[ CAS No. 61090-37-7 ] {[proInfo.proName]}

Name: 61090-37-7|2,3-Dihydrobenzofuran-4-amine|97%
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SKU: A183120
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Quality Control of [ 61090-37-7 ]

COA NMR CNMR HPLC LC-MS

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SDS Specification

Alternatived Products of [ 61090-37-7 ]

Product Details of [ 61090-37-7 ]

CAS No. :	61090-37-7	MDL No. :	MFCD06659470
Formula :	C₈H₉NO	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	RWPLKRGISDOAAG-UHFFFAOYSA-N
M.W :	135.16	Pubchem ID :	11701043
Synonyms :

Calculated chemistry of [ 61090-37-7 ]

Physicochemical Properties

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.25
Num. rotatable bonds :	0
Num. H-bond acceptors :	1.0
Num. H-bond donors :	1.0
Molar Refractivity :	40.19
TPSA :	35.25 Å²

Pharmacokinetics

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	No
Log Kp (skin permeation) :	-6.24 cm/s

Lipophilicity

Log Po/w (iLOGP) :	1.55
Log Po/w (XLOGP3) :	1.25
Log Po/w (WLOGP) :	1.21
Log Po/w (MLOGP) :	1.09
Log Po/w (SILICOS-IT) :	1.82
Consensus Log Po/w :	1.38

Druglikeness

Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Water Solubility

Log S (ESOL) :	-1.91
Solubility :	1.66 mg/ml ; 0.0123 mol/l
Class :	Very soluble
Log S (Ali) :	-1.59
Solubility :	3.49 mg/ml ; 0.0258 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.3
Solubility :	0.682 mg/ml ; 0.00505 mol/l
Class :	Soluble

Medicinal Chemistry

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.66

Safety of [ 61090-37-7 ]

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 [ 61090-37-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Upstream synthesis route of [ 61090-37-7 ]
Downstream synthetic route of [ 61090-37-7 ]

[ 61090-37-7 ] Synthesis Path-Upstream 1~6

1
[ 76093-72-6 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
67.7%	With hydrogen bromide In water at 110℃; for 16 h;	Synthesis of 4-amino-2,3-dihydrobenzofuran (1c) The compound 1b (4.10 g, 16.3 mmol) was dissolved in hydrobromic acid (HBr) (48percent aqueous, 20.0 mL, commercial product), and the mixed solution was stirred by heating at 110°C for 16 hours. After the mixed solution was allowed to cool to room temperature, sodium hydroxide granules were gradually added at 0°C so that the pH was adjusted to about 9. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (50 mL * 4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by a medium-pressure column chromatography (Smart Flash EPCLC W-Prep 2XY system) (n-hexane/EtOAc =1/1), and thus 4-amino-2,3-dihydrobenzofuran (compound 1c) (1.49 g, 11.0 mmol, 67.7percent) was obtained as a colorless solid. TLC R_f = 0.30 (n-hexane/EtOAc = 1/1) ¹H NMR (400 MHz, CDCl₃) δ 6.94 (dd, J = 8.4, 8.4 Hz, 1H), 6.28 (dd, J = 0.4, 7.6 Hz, 1H), 6.23 (dd, J = 0.4, 7.6 Hz, 1H), 4.59 (t, J = 8.4 Hz, 2H), 3.60 (brs, 2H), 3.02 (t, J = 8.4 Hz, 2H)
67.6%	With water; hydrogen bromide In neat (no solvent) at 20 - 110℃; for 16 h;	Synthesis of 4-amino-2,3-dihydrobenzofuran (1c) The compound 1b (4.10 g, 16.3 mmol) was dissolved in hydrobromic acid (HBr) (48percent aqueous, 20.0 mL, commercial product), and the mixed solution was stirred by heating at 110° C. for 16 hours. After the mixed solution was allowed to cool to room temperature, sodium hydroxide granules were gradually added at 0° C. so that the pH was adjusted to about 9. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (50 mL*4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by a medium-pressure column chromatography (Smart Flash EPCLC W-Prep 2XY system) (n-hexane/EtOAc=1/1), and thus 4-amino-2,3-dihydrobenzofuran (compound 1c) (1.49 g, 11.0 mmol, 67.6percent) was obtained as a colorless solid. TLC R_f=0.30 (n-hexane/EtOAc=1/1) ¹H NMR (400 MHz, CDCCl₃) δ (6.94 (dd, J=8.4, 8.4 Hz, 1H), 6.28 (dd, J=0.4, 7.6 Hz, 1H), 6.23 (dd, J=0.4, 7.6 Hz, 1H), 4.59 (t, J=8.4 Hz, 2H), 3.60 (brs, 2H), 3.02 (t, J=8.4 Hz, 2H)
40%	Stage #1: With hydrogen bromide In water at 100℃; Stage #2: With sodium hydroxide In water	Synthesis of 2,3-dihydrobenzofuran-4-amine Into a 210 mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (10.5 g, 41.83 mmol, 1.00 equiv). To the mixture was added HBr (48percent) (100 mL). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 100° C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). Adjustment of the pH to 9 was accomplished by the addition of NaOH. The resulting solution was extracted with EtOAc and the organic layers combined. The resulting mixture was washed with H₂O. The mixture was dried over Na₂SO₄ and concentrated by evaporation under vacuum using a rotary evaporator. This resulted in 2.5 g (40percent) of 2,3-dihydrobenzofuran-4-amine as yellow oil.

40%	Stage #1: With hydrogen bromide In water at 100℃; for 16 h; Stage #2: With sodium hydroxide In water	Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 °C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40percent yield as yellow oil.
40%	Stage #1: With hydrogen bromide In water at 100℃; Stage #2: With sodium hydroxide In water	Synthesis of 2,3-dihydrobenzofuran-4-amine Into a 210 mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (10.5 g, 41.83 mmol, 1.00 equiv). To the mixture was added HBr (48percent) (100 mL). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 100° C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). Adjustment of the pH to 9 was accomplished by the addition of NaOH. The resulting solution was extracted with EtOAc and the organic layers combined. The resulting mixture was washed with H₂O. The mixture was dried over Na₂SO₄ and concentrated by evaporation under vacuum using a rotary evaporator This resulted in 2.5 g (40percent) of 2,3-dihydrobenzofuran-4-amine as yellow oil.
40%	Stage #1: at 100℃; for 16 h; Stage #2: With sodium hydroxide In water	4. Synthesis of 2,3-dihydrobenzofuran-4-amine; Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100° C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3.x.100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40percent yield as yellow oil.
40%	Stage #1: With hydrogen bromide In water at 100℃; for 16 h; Stage #2: With sodium hydroxide In water	4. Synthesis of 2,3-dihydrobenzofuran-4-amine.Concentrated hydrobromic acid (100 mL) was added to iV-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 ⁰C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4- amine in 40percent yield as yellow oil.
40%	Stage #1: at 100℃; for 16 h;	Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100° C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3.x.100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40percent yield as yellow oil.
40%	Stage #1: at 100℃; for 16 h;	4. Synthesis of 2,3-dihvdrobenzofuran-4-amine.Concentrated hydrobromic acid (100 mL) was added to 7v~-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 °C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4- amine in 40percent yield as yellow oil.
40%	Stage #1: With hydrogen bromide In water at 100℃; for 16 h; Stage #2: With sodium hydroxide In water	Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100° C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3*100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40percent yield as yellow oil.

Reference： [1] Patent: EP2881397, 2015, A1, . Location in patent: Paragraph 0053; 0058; 0059
[2] Patent: US2016/303089, 2016, A1, . Location in patent: Paragraph 0161; 0168; 0169; 0170; 0171
[3] Patent: US2008/318941, 2008, A1, . Location in patent: Page/Page column 39
[4] Patent: WO2009/23844, 2009, A2, . Location in patent: Page/Page column 127-128
[5] Patent: US2008/200471, 2008, A1, . Location in patent: Page/Page column 60; 61-62
[6] Patent: US2010/16297, 2010, A1, . Location in patent: Page/Page column 35
[7] Patent: WO2010/21797, 2010, A1, . Location in patent: Page/Page column 93
[8] Patent: US2010/29629, 2010, A1, . Location in patent: Page/Page column 61
[9] Patent: WO2010/24980, 2010, A1, . Location in patent: Page/Page column 111
[10] Patent: US2010/22581, 2010, A1, . Location in patent: Page/Page column 45; 46

2
[ 327183-29-9 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
92%	Stage #1: With hydrogen bromide In water; acetic acid at 20℃; for 4 h; Heating / reflux Stage #2: With sodium hydroxide In water; acetic acid	2-(2'-Hydroxyethyl)-3-methoxy-N-tert-butoxycarbonyl-aniline (158 g, 0.59 mol) was added portionwise to a stirred solution of hydrogen bromide in acetic acid (30percent, 1.7 L) at room temperature. The reaction was then heated to reflux for 4 h. The reaction mixture was cooled to room temperature, basified to pH 14 with aqueous sodium hydroxide solution (6 N) and extracted with dichloromethane (3*2 L). The organic extracts were combined, dried (magnesium sulphate) and evaporated to give the title compound as an orange oil (78 g, 92percent); NMR (400 MHz, CDCl₃) δ_H 2.99 (2H, t, J 8.5 Hz), 3.55 (2H, br s), 4.57 (2H, t, J 8.5 Hz), 6.19 (1H, d, J 7.5 Hz), 6.25 (2H, d, J 7.5 Hz), 6.92 (1H, t, J 8.0 Hz); IR ν_max (Nujol)/cm^-1 2853, 2610, 1544, 1462, 1262, 1234, 986 and 761.

Reference： [1] Patent: US2005/187282, 2005, A1, . Location in patent: Page/Page column 9-10
[2] Tetrahedron Letters, 2007, vol. 48, # 17, p. 3039 - 3041

3
[ 801282-09-7 ]
[ 61090-37-7 ]

Reference： [1] Patent: WO2004/103996, 2004, A1, . Location in patent: Page 52

4
[ 69227-65-2 ]
[ 61090-37-7 ]

Reference： [1] Patent: US3963717, 1976, A,

5
[ 536-90-3 ]
[ 61090-37-7 ]

Reference： [1] Patent: EP2881397, 2015, A1,
[2] Patent: US2016/303089, 2016, A1,

6
[ 56619-93-3 ]
[ 61090-37-7 ]

Reference： [1] Patent: EP2881397, 2015, A1,
[2] Patent: US2016/303089, 2016, A1,

[ 61090-37-7 ] Synthesis Path-Downstream 1~56

1
[ 61090-37-7 ]
[ 76093-76-0 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1333 - 1335

2
[ 61090-37-7 ]
2,3-Dihydro-benzofuran-4-diazonium; chloride [ No CAS ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1333 - 1335

3
[ 302-17-0 ]
[ 61090-37-7 ]
<i>N</i>-(2,3-dihydro-benzofuran-4-yl)-2-hydroxyimino-acetamide [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

4
[ 821-48-7 ]
[ 61090-37-7 ]
1-(2,3-dihydroisobenzofuran-4-yl)piperazine hydrochloride [ No CAS ]

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 3039 - 3041

5
[ 327183-29-9 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
92%		2-(2'-Hydroxyethyl)-3-methoxy-N-tert-butoxycarbonyl-aniline (158 g, 0.59 mol) was added portionwise to a stirred solution of hydrogen bromide in acetic acid (30%, 1.7 L) at room temperature. The reaction was then heated to reflux for 4 h. The reaction mixture was cooled to room temperature, basified to pH 14 with aqueous sodium hydroxide solution (6 N) and extracted with dichloromethane (3*2 L). The organic extracts were combined, dried (magnesium sulphate) and evaporated to give the title compound as an orange oil (78 g, 92%); NMR (400 MHz, CDCl3) deltaH 2.99 (2H, t, J 8.5 Hz), 3.55 (2H, br s), 4.57 (2H, t, J 8.5 Hz), 6.19 (1H, d, J 7.5 Hz), 6.25 (2H, d, J 7.5 Hz), 6.92 (1H, t, J 8.0 Hz); IR numax (Nujol)/cm-1 2853, 2610, 1544, 1462, 1262, 1234, 986 and 761.

Reference： [1]Patent: US2005/187282,2005,A1 .Location in patent: Page/Page column 9-10
[2]Tetrahedron Letters,2007,vol. 48,p. 3039 - 3041

6
[ 61090-37-7 ]
[ 170728-95-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

7
[ 61090-37-7 ]
[ 327183-31-3 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

8
[ 61090-37-7 ]
[ 327183-18-6 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

9
[ 61090-37-7 ]
[ 327183-27-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

10
[ 61090-37-7 ]
[ 327183-28-8 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2004,vol. 14,p. 2367 - 2370

11
[ 61090-37-7 ]
[ 76093-75-9 ]

Reference： [1]Journal of Heterocyclic Chemistry,1980,vol. 17,p. 1333 - 1335

12
[ 61090-37-7 ]
[ 762-42-5 ]
C₁₄H₁₅NO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	In methanol; at 18 - 22℃; for 3h;Heating / reflux;	Dimethyl acetylene DICARBOXYLATE A3 (0.16 mL, 1.33 MMOL) was added to solution of aniline H5 (0. 18 g, 1.33 MMOL) in MeOH (3.0 mL) at R. T. The solution was heated at reflux for 3 h., cooled to R. T. and a saturated NAZI solution was added. The mixture was extracted with EtOAc (3x) and the combined organic layers were then dried, filtered and concentrated followed by purification by flash column chromatography (9: 1 to 1 : 1 hex : EtOAc) to afford the desired olefin H6 (0.29 g, 78%).

Reference： [1]Patent: WO2004/103996,2004,A1 .Location in patent: Page 52-53

13
[ 801282-09-7 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; water; In methanol; for 48h;Heating / reflux;	HCI (4.0 mL, 6. 0M) was added to a solution of amide H4 (0.27 g, 1.22 MMOL) in MEOH (4.0 mL) at 23 C. THE reaction was then heated to reflux for 48 h, NaHCO3 (saturated, aq) was added and was extracted with EtOAc. The combined organic layers were dried, filtered and concentrated to obtain the desired aniline H5 which was of sufficient purity to employ in further transformations.

Reference： [1]Patent: WO2004/103996,2004,A1 .Location in patent: Page 52

14
C₁₇H₂₁ClN₄O₃S [ No CAS ]
[ 61090-37-7 ]
C₂₅H₂₉N₅O₄S [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	hydrogenchloride; In ethanol; water; for 3h;Heating / reflux;	To intermediate 31 (0.042g) in ethanol (3ML) was added 2, 3-DIHYDRO-1-BENZOFURAN-4- amine (Journal of Heterocyclic Chemistry (1980), 17 (6), 1333-5,0. 016g) and concentrated hydrochloric acid (0. 1ML), and the mixture was heated under reflux for 3h. The solvent was evaporated to give the crude product (0.070g), which was purified by mass directed HPLC (Method A); 2N hydrochloric acid (0. 5ml) was added to the product fractions, and the solvents evaporated to give the title compound (0. 0041g). LC/MS Rt 1. 89min M/Z 496 [MH+]

Reference： [1]Patent: WO2005/30212,2005,A1 .Location in patent: Page/Page column 51

15
[ 888011-96-9 ]
[ 61090-37-7 ]
[ 888011-97-0 ]

Yield	Reaction Conditions	Operation in experiment
		Intermediate 4 (5.35g) was suspended in acetonitrile (50ml), 2,3-dihydro-1- benzofuran-4-ylamine (J. Het. Chem (1980), 17(6), 1333-5) (3.1g) was added, and the mixture was heated at 850C for 72h. The mixture was filtered and the residue suspended in a mixture of water (100ml) and saturated sodium carbonate solution (30ml). After stirring for 1h, the solid was filtered off and re-suspended in water (100ml) and stirred for 15 minutes. The solid was filtered off and washed with water to give the title compound as a yellow solid (5.88g). LC/MS R, 2.9min m/z 355 [MH+].
	In acetonitrile; at 85℃; for 72h;	Intermediate 5. 6-Chloro-4-(2,3-dihvdro-1-benzofuran-4-ylamino)-8-methyl-1 J- naphthyridine-3-carboxamide.lntermediate 4 (5.35g) was suspended in acetonitrile (50ml), 2,3-dihydro-1-benzofuran-4- ylamine (J. Het. Chem (1980), 17(6), 1333-5) (3.1g) was added, and the mixture was heated at 850C for 72h. The mixture was filtered and the residue suspended in a mixture of water (100ml) and saturated sodium carbonate solution (30ml). After stirring for 1 h, the solid was filtered off and re-suspended in water (100ml). The solid was filtered off and washed with water to give the title compound as a yellow solid (5.88g). LC/MS Rt 2.9min m/z 355 [MH+].

Reference： [1]Patent: WO2006/53784,2006,A2 .Location in patent: Page/Page column 20
[2]Patent: WO2006/97340,2006,A1 .Location in patent: Page/Page column 7, 22

16
[ 75-30-9 ]
[ 61090-37-7 ]
N-isopropyl-2,3-dihydro-4-benzofuranamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In methanol;	STEP A Preparation of N-isopropyl-<strong>[61090-37-7]2,3-dihydro-4-benzofuranamine</strong> To a solution of 19.7 g. of <strong>[61090-37-7]2,3-dihydro-4-benzofuranamine</strong> in 150 ml. of methanol is added 11 ml. of isopropyliodide and 15.5 ml. of triethylamine. The solution is refluxed for 40 hours and then concentrated in vacuo. The resultant oil is extracted and combined, filtered through Celite, and the ether removed in vacuo to give an oil of N-isopropyl-<strong>[61090-37-7]2,3-dihydro-4-benzofuranamine</strong>.

Reference： [1]Patent: US3963717,1976,A

17
[ 69227-65-2 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
	rhodium; In ethanol; hydrogen;	EXAMPLE C 2,3-Dihydro-4-benzofuranamine: A mixture of 3.0 g. of 4-nitrobenzofuran, 0.5 g of 5% Rhodium on carbon and 25 ml. of ethanol is hydrogenated in a Parr apparatus at a hydrogen pressure of 50 p.s.i. and temperature of 35C. until the uptake of hydrogen ceases. The catalyst is removed by filtration and the filtrate evaporated in vacuo to obtain an oil of 2,3-dihydro-4-benzofuranamine.

Reference： [1]Patent: US3963717,1976,A

19
[ 76093-72-6 ]
[ 61090-37-7 ]

Yield	Reaction Conditions	Operation in experiment
67.7%	With hydrogen bromide; In water; at 110℃; for 16h;	Synthesis of 4-amino-2,3-dihydrobenzofuran (1c) The compound 1b (4.10 g, 16.3 mmol) was dissolved in hydrobromic acid (HBr) (48% aqueous, 20.0 mL, commercial product), and the mixed solution was stirred by heating at 110C for 16 hours. After the mixed solution was allowed to cool to room temperature, sodium hydroxide granules were gradually added at 0C so that the pH was adjusted to about 9. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (50 mL * 4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by a medium-pressure column chromatography (Smart Flash EPCLC W-Prep 2XY system) (n-hexane/EtOAc =1/1), and thus 4-amino-2,3-dihydrobenzofuran (compound 1c) (1.49 g, 11.0 mmol, 67.7%) was obtained as a colorless solid. TLC Rf = 0.30 (n-hexane/EtOAc = 1/1) 1H NMR (400 MHz, CDCl3) delta 6.94 (dd, J = 8.4, 8.4 Hz, 1H), 6.28 (dd, J = 0.4, 7.6 Hz, 1H), 6.23 (dd, J = 0.4, 7.6 Hz, 1H), 4.59 (t, J = 8.4 Hz, 2H), 3.60 (brs, 2H), 3.02 (t, J = 8.4 Hz, 2H)
67.6%	With water; hydrogen bromide; In neat (no solvent); at 20 - 110℃; for 16h;	Synthesis of 4-amino-2,3-dihydrobenzofuran (1c) The compound 1b (4.10 g, 16.3 mmol) was dissolved in hydrobromic acid (HBr) (48% aqueous, 20.0 mL, commercial product), and the mixed solution was stirred by heating at 110 C. for 16 hours. After the mixed solution was allowed to cool to room temperature, sodium hydroxide granules were gradually added at 0 C. so that the pH was adjusted to about 9. Subsequently, the mixture was extracted with ethyl acetate (EtOAc) (50 mL*4). The combined organic layer was dried over sodium sulfate and filtered. The filtrate was concentrated under reduced pressure. The residue was purified by a medium-pressure column chromatography (Smart Flash EPCLC W-Prep 2XY system) (n-hexane/EtOAc=1/1), and thus 4-amino-2,3-dihydrobenzofuran (compound 1c) (1.49 g, 11.0 mmol, 67.6%) was obtained as a colorless solid. TLC Rf=0.30 (n-hexane/EtOAc=1/1) 1H NMR (400 MHz, CDCCl3) delta (6.94 (dd, J=8.4, 8.4 Hz, 1H), 6.28 (dd, J=0.4, 7.6 Hz, 1H), 6.23 (dd, J=0.4, 7.6 Hz, 1H), 4.59 (t, J=8.4 Hz, 2H), 3.60 (brs, 2H), 3.02 (t, J=8.4 Hz, 2H)
40%		Synthesis of 2,3-dihydrobenzofuran-4-amine Into a 210 mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (10.5 g, 41.83 mmol, 1.00 equiv). To the mixture was added HBr (48%) (100 mL). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 100 C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). Adjustment of the pH to 9 was accomplished by the addition of NaOH. The resulting solution was extracted with EtOAc and the organic layers combined. The resulting mixture was washed with H2O. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator. This resulted in 2.5 g (40%) of 2,3-dihydrobenzofuran-4-amine as yellow oil.

40%		Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40% yield as yellow oil.
40%		Synthesis of 2,3-dihydrobenzofuran-4-amine Into a 210 mL sealed tube purged and maintained with an inert atmosphere of nitrogen, was placed N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (10.5 g, 41.83 mmol, 1.00 equiv). To the mixture was added HBr (48%) (100 mL). The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 100 C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). Adjustment of the pH to 9 was accomplished by the addition of NaOH. The resulting solution was extracted with EtOAc and the organic layers combined. The resulting mixture was washed with H2O. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator This resulted in 2.5 g (40%) of 2,3-dihydrobenzofuran-4-amine as yellow oil.
40%		4. Synthesis of 2,3-dihydrobenzofuran-4-amine; Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3×100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40% yield as yellow oil.
40%		4. Synthesis of 2,3-dihydrobenzofuran-4-amine.Concentrated hydrobromic acid (100 mL) was added to iV-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 0C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4- amine in 40% yield as yellow oil.
40%		Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3×100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40% yield as yellow oil.
40%		4. Synthesis of 2,3-dihvdrobenzofuran-4-amine.Concentrated hydrobromic acid (100 mL) was added to 7v~-(2-(2-hydroxyethyl)-3- methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 C for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4- amine in 40% yield as yellow oil.
40%		Concentrated hydrobromic acid (100 mL) was added to N-(2-(2-hydroxyethyl)-3-methoxyphenyl)pivalamide (41.8 mmol) and the reaction mixture was heated at 100 C. for 16 h. The pH of the solution was adjusted to 9 with solid sodium hydroxide and the solution was extracted with ethyl acetate (3*100 mL). The combined organic layers were was washed with water (50 mL), dried (sodium sulfate), and concentrated to provide 2,3-dihydrobenzofuran-4-amine in 40% yield as yellow oil.

Reference： [1]Patent: EP2881397,2015,A1 .Location in patent: Paragraph 0053; 0058; 0059
[2]Patent: US2016/303089,2016,A1 .Location in patent: Paragraph 0161; 0168; 0169; 0170; 0171
[3]Patent: US2008/318941,2008,A1 .Location in patent: Page/Page column 39
[4]Patent: WO2009/23844,2009,A2 .Location in patent: Page/Page column 127-128
[5]Patent: US2008/200471,2008,A1 .Location in patent: Page/Page column 60; 61-62
[6]Patent: US2010/16297,2010,A1 .Location in patent: Page/Page column 35
[7]Patent: WO2010/21797,2010,A1 .Location in patent: Page/Page column 93
[8]Patent: US2010/29629,2010,A1 .Location in patent: Page/Page column 61
[9]Patent: WO2010/24980,2010,A1 .Location in patent: Page/Page column 111
[10]Patent: US2010/22581,2010,A1 .Location in patent: Page/Page column 45; 46

20
[ 61090-37-7 ]
[ 1049652-18-7 ]

Yield	Reaction Conditions	Operation in experiment
40%		Synthesis of 2,3-dihydrobenzofuran-4-sulfonyl Chloride Into a 250 mL 3-necked round-bottom flask, was placed a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (2.2 g, 16.30 mmol, 1.00 equiv) in CHCN (200 mL). To the above was added HOAc (9 g) dropwise with stirring, while cooling to a temperature of 0 C. To the above was added HCl (9 g) dropwise with stirring, while cooling to a temperature of 0 C. This was followed by the addition of a solution of NaNO2 (1.52 g, 22.03 mmol, 1.50 equiv) in H2O (2 mL), which was added dropwise with stirring, while cooling to a temperature of 0 C. The mixture was stirred for 30 min and was bubbled SO2 for 2 h, while cooling to a temperature of 0 C. This was followed by the addition of a solution of CuCl2.2H2O (3.4 g, 20.00 mmol, 1.20 equiv) in H2O (3 mL), which was added dropwise with stirring. The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 15 C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). The reaction mixture was then quenched by the adding of H2O/ice. The resulting solution was extracted one time with of EtOAc and the organic layers combined. The resulting mixture was washed with H2O. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluding through a column with a 1:70 EtOAc/PE solvent system. This resulted in 1.42 g (40%) of 2,3-dihydrobenzofuran-4-sulfonyl chloride as a yellow solid. LC-MS (ES, m/z): [M+C5H11N2-Cl+H]+ calcd for C13H19N2O3S 283, found 283 1H NMR (300 MHz, CDCl3, delta) 7.4 (d, 1H) 7.3 (d, 1H), 7.1 (d, 1H), 4.7 (m, 2H), 3.6(m, 2H).
40%		Hydrochloric acid (9.0 g) was added dropwise to a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 C.Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried <n="130"/>(sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, 1H), 7.30 (d, 1H), 7.10 (d, 1H), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) m/z 283 [M+C5H11N2-C1+H]+.
40%		Synthesis of 2,3-dihydrobenzofuran-4-sulfonyl chloride Into a 250 mL 3-necked round-bottom flask, was placed a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (2.2 g, 16.30 mmol, 1.00 equiv) in CHCN (200 mL). To the above was added HOAc (9 g) dropwise with stirring, while cooling to a temperature of 0 C. To the above was added HCl (9 g) dropwise with stirring, while cooling to a temperature of 0 C. This was followed by the addition of a solution of NaNO2 (1.52 g, 22.03 mmol, 1.50 equiv) in H2O (2 mL), which was added dropwise with stirring, while cooling to a temperature of 0 C. The mixture was stirred for 30 min and was bubbled SO2 for 2 h, while cooling to a temperature of 0 C. This was followed by the addition of a solution of CuCl2.2H2O (3.4 g, 20.00 mmol, 1.20 equiv) in H2O (3 mL), which was add stirring. The resulting solution was allowed to react, with stirring, overnight while the temperature was maintained at 15 C. in a bath of oil. The reaction progress was monitored by TLC (EtOAc/PE=1:2). The reaction mixture was then quenched by the adding of H2O/ice. The resulting solution was extracted one time with of EtOAc and the organic layers combined. The resulting mixture was washed with H2O. The mixture was dried over Na2SO4 and concentrated by evaporation under vacuum using a rotary evaporator. The residue was purified by eluding through a column with a 1:70 EtOAc/PE solvent system. This resulted in 1.42 g (40%) of 2,3-dihydrobenzofuran-4-sulfonyl chloride as a yellow solid. LC-MS (ES, m/z): [M+C5H11N2-Cl+H]+ calcd for C13H19N2O3S 283, found 283 1H NMR (300 MHz, CDCl3, delta) 7.4(d, 1H)7.3(d, 1H),7.1(d, 1H),4.7(m,2H),3.6(m,2H).

40%		5. Synthesis of 2,3-dihydrobenzofuran-4-sulfonyl chloride; Hydrochloric acid (9.0 g) was added dropwise to a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 C. Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, 1H), 7.30 (d, 1H), 7.10 (d, 1H), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) m/z 283 [M+C5H11N2-Cl+H]+.
40%		5. Synthesis of 2,3-dihvdrobenzofuran-4-sulfonyl chloride.Hydrochloric acid (9.0 g) was added dropwise to a solution of 2,3-dihydrobenzofuran-4- amine (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 0C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 0C. Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, IH), 7.30 (d, IH), 7.10 (d, IH), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) m/z 283 [M+C5H11N2-C1+H]+.
40%	With hydrogenchloride; copper(II) choride dihydrate; sulfur dioxide; acetic acid; sodium nitrite; In water; acetonitrile;	Hydrochloric acid (9.0 g) was added dropwise to a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 C. Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, 1H), 7.30 (d, 1H), 7.10 (d, 1H), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) ml/283 [M+C5H11N2-Cl+H]+.
40%		5. Synthesis of 2,3-dihydrobenzofuran-4-sulfonyl chloride.Hydrochloric acid (9.0 g) was added dropwise to a solution of 2,3-dihydrobenzofuran-4- amine (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 0C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 0C. Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, IH), 7.30 (d, IH), 7.10 (d, IH), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) m/z 283 [M+C5H11N2-C1+H]+.
40%		Hydrochloric acid (9.0 g) was added dropwise to a solution of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (16.3 mmol) and acetic acid (9.0 g) in acetonitrile (200 mL) at 0 C. A solution of sodium nitrite (22.0 mmol) in water (2 mL) was subsequently added and the mixture was maintained for 30 min at 0 C. Sulfur dioxide gas was passed through the reaction mixture for 2 h whereupon a solution of copper(II) chloride dihydrate (20.0 mmol) in water (3 mL) was added. Sulfur dioxide gas was passed through the reaction mixture for an additional 2 h. The reaction mixture was allowed to warm to rt and was maintained for 16 h. The reaction mixture was diluted with ice water (200 mL) and the resulting mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (200 mL), dried (sodium sulfate), and concentrated. The residue was purified by Flash chromatography (1/70 ethyl acetate/petroleum ether) to provide 2,3-dihydrobenzofuran-4-sulfonyl chloride in 40% yield as a yellow solid. Data: 1H NMR (CDCl3) delta 7.40 (d, 1H), 7.30 (d, 1H), 7.10 (d, 1H), 4.70 (m, 2H), 3.60 (m, 2H). LC/MS (ES) m/z 283 [M+C5H11N2-Cl+H]+.

Reference： [1]Patent: US2008/318941,2008,A1 .Location in patent: Page/Page column 39-40
[2]Patent: WO2009/23844,2009,A2 .Location in patent: Page/Page column 127-129
[3]Patent: US2008/200471,2008,A1 .Location in patent: Page/Page column 60; 62
[4]Patent: US2010/16297,2010,A1 .Location in patent: Page/Page column 35
[5]Patent: WO2010/21797,2010,A1 .Location in patent: Page/Page column 93
[6]Patent: US2010/29629,2010,A1 .Location in patent: Page/Page column 61
[7]Patent: WO2010/24980,2010,A1 .Location in patent: Page/Page column 111; 112
[8]Patent: US2010/22581,2010,A1 .Location in patent: Page/Page column 45; 46

21
[ 801315-20-8 ]
[ 61090-37-7 ]
C₁₉H₁₇N₃O₄S [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2009,vol. 19,p. 1380 - 1385

22
[ 302-17-0 ]
[ 61090-37-7 ]
[ 7757-82-6 ]
C₁₀H₁₀N₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
38%		A mixture of <strong>[61090-37-7]2,3-dihydro-4-benzofuranamine</strong> (72.3 g, 0.54 mol), hydroxylamine hydrochloride (131.3 g, 1.8 mol), conc. hydrochloric acid (45 mL) and water (1265 mL) was stirred at room temperature for 30 min. A solution of chloral hydrate (98.2 g, 0.59 mol) in water (1265 mL) was added followed by solid sodium sulphate (767 g, 5.4 mol) and the reaction was heated to reflux for 1 h. The reaction was cooled to room temperature and the solid was collected by filtration. The solid was suspended in ethyl acetate (250 mL) and water (250 mL) and then extracted with ethyl acetate (3*250 mL). The organic extracts were combined, dried (magnesium sulphate) and concentrated in vacuo to afford the title compound (41 g, 38%) as a pale brown solid; NMR (400 MHz, DMSO-d6) deltaH 3.12 (2H, t, J 9.0 Hz), 4.52 (2H, t, J 8.5 Hz), 6.58 (1H, d, J 8.0 Hz), 7.06 (1H, t, J 8.5 Hz), 7.14 (1H, d, J 8.5 Hz), 7.7 (1H, s), 9.66 (1H, br s), 12.19 (1H, br s); IR numax (Nujol)/cm-1 3389, 3160, 2923, 1661, 1620, 1607, 1540, 1453, 1238, 1060, 1029, 982 and 780.

Reference： [1]Patent: US2005/187282,2005,A1 .Location in patent: Page/Page column 10

23
[ 61090-37-7 ]
N-(5-bromo-2,3-dihydrobenzofuran-4-yl)acetamide [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1
[3]Patent: WO2020/18975,2020,A1

24
[ 61090-37-7 ]
5-bromo-4-thioacetylamino-2,3-dihydrobenzofuran [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

25
[ 61090-37-7 ]
2-methyl-7,8-dihydrobenzofuro[4,5-d]thiazole [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

26
[ 61090-37-7 ]
(Z)-1-[1-ethyl-7,8-dihydrobenzofuro[4,5-d]thiazol-2(1H)-ylidene]propan-2-one [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

27
[ 61090-37-7 ]
1-ethyl-2-methyl-7,8-dihydrobenzofuro[4,5-d]thiazol-1-ium iodide [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

28
[ 536-90-3 ]
[ 61090-37-7 ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

29
[ 56619-93-3 ]
[ 61090-37-7 ]

Reference： [1]Patent: EP2881397,2015,A1
[2]Patent: US2016/303089,2016,A1

30
[ 61090-37-7 ]
C₁₀H₉Br₂NO₂ [ No CAS ]

Reference： [1]Patent: EP2881397,2015,A1

31
[ 108-24-7 ]
[ 61090-37-7 ]
N-(2,3-dihydrobenzofuran-4-yl)acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80.1%	at 20℃; for 16h;	Synthesis of 4-acetylamino-2,3-dihydrobenzofuran (1d) The compound 1c (2.00 g, 14.8 mmol) was dissolved in acetic anhydride (15.0 mL, commercial product), and the mixed solution was stirred at room temperature for 16 hours. After the reaction was completed, the mixture was concentrated under reduced pressure. The resultant brown solid was recrystallized with ethyl acetate (EtOAc), and thus 4-acetylamino-2,3-dihydrobenzofuran (compound 1d) (2.10 g, 11.9 mmol, 80.1%) was obtained as a colorless solid. TLC Rf = 0.15 (n-hexane/EtOAc = 1/1) 1H NMR (400 MHz, CDCl3) delta 7.18 (d, J = 6.4 Hz, 1H), 7.09 (t, J = 6.4 Hz, 1H), 7.04 (brs, 1H), 6.62 (d, J = 6.0 Hz, 1H), 4.59 (t, J = 6.8 Hz, 2H), 3.13 (t, J = 6.8 Hz, 2H), 2.18 (s, 3H)
80.1%	In neat (no solvent); for 16h;	Synthesis of 4-acetylamino-2,3-dihydrobenzofuran (1d) The compound 1c (2.00 g, 14.8 mmol) was dissolved in acetic anhydride (15.0 mL, commercial product), and the mixed solution was stirred at room temperature for 16 hours. After the reaction was completed, the mixture was concentrated under reduced pressure. The resultant brown solid was recrystallized with ethyl acetate (EtOAc), and thus 4-acetylamino-2,3-dihydrobenzofuran (compound 1d) (2.10 g, 11.9 mmol, 80.1%) was obtained as a colorless solid. TLC Rf=0.15 (n-hexane/EtOAc=1/1) 1H NMR (400 MHz, CDCl3) delta 7.18 (d, J=6.4 Hz, 1H), 7.09 (t, J=6.4 Hz, 1H), 7.04 (brs, 1H), 6.62 (d, J=6.0 Hz, 1H), 4.59 (t, J=6.8 Hz, 2H), 3.13 (t, J=6.8 Hz, 2H), 2.18 (s, 3H)
65%	at 20℃; for 16h;	A mixture of <strong>[61090-37-7]2,3-dihydrobenzofuran-4-amine</strong> (4.0 g, 29.6 mmol) in acetic anhydride (40 mL, 59.2 mmol) was stirred at room temperature. After 16 hours, the reaction mixture was concentrated to give A-(2,3-dihydrobenzofuran-4-yl)acetamide (3.4 g, yield: 65%) as a white solid, which was used in the next step without further purification. MS: m/z 178.0 (M+H+).

Reference： [1]Patent: EP2881397,2015,A1 .Location in patent: Paragraph 0053; 0060; 0061
[2]Patent: US2016/303089,2016,A1 .Location in patent: Paragraph 0161; 0172; 0173; 0174; 0175
[3]Patent: WO2020/18975,2020,A1 .Location in patent: Paragraph 0796

32
[ 61090-37-7 ]
N-(5-(7,8-dihydrobenzofuro[4,5-d]thiazol-2-yl)pyridin-3-yl)acetamide [ No CAS ]

Reference： [1]Patent: WO2018/69468,2018,A1

33
[ 61090-37-7 ]
1-(2,3-dihydrobenzofuran-4-yl)thiourea [ No CAS ]

Reference： [1]Patent: WO2018/69468,2018,A1

34
[ 61090-37-7 ]
5-bromo-7,8-dihydrobenzofuro[4,5-d]thiazol-2-amine [ No CAS ]

Reference： [1]Patent: WO2018/69468,2018,A1

35
[ 61090-37-7 ]
5-bromo-7,8-dihydrobenzofuro[4,5-d]thiazole [ No CAS ]

Reference： [1]Patent: WO2018/69468,2018,A1

36
[ 61090-37-7 ]
7,8-dihydrobenzofuro[4,5-d]thiazole [ No CAS ]

Reference： [1]Patent: WO2018/69468,2018,A1

37
[ 61090-37-7 ]
[ 532-55-8 ]
N-((2,3-dihydrobenzofuran-4-yl)carbamothioyl)benzamide [ No CAS ]