[ CAS No. 443-89-0 ] {[proInfo.proName]}

Name: 443-89-0|2-Fluoro-6-methylaniline|97%
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Quality Control of [ 443-89-0 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 443-89-0 ]

Product Details of [ 443-89-0 ]

CAS No. :	443-89-0	MDL No. :	MFCD06658252
Formula :	C₇H₈FN	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CMVJYZNBMRJICR-UHFFFAOYSA-N
M.W :	125.14	Pubchem ID :	14155411
Synonyms :

Calculated chemistry of [ 443-89-0 ]

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) :	1.64
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 :	1.95

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 [ 443-89-0 ]

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

Application In Synthesis of [ 443-89-0 ]

* 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 [ 443-89-0 ]
Downstream synthetic route of [ 443-89-0 ]

[ 443-89-0 ] Synthesis Path-Upstream 1~2

1
[ 3013-27-2 ]
[ 443-89-0 ]

Reference： [1] Acta Chemica Scandinavica (1947-1973), 1955, vol. 9, p. 1079,1083

2
[ 443-89-0 ]
[ 3013-27-2 ]

Yield	Reaction Conditions	Operation in experiment
65.9%	With 3-chloro-benzenecarboperoxoic acid In 1,2-dichloro-ethane at 20 - 70℃; for 4 h; Inert atmosphere	Fluoro-3-methyl-2-nitrobenzene To a solution of 2-fluoro-6-methylaniline (8.5 g, 67.9 mmol) in DCE (150 mL), m- CPBA (58.6 g, 272 mmol) was added slowly under nitrogen at RT. The reaction mixture was stirred at 70 °C for 4 h. DCM (500 mL) was added. Then it was washed with 1 N NaOH (200 mL x4). The combined organic layers was dried and concentrated under a stream of nitrogen at 50 °C to give 1 1.2 g (65.9percent) of the title compound.

Reference： [1] Patent: WO2015/92713, 2015, A1, . Location in patent: Page/Page column 118

[ 443-89-0 ] Synthesis Path-Downstream 1~88

1
[ 29745-44-6 ]
[ 443-89-0 ]
[ 933449-53-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1386 - 1391

2
[ 443-89-0 ]
[ 933449-59-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1386 - 1391

3
[ 443-89-0 ]
pyridine-2-carboxylic acid [2-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-6-fluoro-phenyl]-amide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2007,vol. 17,p. 1386 - 1391

4
[ 443-89-0 ]
N,N-diethyl-glycine-(2-fluoro-6-methyl-anilide) [ No CAS ]

Reference： [1]Acta Chemica Scandinavica (1947),1955,vol. 9,p. 1079,1083

Yield	Reaction Conditions	Operation in experiment
3.8 g (80%)		EXAMPLE 86 Preparation of 2-fluoro-6-methylaniline A solution of 8.15 g (38.5 mmol) of N-t-butoxycarbonyl-2-fluoroaniline in 30 ml of dry THF was cooled to -70 C., and 46.3 ml (93 mmol) of 2.0M t-butyllithium in pentane was added dropwise at a rate sufficient to maintain the temperature below -65 C. When the addition was complete the reaction mixture was stirred at -70 C. for 15 minutes, warmed to -20 C. and stirred for 2.5 hours. A solution of 6.8 g (30 mmol) of methyl iodide in THF was added and the reaction was allowed to warm to room temperature. The reaction mixture was partitioned between ether and water, and the organic layer was washed with saturated aqueous NaCl and dried (MgSO4). Evaporation at reduced pressure gave a yellow solid which was added to 25 ml of 3N HCl and heated at reflux for 3 hours. After cooling to room the pH of the solution was adjusted to pH 7, and the solution was extracted twice with methylene chloride. The combined organic phases were washed with water and dried (MgSO4). Evaporation at reduced pressure gave a yellow oil which was Kugelrohr distilled to yield 3.8 g (80%) of the desired product as a liquid, bp 91-93 C. (0.1 mm). IR and 1 H NMR spectra were in agreement with the assigned structure. Analysis: Calculated for C7 H8 FN: C, 67.20; H, 6.45; N, 11.20; Found: C, 67.61; H, 6.09; N, 11.53.
3.8 g (80%)		EXAMPLE 102 Preparation of 2-fluoro-6-methylaniline A solution of 8.15 g (38.5 mmol) of N-t-butoxycarbonyl-2-fluoroaniline in 30 ml of dry THF was cooled to -70 C., and 46.3 ml (93 mmol) of 2.0M t-butyllithium in pentane was added dropwise at a rate sufficient to maintain the temperature below -65 C. When the addition was complete the reaction mixture was stirred at -70 C. for 15 minutes, warmed to -20 C. and stirred for 2.5 hours. A solution of 6.8 g (30 mmol) of methyl iodide in THF was added and the reaction was allowed to warm to room temperature. The reaction mixture was partitioned between ether and water, and the organic layer was washed with saturated aqueous NaCl and dried (MgSO4). Evaporation at reduced pressure gave a yellow solid which was added to 25 ml of 3N HCl and heated at reflux for 3 hours. After cooling to room temperature the pH of the solution was adjusted to pH 7, and the solution was extracted twice with methylene chloride. The combined organic phases were washed with water and dried (MgSO4). Evaporation at reduced pressure gave a yellow oil which was Kugelrohr distilled to yield 3.8 g (80%) of the desired product as a liquid, b.p. 91-93 C. (0.1 mm). IR and 1 H NMR spectra were in agreement with the assigned structure. Analysis: Calculated for C7 H8 FN: C, 67.20; H, 6.45; N, 11.20. Found: C, 67.61; H, 6.09; N, 11.53.
3.8 g (80%)		Example 86 - Preparation of 2-fluoro-6-methylaniline A solution of 8.15 g (38.5 mmol) of N- t -butoxycarbonyl-2-fluoroaniline in 30 ml of dry THF was cooled to -70C, and 46.3 ml (93 mmol) of 2.0 M t -butyllithium in pentane was added dropwise at a rate sufficient to maintain the temperature below -65C. When the addition was complete the reaction mixture was stirred at -70C for 15 minutes, warmed to -20C and stirred for 2.5 hours. A solution of 6.8 g (30 mmol) of methyl iodide in THF was added and the reaction was allowed to warm to room temperature. The reaction mixture was partitioned between ether and water, and the organic layer was washed with saturated aqueous NaCl and dried (MgSO4). Evaporation at reduced pressure gave a yellow solid which was added to 25 ml of 3N HCl and heated at reflux for 3 hours. After cooling to room the pH of the solution was adjusted to pH 7, and the solution was extracted twice with methylene chloride. The combined organic phases were washed with water and dried (MgSO4). Evaporation at reduced pressure gave a yellow oil which was Kugelrohr distilled to yield 3.8 g (80%) of the desired product as a liquid, bp 91-93C (0.1 mm). IR and 1H NMR spectra were in agreement with the assigned structure.

6
[ 443-89-0 ]
[ 1315692-86-4 ]

Reference： [1]Synthesis,2011,p. 1604 - 1608

7
[ 443-89-0 ]
C₁₃H₂₃BFNO₂Si₂ [ No CAS ]

Reference： [1]Synthesis,2011,p. 1604 - 1608

8
[ 443-89-0 ]
[ 1315692-92-2 ]

Reference： [1]Synthesis,2011,p. 1604 - 1608

9
[ 443-89-0 ]
C₁₉H₃₅BFNO₂Si₂ [ No CAS ]

Reference： [1]Synthesis,2011,p. 1604 - 1608

10
[ 443-89-0 ]
[ 91166-50-6 ]
C₁₅H₂₉FN₂Si₂ [ No CAS ]

Reference： [1]Synthesis,2011,p. 1604 - 1608

11
[ 443-89-0 ]
[ 188937-14-6 ]
[ 1452232-02-8 ]

Yield	Reaction Conditions	Operation in experiment
		Example 103A 4-ethyl-N-(2-fluoro-6-methylphenyl)-2-(methylthio)pyrimidine-5-carboxamide To a solution of Example 28B (539 mg, 2.72 mmol) in dichloromethane (5440 mul) was added a catalytic amount of N,N-dimethylformamide (5.27 mul, 0.068 mmol). The free-flowing slurry was cooled to 5 C. Oxalyl chloride (250 mul, 2.86 mmol) was added dropwise via syringe. The reaction mixture was allowed to proceed at 5-10 C. for 1 hour, then the cooling bath was removed and the mixture stirred at ambient temperature for an additional hour. To the slurry was added <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (357 mg, 2.86 mmol). The reaction mixture was then stirred at ambient temperature for 16 hours. The reaction mixture was poured into a 125 mL separatory funnel, diluted with 50 mL of dichloromethane and the organic layer was washed with water (140 mL), 1 molar aqueous phosphoric acid (140 mL), and saturated aqueous brine (1*40 mL), dried over magnesium sulfate, filtered and concentrated. The crude product was recrystallized in ethyl acetate/hexane mixture to afford the title compound.

Reference： [1]Patent: US2013/225589,2013,A1 .Location in patent: Paragraph 0634

12
[ 443-89-0 ]
4-bromo-2-fluoro-6-methylbenzeneamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
92.8%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.5h;Cooling with ice;	Step A: Under the ice water bath, NBS (5.0 g, 28.1 mmol) In DMF (20 mL) was added dropwise to a solution of <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (3.5 g, 28.0 mmol) In DMF (10 mL). After the addition was complete, stirring was continued for 5 minutes. The ice-water bath was then removed and the reaction mixture was stirred at room temperature for 0.5 hours. Water (150 mL) was added, extracted with ethyl acetate (80 mL x 3) The combined organic phases were washed sequentially with saturated sodium bicarbonate solution (40 mL × 2) and saturated brine (40 mL × 2) Drying over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give 4-bromo-<strong>[443-89-0]2-fluoro-6-methylaniline</strong> (42) (5.3 g). The yield is 92.8%.
91%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 7h;Inert atmosphere; Cooling with ice;	full text is not avalable from article
84%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 1h;	A mixture of <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (5.0 g, 40.0 mmol) and NBS (7.8 g, 44.0 mmol) in DMF (45 mL) was stirred at rt for lh. The mixture was diluted with water (100 mL) and extracted with DCM (50 mL*3). The combined organic layer was washed with brine (50 mL), dried over Na2S04, filtered and concentrated in vacuo. The residue was purified by column (PE:EA = 1 :4/l) to afford 4-bromo-<strong>[443-89-0]2-fluoro-6-methylaniline</strong> (6.8 g, 84%) as a brown solid.

60%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.166667h;Cooling with ice; Inert atmosphere;	To a round bottom flask were added 2-fluoro-6- methylaniline (7 g, 56 mmol) and anhydrous DMF (100 mL). The reaction mixture was cooled in an ice bath, placed under a nitrogen atmosphere, and treated with N-bromosuccinimide (10 g, 56 mmol). The reaction was allowed to warm to rt and was stirred at rt for 10 min. The reaction mixture was poured into a water solution of diluted brine and extracted with EtOAc. The combined organic extracts were washed with diluted brine (3X), dried (MgSC^), filtered through a pad of silica, and concentrated to dryness. The residue was purified by flash column chromatography yield the title Compound (6.84 g, 60% yield) as a yellow foam
60%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.166667h;Cooling with ice; Inert atmosphere;	4-Bromo-<strong>[443-89-0]2-fluoro-6-methylaniline</strong>. To a round bottom flask were added 2-fluoro-6- methylaniline (7 g, 56 mmol) and anhydrous DMF (100 mL). The reaction mixture was cooled in an ice bath, placed under a nitrogen atmosphere, and treated with N-bromosuccinimide (10 g, 56 mmol). The reaction was allowed to warm to rt and was stirred at rt for 10 min. The reaction mixture was poured into a water solution of diluted brine and extracted with EtOAc. The combined organic extracts were washed with diluted brine (3X), dried over anhydrous MgSC>4, filtered through a pad of silica, and concentrated to dryness. The residue was purified by flash column chromatography to yield the title compound (6.84 g, 60% yield) as a yellow foam. MS (ESI): mass calcd. for C7H7BrFN, 203.0; m/z found, 204 [M+H]+.
60%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.166667h;Cooling with ice; Inert atmosphere;	To a round bottom flask were added 2-fluoro-6- methylaniline (7 g, 56 mmol) and anhydrous DMF (100 mL). The reaction mixture was cooled in an ice bath, placed under a nitrogen atmosphere, and treated with N-bromosuccinimide (10 g,56 mmol). The reaction was allowed to warm to rt and was stirred at rt for 10 mm. The reaction mixture was poured into a water solution of diluted brine and extracted with EtOAc. The combined organic extracts were washed with diluted brine (3X), dried (Mg504), filtered through a pad of silica, and concentrated to dryness. The residue was purified by flash column chromatography yield the title compound (6.84 g, 60% yield) as a yellow foam.
60%	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.166667h;Cooling with ice; Inert atmosphere;	To a round bottom flask were added <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (7 g, 56 mmol) and anhydrous DMF (100 mL). The reaction mixture was cooled in an ice bath, placed under a nitrogen atmosphere, and treated with N-bromosuccinimide (10 g, 56 mmol). The reaction was allowed to warm to rt and was stirred at rt for 10 min. The reaction mixture was poured into a water solution of diluted brine and extracted with EtOAc. The combined organic extracts were washed with diluted brine (3X), dried over anhydrous MgSO 4, filtered through a pad of silica, and concentrated to dryness. The residue was purified by flash column chromatography to yield the title compound (6.84 g, 60% yield) as a yellow foam. MS (ESI) : mass calcd. for C 7H 7BrFN, 203.0 m/z found, 204 [M+H] +.
	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.5h;Inert atmosphere; Cooling with ice;	A solution of <strong>[443-89-0]2-fluoro-6-methylbenzenamine</strong> (32 mmol, 4 g) in DMF (40 ml_) under nitrogen atmosphere was cooled in an ice bath and treated with NBS (32 mmol, 5.7 g). The reaction mixture was stirred 30 min at room temperature. The mixture was diluted with ethyl acetate and the organic layer washed by water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound which was used in the next step without further purification (6 g, Yield: 91 %). 1 H NMR (400 MHz, CDCI3) delta 7.03 (1 H, dd, J = 9.6 & 2 Hz), 6.98 (1 H, brs), 2.17 (3H, s) LC-MS: tR = 3.28 [M+H] + = 204/206 (method 3)
	With N-Bromosuccinimide; In N,N-dimethyl-formamide; at 20℃; for 0.5h;Cooling with ice; Inert atmosphere;	A solution of <strong>[443-89-0]2-fluoro-6-methylbenzenamine</strong> (32 mmol, 4 g) in DMF (40 ml_) was cooled in an ice bath, place under a nitrogen atmosphere, treated with NBS (32 mmol, 5.7 g). The reaction mixture was stirred 30 min at room temperature. The mixture was diluted with ethyl acetate and the organic layer washed by water, brine, dried over anhydrous sodium sulfate, filtered and concentrated to afford the title compound which was used in the next step without further purification (6 g, Yield :91 %). 1 H NMR (400 MHz, CDCI3) delta 7.03 (1 H, dd, J = 9.6 & 2 Hz), 6.98 (1 H, brs), 2.17 (3H, s) LC-MS: tR = 3.28 [M+H] + = 204/206 (method 3)
7.6 g		3.113. Intermediate 26: 4-Amino-3- uoro-5-methyl-benzonitrile 3.113.1. Step i): 4-Bromo-2-fluoro-6-methyl-phenylamine At room temperature, 2-Fluoro-6-methyl-phenylamine (1.0 eq, 5.0 g) and KOAc (1.0 eq, 3.9 g) are stirred in AcOH for lh.At 0C, BR2 (1.0 eq, 2.04 mL) is added. The reaction mixture is kept at this temperature for 10 min. The resulting mixture is diluted with EtOAc. The organic phase is washed with aq. sat. NaHC03 and aq. Na2S203, dried over anhydrous Na2S04. After concentration under reduced pressure, the residue is purified by silica chromatography (petroleum ether/EtOAc; 9: 1 to 8:2) to give the desired product, (m = 7.6 g).

Reference： [1]Patent: CN105949149,2016,A .Location in patent: Paragraph 0130-0132
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881
[3]Patent: WO2019/213403,2019,A1 .Location in patent: Paragraph 00364
[4]Journal of Medicinal Chemistry,2016,vol. 59,p. 1854 - 1868
[5]Patent: WO2014/72419,2014,A1 .Location in patent: Page/Page column 19
[6]Patent: WO2017/100662,2017,A1 .Location in patent: Page/Page column 107
[7]Patent: WO2017/100668,2017,A1 .Location in patent: Page/Page column 147
[8]Patent: WO2018/103060,2018,A1 .Location in patent: Page/Page column 106
[9]Patent: WO2018/103058,2018,A1 .Location in patent: Page/Page column 147
[10]Patent: WO2013/149996,2013,A1 .Location in patent: Page/Page column 51
[11]Patent: WO2013/149997,2013,A1 .Location in patent: Page/Page column 95
[12]Patent: WO2017/12647,2017,A1 .Location in patent: Paragraph 0648

13
[ 443-89-0 ]
4-amino-3-fluoro-5-methylbenzonitrile [ No CAS ]

Reference： [1]Patent: WO2013/149996,2013,A1
[2]Patent: WO2013/149997,2013,A1
[3]Journal of Medicinal Chemistry,2016,vol. 59,p. 1854 - 1868
[4]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881
[5]Patent: WO2017/12647,2017,A1
[6]Patent: CN105949149,2016,A
[7]Patent: WO2019/213403,2019,A1

14
[ 443-89-0 ]
3-fluoro-4-iodo-5-methylbenzonitrile [ No CAS ]

Reference： [1]Patent: WO2013/149996,2013,A1
[2]Patent: WO2013/149997,2013,A1
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

15
[ 443-89-0 ]
3-fluoro-5-methyl-4-vinylbenzonitrile [ No CAS ]

Reference： [1]Patent: WO2013/149996,2013,A1
[2]Patent: WO2013/149997,2013,A1
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

16
[ 443-89-0 ]
3-fluoro-4-formyl-5-methylbenzonitrile [ No CAS ]

Reference： [1]Patent: WO2013/149996,2013,A1
[2]Patent: WO2013/149997,2013,A1
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

17
[ 443-89-0 ]
3-fluoro-4-formyl-5-methylbenzoic acid [ No CAS ]

Reference： [1]Patent: WO2013/149996,2013,A1
[2]Patent: WO2013/149997,2013,A1
[3]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

18
[ 1595279-99-4 ]
[ 443-89-0 ]
[ 1595280-00-4 ]

Yield	Reaction Conditions	Operation in experiment
30 mg	With N-ethyl-N,N-diisopropylamine; Diphenylphosphinic chloride; In dichloromethane; at 20℃; for 48h;	In a 100 mL round-bottomed flask, (5)-ethyl l-((lS,)-2-((lS,)-2-(ieri- butoxycarbonyl(methyl)amino)propanamido)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3- dihydro-lH-pyrrolo[2,3-b]pyridine-2-carboxylate (188 mg, 363 muiotaetaomicron, Eq: 1.00) was combined with THF (3 mL) and ethanol (1 mL) to give a colorless solution. Aqueous 1 M LiOH (1.1 mL, 1.1 mmol, Eq: 3) was added and the reaction was stirred at rt for 1 h. Aqueous 0.1 M KHSO4(10 mL) was added and the resulting mixture was extracted with EtOAc. The combined organic layers were dried over Na2S04 and concentrated in vacuo to give (5')-l-((5)-2-((5)-2-(tert-butoxycarbonyl(methyl)armno)propanarmdo)-2-(tetrahydro- 2H-pyran-4-yl)acetyl)-2,3-dihydro-lH-pyrrolo[2,3-b]pyridine-2-carboxylic acid (135 mg), m/z = 491 (M+H).

Reference： [1]Patent: WO2014/56871,2014,A1 .Location in patent: Page/Page column 82

19
[ 103515-22-6 ]
[ 443-89-0 ]
N-(2-fluoro-6-methylphenyl)-2,3-(9,10-dihydroanthracene-9,10-diyl)succinimide [ No CAS ]

Reference： [1]European Journal of Organic Chemistry,2014,vol. 2014,p. 4993 - 4998

20
[ 443-89-0 ]
[ 76-05-1 ]
2,2,2-trifluoro-N-(2-hydroxy-6-methylphenyl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
68%	With Oxone; In 1,4-dioxane; at 90℃;Schlenk technique; Inert atmosphere;	General procedure: A Schlenk tube was charged with Oxone (0.398 g, 0.648mmol) and trifloroacetic acid (0.099 mL, 1.296 mmol) in anhydrous dioxane (2 mL) under argon. To this mixture was added 2-fluoroaniline (0.06 g, 0.54 mmol), and the reaction mixture was heated to 90 C under argon until starting material was consumed. As the reaction progressed, the color turned from lightred to dark red. The mixture was then cooled to room temperature and washed with a saturated aqueous sodium bicarbonate.The mixture was extracted with EtOAc (2 × 20 mL) and the combined organic layers were dried over Na2SO4. After filtering andremoval of the solvent under reduced pressure in vacuo, theresidue was purified by silica gel (100-200 mesh) column chromatography(hexane-EtOAc, 9:1), to afford a pale-brown solid(65%) of 2-hydroxy-N-trifluoroacetanilides from 2-fluoroaniline(2a).

Reference： [1]Synlett,2015,vol. 26,p. 1258 - 1262

21
[ 443-89-0 ]
C₃₂H₃₈N₄O₅S [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

22
[ 443-89-0 ]
ethyl 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

23
[ 443-89-0 ]
(S)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

24
[ 443-89-0 ]
(S)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]
(R)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1
[3]Patent: WO2015/92713,2015,A1
[4]Patent: WO2015/92713,2015,A1

25
[ 443-89-0 ]
(S)-ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-methylphenyl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1
[3]Patent: WO2016/202253,2016,A1

26
[ 443-89-0 ]
(S)-ethyl 3-(3-(chloromethyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

27
[ 443-89-0 ]
(S)-ethyl 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

28
[ 443-89-0 ]
3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1

29
[ 443-89-0 ]
ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-(trifluoromethyl)phenyl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1

30
[ 443-89-0 ]
ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1

31
[ 443-89-0 ]
3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

32
[ 443-89-0 ]
[ 3013-27-2 ]

Yield	Reaction Conditions	Operation in experiment
65.9%	With 3-chloro-benzenecarboperoxoic acid; In 1,2-dichloro-ethane; at 20 - 70℃; for 4h;Inert atmosphere;	Fluoro-3-methyl-2-nitrobenzeneTo a solution of <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (8.5 g, 67.9 mmol) in DCE (150 mL), m- CPBA (58.6 g, 272 mmol) was added slowly under nitrogen at RT. The reaction mixture was stirred at 70 C for 4 h. DCM (500 mL) was added. Then it was washed with 1 N NaOH (200 mL x4). The combined organic layers was dried and concentrated under a stream of nitrogen at 50 C to give 1 1.2 g (65.9%) of the title compound.

Reference： [1]Patent: WO2015/92713,2015,A1 .Location in patent: Page/Page column 118

33
[ 443-89-0 ]
[ 160984-53-2 ]

Reference： [1]Patent: WO2015/92713,2015,A1

34
[ 443-89-0 ]
4-bromo-N-ethyl-3-methyl-2-nitroaniline [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2016/202253,2016,A1

35
[ 443-89-0 ]
4-bromo-N1-ethyl-3-methylbenzene-1,2-diamine [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2016/202253,2016,A1

36
[ 443-89-0 ]
5-bromo-1-ethyl-4-methyl-1H-benzo[d][1,2,3]-triazole [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2016/202253,2016,A1

37
[ 443-89-0 ]
(E)-ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)acrylate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2016/202253,2016,A1

38
[ 443-89-0 ]
ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-methylphenyl)propanoate [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1
[3]Patent: WO2016/202253,2016,A1

39
[ 443-89-0 ]
3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

40
[ 443-89-0 ]
3-(3-((5-ethyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

41
[ 443-89-0 ]
3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1
[3]Patent: WO2015/92713,2015,A1
[4]Patent: WO2015/92713,2015,A1

42
[ 443-89-0 ]
3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/92713,2015,A1
[2]Patent: WO2015/92713,2015,A1

43
[ 443-89-0 ]
[ 98-59-9 ]
N-(2-fluoro-6-methylphenyl)-4-methylbenzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With pyridine; at 0 - 25℃; for 8h;Inert atmosphere;	[0414] To a solution of <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (5 g, 40.0 mmol) in pyridine (24.6 mL, 304 mmol), was added tosyl chloride (1 1.43 g, 59.9 mmol) in portions at 0 C under nitrogen. The reaction was stirred at 25 C for 8 hours, then diluted with water (30 mL) and acidified with 1M HC1 solution (pH = 2). The yellow precipitate was collected and washed with CH2CI2 (100 mL x 2) to afford the title compound as yellow solid, which was used directly without further purification. 1H-NMR (400 MHz, CDC13) delta 7.57 (2H, d, J= 8.4 Hz), 7.22 (2H, d, J= 8.4 Hz), 7.08-7.1 1 (1H, m), 6.73 (1H, t, J= 8.8 Hz), 6.06 (1H, s), 2.42 (3H, s), 2.40 (3 H, s).

Reference： [1]Patent: WO2015/95792,2015,A1 .Location in patent: Paragraph 0414

44
[ 443-89-0 ]
(S)-3-(4-((3-chloro-1-ethyl-1H-pyrazol-4-yl)sulfonyl)-5-methyl-6-((((1,1,1-trifluoro-2-methylpropan-2-yl)oxy)carbonyl)amino)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)-2,2-dimethylpropanoic acid [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

45
[ 443-89-0 ]
N-(4-cyano-2-hydroxy-4-methylpentyl)-N-(2-fluoro-6-methylphenyl)-4-methylbenzenesulfonamide [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

46
[ 443-89-0 ]
2,2-dimethyl-3-(5-methyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propanenitrile [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

47
[ 443-89-0 ]
2,2-dimethyl-3-(5-methyl-6-nitro-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)propanenitrile [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

48
[ 443-89-0 ]
3-(6-amino-5-methyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-yl)-2,2-dimethylpropanenitrile [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

49
[ 443-89-0 ]
1,1,1-trifluoro-2-methylpropan-2-yl (2-(2-cyano-2-methylpropyl)-5-methyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

50
[ 443-89-0 ]
(S)-1,1,1-trifluoro-2-methylpropan-2-yl (2-(2-cyano-2-methylpropyl)-5-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

51
[ 443-89-0 ]
(S)-1,1,1-trifluoro-2-methylpropan-2-yl (4-((3-chloro-1-ethyl-1H-pyrazol-4-yl)sulfonyl)-2-(2-cyano-2-methylpropyl)-5-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

52
[ 443-89-0 ]
(S)-1,1,1-trifluoro-2-methylpropan-2-yl (4-((3-chloro-1-ethyl-1H-pyrazol-4-yl)sulfonyl)-2-(2,2-dimethyl-3-oxopropyl)-5-methyl-3,4-dihydro-2-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

53
[ 443-89-0 ]
(S)-1,1,1-trifluoro-2-methylpropan-2-yl (2-(2-cyano-2-methylpropyl)-5-methyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]
(R)-1,1,1-trifluoro-2-methylpropan-2-yl (2-(2-cyano-2-methylpropyl)-5-methyl-4-tosyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)carbamate [ No CAS ]

Reference： [1]Patent: WO2015/95792,2015,A1

54
[ 443-89-0 ]
1,3-bis(2-fluoro-6-methylphenyl)-4,5-dihydro-1H-imidazol-3-ium chloride [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 772 - 775
[2]Patent: WO2017/100585,2017,A1

55
[ 443-89-0 ]
(1,3-bis(2-fluoro-6-methylphenyl)-2-imidazolidinylidene)dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 772 - 775
[2]Patent: WO2017/100585,2017,A1

56
[ 443-89-0 ]
C₂₇H₂₈Cl₂F₂N₂ORu [ No CAS ]

Reference： [1]Organic Letters,2016,vol. 18,p. 772 - 775

57
[ 79-37-8 ]
[ 443-89-0 ]
N1,N2-bis(2-fluoro-6-methylphenyl)oxalamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
35.7%	With triethylamine; sodium hydroxide; In tetrahydrofuran; water; at 0 - 20℃; for 1h;Inert atmosphere;	To a 500 mL round bottom flask equipped with a magnetic stir bar was added 2-methyl-6- fluoroaniline (15.0 mL, 130 mmol), tetrahydrofuran /water (1 : 1, 200 mL), NaOH (5.19 g, 130 mmol), and triethylamine (0.90 mL, 6.5 mmol). The suspension was stirred vigorously at 0 C and oxalyl chloride (6.58 mL, 77.8 mmol) was added dropwise. After complete addition, the reaction was stirred for 1 hour while warming to ambient temperature. The resulting solid was isolated by filtration, washed with 1M HC1 (50 mL), water (3 x 50 mL), and diethyl ether (2 x 50 mL) then dried under vacuum to afford N1,N2-bis(2-fluoro-6-methylphenyl)oxalamide (7.05 g, 35.7% yield).?H NMR (400 MHz, DMSO-de) delta 10.52 (s, 1H), 7.32-7.24 (m, 2H), 7.19-7.11 (m, 4H), 2.24 (s, 6H)

Reference： [1]Organic Letters,2016,vol. 18,p. 772 - 775
[2]Patent: WO2017/100585,2017,A1 .Location in patent: Page/Page column 66
[3]Organic Letters,2017,vol. 19,p. 3033 - 3036

58
[ 443-89-0 ]
[ 1609687-15-1 ]
[ 1609687-25-3 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1854 - 1868

59
[ 443-89-0 ]
[ 1609686-92-1 ]

Reference： [1]Journal of Medicinal Chemistry,2016,vol. 59,p. 1854 - 1868

60
[ 443-89-0 ]
4-chloro-2-fluoro-6-methylaniline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	With N-chloro-succinimide; In N,N-dimethyl-formamide; at 20℃;	4-Chloro-<strong>[443-89-0]2-fluoro-6-methylaniline</strong> To a solution of <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (1 equiv.) in DMF (0.8 M) was added NCS (1.2 equiv.). The reaction was stirred at room temperature. Water and ethyl acetate were added to the solution and the layers were separated. The organic layer was washed with H2O, dried with Na2SO4 and concentrated. The resulting residue was purified by column chromatography on silica gel to give 4-chloro-<strong>[443-89-0]2-fluoro-6-methylaniline</strong> (58%) as a brown oil. 1H NMR (400 MHz, DMSO-d6) delta ppm: 10.33 (dd, J=10.8, 2.0 Hz, 1H), 6.87 (s, 1H), 4.53 (brs. 2H), 2.11 (s, 3H).

Reference： [1]Patent: US2016/96841,2016,A1 .Location in patent: Paragraph 0358

61
[ 443-89-0 ]
5-chloro-1-fluoro-2-isothiocyanato-3-methylbenzene [ No CAS ]

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

62
6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxylic acid [ No CAS ]
[ 443-89-0 ]
N-(2-fluoro-6-methylphenyl)-6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)benzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
23%		Route 1: Amide coupling of the thiophene carboxylic acid (II) with <strong>[443-89-0]2-fluoro-6-methylaniline</strong>. To a solution of 6-(4-(5-methyl-2-(7-oxa-2-azaspiro[3.5]nonan-2-yl)nicotinamido)benzoyl)-5,6- dihydro-4/-/-benzo[0]thieno[2,3-c]azepine-2-carboxylic acid (400 mg, 0.657 mmol) in DCM (40 ml_) was added 1-chloro-A/,A/,2-trimethylprop-1-en-1 -amine (174 muIota_, 1.31 mmol). The reaction was stirred at RT for 1.5 hr and was then concentrated in vacuo. The residue was taken up in DCM (40 ml_) and an aliquot of this solution (5.0 ml_, 0.080 mmol) was added to 2-fluoro-6- methylaniline (100 mg, 0.797 mmol) and the reaction mixture stirred at RT for 3 days. The volatiles were evaporated in vacuo and the resulting residue was purified by preparative HPLC to afford Compound (I), as an off-white solid (14 mg, 23% yield); R' 1.85 min; m/z 716 (M+H)+ (ES+); 1 H NMR delta: 1.62 (4H, br t), 2.17 (3H, s), 2.26 (3H, s), 3.14-3.37 (assume 3H, obscured by solvent), 3.46 (4H, br t), 3.60 (4H, s), 4.90-4.98 (1 H, br), 6.88 (1 H, br d), 7.02 (2H, br d), 7.10-7.16 (3H, over-lapping m), 7.25-7.31 (2H, over-lapping m), 7.48 (1 H, d), 7.52 (2H, br d), 7.82 (1 H, dd), 7.95 (1 H, s), 8.04 (1 H, dd), 10.03 (1 H, s), 10.37 (1 H, s).

Reference： [1]Patent: WO2016/55791,2016,A1 .Location in patent: Page/Page column 21

63
6-(4-nitrobenzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carbonylchloride [ No CAS ]
[ 443-89-0 ]
N-(2-fluoro-6-methylphenyl)-6-(4-nitrobenzoyl)-5,6-dihydro-4H-benzo[b]thieno[2,3-d]azepine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1573 g	With pyridine; In dichloromethane; at 18 - 35.2℃;Inert atmosphere; Large scale;	W-(2-Fluoro-6-methylphenyl)-6-(4-nitrobenzoyl)-5,6-dihydro-4H-benzo[/3]thieno[2,3-cfl azepi ne-2-carboxam ide. A suspension in DCM (15.6 L), of 6-(4-nitrobenzoyl)-5,6-dihydro-4/-/-benzo[ 5]thieno[2,3-c] azepine-2-carboxylic acid (1714 g, 1560 g active material, 3.955 mol) was placed under a nitrogen atmosphere and DMF (6.2 ml_, 79.1 mmol) was added to the mixture. Oxalyl chloride (690 ml_, 7.91 mol) was then added slowly over 40 min in order to control gas evolution (an exotherm from 16.9-18.3C was observed) and the reaction mixture was stirred at 18-25C overnight. TLC analysis (8% methanol in DCM) indicated that some of the thiophene carboxylic acid starting material remained and additional oxalyl chloride (300 ml_, 3.44 mol) was added to the mixture. After stirring at 18-25C for 3 hr the reaction was complete and the resulting mixture was concentrated in vacuo to provide 6-(4-nitrobenzoyl)-5,6-dihydro-4/-/- benzo[6]thieno[2,3-c(]azepine-2-carbonyl chloride as a dark yellow solid (1 H NMR indicated the presence of 15.4% DCM and 0.5% DMF). The crude acid chloride so obtained was suspended in DCM (7.8 L) under a nitrogen atmosphere and was treated with pyridine (480 ml_, 5.93 mol). 2-Fluoro-6-methylaniline (475 ml_, 4.1 1 mol) was then added slowly over 15 min, with cooling from an ice / water bath, (resulting in an exotherm from 20.9-35.2C). The mixture formed a solution and was stirred at 18-25C overnight at which point the reaction was determined to be complete (HPLC 250 nm). The resulting suspension was divided into two equal portions, each of which were diluted with water (7.8 L), stirred for 1 hr at 18-25C and then the solids collected by filtration. The two filter cakes were each washed with water (1.8 L) and with DCM (2 x 1.6 L) and combined. The solid was dried in an oven at 50C to provide the title compound as an off-white solid, (1573 g, 79% active yield, 1 H NMR purity >95%, containing 1.98% DCM and 0.56% of pyridine.HCI); R* 12.76 min; m/z 502.4 (M+H)+ (ES+).

Reference： [1]Patent: WO2016/55791,2016,A1 .Location in patent: Page/Page column 26

64
[ 443-89-0 ]
(1s,4s)-4-(8-(4-chloro-2-fluoro-6-methylphenylamino)-2-(tetrahydro-2H-pyran-4-ylamino)-9H-purin-9-yl)cyclohexanecarboxamide [ No CAS ]

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

65
2-adamantyl-5-isocyano-1H-indole [ No CAS ]
[ 443-89-0 ]
1-(2-adamantyl-1H-indole-5-yl)-3-(2-fluoro-6-methylphenyl)urea [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91.6%	In toluene; at 50℃;	In a dry 25 ml in the reaction bottle, sequentially adding a first 2-adamantyl-5-phenyl -1H-indole, (0.292g, 0 . 01mol), toluene (15 ml), <strong>[443-89-0]2-fluoro-6-methylaniline</strong> (0.125g, 0 . 01mol), the temperature is increased to 50 C reaction 3-4h, TLC detection reaction has been completely, stopping reaction. Cooling, filtering, vacuum 45 C24h obtaining white solid product 1 - (2-adamantyl -1H-Indol-5-yl) - 3 - (2-fluoro-6-methyl-phenyl) urea, number HY-14-07-02-4,0 . 382g, yield 91.6% ; purity : 95.3%.

Reference： [1]Patent: CN105348168,2016,A .Location in patent: Paragraph 0059; 0060; 0061

66
[ 6999-03-7 ]
[ 443-89-0 ]
C₁₆H₂₀FNSi [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76.9%	With tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; for 12h;Reflux;	500mL 4-neckround bottom flask, 1bromo4methylgive silyl benzene (1bromo4trimethylsilylbenzene)12 g (0.052 mole) and6methylaniline7.1 g 2fluoro(0.058 mole) and Pd2 (dba) 31.0 g (0.001 mole) and sodium tbutoxide10.1 g (0.105 mole)and 0.7 g BINAP (0.001 mole) and the mixture, 200 mL of toluene were put into 12 sigan under reflux. To complete the reaction, and the organic layer was separated and the water layer was extracted twice with 100 mL toluene. Formed organiclayer was concentrated under reduced pressure. Intermediate 1d(11 g, 76.9%) was obtained as a column chromatography

Reference： [1]Patent: KR2015/129486,2015,A .Location in patent: Paragraph 0196; 0209-0212

67
[ 6999-03-7 ]
[ 443-89-0 ]
C₅₆H₄₅FN₂Si [ No CAS ]

Reference： [1]Patent: KR2015/129486,2015,A

68
[ 109-49-9 ]
[ 443-89-0 ]
1-(2-fluoro-6-methylphenyl)-2,5-dimethyl-1H-pyrrole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
60%	With palladium(II) trifluoroacetate; oxygen; In toluene; at 100℃;	General procedure: All the reactions were carried out under aerobic atmosphere. To a solution of substrate 5-hexen-2-one 1 (0.6 mmol, 1.2 mmol for the diamines substrates) and amines 2 (0.5 mmol) in toluene (2.0 mL) was added to Pd(OCOCF3)2 (0.05 mmol, 16.5 mg). The mixture with O2 balloon was stirred at 100 C overnight. The substrate was consumed completely monitored by TLC. The mixture was cooled to room temperature, filtered through celite, washed with ethylacetate and concentrated under vacuum. The resulting residue was purified by column chromatography using hexane/ethyl acetate (v/v, 20/1 to 10/1) as the eluent to give the desired product.

Reference： [1]Tetrahedron Letters,2016,vol. 57,p. 5215 - 5218

69
[ 443-89-0 ]
(rac)-4-((3aS,4S,9bR)-8-(difluoromethoxy)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl)-3-fluoro-5-methylbenzoic acid [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

70
[ 443-89-0 ]
(+/-)-4-((3aS,4R,9bR)-8-(difluoromethoxy)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-4-yl)-3-fluoro-5-methylbenzoic acid [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

71
[ 443-89-0 ]
(+/-)-4-((3aS,4R,9bR)-8-(difluoromethoxy)-2,3,3a,4,5,9b-hexahydro-1H-cyclopenta[c]quinolin-4-yl)-3-fluoro-5-methylbenzoic acid [ No CAS ]

Reference： [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,2016,vol. 55B,p. 854 - 881

72
[ 443-89-0 ]
N-(2-fluoro-6-methylphenyl)-2',4'-dimethyl-4,5'-bi-1,3-thiazol-2-amine [ No CAS ]

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 167,p. 312 - 323

73
[ 443-89-0 ]
[ 75-04-7 ]
[ 160984-53-2 ]

Reference： [1]Patent: WO2016/202253,2016,A1 .Location in patent: Page/Page column 262; 263

74
[ 443-89-0 ]
(R)-ethyl 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(hydroxymethyl)-4-methylphenyl)propanoate [ No CAS ]