20781-20-8|(2,4-Dimethoxyphenyl)methanamine| Ambeed

HazMat Fee +

There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.

Type	HazMat fee for 500 gram (Estimated)
Excepted Quantity	USD 0.00
Limited Quantity	USD 15-60
Inaccessible (Haz class 6.1), Domestic	USD 80+
Inaccessible (Haz class 6.1), International	USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic	USD 100+
Accessible (Haz class 3, 4, 5 or 8), International	USD 200+

Structure of 20781-20-8

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}

Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size	Price	VIP Price	US Stock	Global Stock	In Stock
{[ item.pr_size ]}		Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

{[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

Quality Control of [ 20781-20-8 ] Purity: 98% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 20781-20-8 ]

CAS No. :	20781-20-8
Formula :	C₉H₁₃NO₂
M.W :	167.21
SMILES Code :	NCC1=CC=C(OC)C=C1OC
MDL No. :	MFCD00052393
InChI Key :	QOWBXWFYRXSBAS-UHFFFAOYSA-N
Pubchem ID :	597250

Safety of [ 20781-20-8 ]

GHS Pictogram:
Signal Word:	Danger
Hazard Statements:	H314
Precautionary Statements:	P501-P264-P280-P303+P361+P353-P301+P330+P331-P363-P304+P340+P310-P305+P351+P338+P310-P405
Class:	8
UN#:	2735
Packing Group:	Ⅲ

Computational Chemistry of [ 20781-20-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	12
Num. arom. heavy atoms	6
Fraction Csp3	0.33
Num. rotatable bonds	3
Num. H-bond acceptors	3.0
Num. H-bond donors	1.0
Molar Refractivity	47.1
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	44.48 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	2.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.25
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.01
Log P_o/w (MLOGP)? MLOGP: Topological method implemented from Moriguchi I. et al. 1992 Chem. Pharm. Bull. Moriguchi I. et al. 1994 Chem. Pharm. Bull. Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.	0.92
Log P_o/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	1.44
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.32

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.84
Solubility	2.44 mg/ml ; 0.0146 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.78
Solubility	2.76 mg/ml ; 0.0165 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.69
Solubility	0.341 mg/ml ; 0.00204 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble

Pharmacokinetics

GI absorption? Gatrointestinal absorption: according to the white of the BOILED-Egg	High
BBB permeant? BBB permeation: according to the yolk of the BOILED-Egg	Yes
P-gp substrate? P-glycoprotein substrate: SVM model built on 1033 molecules (training set) and tested on 415 molecules (test set) 10-fold CV: ACC=0.72 / AUC=0.77 External: ACC=0.88 / AUC=0.94	No
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.83 / AUC=0.90 External: ACC=0.84 / AUC=0.91	No
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) and tested on 3000 molecules (test set) 10-fold CV: ACC=0.80 / AUC=0.86 External: ACC=0.80 / AUC=0.87	No
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) and tested on 2075 molecules (test set) 10-fold CV: ACC=0.78 / AUC=0.85 External: ACC=0.71 / AUC=0.81	No
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) and tested on 1068 molecules (test set) 10-fold CV: ACC=0.79 / AUC=0.85 External: ACC=0.81 / AUC=0.87	No
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) and tested on 2579 molecules (test set) 10-fold CV: ACC=0.77 / AUC=0.85 External: ACC=0.78 / AUC=0.86	No
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from Potts RO and Guy RH. 1992 Pharm. Res.	-6.43 cm/s

Druglikeness

Lipinski? Lipinski (Pfizer) filter: implemented from Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev. MW ≤ 500 MLOGP ≤ 4.15 N or O ≤ 10 NH or OH ≤ 5	0.0
Ghose? Ghose filter: implemented from Ghose AK. et al. 1999 J. Comb. Chem. 160 ≤ MW ≤ 480 -0.4 ≤ WLOGP ≤ 5.6 40 ≤ MR ≤ 130 20 ≤ atoms ≤ 70	None
Veber? Veber (GSK) filter: implemented from Veber DF. et al. 2002 J. Med. Chem. Rotatable bonds ≤ 10 TPSA ≤ 140	0.0
Egan? Egan (Pharmacia) filter: implemented from Egan WJ. et al. 2000 J. Med. Chem. WLOGP ≤ 5.88 TPSA ≤ 131.6	0.0
Muegge? Muegge (Bayer) filter: implemented from Muegge I. et al. 2001 J. Med. Chem. 200 ≤ MW ≤ 600 -2 ≤ XLOGP ≤ 5 TPSA ≤ 150 Num. rings ≤ 7 Num. carbon > 4 Num. heteroatoms > 1 Num. rotatable bonds ≤ 15 H-bond acc. ≤ 10 H-bond don. ≤ 5	1.0
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat implemented from Martin YC. 2005 J. Med. Chem.	0.55

Medicinal Chemistry

PAINS? Pan Assay Interference Structures: implemented from Baell JB. & Holloway GA. 2010 J. Med. Chem.	0.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	0.0 alert: heavy_metal
Leadlikeness? Leadlikeness: implemented from Teague SJ. 1999 Angew. Chem. Int. Ed. 250 ≤ MW ≤ 350 XLOGP ≤ 3.5 Num. rotatable bonds ≤ 7	No; 1 violation:MW<1.0
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties, trained on 12'782'590 molecules and tested on 40 external molecules (r² = 0.94)	1.28

Application In Synthesis of [ 20781-20-8 ]

* 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.

Downstream synthetic route of [ 20781-20-8 ]

[ 20781-20-8 ] Synthesis Path-Downstream 1~29

1
[ 5926-51-2 ]
[ 20781-20-8 ]
[ 541-59-3 ]

Yield	Reaction Conditions	Operation in experiment
	In acetic acid;	Scheme C-6 illustrates the synthesis of the maleimide pyrazole scaffold C-63 wherein R4 is hydrogen. The synthesis starts with the condensation reaction of <strong>[5926-51-2]bromomaleic anhydride</strong> B77 with 2,4-dimethoxybenzylamine in acetic acid and acetic anhydride, giving rise to intermediate B78.
	In acetic acid;	Scheme C-6 illustrates the synthesis of the maleimide pyrazole scaffold C-63 wherein R4 is hydrogen. The synthesis starts with the condensation reaction of <strong>[5926-51-2]bromomaleic anhydride</strong> B77 with 2,4-dimethoxybenzylamine in acetic acid and acetic anhydride, giving rise to intermediate B78.

References: [1]Patent: US6423713,2002,B1 .
[2]Patent: US6514977,2003,B1 .

2
[ 20781-20-8 ]
[ 51997-51-4 ]
1-(9H-carbazol-4-yloxy)-3-[(2,4-dimethoxybenzyl)-amino]propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94.2%	In ipa; ethyl acetate; for 4.5h;Heating / reflux;	To a stirred solution of Epoxy carbazole (5gm, 0.0209 mole) in IPA (20 ml), 2,4-dimethoxybenzylamine (9.42 ml, 0.06276 moles) was added, and the reaction mixture was heated to reflux for 3 hours. Subsequently the reaction mixture was cooled and IPA was stripped off. To the semisolid residue obtained, ethyl acetate (50 ml) was added and it was refluxed for 1.5 hours, until everything dissolved. A light yellow colored clear solution was finally obtained, which was stirred at room temperature for 5 hours when it completely crystallized out as a white solid (8 g, 94.2%), m.p: 152-154 0C, 1H NMR (400 MHz, CDCl3): delta 2.89(m IH), 2.99(d IH), 3.74(s 3H), 3.78(s 3H), 3.8 l(d 2H), 4.27(m, 3H)5 6.42(m 2H), 6.65(d IH), 7.08(d IH), 7.14(m 2H), 7.29(m IH), 7.35(d IH), 7.43(d IH), 8.22(d IH), 9.42(s IH); m/zM+1406.

References: [1]Patent: WO2007/42912,2007,A2 .Location in patent: Page/Page column 20.

3
[ 20781-20-8 ]
[ 51997-51-4 ]
(2R)-1-(9H-carbazol-4-yloxy)-3-[(2,4-dimethoxybenzyl)-amino]propan-2-ol [ No CAS ]
(2S)-1-(9H-carbazol-4-yloxy)-3-[(2,4-dimethoxybenzyl)-amino]propan-2-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In isopropyl alcohol; for 3h;Heating / reflux;	Step 2: Preparation of 1-(9H-carbazol-4-yloxy)-3-[(2,4-dimethoxybenzyl)amino]propan-2-ol To a stirred solution of Epoxy carbazole (5 gm, 0.0209 mole) in IPA (20 ml), 2,4-dimethoxybenzylamine (9.42 ml, 0.06276 moles) was added, and the reaction mixture was heated to reflux for 3 hours. Subsequently the reaction mixture was cooled and IPA was stripped off. To the semisolid residue obtained, ethyl acetate (50 ml) was added and it was refluxed for 1.5 hours, until everything dissolved. A light yellow colored clear solution was finally obtained, which was stirred at room temperature for 5 hours when it completely crystallized out as a white solid (8 g, 94.2%), m.p: 152-154 C., 1H NMR (400 MHz, CDCl3): delta 2.89(m 1H), 2.99(d 1H), 3.74(s 3H), 3.78(s 3H), 3.81(d 2H), 4.27(m, 3H), 6.42(m 2H), 6.65(d 1H), 7.08(d 1H), 7.14(m 2H), 7.29(m 1H), 7.35(d 1H), 7.43(d 1H), 8.22(d 1H), 9.42(s 1H); m/zM+1 406.

References: [1]Patent: US2007/111998,2007,A1 .Location in patent: Page/Page column 10.

4
[ 20781-20-8 ]
[ 1885-81-0 ]
[ 10165-86-3 ]
[ 501-52-0 ]
[ 947756-65-2 ]

Yield	Reaction Conditions	Operation in experiment
	In trifluoroethanol; at 20℃; for 4h;	Step A: Methyl 6-{2-[(4-chlorophenyl)amino]-1-[(2,4-dimethoxybenzyl)(3-phenylpropanoyl)-amino]-2-oxoethyl}nicotinate Dihydrocinnamic acid (46 mg, 0.30 mmol), 4-chlorophenylisocyanide (42 mg, 0.30 mmol) and 2,4-dimethoxybenzylamine (61 mg, 0.36 mmol) were added to a solution of methyl 6-formylnicotinate (see Langlois, Y. et al, Tetrahedron. 1975, 31, 419-22) (50 mg, 0.30 mmol) in 400 muL of TFE. The solution was allowed to stir for 4 h at room temperature and then purified by flash chromatography (12-100percent ethyl acetate in hexanes to give the desired product. MS cal'd 602 (MH+), exp 602 (MH+).

References: [1]Patent: US2009/69250,2009,A1 .Location in patent: Page/Page column 48.

5
[ 20781-20-8 ]
[ 133446-99-8 ]
[ 1214900-77-2 ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;	To a solution of the above product in 40 ml DMF at rt was added 2,4- dimethoxybenzyl amine (2.7 ml, 17.98 mmol, 1.2 eq.), potassium carbonate (4.1 g, 30.12 mmol, 2 eq.) and the mixture stirred overnight at rt. It was diluted with ethyl acetate, washed 2x with water, 1 N HCI, brine, dried over MgSO4, filtered, concentrated and purified by chromatography using 5% ethyl acetate in dichloromethane to provide 2.43 g of P29.

References: [1]Patent: WO2011/17296,2011,A1 .Location in patent: Page/Page column 66.

6
[ 149057-19-2 ]
[ 20781-20-8 ]
[ 1311150-53-4 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 3142 - 3147.

7
[ 20781-20-8 ]
[ 1204-06-4 ]
[ 1610703-55-3 ]

Yield	Reaction Conditions	Operation in experiment
48%		General procedure: To a solution of the acid derivative (1mmol) in CH2Cl2 were added triethylamine (2mmol) and ethyl chloroformate (1mmol), followed by stirring at 0C for 30min. After addition of the appropriate amine derivative (1.2mmol), the mixture was stirred for an additional 1h at 0C. Then, the reaction mixture was warmed to room temperature and stirred overnight. After the solvent was evaporated under reduced pressure, acetone was added, filtered, and evaporated. The residue was dissolved in CH2Cl2, and the organic phase was washed with a 1% NaHCO3 solution and brine, dried over Na2SO4, and evaporated under vacuum. The final residue was purified by flash column chromatography (Combiflash Rf) using CH2Cl2-MeOH (0-5%) as eluents. 4.3.9 (E)-N-(2,4-Dimethoxybenzyl)-3-(1H-indol-3-yl)acrylamide 3i Yield 48%, mp 164-166 C; IR (FTIR/FTNIR-ATR): 1644 cm-1 (C=O), 3241 cm-1 (N-H). 1H NMR (DMSO-d6) delta: 11.54 (1H, s), 8.07 (1H, t, J = 6 Hz), 7.92 (1H, d, J = 8 Hz), 7.74 (1H, s), 7.61 (1H, d, J = 15.6 Hz), 7.45 (1H, d, J = 7.6 Hz), 7.18 (3H, m), 6.71 (1H, d, J = 16 Hz), 6.57 (1H, s), 6.50 (1H, d, J = 8 Hz), 4.28 (2H, d, J = 5.6 Hz), 3.81 (3H, s), 3.74 (3H, s). 13C NMR (DMSO-d6) delta: 166.9, 160.4, 158.4, 138.0, 133.6, 131.0, 129.8, 125.5, 122.8, 120.9, 120.7, 119.8, 116.9, 112.9, 112.8, 104.9, 98.8, 56.0, 55.8, 37.7; HRMS C20H21N2O3 [M+H]+ Calcd 337.1552, Found m/z 337.1539.

References: [1]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 3096 - 3104.

8
[ 20781-20-8 ]
2-(((tert-butyldimethylsilyl)oxy)methyl)-3-tosyl-7,8,9,10-tetrahydrocyclohepta[e]indol-6(3H)-one [ No CAS ]
[ 1186-73-8 ]
methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-10-(2,4-dimethoxybenzyl)-7-hydroxy-9-oxo-1-tosyl-1,4,5,6,9,10-hexahydropyrido[2’,3’:3,4]cyclohepta[1,2-e]indole-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
52%		To a solution of 2-(((tert-butyldimethylsilyl)oxy)methyl)-3-tosyl-7,8,9,10- tetrahydrocyclohepta[e]indol-6(3H)-one (650 mg, 1.3 mmol) in CH2C12 (6 mL) was added 2- ,4-dimethoxybenzylamine (0.22 mL, 1.43 mmol) and triethylamine (0.54 mL, 3.9 mmol). The mixture was cooled to 0 C. To the mixture was added a TiCl4 solution (1 M CH2C12, 0.85 mL, 0.85 mmol) dropwise via syringe over 5 min. The mixture was allowed to warm to room temperature and was stirred overnight. The excess reagent was quenched with aqueous saturated NaHC03 (3 mL). The organic phase was separated with vigorous shaking using a PTFE phase separator, dried over Na2S04, filtered, and concentrated. The residue was combined with <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (342 mg, 1.8 mmol) in Ph20 (2.6 mL). The mixture was placed in a pre-heated aluminum block at 230 C and stirred for 15 minutes. The reaction vessel was removed from the heating block and allowed to cool to room temperature. The crude reaction mixture was loaded directly onto a silica gel column, eluting with 0-60% EtOAc in hexanes to yield a yellow powder (0.52 g, 52%). LC-MS: 773.4 [M+H]+, RT 1.97 min. 1H NMR (500 MHz, acetone- 6) delta ppm 0.18 (s, 6H), 0.98 (s, 9H), 1.34 (m, 1H), 1.92 (m, 1H), 2.01 (m, 1H), 2.26 (m, 1H), 2.39 (s, 3H), 2.90 (m, 2H), 3.38 (s, 3H), 3.68 (s, 3H), 3.90 (s, 3H), 4.96 (d, J=15.6 Hz, 2H), 5.17 (m, 2H), 6.16 (d, J=8.3 Hz, 1H), 6.30 (d, J=2.3 Hz, 1H), 6.61 (d, J=8.3 Hz, 1H), 6.91 (s, 1H), 7.25 (d, J=8.6 Hz, 1H), 7.43 (d, J=7.8 Hz, 2H), 7.94-8.00 (m, 3H), 13.79 (br. s, 1H).

References: [1]Patent: WO2016/25933,2016,A2 .Location in patent: Page/Page column 172.

9
[ 20781-20-8 ]
3-tosyl-7,8,9,10-tetrahydrocyclohepta[e]indol-6(3H)-one [ No CAS ]
[ 1186-73-8 ]
methyl 10-(2,4-dimethoxybenzyl)-7-hydroxy-9-oxo-1-tosyl-1,4,5,6,9,10-hexahydropyrido[2’,3‘:3,4]cyclohepta[1,2-e]indole-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
49%		To a solution of 3-tosyl-7,8,9,10-tetrahydrocyclohepta[e]indol-6(3H)-one (670 mg, 1.9 mmol) in CH2C12 (10 mL) was added 2-,4-dimethoxybenzylamine (0.32 mL, 2.1 mmol) and triethylamine (0.79 mL, 5.7 mmol). The mixture was cooled to 0 C. To the mixture was added a TiCl4 solution (1 M CH2C12, 1.24 mL, 1.24 mmol) dropwise via syringe over 5 min. The mixture was allowed to warm to room temperature and was stirred overnight. The excess reagent was quenched with aqueous saturated NaHC03 (5 mL). The organic phase was separated with vigorous shaking using a PTFE phase separator, dried over Na2S04, filtered, and concentrated. The residue was combined with <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (650 mg, 3.4 mmol) in Ph20 (3.8 mL). The mixture was placed in a pre-heated aluminum block at 220 C and stirred for 15 min. The reaction vessel was removed from the heating block and allowed to cool to room temperature. The crude reaction mixture was loaded directly onto a silica gel column, eluting with 0-100% EtOAc in hexanes to yield a yellow powder (0.58 g, 49%). LC-MS: 629.1 [M+H]+, RT 1.47 min. 1H NMR (500 MHz, acetone- 6) delta ppm 1.33 (m, 1H), 1.87-2.03 (m, 2H), 2.25 (m, 1H), 2.39 (s, 3H), 2.92 (m, 2H), 3.32 (s, 3H), 3.67 (s, 3H), 3.90 (s, 3H), 4.95 (d, J=15.6 Hz, 1H), 5.28 (d, J=15.2 Hz, 1H), 6.15 (m, 1H), 6.27 (m, 1H), 6.62 (d, J=8.2 Hz, 1H), 6.96 (m, 1H), 7.29 (d, J=8.2 Hz, 1H), 7.46 (m, 2H), 7.81 (d, J=8.6 Hz, 1H), 7.91 (d, J=3.8 Hz, 1H), 7.98 (m, 2H), 13.77 (br. s, 1H).

References: [1]Patent: WO2016/25933,2016,A2 .Location in patent: Page/Page column 174; 175.

10
[ 129790-37-0 ]
[ 20781-20-8 ]
[ 1186-73-8 ]
methyl 9-bromo-1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-1,2,5,6-tetrahydrobenzo[2,3]thiepino[4,5-b]pyridine-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%		Step 1: Methyl 9-bromo-l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-l,2,5,6-tetrahydrobenzo[2,3]thiepino[4,5-b]pyridine-3-carboxylate To a stirring solution of 8-bromo-3,4-dihydrobenzo[b]thiepin-5(2H)-one (Intermediate 9, Step 2, 36.2 g, 141 mmol), (2,4-dimethoxyphenyl)methanamine (25.9 g, 23.3 mL, 155 mmol), triethylamine (42.7 g, 58.7 mL, 423 mmol) in CH2C12(300 mL) at 0 C was added T1CI4(1M CH2C12, 71 mL, 71 mmol) dropwise. After the addition, the mixture was brought to room temperature and stirred overnight. The reaction was quenched with satd. NaHC03solution (3 mL) and the mixture was diluted with CH2C12(120 mL). The CH2C12layer was separated using a phase separator cartridge and the aqueous layer was extracted with CH2C12(2 x 30 mL). The combined organic phases were evaporated to dryness followed by the addition of <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (53.6 g, 282 mmol) and diphenyl ether (280 mL). The mixture was stirred at 230 C for 15 min., then cooled and chromato graphed (ethyl acetate in hexanes, 0-100 % gradient) to obtain the title compoundas a light brown solid (47.6 g, 64%). LC-MS: 532.0, 534.0 [M+H]+, RT 1.59 min.

References: [1]Patent: WO2016/25932,2016,A1 .Location in patent: Page/Page column 125.

11
[ 20781-20-8 ]
9-tosyl-3,4-dihydro-2H-thiepino[3,2-f]indol-5(9H)-one [ No CAS ]
[ 1186-73-8 ]
methyl 1-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-9-tosyl-2,5,6,9-tetrahydro-1H-pyrido[2',3':4,5]thiepino[3,2-f]indole-3-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%		Step 1: Methyl l-(2,4-dimethoxybenzyl)-4-hydroxy-2-oxo-9-tosyl-2,5,6,9-tetrahydro- 1H-pyrido[2',3':4,5]thiepino[3,2-f]indole-3-carboxylate o a stirring solution of Intermediate 9 (1.02 g, 2.75 mmol), (2,4-dimethoxyphenyl)methanamine (0.51 g, 0.45 mL, 3.03 mmol), triethylamine (0.83 g, 1.14 mL, 8.25 mmol) in CH2C12(6.0 mL) at 0 C was added a solution of TiCl4(1M in CH2C12,1.4 mL, 1.4 mmol) dropwise. After the addition, the mixture was brought to roomtemperature and stirred overnight. The reaction was quenched with satd. NaHC03solution (3 mL) and the mixture was diluted with CH2C12(12 mL). The CH2C12layer was separated and the aqueous layer was extracted with CH2C12(2 x 3 mL). The combined organics were evaporated to dryness followed by the addition of <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (1.05 g,5.5 mmol) and diphenyl ether (5.0 mL). The mixture was stirred at 230 C for 10 min, then cooled to room temperature and loaded directly onto a silica gel column. The product was chromato graphed (ethyl acetate in CH2C120-50 %) to furnish the title compound as a light brown solid (1.10 g, 62%). LC-MS: 647.2 [M+H]+, RT 1.57 min.

References: [1]Patent: WO2016/25932,2016,A1 .Location in patent: Page/Page column 154.

12
[ 5400-79-3 ]
[ 20781-20-8 ]
ethyl 3-(2,4-dimethoxybenzylamino)cyclopentanecarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
44%	With sodium tris(acetoxy)borohydride; acetic acid; In tetrahydrofuran; at 0 - 20℃; for 14h;	2,4-dimethoxybenzyl amine (556 mg, 4.66 mmol, 1.0 eq.), sodium triacetoxyborohydride (446 mg, 3.32 mmol, 1.4 eq.) and acetic acid (200 mg, 3.32 mmol, 1.0 eq.) were added to a solution of <strong>[5400-79-3]ethyl 3-oxocyclopentanecarboxylate</strong> (520 mg, 3.32 mmol, 1.0 eq.) in tetrahydrofuran (5 mL) at 0 C. The reaction was stirred at room temperature for 14 hours, quenched with saturated NaHCO3 (10 mL). The aqueous phase was extracted with ethyl acetate (10 mL*2). The combined organic phases were dried over anhydrous sodium sulfate, and concentrated to give the crude product, which was purified by silica gel column chromatography (eluent: petroleum ether:ethyl acetate=1:1) to give the title compound (250 mg, yield: 44%).

References: [1]Patent: US2016/200730,2016,A1 .Location in patent: Paragraph 0445; 0446.

13
[ 20781-20-8 ]
[ 7579-20-6 ]
C₁₅H₁₇N₃O₃ [ No CAS ]

References: [1]Patent: WO2016/68580,2016,A2 .Location in patent: Page/Page column 72.

14
[ 20781-20-8 ]
2-methyl-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(1H)-one [ No CAS ]
[ 1186-73-8 ]
methyl 10-(2,4-dimethoxybenzyl)-7-hydroxy-2-methyl-9-oxo-3,4,5,6,9,10-hexahydroimidazo[4’,5’:6,7]cyclohepta[1,2-b]pyridine-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14%		TiC14 (1.0 M in CH2C12, 6.44 mL, 6.44 mmol) was added to a solution of 2-methyl-5,6,7,8-tetrahydrocyclohepta[dlinildazol-4(1H)-one (Intermediate 3, step 2, 0.96 g, 5.85 mmol), (2,4- dimethoxyphenyl)methanamine (1.08 g, 6.44 mmol), triethylamine (3.19 g, 4.39 mL, 31.61mmol), and CH2C12 (10.0 mL) at 0 C. The mixture was stirred at 0 C for 0.5 h. The mixture was brought to room temperature and stirred overnight. The reaction was diluted with CH2C12 and quenched with saturated aqueous NaHCO3 The organic phase was separated using a phase separator cartridge. The aqueous layer was extracted with CH2C12. The organic layerswere combined and evaporated to dryness. The residue, <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (2.22 g, 11.7 mmol), and diphenyl ether (25 mL) were stirred at 200C for 10 mm. The mixture was cooled to room temperature and purified by silica gel column chromatography (0-20% MeOH in CH2C12) followed by reversed phase C18 chromatography, (0-50% acetonitrile in water) to afford the title compound (0.36 g, 14%).LC-MS 438.3 [M-Hf, RT 1.04 mm

References: [1]Patent: WO2016/109706,2016,A1 .Location in patent: Page/Page column 246; 247.

15
[ 20781-20-8 ]
2-(((tert-butyldimethylsilyl)oxy)methyl)-1-ethyl-5,6,7,8-tetrahydrocyclohepta[d]imidazol-4(1H)-one [ No CAS ]
[ 1186-73-8 ]
methyl 2-(((tert-butyldimethylsilyl)oxy)methyl)-10-(2,4-dimethoxybenzyl)-3-ethyl-7-hydroxy-9-oxo-3,4,5,6,9,10-hexahydroimidazo[4',5':6,7]cyclohepta[1,2-b]pyridine-8-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
40%		To a solution of the product of step 1, triethylamine (324 mg, 0.45 mL, 3.21 mmol) and (2,4- dimethoxyphenyl)methanamine (195 mg, 0.18 mL, 1.17 mmol) in CH2CI2 at 0 C (2.5 mL), was added TiCl4 (0.64 mL, 1.0 M in CH2C12, 0.64 mmol). The mixture was stirred at 0 C for 15 min. The mixture was brought to room temperature and stirred overnight. The mixture was diluted with CH2CI2 and quenched at 0 C with saturated NaHCC>3 solution. The organic layer was separated using a phase separator cartridge, and the aqueous layer was washed with additional CH2CI2. The CH2CI2 solution was concentrated under reduced pressure. To the residue, diphenyl ether (5.0 mL) and <strong>[1186-73-8]trimethyl methanetricarboxylate</strong> (380 mg, 2.0 mmol) were added. The mixture was stirred at 200 C for 10 min and then cooled. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (0-100% gradient EtOAc in CH2CI2) to afford the title compound as a yellow oil (200 mg, 40%). (2670) LC-MS 598.5 [M+H]+, RT 1.81 min

References: [1]Patent: WO2016/109706,2016,A1 .Location in patent: Page/Page column 200.

16
[ 21279-62-9 ]
[ 20781-20-8 ]
3-[(2,4-dimethoxybenzyl)amino]pyrazine-2-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With pyridine; In methanol; at 140℃; for 0.5h;Sealed tube; Microwave irradiation;	General procedure: Compounds 1-6 were prepared according to conventional organic synthesis methods. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was dissolved in THF (20 mL) in a round bottom flask and after that treated with two equivalents of the corresponding benzylamine and an equimolar amount of triethylamine. The reaction was conducted with continuous stirring and heating (70 C) under reflux in an oil bath for 15 h. Compounds 7-15 were synthesised using a microwave reactor with a focused field. 3-Chloropyrazine-2-carboxamide (1.27 mmol) was put into a thick-walled tube together with the corresponding benzylamine (2.54 mmol), pyridine (1.27 mmol), methanol (approx. 5 mL) and a magnetic stir bar and then sealed with a special cap. The reaction parameters were set according to the previously published paper as follows-140 C, 30 min, 200 W [29]. Reaction progress was checked by TLC (hexane:ethyl acetate-1:1). Regardless of the synthesis method used,all reaction mixtures were adsorbed on silica and subjected to preparative flash chromatography (hexane and ethyl acetate, gradient elution, detection wavelengths 260 nm and 280 nm). Products were recrystallized from ethanol or ethanol and water if necessary. All final substances were chemically characterized (1H-NMR, 13C-NMR, IR, melting point and elemental analysis).

References: [1]Molecules,2017,vol. 22.

17
[ 20781-20-8 ]
[ 70049-46-6 ]
2-chloro-N-(2,4-dimethoxybenzyl)-6-methoxyquinolin-4-amine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With triethylamine; In dimethyl sulfoxide; at 90℃; for 48h;	To a mixture of 2,4- dichloro-<strong>[70049-46-6]6-methoxyquinoline</strong> (6.0 g, 26.3 mmol) and (2,4-dimethoxyphenyl)methanamine (6.60 g, 39.5 mmol) in DMSO (80 ml) was added Et3N (11.00 ml, 79 mmol). The reaction mixture was stirred at 90 °C for 48 h. Then the reaction was cooled to 20 °C, and dilutedwith EtOAc (100 mL) and water (100 mL). The aqueous layer was extracted with EtOAc (3 x 100 mL). The combined organic layers were dried over Na2504, filtered and concentrated in vacuo. The resulting residue was purified by column chromatography (5i02, PE:EtOAc =10:1 to 1:1) to give the title compound.

References: [1]Patent: WO2017/155765,2017,A1 .Location in patent: Page/Page column 68.

18
[ 50-00-0 ]
[ 1198-14-7 ]
[ 20781-20-8 ]
5-bromo-7-(((2,4-dimethoxybenzyl)amino)methyl)quinolin-8-ol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
28%		The solution of 2,4-dimethoxybenzylamine (248 mu, 0.276 g, 1.65 mmol) in ethanol (4 mL) was added 37percent formaldehyde (62 mu, 0.049 g, 1.65 mmol). The mixture was stirred for 1 hour. Then the solution of <strong>[1198-14-7]5-bromoquinolin-8-ol</strong> (0.336 g, 1.5 mmol) in ethanol (5 mL) was added to the reaction mixture. After that the mixture was refluxed at 50°C for 56 hours. The reaction mixture was allowed to cool down and the obtained precipitate was filtered off, washed with ethanol and crystallized from ethanol to give the titled compound (0.170 g, 28percent) as yellow crystals. Mp. 146-148 °C. 1 H NMR (300 MHz, CDCI3): delta 3.80-3.82 (d, 8H), 4.07(s, 2H), 6.44 (d, 2H), 7.08 (d, 1 H), 7.46-7.51 (m, 1 H), 7.62 (s, 1 H), 8.46 (d, 1 H), 8.89 (s, 1 H). 13C NMR (75 MHz, CDCI3): delta 47.7, 49.5, 55.2, 55.3, 98.6, 103.7, 109.1 , 118.8, 120.6, 122.1 , 127.0, 130.9, 131.0, 135.2, 140.0, 149.0, 153.1 , 158.7, 160.5. LCMS RT= 4.12 min. ESI+ m/z: 403.5 [M+H+].

References: [1]Patent: WO2017/175018,2017,A2 .Location in patent: Page/Page column 46; 48; 49.

19
[ 20781-20-8 ]
[ 112811-71-9 ]
1-cyclopropyl-7-(2,4-dimethoxybenzylamino)-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylate ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In dimethyl sulfoxide; N,N-dimethyl-formamide; at 120℃; for 6h;	A three-necked flask was charged with 100 g of <strong>[112811-71-9]1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylate ethyl ester</strong>,Then add 600mL DMF: DMS0 = 1: 1 mixed solvent, stirred, was added 2,4-dimethoxybenzylamine 54mL, heated to 120 C for 6h, cooled,The reaction solution was poured into 1mol / L dilute hydrochloric acid, stirred, added 500mLEA extraction, the organic layer was separated, the aqueous phase was extracted with EA300mLX2,The combined organic layers were dried and evaporated to dryness to give 92.3 g of the yellow product which was used in the next step without further purification.

References: [1]Patent: CN104292158,2017,B .Location in patent: Paragraph 0050-0052.

20
[ 13726-16-4 ]
[ 20781-20-8 ]
C₁₇H₁₈ClNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 20 - 25℃; for 24h;Inert atmosphere;	5) 3-(tert-butyl)-N-(4-chloro-3-methoxybenzyl)-1-methyl-1H-pyrazole-5-carboxamide To a solution of aldehyde (200 mg, 1.17 mmol, 1.0 eq) in toluene (20 mL) was added 2,4-dimethoxybenzyl amine (215 mg, 1.29 mmol, 1.1 eq) and the reaction mixture was stirred at room temperature for 24 h. Toluene was removed to give a residue, which was taken in MeOH (30 mL) and then NaBH4 (87 mg, 2.34 mmol, 2.0 eq) was added slowly. The reaction mixture was stirred at room temperature for 6 h. Solvent was removed and the residue was extracted in Ethyl acetate and stirred with saturated aq NaHCO3 for 1 h. The organic layer was collected, dried and solvent was removed to give the crude amine, which was used in the next step without further purification. To a solution of the crude amine (1.17 mmol, 1.0 eq) in DMF (10 mL) was added the acid (234 mg, 1.29 mmol, 1.1 eq), DIEA (755 mg, 5.85 mmol, 5 eq) and HBTU (532 mg, 1.40 mmol, 1.2 eq) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with ethyl acetate (200 mL) and washed with 10percent aqHCl (150 mL), sat NaHCO3 (150 mL) and water (4*50 mL). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was purified by column chromatography (EtOAc/Hexane 25percent to 75percent)) to give the amide, which was directly used in the next step. The amide was treated with 95percent TFA:H2O for 12 h. TFA was removed and azeotroped with toluene to give a residue, which was purified by column chromatography (EtOAc/Hexane 10percent to 50percent) to give the desired product in 37percent (147 mg, >95percent purity). Mass Spectrum (LCMS, ESI Pos.) Calcd. For C17H23ClN3O2: 336.0 (M+H), Found 336.0.

References: [1]Patent: US2018/118679,2018,A1 .Location in patent: Paragraph 0221-0222.

21
[ 20781-20-8 ]
[ 103438-86-4 ]
C₁₆H₁₆FNO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 20 - 25℃; for 24h;Inert atmosphere;	10) 3-cyclopropyl-N-(3-(cyclopropylmethoxy)-2-fluorobenzyl)-1-methyl-1H-pyrazole-5-carboxamide To a solution of aldehyde (1.0 g, 7.14 mmol, 1.0 eq) in toluene (20 mL) was added 2,4-dimethoxybenzyl amine (1.2 g, 7.14 mmol, 1.0 eq) and the reaction mixture was stirred at room temperature for 24 h. Toluene was removed to give a residue, which was taken in MeOH (25 mL) and then NaBH4 (540 mg, 14.28 mmol, 2.0 eq) was added slowly. The reaction mixture was stirred at room temperature for 6 h. Solvent was removed and the residue was extracted in Ethyl acetate and stirred with saturated aq NaHCO3 for 1 h. The organic layer was collected, dried and solvent was removed to give the crude amine, which was used in the next step without further purification. To a solution of the crude amine (7.14 mmol, 1.0 eq) in DMF (10 mL) was added the acid (1.20 g, 7.14 mmol, 1.0 eq), DIEA (4.61 g, 35.72 mmol, 5 eq) and HBTU (3.25 g, 8.57 mmol, 1.2 eq) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with ethyl acetate (20 mL) and washed with 10% aqHCl (130 mL), sat NaHCO3 (130 mL) and water (430 mL). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was taken in 25 mL of methanol and NaOH (286 mg, 7.14 mmol, 1.0 eq) was added and stirred at room temperature for 24 h. Methanol was removed and the residue was neutralized with 10% aq HCl. The reaction mixture was then extracted with ethyl acetate (2). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was purified by column chromatography (EtOAc/Hexane) to give the amide. To a solution of the hydroxy amide (360 m g, 0.82 mmol, 1.0 eq) in DMF (10 mL) was added Cs2CO3 (1.34 g, 615 mmol, 2.0 eq) and stirred at room temperature for 20 min. Then bromide (221 mg, 1.64 mmol, 2 eq) was added and stirred at rt for 24 h. The reaction mixture was then diluted with Ethyl acetate (25 mL) and washed with water (4*). Organic layer was collected, dried (MgSO4) and evaporated to give a residue, which was then treated with 95% TFA:H2O for 12 h. TFA was removed and azeotroped with toluene to give a residue, which was purified by column chromatography (EtOAc/Hexane 10% to 50%) to give the desired product (22 mg, >95% purity). Mass Spectrum (LCMS, ESI Pos.) Calcd. For C19H22CFN3O2: 344.0 (M+H), Found 344.0.

References: [1]Patent: US2018/118679,2018,A1 .Location in patent: Paragraph 0231-0233.

22
[ 20781-20-8 ]
[ 66495-88-3 ]
C₁₇H₁₉NO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In toluene; at 20 - 25℃; for 24h;Inert atmosphere;	39) N-(3-(cyclopentylmethoxy)-2-methoxybenzyl)-3-cyclopropyl-1-methyl-1H-pyrazole-5-carboxamide To a solution of aldehyde (10.0 g, 65.79 mmol, 1.0 eq) in toluene (100 mL) was added 2,4-dimethoxybenzyl amine (10.89 g, 65.79 mmol, 1.0 eq) and the reaction mixture was stirred at room temperature for 24 h. Toluene was removed to give a residue, which was taken in MeOH (100 mL) and then NaBH4 (4.97 g, 131.58 mmol, 2.0 eq) was added slowly. The reaction mixture was stirred at room temperature for 6 h. Solvent was removed and the residue was extracted in Ethyl acetate and stirred with saturated aq NaHCO3 for 1 h. The organic layer was collected, dried and solvent was removed to give the crude amine, which was used in the next step without further purification. To a solution of the crude amine (7.26 mmol, 1.0 eq) in DMF (20 mL) was added the acid (1.21 g, 7.26 mmol, 1.0 eq), DIEA (4.68 g, 36.30 mmol, 5 eq) and HBTU (3.30 g, 8.71 mmol, 1.2 eq) and the reaction mixture was stirred at rt for 12 h. The reaction mixture was then diluted with ethyl acetate (100 mL) and washed with 10% aq HCl (150 mL), sat NaHCO3 (150 mL) and water (450 mL). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was taken in 150 mL of methanol and NaOH (290 mg, 7.26 mmol, 1.0 eq) was added and stirred at room temperature for 24 h. Methanol was removed and the residue was neutralized with 10% aq HCl. The reaction mixture was then extracted with ethyl acetate (2). Organic layer was collected, dried (MgSO4) and evaporated to give a crude product, which was purified by column chromatography (EtOAc/Hexane) to give the amide. To a solution of the hydroxy amide (500 mg, 1.07 mmol, 1.0 eq) in DMF (15 mL) was added Cs2CO3 (1.04 g, 3.21 mmol, 3.0 eq) and stirred at room temperature for 20 min. Then bromide (261 mg, 1.60 mmol, 1.5 eq) was added and stirred at rt for 24 h. The reaction mixture was then diluted with ethyl acetate (25 mL) and washed with water (4*). Organic layer was collected, dried (MgSO4) and evaporated to give a residue, which was then treated with 95% TFA:H2O for 12 h. TFA was removed and azeotroped with toluene to give a residue, which was purified by column chromatography (EtOAc/Hexane 10% to 50%) to give the desired product. Mass Spectrum (LCMS, ESI Pos.) Calcd. For C12H30N2O3: 384.0 (M+H), Found 362.0.

References: [1]Patent: US2018/118679,2018,A1 .Location in patent: Paragraph 0293-0295.

23
[ 873975-41-8 ]
[ 50-00-0 ]
[ 20781-20-8 ]
[ 10601-99-7 ]
N-(2-((2-azidoethyl)amino)-2-oxoethyl)-N-(2,4-dimethoxybenzyl)-3-ethynylbenzamide [ No CAS ]