Name: 29668-43-7|2,3-Dihydrobenzo[b][1,4]dioxine-5-carbaldehyde|95%
Brand: Ambeed
SKU: A289316
Rating: 93 (28 reviews)

1
[ 2537-48-6 ]
[ 29668-43-7 ]
[ 261633-78-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	Stage #1: diethyl 1-cyanomethylphosphonate With sodium hydride In tetrahydrofuran at 0℃; for 0.166667h; Stage #2: 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde In tetrahydrofuran at -78℃; for 1.5h;

Reference： [1]Charton, Isabelle; Mamai, Ahmed; Bennejean, Caroline; Renard, Pierre; Howell, Edward H.; Guardiola-Lemaitre, B.Eatrice; Delagrange, Philippe; Morgan, Peter J.; Viaud, Marie-Claude; Guillaumet, G.Erald [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 1, p. 105 - 114]

2
[ 624-73-7 ]
[ 24677-78-9 ]
[ 29668-43-7 ]

Yield	Reaction Conditions	Operation in experiment
96%	With caesium carbonate In N,N-dimethyl-formamide at 110℃; for 2h;

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

3
[ 29668-43-7 ]
[ 274910-19-9 ]

Yield	Reaction Conditions	Operation in experiment
89%	With methanol; sodium tetrahydroborate; at 20℃; for 1h;	2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (615 mg, 3.74 mmol) is dissolved in dehydrated methanol (3 mL), sodium borohydride (270 mg, 7.1 mmol) is added thereto little by little, and the mixture is stirred at room temperature for 1 hour. The solvent is removed under reduced pressure, water is added, the mixture is extracted with dichloromethane, and the organic layer is washed with water. The organic layer is dried, the solvent is distilled off under reduced pressure, and pale yellow liquid of 556 mg is obtained in 89% yield.
	With sodium borohydrid; In ethanol; water; ethyl acetate;	(2) 2,3-ethylenedioxybenzyl alcohol 3.15 g of 2,3-ethylenedioxybenzaldehyde was dissolved in 50 ml of ethanol. Then, 1.17 g of sodium borohydride was added thereto, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure and then suspended with an addition of 100 ml of ethyl acetate. The suspension was washed with 100 ml of water and then with 100 ml of saturated sodium chloride aqueous solution. The separated ethyl acetate layer was dried over anhydrous magnesium sulfate. The inorganic salt was removed by filtration, and the filtrate was concentrated under reduced pressure and then purified by silica gel column chromatography (n-hexane/ethyl acetate=2/1) to obtain 1.78 g of the above identified compound as white solid. Rf: 0.2 (n-hexane/ethyl acetate=2/1).

Reference： [1]Patent: US2020/131193,2020,A1 .Location in patent: Paragraph 0223-0224
[2]Tetrahedron Letters,2004,vol. 45,p. 803 - 807
[3]Patent: US5122523,1992,A

4
[ 29668-43-7 ]
C-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-methyleneamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With polyethylene glycol polyamide resin In trimethyl orthoformate	14.1 Step 1. Step 1. Synthesis of C-(2,3-Dihydro-benzo[1,4]dioxin-5-yl)-methyleneamine To a suspension of amine bound on a rink resin (1 eq) in trimethylorthoformate was added 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde (2 eq). This mixture was shaken overnight, filtered and the solid dried.

Reference： [1]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - US2008/45528, 2008, A1 Location in patent: Page/Page column 46

5
[ 29668-43-7 ]
2H,3H-benzo[e]1,4-dioxan-5-ylmethoxymethane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 43 percent / KOH / dimethylsulfoxide / 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

6
[ 29668-43-7 ]
(2H,3H-benzo[e]1,4-dioxan-5-ylmethoxy)methoxymethane [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 87 percent / diisopropylethylamine / 0 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

7
[ 29668-43-7 ]
[ 669051-21-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3: 89 percent / KOH / dimethylsulfoxide / 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

8
[ 29668-43-7 ]
[ 524005-43-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

9
[ 29668-43-7 ]
[ 669051-26-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3: 60 percent / diisopropylethylamine / 0 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

10
[ 29668-43-7 ]
C₁₀H₁₃BO₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 89 percent / KOH / dimethylsulfoxide / 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

11
[ 29668-43-7 ]
C₁₁H₁₅BO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 60 percent / diisopropylethylamine / 0 - 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

12
[ 29668-43-7 ]
[ 669051-30-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3: 89 percent / TEA; 4-dimethylaminopyridine / CH₂Cl₂ / 0 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

13
[ 29668-43-7 ]
2-methoxy-5-[5-(methoxymethyl)(2H,3H-benzo[e]1,4-dioxin-6-yl)]-cyclohepta-2,4,6-trien-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 89 percent / KOH / dimethylsulfoxide / 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C 5.1: 26 mg / tetrabutylammonium bromide; K₂CO₃; Pd(OAc)2 / H₂O / 70 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

14
[ 29668-43-7 ]
5-[5-(hydroxymethyl)(2H,3H-benzo[e]1,4-dioxin-6-yl)]-2-methoxycyclohepta-2,4,6-trien-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 89 percent / TEA; 4-dimethylaminopyridine / CH₂Cl₂ / 0 - 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C 5.1: 72 mg / tetrabutylammonium bromide; K₂CO₃; Pd(OAc)2 / H₂O / 70 °C 6.1: 64 percent / tetrabutylammonium fluoride / tetrahydrofuran / 1 h

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

15
[ 29668-43-7 ]
2-methoxy-5-{5-[(methoxymethoxy)methyl](2H,3H-benzo[e]1,4-dioxin-6-yl)}cyclohepta-2,4,6-trien-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 60 percent / diisopropylethylamine / 0 - 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C 5.1: 18.8 mg / tetrabutylammonium bromide; K₂CO₃; Pd(OAc)2 / H₂O / 70 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

16
[ 29668-43-7 ]
C₁₅H₂₅BO₅Si [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 89 percent / TEA; 4-dimethylaminopyridine / CH₂Cl₂ / 0 - 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

17
[ 29668-43-7 ]
[ 669051-38-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: 88 percent / sodium borohydride; aq.NaOH / methanol / 0 - 20 °C 2.1: 71 percent / N-bromosuccinimide / tetrahydrofuran / 0 - 20 °C 3.1: 89 percent / TEA; 4-dimethylaminopyridine / CH₂Cl₂ / 0 - 20 °C 4.1: n-BuLi / tetrahydrofuran / 0.58 h / -78 °C 4.2: triisopropyl borate / tetrahydrofuran / 18 h / -78 - 20 °C 5.1: 72 mg / tetrabutylammonium bromide; K₂CO₃; Pd(OAc)2 / H₂O / 70 °C

Reference： [1]Deveau, Amy Morin; Macdonald, Timothy L. [Tetrahedron Letters, 2004, vol. 45, # 4, p. 803 - 807]

18
[ 29668-43-7 ]
[ 261633-79-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 °C 1.2: 91 percent / tetrahydrofuran / 1.5 h / -78 °C 2.1: 63 percent / lithium aluminum hydride / diethyl ether / 5 h / Heating

Reference： [1]Charton, Isabelle; Mamai, Ahmed; Bennejean, Caroline; Renard, Pierre; Howell, Edward H.; Guardiola-Lemaitre, B.Eatrice; Delagrange, Philippe; Morgan, Peter J.; Viaud, Marie-Claude; Guillaumet, G.Erald [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 1, p. 105 - 114]

19
[ 29668-43-7 ]
N-[3-(2,3-Dihydro-1,4-benzodioxin-5-yl)propyl]acetamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 °C 1.2: 91 percent / tetrahydrofuran / 1.5 h / -78 °C 2.1: 63 percent / lithium aluminum hydride / diethyl ether / 5 h / Heating 3.1: 77 percent / pyridine / 2 h / 20 °C

Reference： [1]Charton, Isabelle; Mamai, Ahmed; Bennejean, Caroline; Renard, Pierre; Howell, Edward H.; Guardiola-Lemaitre, B.Eatrice; Delagrange, Philippe; Morgan, Peter J.; Viaud, Marie-Claude; Guillaumet, G.Erald [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 1, p. 105 - 114]

20
[ 29668-43-7 ]
N-[3-(2,3-Dihydro-1,4-benzodioxin-5-yl)propyl]butanamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sodium hydride / tetrahydrofuran / 0.17 h / 0 °C 1.2: 91 percent / tetrahydrofuran / 1.5 h / -78 °C 2.1: 63 percent / lithium aluminum hydride / diethyl ether / 5 h / Heating 3.1: 56 percent / triethylamine / CH₂Cl₂ / 0.5 h / 0 °C

Reference： [1]Charton, Isabelle; Mamai, Ahmed; Bennejean, Caroline; Renard, Pierre; Howell, Edward H.; Guardiola-Lemaitre, B.Eatrice; Delagrange, Philippe; Morgan, Peter J.; Viaud, Marie-Claude; Guillaumet, G.Erald [Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 1, p. 105 - 114]

21
[ 141-82-2 ]
[ 29668-43-7 ]
[ 209256-68-8 ]

Yield	Reaction Conditions	Operation in experiment
84.6%	With pyrrolidine In pyridine for 2h; Heating / reflux;	12; 13.i A mixture of 2,3-dihydrobenzodioxin-5-carboxaldehyde (Morishima, et al., Eur. Pat. Appl. 309,766, 5 Apr 89) (9.25 g, 56.4 mmol), malonic acid (11.73 g, 112.8 mmol), pyrrolidine (1 mL), and pyridine (25 mL) was heated to reflux for 2 hr, cooled, and then poured into ice water (300 mL). The white precipitate was filtered, washed with 1N HCl, and air dried (9.83 g, 84.6%).

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - EP1027043, 2004, B1 Location in patent: Page/Page column 22; 23

22
[ 24677-78-9 ]
[ 106-93-4 ]
[ 29668-43-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 16h;
91%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 15h;	285.1 A solution of 2,3-dihydroxybenzaldehyde (10.00 g, 72.40 mmol), 1,2-dibromoethane (18.72 mL, 217.20 mmol) and potassium carbonate (30.0 g, 217.20 mmol) in DMF (200 mL) was stirred at 70°C for 15 hr. The reaction mixture was cooled, water was added thereto, and the mixture was extracted three times with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The precipitate was collected by filtration with cooled hexane to give 2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (10.86 g, 66.2 mmol, 91%) as pale yellow crystals.
91%	With potassium carbonate In N,N-dimethyl-formamide at 70℃;	60.1 Step 1: Dissolve 2,3-dihydroxybenzaldehyde (2.49g, 18mmol) in DMF (100mL),Add 1,2-dibromoethane (13.53g, 72mmol) and potassium carbonate (9.95g, 72mmol), and stir overnight at 70°C. A 1.2N aqueous hydrochloric acid solution (100 mL) was added and extracted three times with ethyl acetate, washed with saturated brine, concentrated, and the residue was separated and purified by silica gel column chromatography (ethyl acetate/petroleum ether = 1/8) to obtain a colorless oil INT -55 (2.69g, yield 91%).

91%	With potassium carbonate In N,N-dimethyl-formamide at 70℃;
70%	With sodium hydroxide; tetrabutylammomium bromide In water for 4h; Heating / reflux;	8 2,3-Dihydroxybenzaldehyde (58 g, 420 mmol) was added to a refluxing mixture of dibromoethane (107.4 g. 570 mmol), sodium hydroxide (35.7 g, 890 mmol) and tetrabutyl ammonium bromide ( 3 g) in water (50 mL). After heating at reflux for 4 h, the mixture was cooled and the organic layer separated, washed with base, dried over sodium sulfate and concentrated in vacuo. The residue was Kugelrohr distilled at 135° to give the product (48 g, 70%) which solidified on standing (mp 61-62°C).
68%	With potassium carbonate In acetone at 30℃; for 14h;	1 Preparation of 2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde (LXVI) To a solution of 2,3-dihydroxybenzaldehyde (LXV) (5 g, 36.2 mmol, 1.0 eq) in acetone (300 mL) was added potassium carbonate (10 g, 72.5 mmol, 2 eq) and 1,2-dibromoethane (6.8 g, 36.2 mmol, 1 eq) in acetone (50 mL) dropwise over 2 h. The mixture was stirred at 30° C. for 12 h. The solid was filtered off, the filtrate was concentrated in vacuo and purified by chromatography on silica gel (PE:EtOAc=10:1) to give 2,3-dihydrobenzo[b][1,4]dioxine-5-carbaldehyde (LXVI) as a colorless oil. (4.02 g, 26.4 mmol, 68%) ESIMS found C9H8O3 z 165.0 (M+H)
64%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h;	4.1.1.28. 2,3-Dihydro-1,4-benzodioxin-5-carbaldehyde To an N,N-dimethylformamide solution (360 ml) of 2,3-dihydroxybenzaldehyde (5.16 g, 37.4 mmol) were added 1,2-dibromoethane (3.86 ml, 44.6 mmol) and potassium carbonate (13.94 g, 100.9 mmol). The resulting mixture was stirred at 70 °C for 3 h. After the reaction mixture was cooled to room temperature, the solid component was filtered out. The filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate-n-hexane = 1:5) to give the title compound (3.90 g, 23.8 mmol, 64%). MS (ESI) m/z 165 (M+H)+. 1H NMR (CDCl3) δ 4.31-4.35 (2H, m), 4.38-4.41 (2H, m), 6.91 (1H, t, J = 7.8 Hz), 7.10 (1H, dd, J = 8.1, 1.7 Hz), 7.38-7.41 (1H, m), 10.37 (1H, s). IR (ATR) cm-1: 2879, 1680, 1597, 1477, 1282, 1248, 1203, 1082, 887, 781, 723.
54%	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h;	18 Synthesis of 2,3-dihydrobenzo[b][1,4]dioxin-5-carbaldehyde 2,3-dihydroxybenzaldehyde (1003 mg, 7.24 mmol) is dissolved in N, N-dimethylformamide (70 mL), potassium carbonate (2701 mg, 19.5 mmol), 1,2-dibromoethane (0.75 mL, 8.7 mmol) is added thereto, and the mixture is stirred at 70° C. for 3 hours. After cooled to room temperature, the mixture is filtered through celite, and the solvent is removed under reduced pressure. The crude product is purified by silica gel column chromatography (hexane:ethyl acetate=5:1) and yellow solid of 644 mg is obtained in 54% yield.
6 g	Stage #1: 2,3-dihydroxybenzaldehyde With potassium carbonate In N,N-dimethyl-formamide at 60 - 70℃; for 1h; Stage #2: ethylene dibromide In N,N-dimethyl-formamide at 80 - 90℃; for 16h;	1 Intermediate-6 Methyl 2-((2-chloro-6-fluorophenyl)amino)-7,8-dihydro- 1H- [l,4]dioxino[2',3':3,4]benzo[ -d]imidazole-5-carboxylate Step 1 :- Preparation of 2, 3-dihydrobenzo[b][l,4]dioxine-5-carbaldehyde A solution of 2,3-dihydroxybenzaldehyde (5.0 g, 36.20 mmol) in DMF (70 mL) was heated to 60-70°C and potassium carbonate (19.87 g, 144 mmol) was added. The reaction mass was further stirred for 1 h at same temperature. Then 1,2- dibromoethane (27.07 g, 144 mmol) was added and the reaction was continued stirring at 80-90°C for 16 h. After completion of reaction, reaction mixture was concentrated under reduced pressure and then diluted with water. Solid obtained was filtered off and dried to afford 6.0 g of desired product. 1H NMR (DMSO- 6): δ 4.32 (dd, 2H), 4.39 (dd, 2H), 6.94 (t, J= 7.8 Hz, 1H), 7.16 (d, J= 7.8 Hz, 1H), 7.26 (d, J = 7.8 Hz, 1H), 10.28 (s, 1H).
	With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 3h;	70 Referential Example 70; 2,3-Dihydro-1,4-benzodioxin-5-carbaldehyde [Show Image] To an N,N-dimethylformamide solution (360 mL) of 2,3-dihydroxybenzaldehyde (5.16 g) were added 1,2-dibromoethane (3.86 mL) and potassium carbonate (13.94 g). The resulting mixture was stirred at 70°C for 3 hours. After the reaction mixture was cooled to room temperature, the solid component was filtered. The filtrate thus obtained was concentrated under reduced pressure. The residue thus obtained was subjected to silica gel column chromatography (hexane:ethyl acetate=5:1) to give the title compound (3.90 g). MS (ESI)m/z:165(M++H). 1H-NMR(CDCl3) δ:4.31-4.35 (2H,m),4.38-4.41(2H,m),6.91(1H,t,J=7.8Hz),7.10(1H,dd,J=8.1,1.7Hz),7.38-7.41(1H,m),10.37(1H,s). IR(ATR)cm- 1:2879,1680,1597,1477,1282,1248,1203,1082,887,781,723.

Reference： [1]Location in patent: scheme or table Grudzien, Krzysztof; Malinska, Maura; Barbasiewicz, Michal [Organometallics, 2012, vol. 31, # 9, p. 3636 - 3646]
[2]Current Patent Assignee: ACTION MEDICAL TECHNOLOGIES - TW2016/2105, 2016, A Location in patent: Paragraph 1198
[3]Current Patent Assignee: CAS CENTER FOR EXCELLENCE IN MOLECULAR CELL SCIENCE; SHANGHAITECH UNIVERSITY; CENTER FOR EXCELLENCE IN MOLECULAR CELL SCIENCE CHINESE ACAD OF SCIENCES - CN113277974, 2021, A Location in patent: Paragraph 0564-0566
[4]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]
[5]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - EP1027043, 2004, B1 Location in patent: Page/Page column 21
[6]Current Patent Assignee: BIOSPLICE THERAPEUTICS INC - US2014/243349, 2014, A1 Location in patent: Paragraph 1748; 1749
[7]Location in patent: experimental part Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]
[8]Current Patent Assignee: KANTO KAGAKU HOLDINGS K.K. - US2020/131193, 2020, A1 Location in patent: Paragraph 0221-0222
[9]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1 Location in patent: Page/Page column 62-63
[10]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1939205, 2008, A1 Location in patent: Page/Page column 207

23
[ 29668-43-7 ]
[ 860653-20-9 ]

Yield	Reaction Conditions	Operation in experiment
24%	Stage #1: N-allyl-4-chloroaniline With boron trichloride In toluene at 90℃; for 4h; Stage #2: 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde With triethylamine In toluene at 0 - 20℃; for 16.5h;

Reference： [1]Current Patent Assignee: BAYER AG - WO2005/68472, 2005, A1 Location in patent: Page/Page column 40-41

24
[ 29668-43-7 ]
[ 880782-74-1 ]

Yield	Reaction Conditions	Operation in experiment
40%	Stage #1: N-trityl-4⁽⁵⁾-iodoimidazole With ethylmagnesium bromide In tetrahydrofuran; dichloromethane at -10℃; for 0.75h; Stage #2: 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde In tetrahydrofuran; dichloromethane at -10℃; for 0.75h; Stage #3: With water; ammonium chloride In tetrahydrofuran; dichloromethane	A.A A solution of 2,3-dihydro-1,4-benzodioxin-5-ylmethanol (Intermediate A1) (commercially available from Aldrich) (3 g, 18.1 mmol) in THF (100 mL) was treated with manganese(IV) oxide, activated (commercially available from Aldrich): MnO2 (10 g, 115 mmol) at rt. The mixture was heated to 35° C. for 2 h and 60° C. for 4 h followed by 18 h at room temperature (rt). The mixture was filtered through celite and the solvent was removed under vacuum. The residue was purified by chromatography on silica gel with 20% EtOAc:hexanes to give 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde (Intermediate A2) 2.6 g (88%). A mixture of 4-iodo-1-tritylimidazole (commercially available) (8.64 g, 19.8 mmol) in dichloromethane (100 mL) at -10° C. was treated with ethyl magnesium bromide (6.3 mL, 19 mmol, 3M in THF) and allowed to react for 45 m. A solution of 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde (Intermediate A2) (2.6 g, 15.9 mmol) in dichloromethane was added via syringe at -10° C. and stirred for 45 m. The mixture was quenched with water (50 mL) and a sat. solution of ammonium chloride (50 mL). The residue was isolated in a typical aqueous workup and purified by chromatography on silica gel with 3 to 5% NH3-MeOH:CH2Cl2 to give (2,3-dihydro-benzo[1,4]dioxin-5-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate A3) as a solid, 2.9 g (40%). A solution of (2,3-dihydro-benzo[1,4]dioxin-5-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate A3) (1 g, 2.11 mmol) in dichloromethane (30 mL) was reacted with TFA:trifluoroacetic acid (5.3 mL, 68 mmol)) and triethylsilane (TES) (2.8 mL, 17 mmol) at rt for 24 h. The mixture was evaporated under reduced pressure and quenched with solid NaHCO3. This material was subjected to an aqueous work-up and the residue was purified by chromatography on silica gel with 5% NH3-MeOH:CH2Cl2 to yield 5-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1H-imidazole (Intermediate A4) 330 mg (72%). A mixture of 5-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1H-imidazole (Intermediate A4) (260 mg, 1.2 mmol) in THF (10 mL) and water (10 mL) was treated with NaHCO3 (1 g, 12 mmol) and phenylchlorothionoformate (0.42 mL, 3.13 mmol) for 3 h at rt. The mixture was diluted with diethyl ether (35 mL) and water (10 mL). The aqueous layer was removed and extracted with ether (2×10 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under vacuum. The residue was treated with triethylamine (1 mL) in methanol (9 mL) at rt for 16 h. The solvent was removed and the product was isolated and purified either by tituration with CH2Cl2:hexane or by chromatography on SiO2 with EtOAc or 3% MeOH:CH2Cl2. This gave 4-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1,3-dihydro-imidazole-2-thione (Compound-1) 150 mg (50%). 1H NMR (300 MHz, DMSO-d6 w/TMS): δ 11.9 (brs, 1H), 11.7 (s, 1H), 6.76-6.65 (m, 3H), 6.41 (s, 1H), 4.28-4.21 (m, 4H), 3.61 (s, 2H).

Reference： [1]Current Patent Assignee: ABBVIE INC - US2006/69144, 2006, A1 Location in patent: Page/Page column 19-20

25
[ 274910-19-9 ]
[ 29668-43-7 ]

Yield	Reaction Conditions	Operation in experiment
88%	With manganese(IV) oxide; In tetrahydrofuran; at 20 - 60℃; for 24h;	A solution of <strong>[274910-19-9]2,3-dihydro-1,4-benzodioxin-5-ylmethanol</strong> (Intermediate A1) (commercially available from Aldrich) (3 g, 18.1 mmol) in THF (100 mL) was treated with manganese(IV) oxide, activated (commercially available from Aldrich): MnO2 (10 g, 115 mmol) at rt. The mixture was heated to 35 C. for 2 h and 60 C. for 4 h followed by 18 h at room temperature (rt). The mixture was filtered through celite and the solvent was removed under vacuum. The residue was purified by chromatography on silica gel with 20% EtOAc:hexanes to give 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde (Intermediate A2) 2.6 g (88%). A mixture of 4-iodo-1-tritylimidazole (commercially available) (8.64 g, 19.8 mmol) in dichloromethane (100 mL) at -10 C. was treated with ethyl magnesium bromide (6.3 mL, 19 mmol, 3M in THF) and allowed to react for 45 m. A solution of 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde (Intermediate A2) (2.6 g, 15.9 mmol) in dichloromethane was added via syringe at -10 C. and stirred for 45 m. The mixture was quenched with water (50 mL) and a sat. solution of ammonium chloride (50 mL). The residue was isolated in a typical aqueous workup and purified by chromatography on silica gel with 3 to 5% NH3-MeOH:CH2Cl2 to give (2,3-dihydro-benzo[1,4]dioxin-5-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate A3) as a solid, 2.9 g (40%). A solution of (2,3-dihydro-benzo[1,4]dioxin-5-yl)-(1-trityl-1H-imidazol-4-yl)-methanol (Intermediate A3) (1 g, 2.11 mmol) in dichloromethane (30 mL) was reacted with TFA:trifluoroacetic acid (5.3 mL, 68 mmol)) and triethylsilane (TES) (2.8 mL, 17 mmol) at rt for 24 h. The mixture was evaporated under reduced pressure and quenched with solid NaHCO3. This material was subjected to an aqueous work-up and the residue was purified by chromatography on silica gel with 5% NH3-MeOH:CH2Cl2 to yield 5-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1H-imidazole (Intermediate A4) 330 mg (72%). A mixture of 5-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1H-imidazole (Intermediate A4) (260 mg, 1.2 mmol) in THF (10 mL) and water (10 mL) was treated with NaHCO3 (1 g, 12 mmol) and phenylchlorothionoformate (0.42 mL, 3.13 mmol) for 3 h at rt. The mixture was diluted with diethyl ether (35 mL) and water (10 mL). The aqueous layer was removed and extracted with ether (2×10 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated under vacuum. The residue was treated with triethylamine (1 mL) in methanol (9 mL) at rt for 16 h. The solvent was removed and the product was isolated and purified either by tituration with CH2Cl2:hexane or by chromatography on SiO2 with EtOAc or 3% MeOH:CH2Cl2. This gave 4-(2,3-dihydro-benzo[1,4]dioxin-5-ylmethyl)-1,3-dihydro-imidazole-2-thione (Compound-1) 150 mg (50%). 1H NMR (300 MHz, DMSO-d6 w/TMS): delta 11.9 (brs, 1H), 11.7 (s, 1H), 6.76-6.65 (m, 3H), 6.41 (s, 1H), 4.28-4.21 (m, 4H), 3.61 (s, 2H).
84%	With manganese(IV) oxide; In dichloromethane; at 20℃; for 2h;	2,3-Dihydro-1,4-benzodioxin-5-ylinethanol (1.01 g, 6.07 mmol) was dissolved in methylene chloride (60 mL). Manganese dioxide (3.81 g, 43.8 mmol) was added, and then the mixture was stirred in a nitrogen atmosphere at room temperature for 24 hours. Manganese dioxide was separated by filtration and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: ethyl acetate/hexane = 1/4) to give the target compound (835 mg, yield: 84%) as a colorless oil. 1H-NMR (CDCl3, 400MHz):delta ppm: 4.32-4.34 (2H, m), 4.38-4.41 (2H, m), 6.91 (1H, t, J=7.8Hz), 7.10 (1H, dd, J=1.6, 7.8Hz), 7.40 (1H, dd, J=1.6, 7.8Hz). MS (EI) m/z: 164.0468 (M+)

Reference： [1]Patent: US2006/69144,2006,A1 .Location in patent: Page/Page column 19-20
[2]Patent: EP1914229,2008,A1 .Location in patent: Page/Page column 89

26
[ 144261-18-7 ]
[ 29668-43-7 ]
[ 201221-22-9 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydroxide; boron trichloride; triethylamine In ethyl acetate; benzene	1.B (5-Chloro-2-neopentylamino-phenyl)-(2,3-ethylenedioxyphenyl)-methanol EXAMPLE 1B (5-Chloro-2-neopentylamino-phenyl)-(2,3-ethylenedioxyphenyl)-methanol A solution of (4-chloro-phenyl)-(neopentyl)-amine (2.24 g, 11.3 mmol) in benzene (6 mL) was added to a solution of boron trichloride (1.0 M in xylenes; 12.5 mL, 12.5 mmol) in benzene (13 mL) at 0° C. under a nitrogen atmosphere. Once the addition was complete, the resulting mixture was heated at reflux for 3 hours, under a steady stream of nitrogen exiting into an aqueous 5N sodium hydroxide trap, and then recooled to 0° C. A solution of 2,3-ethylenedioxybenzaldehyde (1.86 g, 11.3 mmol), triethylamine (2.29 g, 22.7 mmol, 3.2 mL) and benzene (6 mL) was then added and the resulting mixture stirred 3.5 hours before quenching with aqueous 1N hydrochloric acid. After 1 hour, ethyl acetate was added and the resulting mixture was shaken vigorously. The aqueous layer was alkalized with aqueous 5N sodium hydroxide and the layers separated. The aqueous layer was extracted with ethyl acetate (2*). The organic layers were combined, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and purified by flash column chromatography (4:1 hexanes/ethyl acetate) to produce 3.62 g (88%) of the title compound as an off-white foam. 1H NMR (400 MHz, CDCl3) δ 7.11 (dd, 1H), 6.93 (d, 1H), 6.85 (m, 2H), 6.73 (m, 1H), 6.58 (d, 1H), 5.94 (d, 1H), 4.83 (br s, 1H), 4.30 (m, 4H), 3.03 (d, 1H), 2.84 (d, 2H), 0.94 (s, 9H).

Reference： [1]Current Patent Assignee: PFIZER INC - US6537987, 2003, B1

27
[ 110-89-4 ]
[ 141-97-9 ]
[ 29668-43-7 ]
ethyl α-acetyl-β-(2,3-ethylenedioxyphenyl)-acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; sodium hydrogencarbonate In acetic acid; benzene	b Preparation of 1,4-dihydro-2,6-dimethyl-4-(2',3'-ethylenedioxyphenyl)-3,5-pyridinedicarboxylic acid, methyl ethyl ester (IQB-838-V). (b) Preparation of ethyl α-acetyl-β-(2,3-ethylenedioxyphenyl)-acrylate. In a round-bottom flask connected to a Dean-Stark separator containing dried benzene were poured 4.5 g. of 2,3-ethylenedioxybenzaldehyde, 3.5 g. of ethyl acetoacetate and 10 ml. of benzene. The mixture was gently heated until complete dissolution and 0.12 ml. of piperidine and 0.4 ml. of glacial acetic acid were subsequently added. The resulting solution was refluxed for 2 hours until reaction was completed. After cooling, the mixture was diluted with benzene and washed with 3*25 ml. of 5% HCl, 5% sodium bicarbonate and water. The organic layer was decanted, dried over anhydrous magnesium sulfate and the solvent was evaporated under vacuum yielding a viscous oil which solidified slowly on standing and which was recrystallized from ethanol. Yield, 6.5 g. (85%).

Reference： [1]Current Patent Assignee: SANOFI - US4722931, 1988, A

28
[ 24677-78-9 ]
[ 29668-43-7 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium fluoride In <i>N</i>-methyl-acetamide; water; ethylene dibromide	a Preparation of 1,4-dihydro-2,6-dimethyl-4-(2',3'-ethylenedioxyphenyl)-3,5-pyridinedicarboxylic acid, methyl ethyl ester (IQB-838-V). (a) Preparation of 2,3-ethylenedioxybenzaldehyde. 5.52 g (0.04 mol) of 2,3-dihydroxybenzaldehyde were dissolved in 75 ml. of dimethylformamide giving a black solution to which was added 11.6 g. of potassium fluoride. The mixture was cooled in an ice bath and 7.5 g. of 1,2-dibromoethane were added slowly with vigorous stirring. The mixture was subsequently heated for 2 hours at 110°-120° C. giving a black solution. After cooling, this solution was filtered through a glass filter. The remaining inorganic solid in the filter was washed with chloroform to remove any organic product. The filtrates were diluted with 100 ml. of water and were extracted with chloroform. The organic layer was then decanted, washed with 1N sodium hydroxide and water, dried over anhydrous magnesium sulfate and evaporated under vacuum to yield a viscous oil which was used without any further purification for the next step. Yield, 4.5 g. (70%).

Reference： [1]Current Patent Assignee: SANOFI - US4722931, 1988, A

29
[ 18437-66-6 ]
[ 29668-43-7 ]
[ 937058-10-1 ]

Yield	Reaction Conditions	Operation in experiment
49%	Stage #1: N-(t-butoxycarbonyl)-4-chloroaniline With sec.-butyllithium In tetrahydrofuran at -78℃; Cooling with ice; Stage #2: 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde In tetrahydrofuran at 20℃; Cooling with ice; Stage #3: With water; ammonium chloride In tetrahydrofuran at 20℃;	4.1.1.29. tert-Butyl 4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]phenylcarbamate (21) sec-Butyl lithium (0.99 mol/l, 44.3 ml, 43.8 mmol) was added dropwise to a tetrahydrofuran solution (140 ml) of tert-butyl 4-chlorophenylcarbamate (20, 4.16 g, 18.3 mmol) at -78 °C. While warming to -20 °C, the reaction mixture was stirred for 1.5 h. Under ice-cooling, the mixture was stirred for a further 0.5 h, cooled to -78 °C again, and 2,3-dihydro-1,4-benzodioxin-5-carbaldehyde (3.90 g, 23.8 mmol) was added thereto. The reaction mixture was stirred for 2 h while warming to room temperature. Then, satd NH4Cl aq was added to the reaction mixture and the layers were separated. The organic layer was dried over Na2SO4, and then concentrated in vacuo. The residue was purified by silica gel column chromatography (ethyl acetate-n-hexane = 1:9) to give the title compound 21 (3.54 g, 9.0 mmol, 49%). MS (ESI) m/z 318 (M-tBuO)+. 1H NMR (CDCl3) δ 1.50 (9H, s), 3.14 (1H, d, J = 4.9 Hz), 4.22-4.37 (4H, m), 6.04 (1H, d, J = 5.4 Hz), 6.77-6.82 (1H, m), 6.85-6.89 (2H, m), 7.08 (1H, d, J = 2.5 Hz), 7.23 (1H, dd, J = 8.8, 2.5 Hz), 7.91 (2H, d, J = 8.3 Hz), 7.95 (1H, br s).
	Stage #1: N-(t-butoxycarbonyl)-4-chloroaniline With sec.-butyllithium In tetrahydrofuran at -78 - 0℃; for 2h; Stage #2: 2,3-dihydro-benzo[1,4]dioxine-5-carbaldehyde In tetrahydrofuran at -78 - 20℃; for 2h;	71 Referential Example 71; tert-Butyl 4-chloro-2-[2,3-dihydro-1,4-benzodioxin-5-yl(hydroxy)methyl]phenylcarbamate [Show Image] sec-Butyl lithium (0.99 mol/l, 44.3 mL) was added dropwise to a tetrahydrofuran solution (140 mL) of tert-butyl 4-chlorophenylcarbamate (4.16 g) at -78°C. While warming to 0°C, the reaction mixture was stirred for 1.5 hours. Under ice cooling, the mixture was stirred for further 0.5 hour. The reaction mixture was cooled to -78°C again and 2,3-dihydro-1,4-benzodioxin-5-carbaldehyde (3.90 g) was added thereto. The reaction mixture was mildly stirred for 2 hours while warming to room temperature. A saturated aqueous solution of ammonium chloride was then added. A separating operation was performed and the water phase was washed with ethyl acetate. The organic layers were combined and dried over anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give the title compound (3.54 g). MS (ESI)m/z:318 (M+-tBuO). 1H-NMR(CDCl3)δ:1.50(9H,s),3.14(1H,d,J=4.9Hz),4.22-4.37(4H,m),6.04(1H,d,J=5.4Hz),6.77-6.82(1H,m),6.85-6.89(2H,m),7.08(1H,d,J=2.5Hz),7.23(1H,dd,J=8.8,2.5Hz),7.91( 2H,d,J=8.3Hz),7.95(1H,br s).

Reference： [1]Location in patent: experimental part Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]
[2]Current Patent Assignee: DAIICHI SANKYO COMPANY, LIMITED - EP1939205, 2008, A1 Location in patent: Page/Page column 207-208

30
[ 65854-91-3 ]
[ 29668-43-7 ]
[ 1292850-59-9 ]

Yield	Reaction Conditions	Operation in experiment
77%		General procedure: N-Pivaloyl-4-chloroaniline (33, 595 mg, 2.81 mmol) was dissolved in THF (50 ml), and the solution was added sec-butyl lithium c-hexane, n-hexane solution (0.99 M, 5.96 ml, 6.18 mmol) at -78 C, and then stirred at 0 C for 2 h. The mixture was added 2-chloro-3-fluoro-benzaldehyde (490 mg, 3.09 mmol) at the same temperature for 30 min. The reaction mixture was poured saturated with NH4Claq and AcOEt. The organic layer was washed with brine and dried over Na2SO4. The solvent was removed under reduced pressure, and the residue was purified by column chromatography (n-hexane/AcOEt = 9:1) to give the title compound (676 mg, 65%) as light yellow oil.

Reference： [1]Bioorganic and Medicinal Chemistry,2011,vol. 19,p. 1930 - 1949

31
[ 75-52-5 ]
[ 29668-43-7 ]
[ 1176414-01-9 ]

Yield	Reaction Conditions	Operation in experiment
93%	With ammonium acetate at 60℃; for 0.75h; Ultrasound irradiation;	General procedure: (b) Ultrasound: a mixture of aryl aldehyde (1 mmol) and nitromethane (3 mL) was introduced into a glass microwave tube; a catalytic amount of ammonium acetate (0.2 mmol) was added and the tube was placed inside an ultrasound apparatus (Ultrasounds Medi II, Selecta, Spain) preheated at 60 °C. It was exposed for 45 min at 100 W and 18 kHz. The reaction mixture was then cooled and the nitromethane was evaporated on a Büchi microdistillation apparatus. The compounds obtained after isolation and purification showed analytical data in accordance with the assigned structures.

Reference： [1]Location in patent: experimental part Rodríguez, Jose M.; Dolors Pujol [Tetrahedron Letters, 2011, vol. 52, # 21, p. 2629 - 2632]

32
[ 29668-43-7 ]
[ 937058-11-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

33
[ 29668-43-7 ]
[ 937058-12-3 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

34
[ 29668-43-7 ]
[5-chloro-2-(1H-pyrrol-1-yl)phenyl](2,3-dihydro-1,4-benzodioxin-5-yl)methanone [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

35
[ 29668-43-7 ]
[ 937056-02-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux 5.1: trichlorophosphate / 20 °C / Cooling with ice 5.2: 3 h / 50 °C

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

36
[ 29668-43-7 ]
[ 937058-14-5 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux 5.1: trichlorophosphate / 20 °C / Cooling with ice 5.2: 3 h / 50 °C 6.1: toluene / Heating

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

37
[ 29668-43-7 ]
[ 937058-15-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux 5.1: trichlorophosphate / 20 °C / Cooling with ice 5.2: 3 h / 50 °C 6.1: toluene / Heating 7.1: sodium tetrahydroborate / methanol / 1 h / 20 °C

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

38
[ 29668-43-7 ]
[ 937056-03-6 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux 5.1: trichlorophosphate / 20 °C / Cooling with ice 5.2: 3 h / 50 °C 6.1: toluene / Heating 7.1: sodium tetrahydroborate / methanol / 1 h / 20 °C 8.1: trifluoroacetic acid / dichloromethane / 8 h / 20 °C

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

39
[ 29668-43-7 ]
[ 937056-04-7 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: sec.-butyllithium / tetrahydrofuran / -78 °C / Cooling with ice 1.2: 20 °C / Cooling with ice 1.3: 20 °C 2.1: manganese(IV) oxide / dichloromethane / 50 °C 3.1: trifluoroacetic acid 4.1: acetic acid / 1 h / Reflux 5.1: trichlorophosphate / 20 °C / Cooling with ice 5.2: 3 h / 50 °C 6.1: toluene / Heating 7.1: sodium tetrahydroborate / methanol / 1 h / 20 °C 8.1: trifluoroacetic acid / dichloromethane / 8 h / 20 °C 9.1: palladium 10% on activated carbon; hydrogen / water; ethyl acetate / 29 h

Reference： [1]Ichikawa, Masanori; Ohtsuka, Masami; Ohki, Hitoshi; Haginoya, Noriyasu; Itoh, Masao; Sugita, Kazuyuki; Usui, Hiroyuki; Suzuki, Makoto; Terayama, Koji; Kanda, Akira [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 9, p. 3072 - 3093]

40
[ 1530-32-1 ]
[ 29668-43-7 ]
CH₃CHCHC₆H₃OC₂H₄O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With potassium 2-methylbutan-2-olate In tetrahydrofuran; toluene

Reference： [1]Location in patent: scheme or table Grudzien, Krzysztof; Malinska, Maura; Barbasiewicz, Michal [Organometallics, 2012, vol. 31, # 9, p. 3636 - 3646]

41
[ 2688-84-8 ]
[ 29668-43-7 ]
[ 1312470-11-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium tetrahydroborate In methanol

Reference： [1]Wadsworth, Harry; Jones, Paul A.; Chau, Wai-Fung; Durrant, Clare; Morisson-Iveson, Veronique; Passmore, Joanna; O'Shea, Dennis; Wynn, Duncan; Khan, Imtiaz; Black, Andrew; Avory, Michelle; Trigg, William [Bioorganic and medicinal chemistry letters, 2012, vol. 22, # 18, p. 5795 - 5800,6]

42
[ 29668-43-7 ]
methyl 8-(ethylamino)-7-nitro-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 0 - 10 °C 7.2: 18 h / 22 - 26 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

43
[ 29668-43-7 ]
2-((2-chloro-6-fluorophenyl)amino)-N-(3-(trifluoromethyl)phenyl)-7,8-dihydro-1H-[1,4]dioxino[2',3':3,4]benzo[1,2-d]imidazole-5-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C 7.1: iron; hydrogenchloride / methanol / 2 h / 22 - 26 °C 8.1: acetonitrile / 22 - 26 °C 8.2: 18 h / 70 - 80 °C 9.1: trimethylaluminum / toluene / 18 h / 22 - 26 °C / Inert atmosphere

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

44
[ 29668-43-7 ]
[ 4442-53-9 ]

Yield	Reaction Conditions	Operation in experiment
0.332 g		A solution of 2,3-dihydrobenzo[b][l,4]dioxine-5-carbaldehyde (0.500 g, 3.04 mmol) in acetone (10 mL) was stirred at 0-5°C and aqueous solution of sulphamic acid (0.455 g, 4.5 mmol) was added. The reaction mass was stirred for 20 min. Then aqueous solution of sodium chlorite (0.421 g, 4.5 mmol) was added and the reaction was further continued at RT for 18 h. After completion of reaction, reaction mixture was concentrated under reduced pressure and reaction mass was quenched with water. Solid obtained was filtered off and vacuum dried to afford 0.332 g of desired product. 1H NMR (DMSO-de): delta 4.27 (s, 4H), 6.84 (t, J = 7.2 Hz, 1H), 7.02 (d, J = 7.8 Hz, 1H), 7.20 (d, J= 7.5 Hz, 1H), 12.5 (bs, 1H); MS [M+H]+: 181.12.

Reference： [1]Patent: WO2013/153535,2013,A1 .Location in patent: Page/Page column 63

45
[ 29668-43-7 ]
2,3-dihydro-benzo[1,4]dioxine-5-carboxylic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

46
[ 29668-43-7 ]
methyl 6,7-dibromo-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

47
[ 29668-43-7 ]
methyl 6,7-dibromo-8-nitro-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

48
[ 29668-43-7 ]
[ 158504-37-1 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

49
[ 29668-43-7 ]
[ 158504-38-2 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

50
[ 29668-43-7 ]
methyl 7,8-diamino-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C 7.1: iron; hydrogenchloride / methanol / 2 h / 22 - 26 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

51
[ 29668-43-7 ]
methyl 2-((2-chloro-6-fluorophenyl)amino)-7,8-dihydro-1H-[1,4]dioxino [2',3':3,4]benzo[1,2-d]imidazole-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C 7.1: iron; hydrogenchloride / methanol / 2 h / 22 - 26 °C 8.1: acetonitrile / 22 - 26 °C 8.2: 18 h / 70 - 80 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

52
[ 29668-43-7 ]
methyl 8-(methylamino)-7-nitro-2,3-dihydrobenzo[b][1,4]dioxine-5-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: aminosulfonic acid / water; acetone / 0.33 h / 0 - 5 °C 1.2: 18 h / 22 - 26 °C 2.1: potassium carbonate / N,N-dimethyl-formamide / 1 h / 60 - 70 °C 2.2: 16 h / 80 - 90 °C 3.1: acetic anhydride; bromine / 18 h / 60 - 70 °C 4.1: nitric acid / 0.5 h / -55 - -50 °C 5.1: triethylamine; palladium on activated charcoal; hydrogen / methanol / 5 h / 3102.97 Torr 6.1: trifluoroacetic acid; potassium nitrate / 3 h / 22 - 26 °C 7.1: sodium hydride / N,N-dimethyl-formamide / 0 - 10 °C 7.2: 18 h / 22 - 26 °C

Reference： [1]Current Patent Assignee: GLENMARK PHARMACEUTICALS LTD - WO2013/153535, 2013, A1

53
[ 29668-43-7 ]
4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 0.5 h / 20 °C 2: sodium hydroxide / ethanol / 5 h / 80 °C

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

54
[ 29668-43-7 ]
5-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-1-(4-(methylsulfonyl)phenyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 0.5 h / 20 °C 2: sodium hydroxide / ethanol / 5 h / 80 °C

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

55
[ 29668-43-7 ]
5-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-1-(phenylsulfonyl)-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 0.5 h / 20 °C 2: hydrazine / ethanol / 5 h / 80 °C 3: dichloromethane / 4 h / 20 °C

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

56
[ 29668-43-7 ]
5-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-1-tosyl-3-(trifluoromethyl)-4,5-dihydro-1H-pyrazole [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: sodium hydroxide / ethanol / 0.5 h / 20 °C 2: hydrazine / ethanol / 5 h / 80 °C 3: dichloromethane / 4 h / 20 °C

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

57
[ 29668-43-7 ]
C₁₂H₁₁F₃N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: sodium hydroxide / ethanol / 0.5 h / 20 °C 2: hydrazine / ethanol / 5 h / 80 °C

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

58
[ 421-50-1 ]
[ 29668-43-7 ]
C₁₂H₉F₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol at 20℃; for 0.5h;	4.2. General method of synthesis of analogues of chalcones (RB) General procedure: Selected aldehyde (10 mmol) and 1,1,1-trifluoroacetone(10 mmol) in ethanol (25 mL) were refluxed gently for 30 min.Then 40% NaOH (5 mL) was added and the solid was filtered,washed with water and dried to obtain shiny solid RB.

Reference： [1]Yu, Minmin; Yang, Hui; Wu, Kaihua; Ji, Ying; Ju, Lili; Lu, Xiaoyuan [Bioorganic and Medicinal Chemistry, 2014, vol. 22, # 15, p. 4109 - 4118]

59
[ 75-16-1 ]
[ 29668-43-7 ]
1-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)ethanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	In tetrahydrofuran at -10℃; for 3h; Inert atmosphere;	5.2.3. 1-(benzo[d][1,3]dioxol-4-yl)ethanol (4a) General procedure: Method A: to a solution of 3 M methylmagnesium bromide(8.33 mL, 24.98 mmol) in anhydrous THF (25 mL) stirred at 10 Cunder argon was added dropwise a solution of benzo[d][1,3]dioxol-4-carbaldehyde (2.5 g, 16.65 mmol) in anhydrous THF (25 mL). Themixture was stirred at 10 C for 3 h, quenched with a cold saturated solution of ammonium chloride (100 mL), and extracted withEt2O. The combined organic layers were dried over MgSO4, filtered,and evaporated under reduced pressure. Purification by silica column chromatography using CH2Cl2 as eluent gave the desiredalcohol 4a (1.76 g, 64%) as a pale yellow oil.

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

60
[ 29668-43-7 ]
[ 19813-62-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

61
[ 29668-43-7 ]
2-bromo-1-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)ethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: phenyltrimethylammonium bromide dibromide / tetrahydrofuran / 2.5 h / 0 - 20 °C / Inert atmosphere

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

62
[ 29668-43-7 ]
2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-iodoimidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: phenyltrimethylammonium bromide dibromide / tetrahydrofuran / 2.5 h / 0 - 20 °C / Inert atmosphere 4: butan-1-ol / 5 h / Reflux

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

63
[ 29668-43-7 ]
2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: phenyltrimethylammonium bromide dibromide / tetrahydrofuran / 2.5 h / 0 - 20 °C / Inert atmosphere 4: butan-1-ol / 5 h / Reflux 5: 4 h / 170 °C / Sealed tube

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

64
[ 29668-43-7 ]
2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-3-iodo-6-(4-methylpiperazin-1-yl)imidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: phenyltrimethylammonium bromide dibromide / tetrahydrofuran / 2.5 h / 0 - 20 °C / Inert atmosphere 4: butan-1-ol / 5 h / Reflux 5: 4 h / 170 °C / Sealed tube 6: Iodine monochloride / chloroform / 18 h / 20 °C

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

65
[ 29668-43-7 ]
2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-6-(4-methylpiperazin-1-yl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1: tetrahydrofuran / 3 h / -10 °C / Inert atmosphere 2: Dess-Martin periodane / dichloromethane / 16 h / 0 - 20 °C / Inert atmosphere 3: phenyltrimethylammonium bromide dibromide / tetrahydrofuran / 2.5 h / 0 - 20 °C / Inert atmosphere 4: butan-1-ol / 5 h / Reflux 5: 4 h / 170 °C / Sealed tube 6: Iodine monochloride / chloroform / 18 h / 20 °C 7: sodium carbonate; tetrakis(triphenylphosphine) palladium⁽⁰⁾ / water; 1,2-dimethoxyethane / 1 h / 130 °C / Microwave irradiation

Reference： [1]Moine, Espérance; Dimier-Poisson, Isabelle; Enguehard-Gueiffier, Cécile; Logé, Cédric; Pénichon, Mélanie; Moiré, Nathalie; Delehouzé, Claire; Foll-Josselin, Beátrice; Ruchaud, Sandrine; Bach, Stéphane; Gueiffier, Alain; Debierre-Grockiego, Françoise; Denevault-Sabourin, Caroline [European Journal of Medicinal Chemistry, 2015, vol. 105, p. 80 - 105]

66
[ 29668-43-7 ]
6-(2-hydroxyethoxy)biphenyl-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 100 °C / Sealed tube 2.1: chromium dichloride / tetrahydrofuran / 0.08 h / 25 °C / Schlenk technique; Inert atmosphere 2.2: 5 h / 25 °C / Schlenk technique; Inert atmosphere 2.3: 3 h / 25 °C / Schlenk technique; Inert atmosphere

Reference： [1]Cong, Xuefeng; Tang, Huarong; Zeng, Xiaoming [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14367 - 14372]

67
[ 29668-43-7 ]
6-(2-hydroxyethoxy)-4'-methylbiphenyl-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 100 °C / Sealed tube 2.1: chromium dichloride / tetrahydrofuran / 0.08 h / 25 °C / Schlenk technique; Inert atmosphere 2.2: 5 h / 25 °C / Schlenk technique; Inert atmosphere 2.3: 3 h / 25 °C / Schlenk technique; Inert atmosphere

Reference： [1]Cong, Xuefeng; Tang, Huarong; Zeng, Xiaoming [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14367 - 14372]

68
[ 29668-43-7 ]
6-(2-hydroxyethoxy)-4'-methoxybiphenyl-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 100 °C / Sealed tube 2.1: chromium dichloride / tetrahydrofuran / 0.08 h / 25 °C / Schlenk technique; Inert atmosphere 2.2: 5 h / 25 °C / Schlenk technique; Inert atmosphere 2.3: 3 h / 25 °C / Schlenk technique; Inert atmosphere

Reference： [1]Cong, Xuefeng; Tang, Huarong; Zeng, Xiaoming [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14367 - 14372]

69
[ 29668-43-7 ]
4'-fluoro-6-(2-hydroxyethoxy)biphenyl-2-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1.1: 100 °C / Sealed tube 2.1: chromium dichloride / tetrahydrofuran / 0.08 h / 25 °C / Schlenk technique; Inert atmosphere 2.2: 5 h / 25 °C / Schlenk technique; Inert atmosphere 2.3: 3 h / 25 °C / Schlenk technique; Inert atmosphere

Reference： [1]Cong, Xuefeng; Tang, Huarong; Zeng, Xiaoming [Journal of the American Chemical Society, 2015, vol. 137, # 45, p. 14367 - 14372]

70
pyridin-4-ylacetonitrile hydrochloride [ No CAS ]
[ 29668-43-7 ]
(Z)-3-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-2-(pyridin-4-yl)acrylonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95%	With triethylamine In dichloromethane at 0 - 20℃; for 120h; Inert atmosphere;

Reference： [1]Del Fiandra, Claudia; Moccia, Maria; Cerulli, Valentina; Adamo, Mauro F. A. [Chemical Communications, 2016, vol. 52, # 8, p. 1697 - 1700]

71
[ 2181-42-2 ]
[ 29668-43-7 ]
5-(oxiran-2-yl)-2,3-dihydro-1,4-benzodioxine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium hydroxide In dimethyl sulfoxide at 40℃; for 7h; Inert atmosphere;	4.1.45. 2-(3-Chloro-4-methoxyphenyl)oxirane (12a) General procedure: To a mixture of 3-chloro-4-methoxybenzaldehyde (2.00 g,11.7 mmol) and trimethylsulfonium iodide (3.35 g, 16.4 mmol) inDMSO (12 mL) was added potassium hydroxide (0.920 g,16.4 mmol). After stirring at 40 C for 7 h, the reaction mixturewas diluted with EtOAc (50 mL) and washed with H2O (100 mL).The aqueous layer was extracted with EtOAc (50 mL). To the combinedorganic layer was added toluene (100 mL), and the wholewas washed with H2O (100 mL), dried over Na2SO4, filtered andconcentrated in vacuo to give 2.25 g (quant.) of the title compoundas a pale yellow oil. The obtained compound 12a was used in thenext reaction without further purification.

Reference： [1]Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 1, p. 293 - 304]

72
C₃₈H₅₂N₇O₉Pol [ No CAS ]
[ 29668-43-7 ]
C₄₇H₅₈N₇O₁₁Pol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With piperidine In N,N-dimethyl-formamide at 20℃;

Reference： [1]Pels, Kevin; Dickson, Paige; An, Hongchan; Kodadek, Thomas [ACS Combinatorial Science, 2018, vol. 20, # 2, p. 61 - 69]

73
[ 29668-43-7 ]
[ 209256-80-4 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 3 steps 1: pyrrolidine / pyridine / 2 h / Heating / reflux 2: thionyl chloride / dichloromethane / 1 h / Heating / reflux 3: sodium carbonate / water; ethyl acetate / 1.5 h
	Multi-step reaction with 3 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C

Reference： [1]Current Patent Assignee: BRISTOL-MYERS SQUIBB CO - EP1027043, 2004, B1
[2]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

74
[ 89-51-0 ]
[ 29668-43-7 ]
C₁₈H₁₅NO₆ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
61%	With hydroxylamine acetate In toluene for 24h; Reflux; Dean-Stark;	3.2.3. General Procedure for the Preparation of N-Hydroxy THIQ Acids 7a-k General procedure: A mixture of homophthalic acid (180 mg, 1 mmol), hydroxylamine acetate (102 mg, 1.1 mmol) andthe respective aldehyde (1.1 mmol) in toluene (10 mL) was heated at reflux for 24 h in a flask equippeda Dean-Stark distilling trap. A thick precipitate which formed on cooling the reaction mixture to20 C was isolated by filtration, washed with hexane, and crystallized from aqueous methanol toprovide pure title compounds.

Reference： [1]Chupakhin, Evgeny; Bakulina, Olga; Dar’in, Dmitry; Krasavin, Mikhail [Molecules, 2019, vol. 24, # 5]

75
[ 29668-43-7 ]
C₁₈H₁₅NO₆*Fe⁽³⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydroxylamine acetate / toluene / 24 h / Reflux; Dean-Stark 2: water; methanol / UV-irradiation

Reference： [1]Chupakhin, Evgeny; Bakulina, Olga; Dar’in, Dmitry; Krasavin, Mikhail [Molecules, 2019, vol. 24, # 5]

76
[ 29668-43-7 ]
2C₁₈H₁₅NO₆*Fe⁽³⁺⁾ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: hydroxylamine acetate / toluene / 24 h / Reflux; Dean-Stark 2: water; methanol / UV-irradiation

Reference： [1]Chupakhin, Evgeny; Bakulina, Olga; Dar’in, Dmitry; Krasavin, Mikhail [Molecules, 2019, vol. 24, # 5]

77
2-(2-isopropylphenyl)piperazine [ No CAS ]
[ 29668-43-7 ]
1-((2,3-dihydrobenzo[b][1,4]dioxin-5-yl)methyl)-3-(2-isopropylphenyl)piperazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With sodium tris(acetoxy)borohydride In dichloromethane at 20℃; for 12h;	1 Step 1: 1- ( (2, 3-dihydrobenzo [b] [1, 4] dioxin-5-yl) methyl) -3- (2-isopropylphenyl) piperazine A mixture of 2- (2-isopropylphenyl) piperazine (2.6 g, 12.7 mmol) , 2, 3-dihydrobenzo [b] [1, 4] dioxine-5-carbaldehyde (1.9 g, 11.6 mmol) and NaBH (OAc)3(4.9 g, 23.2 mmol) in DCM (20 mL) was stirred at 20 for 12 hrs. The mixture was adjusted pH = 7 by aqueous Na2CO3extracted with DCM (20 mL h 2) . The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The crude product was purified by column chromatography (silica gel, eluent: EA) to give 1- ( (2, 3-dihydrobenzo [b] [1, 4] dioxin-5-yl) methyl) -3- (2-isopropylphenyl) piperazine (3.2 g, yield: 78%) as a yellow solid. MS (ESI, m/e) [M+1]+353.3.

Reference： [1]Current Patent Assignee: BEIGENE LTD. - WO2021/208963, 2021, A1 Location in patent: Paragraph 0807-0809

78
[ 29668-43-7 ]
C₂₅H₂₈N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: acetic acid / tetrahydrofuran / 20 °C / pH 5 6.2: 0.5 h / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

79
[ 29668-43-7 ]
(2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)cyclopropyl)methanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol / 0.5 h / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

80
[ 29668-43-7 ]
2-((2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)cyclopropyl)methyl)-isoindoline-1,3-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 7 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol / 0.5 h / 20 °C 7.1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

81
[ 29668-43-7 ]
(2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)cyclopropyl)methanamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 8 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol / 0.5 h / 20 °C 7.1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 20 °C 8.1: hydrazine hydrate / methanol; dichloromethane / Reflux

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

82
[ 29668-43-7 ]
3-(4-(2-(((2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)cyclopropyl)methyl)amino)ethyl)-trans-cyclohexyl)-1,1-dimethylurea hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 10 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol / 0.5 h / 20 °C 7.1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 20 °C 8.1: hydrazine hydrate / methanol; dichloromethane / Reflux 9.1: acetic acid / tetrahydrofuran / 20 °C / pH 5 9.2: 0.5 h / 20 °C 10.1: hydrogenchloride / dichloromethane; diethyl ether / 0.08 h / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

83
[ 29668-43-7 ]
C₂₃H₃₅N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 9 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: sodium tetrahydroborate / methanol / 0.5 h / 20 °C 7.1: triphenylphosphine; diethylazodicarboxylate / tetrahydrofuran / 20 °C 8.1: hydrazine hydrate / methanol; dichloromethane / Reflux 9.1: acetic acid / tetrahydrofuran / 20 °C / pH 5 9.2: 0.5 h / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

84
[ 29668-43-7 ]
[ 209256-68-8 ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 2 steps 1: dichloromethane / 20 °C 2: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

85
[ 29668-43-7 ]
2-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)-N-methoxy-N-methylcyclopropane-1-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 4 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

86
[ 29668-43-7 ]
C₁₂H₁₂O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 5 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

87
[ 29668-43-7 ]
C₂₅H₃₀N₂O₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Multi-step reaction with 6 steps 1.1: dichloromethane / 20 °C 2.1: lithium hydroxide monohydrate / methanol; tetrahydrofuran; water / 20 °C 3.1: N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.5 h / 20 °C 3.2: 20 °C 4.1: sodium hydride / dimethyl sulfoxide; mineral oil / 1 h / 20 °C 4.2: 20 °C 5.1: diisobutylaluminium hydride / tetrahydrofuran / -78 °C / Inert atmosphere 6.1: acetic acid / tetrahydrofuran / 20 °C / pH 5 6.2: 0.5 h / 20 °C

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

88
[ 21204-67-1 ]
[ 29668-43-7 ]
methyl (E)-3-(2,3-dihydrobenzo[b][1,4]dioxin-5-yl)acrylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	In dichloromethane at 20℃;

Reference： [1]Cheng, Jianjun; Fan, Luyu; Liu, Ruiquan; Tan, Liang; Wang, Huan; Wang, Sheng; Yan, Wenzhong; Yu, Jing [Journal of Medicinal Chemistry, 2021, vol. 64, # 23, p. 17239 - 17258]

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	29668-43-7	MDL No. :	MFCD00239451
Formula :	C₉H₈O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	BJXUCBAQZJITKD-UHFFFAOYSA-N
M.W :	164.16	Pubchem ID :	2795033
Synonyms :

Num. heavy atoms :	12
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.22
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	0.0
Molar Refractivity :	42.7
TPSA :	35.53 Å²

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) :	-6.52 cm/s

Log Po/w (iLOGP) :	1.85
Log Po/w (XLOGP3) :	1.1
Log Po/w (WLOGP) :	1.27
Log Po/w (MLOGP) :	0.43
Log Po/w (SILICOS-IT) :	2.29
Consensus Log Po/w :	1.39

[ CAS No. 29668-43-7 ] {[proInfo.proName]}

Quality Control of [ 29668-43-7 ]

Related Doc. of [ 29668-43-7 ]

Product Details of [ 29668-43-7 ]

Calculated chemistry of [ 29668-43-7 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 29668-43-7 ]

Application In Synthesis of [ 29668-43-7 ]

[ 29668-43-7 ] Synthesis Path-Upstream 1~2

[ 29668-43-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of
[ 29668-43-7 ]

Aldehydes

Related Parent Nucleus of
[ 29668-43-7 ]

Benzodioxans

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

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

Log S (ESOL) :	-1.85
Solubility :	2.29 mg/ml ; 0.014 mol/l
Class :	Very soluble
Log S (Ali) :	-1.44
Solubility :	5.98 mg/ml ; 0.0364 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-2.37
Solubility :	0.703 mg/ml ; 0.00429 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	1.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	2.13

Signal Word:	Warning	Class:
Precautionary Statements:	P264-P273-P280-P305+P351+P338-P337+P313-P501	UN#:
Hazard Statements:	H319-H412	Packing Group:
GHS Pictogram:

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

[ CAS No. 29668-43-7 ] {[proInfo.proName]}

Quality Control of [ 29668-43-7 ]

Related Doc. of [ 29668-43-7 ]

Product Details of [ 29668-43-7 ]

Calculated chemistry of [ 29668-43-7 ]

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[ 29668-43-7 ] Synthesis Path-Upstream 1~2

[ 29668-43-7 ] Synthesis Path-Downstream 1~88

Related Functional Groups of [ 29668-43-7 ]

Aldehydes

Related Parent Nucleus of [ 29668-43-7 ]

Benzodioxans

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[ 29668-43-7 ]

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[ 29668-43-7 ]