[ CAS No. 1978-33-2 ] {[proInfo.proName]}

Name: 1978-33-2|3-Amino-2-fluorotoluene|97%
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Quality Control of [ 1978-33-2 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 1978-33-2 ]

Product Details of [ 1978-33-2 ]

CAS No. :	1978-33-2	MDL No. :	MFCD06410915
Formula :	C₇H₈FN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	WFZUBZAEFXETBF-UHFFFAOYSA-N
M.W :	125.14	Pubchem ID :	22734623
Synonyms :

Calculated chemistry of [ 1978-33-2 ]

Physicochemical Properties

Num. heavy atoms :	9
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.14
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	35.77
TPSA :	26.02 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	Yes
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-5.85 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.58
Log Po/w (XLOGP3) :	1.71
Log Po/w (WLOGP) :	2.14
Log Po/w (MLOGP) :	2.24
Log Po/w (SILICOS-IT) :	2.01
Consensus Log Po/w :	1.94

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	2.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-2.19
Solubility :	0.814 mg/ml ; 0.00651 mol/l
Class :	Soluble
Log S (Ali) :	-1.87
Solubility :	1.68 mg/ml ; 0.0134 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.66
Solubility :	0.273 mg/ml ; 0.00218 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Safety of [ 1978-33-2 ]

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

Application In Synthesis of [ 1978-33-2 ]

* 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.

Upstream synthesis route of [ 1978-33-2 ]
Downstream synthetic route of [ 1978-33-2 ]

[ 1978-33-2 ] Synthesis Path-Upstream 1~1

1
[ 437-86-5 ]
[ 1978-33-2 ]

Reference： [1] Chemische Berichte, 1931, vol. 64, p. 2465,2472

[ 1978-33-2 ] Synthesis Path-Downstream 1~83

1
[ 437-86-5 ]
[ 1978-33-2 ]

Reference： [1]Chemische Berichte,1931,vol. 64,p. 2465,2472

2
[ 1978-33-2 ]
[ 108-24-7 ]
[ 704-37-0 ]

Reference： [1]Chemische Berichte,1931,vol. 64,p. 2465,2472

3
[ 1978-33-2 ]
[ 386-39-0 ]

Reference： [1]Chemische Berichte,1931,vol. 64,p. 2465,2472

4
[ 6191-98-6 ]
[ 1978-33-2 ]
[ 1161829-64-6 ]

Yield	Reaction Conditions	Operation in experiment
48%	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine;	N-(2-Fluoro-3-methylphenyl)-3,3-dimethoxypropanamide:[0219] The crude acid was used in next step (Scheme 4) and amide formation was performed using general procedure in Scheme 1. The amide was obtained in 48% (1.52 g). 1H NMR (400 MHz, CDCl3): delta 8.58 (br s, IH), 8.17-8.11(m, IH), 7.00-6.83(m, 2H), 4.79(t, IH), 3.49 (s, 6H), 2.59(d, 2H), 2.31 (s, 3H).

Reference： [1]Patent: WO2009/76404,2009,A1 .Location in patent: Page/Page column 54; 66

5
[ 1978-33-2 ]
[ 1138036-49-3 ]

Yield	Reaction Conditions	Operation in experiment
63%		Reference Example 185 (2-fluoro-3-methylphenyl)hydrazine To a solution of sodium nitrite (28.7 g) in water (100 mL) was added dropwise a solution of 2-fluoro-4-methylaniline (40 g) in concentrated hydrochloric acid (640 mL) at -20 C., and the mixture was stirred at the same temperature for 1 hr. A solution of tin(II) chloride (121 g) in concentrated hydrochloric acid (200 mL) was added dropwise at -20 C., and the mixture was stirred at 0 C. for 2 hr. The resulting solid was collected by filtration, and washed with water and hexane. The obtained solid was dissolved in water (500 mL), the solution was adjusted to pH 12 with 2 mol/L aqueous sodium hydroxide solution, and extracted twice with dichloromethane. The extract was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the title compound as a white solid (28.4 g, yield 63%). 1H-NMR (CDCl3) delta: 2.24 (3H, d, J=2.4 Hz), 3.54 (2H, brs), 5.30 (1H, brs), 6.59-6.63 (1H, m), 6.89 (1H, dt, J=7.8, 2.0 Hz), 6.94-6.99 (1H, m).

Reference： [1]Patent: US2009/156642,2009,A1 .Location in patent: Page/Page column 66

6
[ 1978-33-2 ]
[ 1432731-51-5 ]

Reference： [1]Patent: WO2013/66736,2013,A1

7
[ 1978-33-2 ]
[ 1432731-52-6 ]

Reference： [1]Patent: WO2013/66736,2013,A1

8
[ 1978-33-2 ]
[ 1432731-53-7 ]

Reference： [1]Patent: WO2013/66736,2013,A1

9
[ 1978-33-2 ]
[ 1432731-54-8 ]

Reference： [1]Patent: WO2013/66736,2013,A1

10
[ 1978-33-2 ]
[ 1432731-55-9 ]

Reference： [1]Patent: WO2013/66736,2013,A1

11
[ 1978-33-2 ]
[ 1432731-56-0 ]

Reference： [1]Patent: WO2013/66736,2013,A1

12
[ 1978-33-2 ]
[ 1432730-61-4 ]

Reference： [1]Patent: WO2013/66736,2013,A1

13
[ 1978-33-2 ]
[ 1432731-51-5 ]

Reference： [1]Patent: WO2013/66736,2013,A1

14
[ 1978-33-2 ]
[ 1432731-58-2 ]

Reference： [1]Patent: WO2013/66736,2013,A1

15
[ 1978-33-2 ]
[ 1432731-60-6 ]

Reference： [1]Patent: WO2013/66736,2013,A1

16
[ 1978-33-2 ]
[ 1432731-61-7 ]

Reference： [1]Patent: WO2013/66736,2013,A1

17
[ 1978-33-2 ]
[ 1432731-64-0 ]

Reference： [1]Patent: WO2013/66736,2013,A1

18
[ 1978-33-2 ]
[ 1432731-62-8 ]
[ 1432731-63-9 ]

Reference： [1]Patent: WO2013/66736,2013,A1

19
[ 1978-33-2 ]
[ 1432730-62-5 ]

Reference： [1]Patent: WO2013/66736,2013,A1

20
[ 25007-54-9 ]
[ 1978-33-2 ]
[ 1432731-50-4 ]

Yield	Reaction Conditions	Operation in experiment
53%	With toluene-4-sulfonic acid; for 1h;Reflux;	3-Amino-2-fluorotoluene (4.89 g, 39.1 mmol), dimethyl 2-oxobutanedioate (6.26 g, 39.1 mmol), and TosicAcid (0.223 g, 1.172 mmol) were heated at reflux under Dean-Stark conditions for 1 hour. The solvent was removed in vacuo and the residue purified by column chromatography on a silica gel column, eluting with EtOAc/hexane (0-15%) to afford Dimethyl (2£)-2-[(2-fluoro-3- methylphenyl)imino]butanedioate (7-6, 5.48 g, 53 % yield) as a clear oil, LCMS shows the compound is 100% pure, LRMS m/z (M+H)+268.2 found, 268.1 required.

Reference： [1]Patent: WO2013/66736,2013,A1 .Location in patent: Page/Page column 144; 145

21
[ 22363-16-2 ]
[ 1978-33-2 ]
[ 1474030-55-1 ]

Reference： [1]MedChemComm,2013,vol. 4,p. 1202 - 1207

22
[ 946198-89-6 ]
[ 1978-33-2 ]
[ 1474030-89-1 ]

Reference： [1]MedChemComm,2013,vol. 4,p. 1202 - 1207

23
[ 1978-33-2 ]
[ 67-68-5 ]
2-fluoro-3-methyl-4-(methylthio)aniline [ No CAS ]
4,4'-methylenebis(2-fluoro-3-methylaniline) [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2015,vol. 13,p. 9742 - 9745

24
[ 392-83-6 ]
[ 1978-33-2 ]
2-fluoro-3-methyl-N-(2-(trifluoromethyl)phenyl)aniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; at 100℃; for 16h;	A mixture of 2-(dicyclohexylphosphino)-2?,4?,6?-triisopropylbiphenyl (133 mg, 0.28 mmol), Cs2CO3 (19.53 g,59.91 mmol). Pd2(dba)3 (183 mg, 0.21 mmol). 1-bromo-2-(trifluoromethyl) benzene (13.48 g, 59.91mmol) and <strong>[1978-33-2]2-fluoro-3-methyl-aniline</strong> A24-1 (6.00 g, 22.29 mmol) in 1,4-dioxane (100 mL) was heated to 100 C for 16 h. Then the reaction was filtered and the filtrate was concentrated in vacuo to give the crude product, which was purified by column chromatography on silica gel (eluting with PE;EA=100:0 to 95:5) to afford compound A24-2. MS (ESI) m / e (M+H): 270.1.

Reference： [1]Patent: WO2015/176267,2015,A1 .Location in patent: Page/Page column 128

25
[ 1978-33-2 ]
N-(2-fluoro-3-methylphenyl)-3-methyl-N-(2-(trifluoromethyl)phenyl)but-2-enamide [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

26
[ 1978-33-2 ]
8-fluoro-4,4,7-trimethyl-1-(2-(trifluoromethyl)phenyl)-3,4-dihydroquinolin-2(1H)-one [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

27
[ 1978-33-2 ]
8-fluoro-4,4-dimethyl-2-oxo-1-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinoline-7-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

28
[ 1978-33-2 ]
(8-fluoro-4,4-dimethyl-1-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinolin-7-yl)methanol [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

29
[ 1978-33-2 ]
(5aR,6S,6aS)-tert-butyl 3-((8-fluoro-4,4-dimethyl-1-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinolin-7-yl)methoxy)-5,5a,6,6a-tetrahydrocyclopropa[4,5]cyclopenta[1,2-c]pyridine-6-carboxylate [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

30
[ 1978-33-2 ]
(5aR,6S,6aS)-3-((8-fluoro-4,4-dimethyl-1-(2-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroquinolin-7-yl)methoxy)-5,5a,6,6a-tetrahydrocyclopropa[4,5]cyclopenta[1,2-c]pyridine-6-carboxylic acid [ No CAS ]

Reference： [1]Patent: WO2015/176267,2015,A1

31
[ 1978-33-2 ]
4-chloro-2-fluoro-3-methylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃;	4-Chloro-<strong>[1978-33-2]2-fluoro-3-methylaniline</strong> To a solution of <strong>[1978-33-2]2-fluoro-3-methylaniline</strong> (1 equiv.) in DMF (0.8 M) was added NCS (1 equiv.). The reaction was stirred at room temperature overnight. Water and ethyl acetate was added to the solution and the layers were separated. The organic layer was washed with H2O, dried over Na2SO4 and concentrated. The resulting residue was purified by column chromatography on silica gel to give 4-chloro-<strong>[1978-33-2]2-fluoro-3-methylaniline</strong> (22%) as yellow oil. 1H NMR (400 MHz, CDCl3) delta ppm: 6.92 (dd, J=1.2, 8.4 Hz, 1H), 6.61 (t, J=9.2 Hz, 1H), 5.20 (s, 2H), 2.18 (d, J=2.5 Hz, 3H).

Reference： [1]Patent: US2016/96841,2016,A1 .Location in patent: Paragraph 0366

32
[ 1978-33-2 ]
1-chloro-2-fluoro-4-isothiocyanato-3-methylbenzene [ No CAS ]

Reference： [1]Patent: US2016/96841,2016,A1

33
[ 1978-33-2 ]
(1s,4s)-4-(8-(4-chloro-3-fluoro-2-methylphenylamino)-2-(tetrahydro-2H-pyran-4-ylamino)-9H-purin-9-yl)cyclohexanecarboxamide [ No CAS ]

Reference： [1]Patent: US2016/96841,2016,A1

34
[ 1978-33-2 ]
(1s,4s)-4-(8-(4-chloro-2-fluoro-3-methylphenylamino)-2-(tetrahydro-2H-pyran-4-ylamino)-9H-purin-9-yl)cyclohexanecarboxamide [ No CAS ]

Reference： [1]Patent: US2016/96841,2016,A1

35
[ 1978-33-2 ]
2-(4-chlorobenzylamino)-4-chloro-7-methyl-8-fluoroquinoline [ No CAS ]

Reference： [1]Patent: WO2017/191599,2017,A1

36
[ 1978-33-2 ]
2-(4-chlorobenzylamino)-4-[4-(tert-butylamino)piperidin-1-yl]-7-methyl-8-fluoroquinoline [ No CAS ]

Reference： [1]Patent: WO2017/191599,2017,A1

37
[ 1978-33-2 ]
2-(4-chlorobenzylamino)-4-chloro-7-fluoro-8-methylquinoline [ No CAS ]

Reference： [1]Patent: WO2017/191599,2017,A1

38
[ 1978-33-2 ]
2-(4-chlorobenzylamino)-4-[4-(tert-butylamino)piperidin-1-yl]-7-fluoro-8-methylquinoline [ No CAS ]

Reference： [1]Patent: WO2017/191599,2017,A1

39
[ 141-82-2 ]
[ 1978-33-2 ]
2,4-dichloro-8-fluoro-7-methylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
27%	With trichlorophosphate; at 80 - 125℃; for 3h;	To <strong>[1978-33-2]2-fluoro-3-methylaniline</strong> (5.0 g, 40 mmol) was added Phosphoryl chloride (100 ml), and then was added portion wise the malonic acid (12.4 g, 120 mmol). The resulting mixture was stirred at 80 C for 1 h. Then, the mixture was stirred at 125 C for 2 h. the reaction mixture was allowed to room temperature and poured in to ice water and extracted with AcOEt (2 X 100 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated under reduced pressure to give crude compound which upon purification by flash chromatography using (silica- gel: 100-200 mesh, AcOEt-petroleum ether; 8:92? 10:90) gave 2.5 g (yield 27%) of a white solid corresponding to 2,4-dichloro-8-fluoro-7-methylquinoline. Mass: (ES+) C10H6Cl2FN, required 229; found 230 [M+H], HPLC/MS method 2.

Reference： [1]Patent: WO2017/191599,2017,A1 .Location in patent: Page/Page column 154

40
[ 141-82-2 ]
[ 1978-33-2 ]
2,4-dichloro-7-fluoro-8-methylquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
33%	With trichlorophosphate; at 80℃; for 16h;	To a <strong>[1978-33-2]2-fluoro-3-methylaniline</strong> (2.0 g, 16 mmol) was added Phosphoryl chloride (40 ml), and then malonic acid (2.4 g, 24 mmol) was added portion wise. The resulting mixture was stirred at 80 C for 16 h. The reaction mixture was allowed to room temperature and poured into ice water mixture. The aqueous layer was extracted with AcOEt (2 X 50 ml). The combined organic layer were dried over Na2SO4, filtered and concentrated under reduced pressure to give a crude compound which upon purification by flash chromatography using (silica-gel: 100-200 mesh, AcOEt-petroleum ether; 2:98? 5:95) gave 1.2 g (yield 33%) of a white solid corresponding to 2,4- dichloro-7-fluoro-8-methylquinoline. Mass:((ES+) C26H32ClFN4 required 229; found 230 [M +H], HPLC/MS method 4.

Reference： [1]Patent: WO2017/191599,2017,A1 .Location in patent: Page/Page column 158; 159

41
ethyl 5-(chlorocarbonyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)-carboxylate [ No CAS ]
[ 1978-33-2 ]
N-(2-fluoro-3-methylphenyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-4,6-dihydropyrrolo[3,4-c]pyrazole-5(1H)-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
34%		To a solution of 120 mg (0.272 mmol [calculation value with the purity defined as 100%]) of ethyl 5-(chlorocarbonyl)-6,6-dimethyl-3-[1-(trimethylsilyl)cyclobutanecarboxamido]-5,6-dihydropyrrolo[3,4-c]pyrazole-2(4H)-carboxylate synthesized in the same way as in Reference Example 4 in 2 ml of 1,4-dioxane, 0.150 ml (0.861 mmol) of DIPEA and 100 mg (0.799 mmol) of <strong>[1978-33-2]2-fluoro-3-methylaniline</strong> were added at room temperature in an argon atmosphere and reacted at 90 C. for 11 hours with stirring. Subsequently, the reaction solution was cooled to room temperature, and 0.150 ml (1.38 mmol) of N,N-dimethylethane-1,2-diamine was added thereto at room temperature and then reacted at room temperature for 16 hours with stirring. After completion of the reaction, ethyl acetate was added to the reaction solution, followed by washing with a 5% aqueous potassium bisulfate solution. After separation into an organic layer and an aqueous layer, the aqueous layer was subjected to extraction twice with ethyl acetate. The whole organic layer thus obtained was dried over anhydrous magnesium sulfate, then filtered, and concentrated under reduced pressure. The obtained concentration residue was subjected to preparative column chromatography (apparatus 1, DIOL silica gel, elution solvent: n-hexane:ethyl acetate=60:40?20:80 (V/V)), and a fraction containing the compound of interest was concentrated under reduced pressure. The obtained concentration residue was dissolved by the addition of methanol, then water was added thereto, and the deposited solid was collected by filtration and dried under reduced pressure to obtain 42.0 mg of the title compound (yield: 34% [calculation value with the purity of the starting material defined as 100%]) as a white solid. Mass spectrum (CI, m/z): 458 [M+1]+. 1H-NMR spectrum (400 MHz, DMSO-d6) delta: 12.27 & 11.76 (br s, total 1H), 9.61 (br s, 1H), 7.88-7.57 (m, 1H), 7.52-7.29 (m, 1H), 7.02-6.92 (m, 2H), 4.62 (br s, 2H), 2.56-2.41 (m, 2H), 2.29-2.13 (m, 5H), 1.93-1.72 (m, 2H), 1.65 (s, 6H), 0.09 (s, 9H).

Reference： [1]Patent: US2018/186818,2018,A1 .Location in patent: Paragraph 0686; 0687; 0688; 0689; 0690

42
[ 1978-33-2 ]
C₁₄H₁₅FN₂O₂S [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9647 - 9665

43
[ 1978-33-2 ]
8-fluoro-7-methylquinoline-5-sulfonyl chloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9647 - 9665

44
[ 1978-33-2 ]
8-tert-butoxy-7-methyl-5-pyrrolidin-1-ylsulfonylquinoline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9647 - 9665

45
[ 1978-33-2 ]
7-methyl-5-(pyrrolidin-1-ylsulfonyl)quinolin-8-ol hydrochloride [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9647 - 9665

46
[ 1978-33-2 ]
[ 56-81-5 ]
8-fluoro-7-methylquinoline [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2018,vol. 61,p. 9647 - 9665

47
[ 1978-33-2 ]
N-(2-fluoro-3-methyl-4-(6-(trifluoromethyl)quinolin-2-yl)phenyl)-1-methyl-1H-pyrazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/18562,2019,A1
[2]Patent: WO2020/18848,2020,A1

48
[ 1978-33-2 ]
N-(2-fluoro-3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1-methyl-1H-pyrazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/18562,2019,A1
[2]Patent: WO2020/18848,2020,A1

49
[ 1978-33-2 ]
4-bromo-2-fluoro-3-methylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With N-Bromosuccinimide; In acetonitrile; at 10 - 20℃; for 1h;Inert atmosphere;	To a stirred solution of <strong>[1978-33-2]2-fluoro-3-methylaniline</strong>(4 g, 31.96 mmol, 1 equiv) in acetonitrile(100 mL), NBS(6.2 g, 35.03 mmol, 1.096 equiv) was added in portions at 10 C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The residue was purified by silica gel column chromatography, with ethyl acetate / petroleum ether (1 :30) as eluent to afford 4-bromo-2- fluoro-3-methylaniline as a red solid in 86% yield.
86%	With N-Bromosuccinimide; In acetonitrile; at 10 - 20℃; for 1h;Inert atmosphere;	To a stirred solution of <strong>[1978-33-2]2-fluoro-3-methylaniline</strong>(4 g, 31.96 mmol, 1 equiv) in acetonitrile(l00 mL), NBS(6.2 g, 35.03 mmol, 1.096 equiv) was added in portions at 10 C under nitrogen atmosphere. The resulting mixture was stirred at room temperature for 1 hour and concentrated under reduced pressure. The residue was purified by silica gel column (0874) chromatography, with ethyl acetate / petroleum ether (1 :30) as eluent to afford 4-bromo-2- fluoro-3-methylaniline as a red solid in 86% yield.
74%	With N-Bromosuccinimide; In acetonitrile; at 25℃; for 4h;	To a solution of <strong>[1978-33-2]2-fluoro-3-methylaniline</strong> (25.0 g, 0.20 mol) in MeCN (200 mL) was added dropwise a solution of NBS (39.1 g, 0.22 mol) in MeCN (100 mL) at 25 C. The reaction mixture was stirred at 25 C for 4 h. The reaction mixture was concentrated in vacuo and purified by silica-gel column chromatography (petroleum ether/EtOAc, 50:1) to give 4-bromo-2-fluoro-3- methylaniline as a brown oil (30 g, yield: 74%). 1H NMR: (400 MHz, DMSO-i) d: 7.02 (dd, J = 8.8 Hz, 1.6 Hz, 1H), 6.55 (t, / = 8.8 Hz, 1H), 5.21 (s, 2H), 2.16 (d, / = 2.4 Hz, 3H).

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174
[2]Patent: WO2019/18562,2019,A1 .Location in patent: Paragraph 0237
[3]Patent: WO2020/18848,2020,A1 .Location in patent: Paragraph 0368
[4]Patent: WO2019/222101,2019,A1 .Location in patent: Page/Page column 61-62

50
[ 1978-33-2 ]
N-(4-bromo-2-fluoro-3-methylphenyl)-1-methyl-1H-pyrazole-5-carboxamide [ No CAS ]

Reference： [1]Patent: WO2019/18562,2019,A1
[2]Patent: WO2020/18848,2020,A1

51
[ 1978-33-2 ]
2,7-dibutyldipyrazolo[1,5-a:1',5'-d]pyrazine-4,9-dione [ No CAS ]
3-butyl-N-(2-fluoro-3-methylphenyl)-1H-pyrazole-5-carboxamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2019,vol. 62,p. 7015 - 7031

52
[ 1978-33-2 ]
C₁₈H₈F₄O₃ [ No CAS ]
13-(2-fluoro-3-methylphenyl)-2,3,6,7-tetrafluoro-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

53
[ 1978-33-2 ]
C₁₈H₄F₈O₃ [ No CAS ]
13-(2-fluoro-3-methylphenyl)-1,2,3,4,5,6,7,8-octafluoro-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

54
C₂₆H₁₆O₃ [ No CAS ]
[ 1978-33-2 ]
17-(2-fluoro-3-methylphenyl)-6,13-dihydro-6,13-[3,4]epipyrrolopentacene-16,18-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

55
[ 1978-33-2 ]
[ 129-64-6 ]
(3aR,4S,7R,7aS)-2-(2-fluoro-3-methylphenyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

56
[ 1978-33-2 ]
[ 5443-16-3 ]
13-(2-fluoro-3-methylphenyl)-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

57
[ 1978-33-2 ]
C₁₈H₁₀F₂O₃ [ No CAS ]
13-(2-fluoro-3-methylphenyl)-2,6-difluoro-9,10-dihydro-9,10-[3,4]epipyrroloanthracene-12,14-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019,vol. 141,p. 12513 - 12517

58
[ 1978-33-2 ]
4-[4-(1H-pyrazol-1-yl)benzyl]-2-fluoro-3-methylaniline [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

59
[ 1978-33-2 ]
4-[4-(1H-pyrazol-1-yl)benzyl]-6-bromo-2-fluoro-3-methylaniline [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

60
[ 1978-33-2 ]
C₁₇H₁₄BrFN₂ [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

61
[ 1978-33-2 ]
1-[4-(5-bromo-3-fluoro-4-iodo-2-methylbenzyl)phenyl]-1H-pyrazole [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

62
[ 1978-33-2 ]
4-[4-(1H-pyrazol-1-yl)benzyl]-6-bromo-2-fluoro-3-methylbenzaldehyde [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

63
[ 1978-33-2 ]
(3S,4S)-3-[[4-[4-(1H-pyrazol-1-yl)benzyl]-6-bromo-2-fluoro-3-methylbenzyl]-amino]-tetrahydro-2H-pyran-4-ol [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

64
[ 1978-33-2 ]
4-fluoro-2-[(3S,4S)-4-hydroxytetrahydro-2H-pyran-3-yl]-5-methyl-6-[4-(1H-pyrazol-1-yl)benzyl]-2,3-dihydro-1H-isoindol-1-one [ No CAS ]

Reference： [1]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174
[2]Organic and Biomolecular Chemistry,2019,vol. 17,p. 8166 - 8174

65
[ 1978-33-2 ]
4-bromo-3-fluoro-2-methylbenzoic acid [ No CAS ]