2 mmol) which was stirred at room temperature for 30 minutes. To this was added (2R ,5R)-4-benzyl-5-chloromethyl-2-methyl-piperazine-1 -carboxylicacid tert-butyl ester (0.5 g, 1.5 mmol) and the reaction was heated to 80 O for 4 h. The reaction was cooled and concentrated in vacuo. The residue was partitioned between EtOAc (10 mL) and saturated (aq) sodium bicarbonate (20 mL). The organic extract was washed with brine (20 mL), dried over sodium sulfate and concentrated in vacuo. Chromatography (silica gel, gradient elution, 0 - 100%, EtOAc in petrol) gave the title compound (0.52 g, 87%) as a clear colourlessoil. MS: [M+H] = 402.

Reference： [1]Current Patent Assignee: OTSUKA HOLDINGS CO LTD - WO2014/60767, 2014, A1 Location in patent: Page/Page column 101; 102

23
[ 2996-58-9 ]
[ 32202-61-2 ]
N-(2,3-dihydro-1H-inden-4-yl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 878 - 887

24
[ 2996-58-9 ]
[ 32202-61-2 ]
N-(2,3-dihydro-1H-inden-5-yl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 878 - 887

25
[ 2996-58-9 ]
[ 1404051-75-7 ]
N-(7-chloro-2,3-dihydro-1H-inden-4-yl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: 4-methyl-2-pyrrolidinone; 7-chloro-2,3-dihydro-1H-inden-4-amine With trichlorophosphate In dichloromethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol

Reference： [1]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

26
[ 2996-58-9 ]
[ 1404052-03-4 ]
N-(7-methyl-2,3-dihydro-1H-inden-4-yl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: 4-methyl-2-pyrrolidinone; 7-methyl-4-amino-indan With trichlorophosphate In dichloromethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol

Reference： [1]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

27
[ 2996-58-9 ]
[ 87-59-2 ]
N-(2,3-dimethylphenyl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: 4-methyl-2-pyrrolidinone; 2,3-Dimethylaniline With trichlorophosphate In dichloromethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol

Reference： [1]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

28
[ 2996-58-9 ]
[ 87-60-5 ]
N-(3-chloro-2-methylphenyl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
51%	Stage #1: 4-methyl-2-pyrrolidinone; 3-chloro-2-methylbenzenamine With trichlorophosphate In dichloromethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol

Reference： [1]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

29
[ 2996-58-9 ]
[ 2217-41-6 ]
N-(5,6,7,8-tetrahydronaphthalen-1-yl)-4-methylpyrrolidin-2-imine hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	Stage #1: 4-methyl-2-pyrrolidinone; 1-amino-5,6,7,8-tetrahydronaphthalene With trichlorophosphate In dichloromethane at 60℃; for 6h; Inert atmosphere; Stage #2: With hydrogenchloride In ethanol

Reference： [1]Gasparik, Vincent; Greney, Hugues; Schann, Stephan; Feldman, Josiane; Fellmann, Lyne; Ehrhardt, Jean-Daniel; Bousquet, Pascal [Journal of Medicinal Chemistry, 2015, vol. 58, # 2, p. 878 - 887]

30
C₁₁H₁₂N₂O₂ [ No CAS ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With water; sodium hydroxide In tetrahydrofuran at 0℃; for 3h;

Reference： [1]Wang, Pei-Long; Li, Yan; Wu, Yun; Li, Chao; Lan, Quan; Wang, Xi-Sheng [Organic Letters, 2015, vol. 17, # 15, p. 3698 - 3701]

31
[ 2996-58-9 ]
methyl 3-(bromomethyl)-4-methoxybenzoate [ No CAS ]
methyl 4-methoxy-3-[(4-methyl-2-oxopyrrolidin-1-yl)methyl]benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methyl-2-pyrrolidinone With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.666667h; Stage #2: methyl 3-(bromomethyl)-4-methoxybenzoate In N,N-dimethyl-formamide at 20℃;	B Step B: methyl 4-methoxy-3-[(4-methyl-2-oxopyrrolidin-l-yl)methyllbenzoate To a solution of 4-methylpyrrolidin-2-one (3.8 g, 38.4 mmol) in DMF (50 mL) at 0 °C was added NaH (1.7 g, 60%, 42.5 mmol). The suspension was stirred at 0 °C for 40 min, and then methyl 3-(bromomethyl)-4-methoxybenzoate (10 g, 38.8 mmol) in DMF (50 mL) was added dropwise. The resulting mixture was stirred at room temperature overnight and then quenched with saturated aqueous NH4C1 (30 mL). The resulting mixture was diluted with water (120 mL) and extracted EtOAc (150 mL x 3). The combined organic phases were washed with H20 (150 mL x 3) and saturated aqueous sodium chloride (150 mL), dried over Na2S04, and concentrated. The residue was purified by column chromatography (PE:EtOAc, 10: 1 to 1 : 1) to give the racemic title compound as yellow oil. 1H NMR (CDCI3, 400 MHz): δ 8.02-7.97 (dd, J= 2.4 Hz, 8.4 Hz, 1H), 7.83 (d, J= 2.0Hz, 1H), 6.90 (d, J= 8.4Hz„ 1H), 5.30 (s, 2H), 3.88 (s, 6H), 3.42-3.37 (m, 1H), 2.96-2.83 (m, 1H), 2.62-2.56 (m, 1H), 2.46-2.37 (m, 1H), 2.11-2.05 (m, 1H), 1.09 (d, J= 6.8Hz, 1H).

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161016, 2015, A1 Location in patent: Page/Page column 54-55

32
[ 2996-58-9 ]
[ 70264-94-7 ]
methyl 3-methoxy-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-methylpyrrolidin-2-one (574 mg, 5.79 mmol) in anhydrous DMF (15 mL) was added NaH (255 mg, 6.37 mmol, 60percent in mineral oil) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min and then a solution of methyl 4-(bromomethyl)-3- methoxybenzoate (1.50 g, 5.79 mmol) in DMF (5 mL) was added dropwise. The reaction mixture was stirred at ambient temperature for 14 h and then quenched with saturated aqueous NH4C1 (10 mL). The resulting mixture was diluted with water (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic phase was washed with H20 (30 mL x 3) and saturated aqueous sodium chloride (30 mL), dried over Na2S04, and concentrated. The residue was purified by silica gel chromatography (petroleum ether :EtO Ac, 20: 1 to 3: 1) to give the racemic title compound. The racemic title compound was resolved by SFC (Chiralpak AD column, eluting with C02:MeOH (0.2percent> NH4OH), 75:25) to give the title compound as the first eluting isomer. MS (ESI) m/z: 278.1 [M+l]+. 1H NMR (400 MHz CDC13): delta 7.61 (dd, J = 1.6, 8.0 Hz, 1H), 7.53 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 4.51 (s, 2H), 3.91 (s, 3H), 3.89 (s, 3H), 3.42- 3.38 (m, 1H), 2.86-2.84 (m, 1H), 2.63-2.57 (m, 1H), 2.47-2.38 (m, 1H), 2.10-2.04 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H).

Reference： [1]Patent: WO2015/161014,2015,A1 .Location in patent: Page/Page column 94

33
[ 2996-58-9 ]
(S)-methyl 3-hydroxy-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 2.1: carbon dioxide; ammonium hydroxide / methanol / Resolution of racemate 3.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C
	Multi-step reaction with 2 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 1.3: Chiralpak AD column / Resolution of racemate; Supercritical conditions 2.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161014, 2015, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2015/161011, 2015, A1

34
[ 2996-58-9 ]
(S)-methyl 3-(4-(5-isopropyl-1,3,4-thiadiazol-2-yl)phenoxy)-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 2.1: carbon dioxide; ammonium hydroxide / methanol / Resolution of racemate 3.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 4.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 1.3: Chiralpak AD column / Resolution of racemate; Supercritical conditions 2.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 3.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161014, 2015, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2015/161011, 2015, A1

35
[ 2996-58-9 ]
(S)-methyl 3-(4-(5-methyl-1,3,4-thiadiazol-2-yl)phenoxy)-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 2.1: carbon dioxide; ammonium hydroxide / methanol / Resolution of racemate 3.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 4.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere
	Multi-step reaction with 3 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 1.3: Chiralpak AD column / Resolution of racemate; Supercritical conditions 2.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 3.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161014, 2015, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2015/161011, 2015, A1

36
[ 2996-58-9 ]
(S)-3-(4-(5-isopropyl-1,3,4-thiadiazol-2-yl)phenoxy)-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 2.1: carbon dioxide; ammonium hydroxide / methanol / Resolution of racemate 3.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 4.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere 5.1: lithium hydroxide; water / methanol / 16 h / 20 °C
	Multi-step reaction with 4 steps 1.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 0.5 h / 0 °C 1.2: 14 h / 20 °C 1.3: Chiralpak AD column / Resolution of racemate; Supercritical conditions 2.1: boron tribromide / dichloromethane / 22 h / 0 - 20 °C 3.1: caesium carbonate; 2,2,6,6-tetramethylheptane-3,5-dione; copper(l) chloride / 1-methyl-pyrrolidin-2-one / 16 h / 80 °C / Inert atmosphere 4.1: water; lithium hydroxide / methanol / 16 h / 20 °C

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161014, 2015, A1
[2]Current Patent Assignee: MERCK & CO INC - WO2015/161011, 2015, A1

37
4-bromo-1-(bromomethyl)-2-methoxybenzene [ No CAS ]
[ 2996-58-9 ]
1-(4-bromo-2-methoxybenzyl)-4-methylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methyl-2-pyrrolidinone With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 0.5h; Stage #2: 4-bromo-1-(bromomethyl)-2-methoxybenzene In N,N-dimethyl-formamide; mineral oil at 20℃; for 2h;	A Step A: (6 -l-(4-bromo-2-methoxybenzyl)-4-methylpyrrolidin-2-one To a solution of 4-methylpyrrolidin-2-one (4.5 g, 45.0 mmol) in anhydrous DMF (150 mL) was added NaH (1.9 g, 47.2 mmol, 60%>) at 0 °C The reaction mixture was stirred at 0 °C for 30 min, and then methyl 4-(bromomethyl)-3-methoxybenzoate (12.0 g, 42.9 mmol, dissolved in 50 mL of DMF) was added dropwise. The reaction mixture was stirred at room temperature for 2h and then quenched with saturated aqueous NH4C1 (100 mL). The resulting mixture was diluted with water (50 mL) and extracted EtOAc (300 mL x 3). The combined organic phase was washed with H20 (50 mL x 3) and saturated aqueous sodium chloride (50 mL), dried over Na2S04, and concentrated. The obtained residue was purified by silica gel chromatography eluting with hexanes:EtOAc (grading from 0 to 100%) to give the racemic title compound. MS (ESI) m/z: 298.0 [M+l]+.

Reference： [1]Current Patent Assignee: MERCK & CO INC - WO2015/161014, 2015, A1 Location in patent: Page/Page column 132-133

38
[ 2996-58-9 ]
[ 70264-94-7 ]
(S)-methyl 3-methoxy-4-((4-methyl-2-oxopyrrolidin-1-yl)methyl)benzoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
		To a solution of 4-methylpyrrolidin-2-one (574 mg, 5.79 mmol) in dry DMF (15 mL) was added NaH (255 mg, 6.37 mmol, 60percent in mineral oil) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min, and then a solution of methyl 4-(bromomethyl)-3- methoxybenzoate (1.50 g, 5.79 mmol) in DMF (5 mL) was added dropwise. The reaction mixture was stirred at ambient temperature for 14 h and then quenched with saturated aqueous NH4CI (10 mL). The resulting mixture was diluted with water (30 mL) and extracted with EtOAc (30 mL x 3). The combined organic phase was washed with H20 (30 mL x 3) and brine (30 mL), dried over Na2S04, and concentrated. The residue was purified by columnchromatography (Si02, petroleum ether: EtOAc = 20: 1 to 3: 1) to give the title compound as a racemate, which was separated by SFC (Chiralpak AD column; eluting with C02/MeOH (0.2percent NH4OH) = 75/25) to give the title compound as the first eluting isomer. MS (ESI) m/z: 278.1 [M + 1]. NMR (400 MHz CDC13): delta 7.61 (dd, J = 1.6, 8.0 Hz, 1H), 7.53 (s, 1H), 7.22 (d, J = 8.0 Hz, 1H), 4.51 (s, 2H), 3.91 (s, 3H), 3.89 (s, 3H), 3.42-3.38 (m, 1H), 2.86-2.84 (m, 1H), 2.63- 2.57 (m, 1H), 2.47-2.38 (m, 1H), 2.10-2.04 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H).

Reference： [1]Patent: WO2015/161011,2015,A1 .Location in patent: Page/Page column 110; 111

39
[ 2996-58-9 ]
[ 1221232-29-6 ]
1-(4-chloroisoquinolin-6-yl)-4-methylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With tris(dibenzylideneacetone)dipalladium⁽⁰⁾ chloroform complex; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In toluene at 100℃; for 3h; Inert atmosphere;	5.1 5.11 -(4-Chloroisoquinolin-6-yl)-4-methylpyrrolidin-2-one 5.1 1-(4-Chloroisoquinolin-6-yl)-4-methylpyrrolidin-2-one Into a 25 mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, were placed 6-bromo-4-chloroisoquinoline (50.0 mg, 0.21 mmol), 4-methylpyrrolidin-2-one (27.5 mg, 0.28 mmol), potassium phosphate (184 mg, 0.86 mmol), tris(dibenzylideneacetone)dipalladium(0) chloroform complex (19.7 mg, 0.02 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (Xantphos, 16.7 mg, 0.03 mmol) and toluene (5 mL). The solution was stirred for 3 h at 100° C. The mixture was concentrated under vacuum. The residue was applied to a silica gel column with dichloromethane/methanol (100:1). This resulted in 23.9 mg (27%) of the title compound as a yellow solid.

Reference： [1]Current Patent Assignee: MERCK KGAA; CANCER RESEARCH UK - US2016/16951, 2016, A1 Location in patent: Paragraph 0309; 0310

40
[ 2996-58-9 ]
3,6-difluoro-9-(oxiran-2-ylmethyl)-9H-carbazole [ No CAS ]
1-(3-(3,6-difluoro-9H-carbazol-9-yl)-2-hydroxypropyl)-4-methylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 4-methyl-2-pyrrolidinone at 20℃; Alkaline conditions; Stage #2: 3,6-difluoro-9-(oxiran-2-ylmethyl)-9H-carbazole for 16h;	General procedure for amides10-47 General procedure: To a stirred solution of a lactam (1.86 equiv.) in dimethyl sulfoxide (0.26 M) was added potassiumtert-butoxide (1.86 equiv.) and the mixture was stirred at room temperature for 1 hour. 3,6-Difluoro-9-(oxiran-2-ylmethyl)-9H-carbazole (1 equiv.) was added and the mixture was stirred at room temperature for 16 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried (anhydrous sodium sulfate), filtered and concentratedin vacuo. The residue was purified by silica gel column to afford the product.

Reference： [1]Humphries, Paul S.; Bersot, Ross; Kincaid, John; Mabery, Eric; McCluskie, Kerryn; Park, Timothy; Renner, Travis; Riegler, Erin; Steinfeld, Tod; Turtle, Eric D.; Wei, Zhi-Liang; Willis, Erik [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 3, p. 293 - 297]

41
[ 2996-58-9 ]
[ 67567-26-4 ]
N-(4-bromo-2,6-difluorophenyl)-4-methylpyrrolidin-2-imine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; trichlorophosphate In toluene for 3h; Reflux;	N-(4-bromo-2,6-difluorophenyl)pyrrolidin-2-imine (2a) General procedure: To a mixture of 4-bromo-2,6-difluoroaniline (1a) (2.76 g, 13.30 mmol), pyrrolidin-2-one ( 2.25 g, 26.50 mmol), TEA (2.00 g, 19.95 mmol), in 20 mL toluene was added POCl3 (3.10 g, 19.95 mmol). The mixture was refluxed for 3 h, After cooling to room temperature, concentrated the reaction, diluted with DCM (100 mL), Saturated Na2CO3 solution was added to the mixture until the pH reached 8-10. The mixture was partitioned between water and dichloromethane. The water phase was extracted twice with dichloromethane. The organic phases were combined and washed with water and brine, dried over anhydrous Na2SO4, concentrated under vacuum, and purified by silica gel column chromatography (DCM/MeOH = 50:1) to give compound 2a as yellow soild (4.50 g).

Reference： [1]Wang, Yan; Liu, Wen-Jian; Yin, Lei; Li, Heng; Chen, Zhen-Hua; Zhu, Dian-Xi; Song, Xiu-Qing; Cheng, Zhen-Zhen; Song, Peng; Wang, Zhan; Li, Zhi-Gang [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 5, p. 974 - 978]

42
[ 2996-58-9 ]
7-chloro-1-(2,4-difluorophenyl)-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]
1-(2,4-difluorophenyl)-7-[(4S)-4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]
1-(2,4-difluorophenyl)-7-[(4R)-4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 100 % de 2: 100 % de	With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane Inert atmosphere; Heating;	GP2; 301; 302; 303 Example 301 1-(2,4-Difluorophenyl)-7-[4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide (diastereomer mixture) General procedure: Potassium carbonate or caesium carbonate (1.5-2.5 eq.) was baked in a reaction vessel under reduced pressure. It was cooled to RT and flooded with argon. Palladium acetate (0.1-0.36 eq.), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos, 0.18-0.36 eq.) and dioxane (0.04-0.12M) were added, and the suspension was degassed in an argon stream at room temperature for 10 min. Subsequently, the appropriate amide (1.0-1.2 eq.) and the appropriate 7-chloro-4-oxo-1,4-dihydro-1,8-naphthyridine (1.0 eq.) were added. The mixture was stirred at 80-110° C. for 1 h (or until conversion was complete by analytical HPLC or thin-layer chromatography with appropriate eluent mixtures). The mixture was cooled to RT and all volatile components were removed under reduced pressure, or alternatively the reaction mixture was poured into water, the pH was adjusted to pH 1 with 1M aqueous hydrochloric acid, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulphate and filtered, and the solvent was removed under reduced pressure. The crude product was then purified either by normal phase chromatography (eluent: cyclohexane/ethyl acetate mixtures or dichloromethane/methanol mixtures) or preparative RP-HPLC (water/acetonitrile gradient). According to GP2, 200 mg (449 μmol) of the compound from Example 67A were reacted with 49.2 mg (471 μmol) of 4-methyl-2-pyrrolidinone (racemate) in the presence of 93.0 mg (673 μmol) of potassium carbonate, 18 mg (81 μmol) of palladium(II) acetate and 93.5 mg (162 μmol) of Xantphos in 4 ml of 1,4-dioxane. Subsequently, the volume of the mixture was concentrated under reduced pressure, and the residue was taken up with 2 ml of 1N aqueous hydrochloric acid and 8 ml of acetonitrile and purified by means of preparative HPLC (column: Chromatorex C18, 10 μm, 125*30 mm, solvent: acetonitrile/0.05% formic acid gradient; 0 to 3 min 10% acetonitrile, to 35 min 90% acetonitrile and for a further 3 min 90% acetonitrile). 92.9 mg (40% of theory, 99% purity) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6): δ [ppm]=10.22 (d, 1H), 8.85 (s, 1H), 8.70 (d, 1H), 8.49 (d, 1H), 7.92-7.82 (m, 1H), 7.68-7.59 (m, 1H), 7.40-7.33 (m, 1H), 4.84-4.70 (m, 1H), 3.76-3.65 (m, 1H), 3.18-3.06 (m, 1H), 2.79-2.65 (m, 1H), 2.46-2.23 (m, 2H), 1.95-1.83 (m, 1H), 1.73-1.59 (m, 1H), 1.06-0.94 (m, 6H). LC-MS (Method 1): Rt=1.19 min; 509 [M+H]+. 89 mg of the title compound (diastereomer mixture) were separated into the diastereomers by chiral HPLC (preparative HPLC: column: Daicel Chiralpak AZ-H 5 μm 250×20 mm; eluent: 25% ethanol, 75% isohexane; temperature: 25° C.; flow rate: 20.2 ml/min; UV detection: 265 nm). This gave (in the sequence of elution from the column) 45.4 mg of diastereomer 1 (100% de) Rt=3.42 min and 37.1 mg (100% de) of diastereomer 2 Rt=3.93 min. [Analytical HPLC: column: Daicel Chiralpak AZ-3 3 μm 50×4.6 mm; eluent: 20% ethanol, 80% isohexane; flow rate: 1 ml/min; UV detection: 220 nm]. Diastereomer 1 was additionally purified by means of preparative HPLC (column: Chromatorex C18, 10 μm, 125×30 mm, solvent: acetonitrile/0.05% formic acid gradient; (0 to 3 min. 10% acetonitrile to 35 min. 90% acetonitrile and a further 3 min. 90% acetonitrile)), and 33.6 mg (15% of theory, 99% purity) of the title compound from Example 302 were obtained. Diastereomer 2 was additionally purified by means of preparative HPLC (column: Chromatorex C18, 10 μm, 125×30 mm, solvent: acetonitrile/0.05% formic acid gradient; (0 to 3 min. 10% acetonitrile to 35 min. 90% acetonitrile and a further 3 min. 90% acetonitrile)), and 26.9 mg (12% of theory, 99% purity) of the title compound from Example 303 were obtained. Example 302 1-(2,4-Difluorophenyl)-7-[4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide (diastereomer 1) 1H-NMR (400 MHz, DMSO-d6): δ [ppm]=10.22 (d, 1H), 8.85 (s, 1H), 8.70 (d, 1H), 8.49 (d, 1H), 7.92-7.83 (m, 1H), 7.68-7.59 (m, 1H), 7.41-7.33 (m, 1H), 4.84-4.70 (m, 1H), 3.76-3.65 (m, 1H), 3.18-3.06 (m, 1H), 2.78-2.65 (m, 1H), 2.46-2.23 (m, 2H), 1.96-1.83 (m, 1H), 1.73-1.60 (m, 1H), 1.07-0.94 (m, 6H). LC-MS (Method 3): Rt=2.27 min; 509 [M+H]+. Example 303 1-(2,4-Difluorophenyl)-7-[4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2R)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide (diastereomer 2) 1H-NMR (400 MHz, DMSO-d6): δ [ppm]=10.22 (d, 1H), 8.85 (s, 1H), 8.70 (d, 1H), 8.49 (d, 1H), 7.92-7.82 (m, 1H), 7.68-7.59 (m, 1H), 7.41-7.32 (m, 1H), 4.83-4.70 (m, 1H), 3.77-3.64 (m, 1H), 3.18-3.07 (m, 1H), 2.78-2.65 (m, 1H), 2.46-2.22 (m, 2H), 1.96-1.84 (m, 1H), 1.73-1.59 (m, 1H), 1.06-0.93 (m, 6H). LC-MS (Method 3): Rt=2.27 min; 509 [M+H]+.

Reference： [1]Current Patent Assignee: BAYER AG - US2018/297994, 2018, A1 Location in patent: Paragraph 0889; 2117-2129

43
[ 2996-58-9 ]
7-chloro-1-(3,5-difluoropyridin-2-yl)-4-oxo-N-[(2S)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]
1-(3,5-difluoropyridin-2-yl)-7-[4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-N-[(2S)-1,1,1-trifluorobutan-2-yl]-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%	With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 80℃; for 1h; Inert atmosphere;	30 GP2 General procedure: Potassium carbonate or cesium carbonate (1.5-2.5 eq.) was baked in a reaction vessel under reduced pressure. The vessel was cooled to RT and flooded with argon. Palladium acetate (0.1-0.36 eq.), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos, 0.18-0.36 eq.) and dioxane (0.04-0.12M) were added, and the suspension was degassed in an argon stream at room temperature for 10 min. Subsequently, the appropriate amide (1.0-10 eq.) and the appropriate 7-chloro-4-oxo-1,4-dihydro-1,8-naphthyridine (1.0 eq.) were added. The mixture was stirred at 80-110° C. for 1 h (or until conversion was complete by analytical HPLC or thin-layer chromatography with appropriate mobile phase mixtures). The mixture was cooled to RT and all volatile components were removed under reduced pressure, or alternatively the reaction mixture was poured into water, the pH was adjusted to pH 1 with 1M aqueous hydrochloric acid, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was then purified either by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate mixtures or dichloromethane/methanol mixtures) or by preparative RP-HPLC (water/acetonitrile gradient). Alternatively, the reaction mixture was diluted with a little acetonitrile, water and formic acid and the crude solution was purified by RP-HPLC (water/acetonitrile gradient).

Reference： [1]Current Patent Assignee: BAYER AG - US2019/241562, 2019, A1 Location in patent: Paragraph 0462; 0831-0834

44
[ 2996-58-9 ]
7-chloro-N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-1-(3,5-difluoropyridin-2-yl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]
N-[(1R)-1-cyclopropyl-2,2,2-trifluoroethyl]-1(3,5-difluoropyridin-2-yl)-7-[4-methyl-2-oxopyrrolidin-1-yl]-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
25%	With palladium diacetate; potassium carbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In 1,4-dioxane at 80℃; for 1h; Inert atmosphere;	27 GP2 General procedure: Potassium carbonate or cesium carbonate (1.5-2.5 eq.) was baked in a reaction vessel under reduced pressure. The vessel was cooled to RT and flooded with argon. Palladium acetate (0.1-0.36 eq.), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos, 0.18-0.36 eq.) and dioxane (0.04-0.12M) were added, and the suspension was degassed in an argon stream at room temperature for 10 min. Subsequently, the appropriate amide (1.0-10 eq.) and the appropriate 7-chloro-4-oxo-1,4-dihydro-1,8-naphthyridine (1.0 eq.) were added. The mixture was stirred at 80-110° C. for 1 h (or until conversion was complete by analytical HPLC or thin-layer chromatography with appropriate mobile phase mixtures). The mixture was cooled to RT and all volatile components were removed under reduced pressure, or alternatively the reaction mixture was poured into water, the pH was adjusted to pH 1 with 1M aqueous hydrochloric acid, the mixture was extracted with ethyl acetate, the combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the solvent was removed under reduced pressure. The crude product was then purified either by normal phase chromatography (mobile phase: cyclohexane/ethyl acetate mixtures or dichloromethane/methanol mixtures) or by preparative RP-HPLC (water/acetonitrile gradient). Alternatively, the reaction mixture was diluted with a little acetonitrile, water and formic acid and the crude solution was purified by RP-HPLC (water/acetonitrile gradient).

Reference： [1]Current Patent Assignee: BAYER AG - US2019/241562, 2019, A1 Location in patent: Paragraph 0462; 0820-0823

45
[ 2996-58-9 ]
[ 86864-60-0 ]
1-(2-((tert-butyldimethylsilyl)oxy)ethyl)-4-methylpyrrolidin-2-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%	With sodium hydride; sodium iodide In tetrahydrofuran; mineral oil for 2h; Inert atmosphere; Reflux;	C.1 Step 1 : l-(2-((fer/-butyldimethylsilyl)oxy)ethyl)-4-methylpyrrolidin-2-one (I-230) (2-bromoethoxy)(/er/-butyl)dimethylsilane (cas: 86864-60-0, 3.18 g, 15 mmol) in 20 mL of THF was added dropwise to an ice-cooled suspension of 4-methylpyrrolidin-2- one (cas: 2996-58-9, 1 g, 1.0 equiv.), Nal (1.5 g, 1.0 equiv.) and NaH (2.4 g, 6.0 equiv.) in THF (50 mL) with stirring under N2. After 2 hours, the ice bath was removed and the reaction mixture was heated to reflux overnight. The reaction was quenched with H20 (50 mL). After removal of the solvent under reduced pressure, the residue was partitioned between EtOAc and H20. The aqueous layer was extracted with EtOAc (3 x 20 mL). The combined organic extracts were dried over MgS04, concentrated and the residue obtained was purified by silica gel chromatography to afford 360 mg (14%) of 1-230 as a pale oil. MS (ESI, pos. ion) m/z: 258 (M+l).

Reference： [1]Current Patent Assignee: CARMOT THERAPEUTICS - WO2019/183577, 2019, A1 Location in patent: Page/Page column 213; 214

46
[ 2996-58-9 ]
[ 24424-99-5 ]
tert-butyl 4-methyl-2-oxopyrrolidine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64.68%	With N,N-dimethyl-4-aminopyridine; triethylamine In tetrahydrofuran at 25℃; for 3h;	Step 3: tert-butyl 4-methyl-2-oxopyrrolidine-1-carboxylate To a mixture of 4-methylpyrrolidin-2-one (10 g, 100.88 mmol), DMAP (6.16 g, 50.44 mmol), TEA (10.21 g, 100.88 mmol) in THF (100 mL) was added (Boc) 2O (44.03 g, 201.75 mmol). The mixture was stirred at 25°C for 3 hours. TLC indicated the reaction was complete. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (Silica gel, Petroleum ether/Ethyl acetate = 100/1 to 50/1). Tert-butyl 4-methyl-2-oxopyrrolidine-1-carboxylate (13 g, 64.68% yield) was obtained as a white solid. 1H NMR (400 MHz, CDCl 3) δ ppm: 3.87 (dd, J=10.7, 7.6 Hz, 1H), 3.29 (dd, J=10.7, 6.9 Hz, 1H), 2.64 (dd, J=17.0, 8.1Hz, 1H), 2.39 (dd, J=14.6, 7.5 Hz, 1H) 2.16 (dd, J=17.0, 8.1Hz, 1H), 1.53 (s, 9 H), 1.14 (d, J=6.6 Hz, 3 H).
40%	With N,N-dimethyl-4-aminopyridine In acetonitrile at 20℃; for 4h;	S117.1 Step 1. Synthesis of Tert-butyl 4-methyl-2-oxopyrrolidine-1-carboxylate To a solution of 4-methylpyrrolidin-2-one (10.0 g, 100.88 mmol) in ACN (100.0 mL) was added DMAP (1.2 g, 10.09 mmol) and Boc2O (26.4 g, 121.10 mmol) at room temperature. The resulting mixture was stirred at room temperature for 4 h. After the reaction was completed, the resulting mixture was concentrated under reduced pressure. The residue was purified by reverse phase flash chromatography with CH3CN/H2O (40/60, v/v) to afford tert-butyl 4-methyl- 2-oxopyrrolidine-1-carboxylate (8.0 g, 40%) as a brown yellow oil. LCMS (ESI, m/z): [M+H]+ =200.1.

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2019/210828, 2019, A1 Location in patent: Paragraph 0330; 0331
[2]Current Patent Assignee: ENLIVEN THERAPEUTICS INC - WO2022/140769, 2022, A1 Location in patent: Paragraph 1087-1088

47
[ 4166-53-4 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: trimethylsilylazide / chloroform / 1.5 h / -20 °C / Inert atmosphere 1.2: 0.25 h / -20 °C / Inert atmosphere 2.1: chloroform / 3 h / 60 °C / Inert atmosphere 2.2: 2 h / 20 °C / Inert atmosphere

Reference： [1]Connon, Stephen J.; Craig, Ryan; Smith, Simon N. [Chemistry - A European Journal, 2020, vol. 26, # 59, p. 13378 - 13382]

48
C₆H₉N₃O₃ [ No CAS ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
90%	Stage #1: C₆H₉N₃O₃ In chloroform at 60℃; for 3h; Inert atmosphere; Stage #2: With dmap In chloroform at 20℃; for 2h; Inert atmosphere;

Reference： [1]Connon, Stephen J.; Craig, Ryan; Smith, Simon N. [Chemistry - A European Journal, 2020, vol. 26, # 59, p. 13378 - 13382]

49
[ 97-65-4 ]
[ 2555-05-7 ]
[ 2996-58-9 ]

Yield	Reaction Conditions	Operation in experiment
	With ammonium hydroxide; 5%-palladium/activated carbon; hydrogen In water at 220℃; Autoclave; Green chemistry; Overall yield = 79.2 percentChromat.;

Reference： [1]Haus, Moritz O.; Hofmann, Jan P.; Konrad, Marc; Louven, Yannik; Palkovits, Regina [Green Chemistry, 2020, vol. 22, # 14, p. 4532 - 4540]

50
[ 2996-58-9 ]
tert-butyl (8-bromo-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)carbamate [ No CAS ]
tert-butyl ((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)(8-(4-methyl-2-oxopyrrolidin-1-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-yl)-carbamate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72.2%	With [(2-di-cyclohexylphosphino-3,6-dimethoxy-2′,4′,6′- triisopropyl-1,1′-biphenyl)-2-(2′-amino-1,1′ -biphenyl)]palladium(II) methanesulfonate; potassium carbonate In <i>tert</i>-butyl alcohol at 25 - 80℃; for 16h; Inert atmosphere;

Reference： [1]Bagal, Sharan K.; Gregson, Clare; O' Donovan, Daniel H.; Pike, Kurt G.; Bloecher, Andrew; Barton, Peter; Borodovsky, Alexandra; Code, Erin; Fillery, Shaun M.; Hsu, Jessie Hao-Ru; Kawatkar, Sameer P.; Li, Chengzhi; Longmire, David; Nai, Youfeng; Nash, Samuel C.; Pike, Andrew; Robinson, James; Read, Jon A.; Rawlins, Phillip B.; Shen, Minhui; Tang, Jia; Wang, Peng; Woods, Haley; Williamson, Beth [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17146 - 17183]

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CAS No. :	2996-58-9	MDL No. :	MFCD00128875
Formula :	C₅H₉NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	YRKRGYRYEQYTOH-UHFFFAOYSA-N
M.W :	99.13	Pubchem ID :	533920
Synonyms :

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H302-H315-H319-H332-H335	Packing Group:	N/A
GHS Pictogram:

Precautionary Statements-General
Code	Phrase
P101	If medical advice is needed,have product container or label at hand.
P102	Keep out of reach of children.
P103	Read label before use
Prevention
Code	Phrase
P201	Obtain special instructions before use.
P202	Do not handle until all safety precautions have been read and understood.
P210	Keep away from heat/sparks/open flames/hot surfaces. - No smoking.
P211	Do not spray on an open flame or other ignition source.
P220	Keep/Store away from clothing/combustible materials.
P221	Take any precaution to avoid mixing with combustibles
P222	Do not allow contact with air.
P223	Keep away from any possible contact with water, because of violent reaction and possible flash fire.
P230	Keep wetted
P231	Handle under inert gas.
P232	Protect from moisture.
P233	Keep container tightly closed.
P234	Keep only in original container.
P235	Keep cool
P240	Ground/bond container and receiving equipment.
P241	Use explosion-proof electrical/ventilating/lighting/equipment.
P242	Use only non-sparking tools.
P243	Take precautionary measures against static discharge.
P244	Keep reduction valves free from grease and oil.
P250	Do not subject to grinding/shock/friction.
P251	Pressurized container: Do not pierce or burn, even after use.
P260	Do not breathe dust/fume/gas/mist/vapours/spray.
P261	Avoid breathing dust/fume/gas/mist/vapours/spray.
P262	Do not get in eyes, on skin, or on clothing.
P263	Avoid contact during pregnancy/while nursing.
P264	Wash hands thoroughly after handling.
P265	Wash skin thouroughly after handling.
P270	Do not eat, drink or smoke when using this product.
P271	Use only outdoors or in a well-ventilated area.
P272	Contaminated work clothing should not be allowed out of the workplace.
P273	Avoid release to the environment.
P280	Wear protective gloves/protective clothing/eye protection/face protection.
P281	Use personal protective equipment as required.
P282	Wear cold insulating gloves/face shield/eye protection.
P283	Wear fire/flame resistant/retardant clothing.
P284	Wear respiratory protection.
P285	In case of inadequate ventilation wear respiratory protection.
P231 + P232	Handle under inert gas. Protect from moisture.
P235 + P410	Keep cool. Protect from sunlight.
Response
Code	Phrase
P301	IF SWALLOWED:
P304	IF INHALED:
P305	IF IN EYES:
P306	IF ON CLOTHING:
P307	IF exposed:
P308	IF exposed or concerned:
P309	IF exposed or if you feel unwell:
P310	Immediately call a POISON CENTER or doctor/physician.
P311	Call a POISON CENTER or doctor/physician.
P312	Call a POISON CENTER or doctor/physician if you feel unwell.
P313	Get medical advice/attention.
P314	Get medical advice/attention if you feel unwell.
P315	Get immediate medical advice/attention.
P320
P302 + P352	IF ON SKIN: wash with plenty of soap and water.
P321
P322
P330	Rinse mouth.
P331	Do NOT induce vomiting.
P332	IF SKIN irritation occurs:
P333	If skin irritation or rash occurs:
P334	Immerse in cool water/wrap n wet bandages.
P335	Brush off loose particles from skin.
P336	Thaw frosted parts with lukewarm water. Do not rub affected area.
P337	If eye irritation persists:
P338	Remove contact lenses, if present and easy to do. Continue rinsing.
P340	Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P341	If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P342	If experiencing respiratory symptoms:
P350	Gently wash with plenty of soap and water.
P351	Rinse cautiously with water for several minutes.
P352	Wash with plenty of soap and water.
P353	Rinse skin with water/shower.
P360	Rinse immediately contaminated clothing and skin with plenty of water before removing clothes.
P361	Remove/Take off immediately all contaminated clothing.
P362	Take off contaminated clothing and wash before reuse.
P363	Wash contaminated clothing before reuse.
P370	In case of fire:
P371	In case of major fire and large quantities:
P372	Explosion risk in case of fire.
P373	DO NOT fight fire when fire reaches explosives.
P374	Fight fire with normal precautions from a reasonable distance.
P376	Stop leak if safe to do so. Oxidising gases (section 2.4) 1
P377	Leaking gas fire: Do not extinguish, unless leak can be stopped safely.
P378
P380	Evacuate area.
P381	Eliminate all ignition sources if safe to do so.
P390	Absorb spillage to prevent material damage.
P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
P301 + P330 + P331	IF SWALLOWED: Rinse mouth. Do NOT induce vomiting.
P302 + P334	IF ON SKIN: Immerse in cool water/wrap in wet bandages.
P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
P303 + P361 + P353	IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.
P304 + P312	IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell.
P304 + P340	IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.
P304 + P341	IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing.
P305 + P351 + P338	IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P306 + P360	IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes.
P307 + P311	IF exposed: call a POISON CENTER or doctor/physician.
P308 + P313	IF exposed or concerned: Get medical advice/attention.
P309 + P311	IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician.
P332 + P313	IF SKIN irritation occurs: Get medical advice/attention.
P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
P335 + P334	Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages.
P337 + P313	IF eye irritation persists: Get medical advice/attention.
P342 + P311	IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician.
P370 + P376	In case of fire: Stop leak if safe to Do so.
P370 + P378	In case of fire:
P370 + P380	In case of fire: Evacuate area.
P370 + P380 + P375	In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion.
P371 + P380 + P375	In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion.
Storage
Code	Phrase
P401
P402	Store in a dry place.
P403	Store in a well-ventilated place.
P404	Store in a closed container.
P405	Store locked up.
P406	Store in corrosive resistant/ container with a resistant inner liner.
P407	Maintain air gap between stacks/pallets.
P410	Protect from sunlight.
P411
P412	Do not expose to temperatures exceeding 50 oC/ 122 oF.
P413
P420	Store away from other materials.
P422
P402 + P404	Store in a dry place. Store in a closed container.
P403 + P233	Store in a well-ventilated place. Keep container tightly closed.
P403 + P235	Store in a well-ventilated place. Keep cool.
P410 + P403	Protect from sunlight. Store in a well-ventilated place.
P410 + P412	Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF.
P411 + P235	Keep cool.
Disposal
Code	Phrase
P501	Dispose of contents/container to ...
P502	Refer to manufacturer/supplier for information on recovery/recycling

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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[ 2996-58-9 ] Synthesis Path-Downstream 1~50

Precautionary Statements-General

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