193537-14-3|Ethyl 6-Boc-2-amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3-carboxylate| Ambeed

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Quality Control of [ 193537-14-3 ] Purity: 97% SDS Specification

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Product Details of [ 193537-14-3 ]

CAS No. :	193537-14-3
Formula :	C₁₅H₂₂N₂O₄S
M.W :	326.41
SMILES Code :	CCOC(=O)C1=C(N)SC2=C1CCN(C2)C(=O)OC(C)(C)C
MDL No. :	MFCD05664039
InChI Key :	XSXVOVXVHBSSSN-UHFFFAOYSA-N
Pubchem ID :	2794740

Safety of [ 193537-14-3 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 193537-14-3 ] Show Less

Physicochemical Properties

Num. heavy atoms	22
Num. arom. heavy atoms	5
Fraction Csp3	0.6
Num. rotatable bonds	6
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	89.99
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	110.1 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	3.4
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	2.78
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.28
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.	1.59
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	2.74
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	2.56

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.39
Solubility	0.134 mg/ml ; 0.00041 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-4.75
Solubility	0.00583 mg/ml ; 0.0000179 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Moderately 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	-2.83
Solubility	0.482 mg/ml ; 0.00148 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	No
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	Yes
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	Yes
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	Yes
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.	-6.32 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	0.0
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.	1.0 alert
Brenk? Structural Alert: implemented from Brenk R. et al. 2008 ChemMedChem	1.0 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<0.0
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)	3.42

Application In Synthesis of [ 193537-14-3 ]

* 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 [ 193537-14-3 ]

[ 193537-14-3 ] Synthesis Path-Downstream 1~35

1
[ 4755-77-5 ]
[ 193537-14-3 ]
[ 474844-00-3 ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

2
[ 79099-07-3 ]
[ 105-56-6 ]
[ 193537-14-3 ]

Yield	Reaction Conditions	Operation in experiment
88%	With sulfur; triethylamine; In ethanol; for 16.0h;	2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester (step a). To a mixture of 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (12.9 g), ethyl cyanoacetate (7.345 g), and sulphur (2.080 g) in absolute ethanol (50 mL) was added triethylamine (9 mL). After stirring for 16 h, the precipitate was collected by filtration and washed with ethanol to give the title compound (18.7 g, 88%). 1H NMR (300 MHz, CDCl3): delta 6.02 (s, 2H), 4.31 (s, 2H), 4.23 (q, 2H, J=7.2 Hz), 3.58 (t, 2H, J=6.0 Hz), 2.72-2.80 (brs, 2H), 1.44 (s, 9H), 1.30 (t, 3H, J=7.2 Hz). LC-MS (ESI) m/z 327.0 (M+H).
87%	With sulfur; triethylamine; In ethanol;	General procedure: To a mixture of cyclohexanone (1) (9.80 g, 100 mmol), ethylcyanoacetate (11.32 g, 200.0 mmol), and sulfur (3.20 g, 100.0 mmol) inabsolute ethanol (200 ml) was added triethylamine (20 ml) and refluxedfor 12 h; the reaction mixture was concentrated and the residue waspartitioned between water and ethyl acetate. The organic layer wasseparated, and concentrated, and the crude product was recrystallizedwith ethanol (150 ml), to give 2. Yield 76%, light yellow crystal.
86%	With morpholine; sulfur; In ethanol; at 20℃;	tert-Butyl 4-oxopiperidine-l-carboxylate (101 g, 505 mmol) was dissolved in ethanol (806 mL), and ethyl cyanoacetate (57.2 g, 505 mmol) and sulfur (17.0 g, 531 mmol) were added. The mixture was stirred for a couple of minutes, and then morpholine (44.0 g, 505 mmol) was added. The reaction was stirred at rt overnight. The precipitate was collected by suction filtration and washed with ethanol to yield 142 g (86%) of the title compound.1H-NMR (400 MHz, DMSOd6): delta = 1.25 (t, 3H), 1.41 (s, 9H), 2.63-2.68 (m, 2H), 3.51 (t, 2H), 4.15 (q, 2H), 4.24 (br. s, 2H), 7.32 (s, 2H).LC/MS (method 5): R, = 2.40 min; MS (ESIpos): m/z = 327 [M+H]+.

83%	With sulfur; diethylamine; In ethanol; at 20℃; for 16.0h;	To a 1-Boc-4-piperidone (25.0 g, 123 mmol) in ethanol (100 mL) solution were added ethyl cyanoacetate (14.2 g, 123 mmol, 1 equiv), diethylamine (12.72 mL, 123 mmol, 1 equiv), and sulfur (4.14 g, 129 mmol, 1.05 equiv). The reaction was stirred at room temperature for 16 h then filtered and washed with ethanol (25 mL) to obtain a white solid (33.11 g, 102 mmol, 83%). 1H NMR (DMSO-d6) delta 7.31 (broad s, 2H), 4.22 (s, 2H), 4.13 (q, 2H), 3.49 (t, 2H), 2.63 (t, 2H), 1.39 (s, 9H), 1.23 (t, 3H); LCMS RT=3.49 min, [M+H]+=326.7.
12%	With morpholine; sulfur; In ethanol; at 20 - 40℃;	General procedure: A mixture of the ketone (1 eq.), cyanoacetate (1 eq.), and elemental sulphur (1eq.) in ethanol were combined and heated at 40-70 C. Morpholine or diethylamne (1 eq.) was added dropwise. The reaction was stirred at 40-70 C for 1-4 hours, and then stirred at room temperature overnight. The resulting precipitate was typically collected by filtration and recrystallised from ethanol or toluene.
	With morpholine; sulfur; In ethanol; at 50℃; for 3.0h;	Example 4A 2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester To a solution of t-butyl-4-oxo-1-piperidinecarboxylate (25.1 g, 0.13 mol), ethyl cyanoacetate (14.8 mL, 0.14 mol) and sulfur (4.4 g, 0.14 mol) in 200 mL ethanol was added morpholine (30.8 mL, 0.35 mol). The mixture was warmed to 50 C. and stirred for 3 hours. The reaction mixture was then cooled to ambient temperature, diluted with diethyl ether and filtered. The residue was washed with H2O and diethyl ether. The filtrate was concentrated under reduced pressure and purified via column chromatography (SiO2, 70% hexanes:ethyl acetate). The resulting material was combined with the filtration residue to afford the title compound. MS (DCI/NH3) m/z 327 (M+H)+.
	With sulfur; triethylamine; In ethanol; at 20℃; for 16.0h;	The N-(tert-Butoxycarbonyl)-4-piperidone, NCCH2CO2Et and Et3N was mixed at roomtemperature then stirring for 16 h, and then heated to 120 C for 16 h in DMF with the formamidineacetate. Then, the intermediate was reacted with POCl3 and DIPEA in toluene to obtain thecompound 7 (yield 89%).

References: [1]Synlett,2010,p. 1351 - 1354.
[2]Patent: US2010/120805,2010,A1 .Location in patent: Page/Page column 44.
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 7316 - 7326.
[4]ChemMedChem,2020,vol. 15,p. 716 - 725.
[5]Bioorganic and Medicinal Chemistry,2019,vol. 27,p. 2268 - 2279.
[6]Patent: WO2009/33581,2009,A1 .Location in patent: Page/Page column 62.
[7]Journal of Enzyme Inhibition and Medicinal Chemistry,2019,vol. 34,p. 909 - 926.
[8]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.
[9]Patent: US2010/298297,2010,A1 .Location in patent: Page/Page column 10; 15.
[10]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.
[11]Chemical Communications,2013,vol. 49,p. 190 - 192.
[12]European Journal of Medicinal Chemistry,2014,vol. 86,p. 270 - 278.
[13]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 7353 - 7361.
[14]Organic and Biomolecular Chemistry,2016,vol. 14,p. 6119 - 6133.
[15]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7089 - 7093.
[16]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.
[17]Patent: US2009/18114,2009,A1 .Location in patent: Page/Page column 18.
[18]MedChemComm,2013,vol. 4,p. 1202 - 1207.
[19]Bioorganic and Medicinal Chemistry,2014,vol. 22,p. 1938 - 1947.
[20]Molecules,2016,vol. 21.
[21]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 1609 - 1613.

3
[ 404-72-8 ]
[ 193537-14-3 ]
2-[3-(3-fluoro-phenyl)-thioureido]-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

4
[ 193537-14-3 ]
[ 851852-78-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

5
[ 193537-14-3 ]
[ 851852-76-1 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

6
[ 193537-14-3 ]
[3-(3-Fluoro-phenyl)-4-oxo-3,4,5,6,7,8-hexahydro-pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-2-ylsulfanyl]-acetic acid hydrazide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

7
[ 193537-14-3 ]
[ 851852-75-0 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

8
[ 193537-14-3 ]
[3-(3-Fluoro-phenyl)-7-methyl-4-oxo-3,4,5,6,7,8-hexahydro-pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-2-ylsulfanyl]-acetic acid hydrazide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

9
[ 193537-14-3 ]
[ 851852-77-2 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

10
[ 193537-14-3 ]
[3-(3-Fluoro-phenyl)-4-oxo-7-propyl-3,4,5,6,7,8-hexahydro-pyrido[4',3':4,5]thieno[2,3-d]pyrimidin-2-ylsulfanyl]-acetic acid hydrazide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

11
[ 193537-14-3 ]
[ 851852-74-9 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

12
[ 193537-14-3 ]
3-(3-fluoro-phenyl)-2-hydrazinocarbonylmethylsulfanyl-4-oxo-3,5,6,8-tetrahydro-4H-9-thia-1,3,7-triaza-fluorene-7-carboxylic acid tert-butyl ester [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2005,vol. 15,p. 1885 - 1889.

13
[ 193537-14-3 ]
2-(hydroxyoxalyl-amino)-6-pyridin-3-ylmethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

14
[ 193537-14-3 ]
2-(hydroxyoxalyl-amino)-6-pyridin-4-ylmethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

15
[ 193537-14-3 ]
2-(oxalylamino)-6-pyridin-2-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

16
[ 193537-14-3 ]
2-(hydroxyoxalyl-amino)-6-(3-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

17
[ 193537-14-3 ]
[ 474844-03-6 ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

18
[ 193537-14-3 ]
2-(ethoxyoxalylamino)-6-pyridin-4-ylmethyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylic acid ethyl ester [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

19
[ 193537-14-3 ]
[ 474844-01-4 ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

20
[ 193537-14-3 ]
2-(hydroxyoxalyl-amino)-6-quinolin-2-ylmethyl-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-3-carboxylic acid [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

21
[ 193537-14-3 ]
[ 474844-05-8 ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

22
[ 193537-14-3 ]
3-ethoxycarbonyl-2-(ethoxyoxalylamino)-4,5,6,7-tetrahydrothieno[2,3-c]pyridin-6-ium trifluoroacetate [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2002,vol. 45,p. 4443 - 4459.

Yield	Reaction Conditions	Operation in experiment
63%	With sulfur; diethylamine; In ethanol; at 70℃; for 3.0h;	General procedure: [00139] Ethyl cyanoacetate (0.53 g, 4.71 mmol), sulfur (0.18 g, 5.68 mmol), and ketone (1.0 g, 4.28 mmol) were suspended in EtOH (10.0 mL). Diethylamine (0.62 g, 8.57 mmol) was added and the mixture was heated to 70 C for 3 h. After the reaction was complete, EtOH was evaporated under reduced pressure resulting in a brown solid, which was dissolved in CH2CI2. The CH2CI2 layer was washed with sat. NH4CI (20.0 mL), deionized H20 (20.0 mL), and sat. NaCl (20.0 mL). After drying with anhydrous NaS04 and filtration, the solvent was evaporated and the crude product was purified by crystallization from cold MeOH to obtain product; [00155] Yield: 63% (4.2 g); silica gel TLC R= 0.49 (40% ethyl acetate in hexanes); ?H-NMR (600 MHz, CDC13): 5 4.36 (s, 2H, H-9), 4.27 (q, 2H, fl6,17 6Hz, H-16), 3.62 (t, 2H, J2,3 6Hz, H-2), 2.81 (t, 2H, J3,2 6Hz, H-3), 1.49 (s, 9H, H-13, 20, 21), 1.35 (t, 3H, f16,17 6Hz, H-17); ?3C-NMR (150 MHz, CDC13): 5166.54 (C-2), 163.44 (C-il), 153.88 (C-13), 130.80 (C-4, 9), 102.61 (C-3), 79.08 (C-iS), 42.48 (C-8),41.45 (C-6), 28.07 (C-20, 19, 16), 14.11 (C-5); mass spectrum (ESI), m/z = 349.1 (M+23) C15H22N204S requires 349.11 (M+23)

24
[ 3473-63-0 ]
[ 193537-14-3 ]
[ 874801-60-2 ]

Yield	Reaction Conditions	Operation in experiment
90%	In N,N-dimethyl-formamide; at 100℃; for 16.0h;	4-Oxo-3,5,6,8-tetrahydro-4H-9-thia-1,3,7-triaza-fluorene-7-carboxylic acid tert-butyl ester (step b). A mixture of 2-amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester (18.5 g) and formamidine acetate (8.85 g) in DMF (100 mL) were heated at 100 C. for 16 h. The reaction mixture was cooled and concentrated. The residues was partitioned between water and ethyl acetate. The organic layer was washed with water 3 times and concentrated to give the title compound (15.8 g, 90%). 1H NMR (400 MHz, CDCl3): delta 7.88 (s, 1H), 4.56-4.62 (brs, 2H), 3.62-3.70 (brs, 2H), 3.02-3.08 (brs, 2H), 1.42 (s, 9H). LC-MS (ESI) m/z 308.1 (M+H).
90.6%	In N,N-dimethyl-formamide; at 100℃;	To a <strong>[193537-14-3]2-Amino-4,7-dihydro-5H-thieno[2,3-c]pyridine-3,6-dicarboxylic acid 6-tert-butyl ester 3-ethyl ester</strong> (5.0 g, 15 mmol) in DMF (50 mL) solution was added formamidine acetate (2.39 g, 23 mmol, 1.5 equiv). The mixture was heated at 100 C. in an oil bath for overnight. The reaction mixture was cooled to rt and then concentrated in vacuo. Ethyl acetate (50 mL) was added to the reaction solid mixture and stirred at rt for 2 h. The mixture was then filtered, rinsed with ethyl acetate (25 mL). The solid was placed in a vacuum oven and dried for overnight to yield a white solid (4.17 g, 90.6%). 1H NMR (CD3OD-d4) delta 8.05 (s, 1H), 4.57 (s, 2H), 3.61 (t, 2H), 2.92 (t, 2H), 1.42 (s, 9H); LCMS RT=2.78 min, [M+H]+=308.0.
88%	In N,N-dimethyl-formamide; at 100℃;	To a solution of 6-tert-butyl 3-ethyl 2-amino-4,7-dihydrothieno[2,3-c]pyridine-3,6(5H)-dicarboxy- late from Example 9A (1.23 kg, 3.77 mol) in DMF (10.3 L) was added formamidine acetate (588 g, 5.65 mol). The mixture was heated to 1000C overnight. The solvent was removed in vacuo. The residue was stirred with ethyl acetate (3 L) for 2 h. The precipitate was collected by suction filtration and rinsed with ethyl acetate. The solid was dried to yield 1.02 kg (88%) of the title compound.1H-NMR (400 MHz, DMSOd6): delta = 1.43 (s, 9H), 2.91-2.96 (m, 2H), 3.62 (t, 2H), 4.58 (s, 2H), 8.05 (s, IH), 12.38 (br. s, IH).LC/MS (method 4): R, = 2.03 min; MS (ESIpos): m/z = 308 [M+H]+.

In N,N-dimethyl-formamide; at 120℃; for 16.0h;

The N-(tert-Butoxycarbonyl)-4-piperidone, NCCH2CO2Et and Et3N was mixed at roomtemperature then stirring for 16 h, and then heated to 120 C for 16 h in DMF with the formamidineacetate. Then, the intermediate was reacted with POCl3 and DIPEA in toluene to obtain thecompound 7 (yield 89%).

References: [1]Patent: US2010/120805,2010,A1 .Location in patent: Page/Page column 44.
[2]Patent: US2010/298297,2010,A1 .Location in patent: Page/Page column 10; 15; 16.
[3]Journal of Medicinal Chemistry,2010,vol. 53,p. 7316 - 7326.
[4]Journal of Enzyme Inhibition and Medicinal Chemistry,2019,vol. 34,p. 909 - 926.
[5]Patent: WO2009/33581,2009,A1 .Location in patent: Page/Page column 62-63.
[6]MedChemComm,2013,vol. 4,p. 1202 - 1207.
[7]Molecules,2016,vol. 21.
[8]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 1609 - 1613.

25
[ 193537-14-3 ]
[ 37636-40-1 ]

References: [1]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 7353 - 7361.

26
[ 193537-14-3 ]
[ 923010-68-8 ]

References: [1]Organic and Biomolecular Chemistry,2016,vol. 14,p. 6119 - 6133.
[2]Bioorganic and Medicinal Chemistry,2009,vol. 17,p. 7353 - 7361.

27
[ 103-80-0 ]
[ 193537-14-3 ]
[ 1351512-19-0 ]

Yield	Reaction Conditions	Operation in experiment
5%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; for 48.0h;	Phenylacetyl chloride (81 muL, 0.614 mmol) was added dropwise to a solution containing 9g (100 mg, 0.307 mmol) and DIPEA (59 muL, 0.34 mmol) in CH2Cl2 (2 mL), and the reaction was stirred for 2 days. The reaction solution was washed with 0.1M HCl and 1M NaOH. The organic layer was concentrated under reduced pressure and the residue was chromatographed on silica gel (hexane/Et2O 4:1) and then recrystallised from hexane (6.1 mg, 5%). 1H NMR (300 MHz, CDCl3) delta 7.45 (m, 5H, C6H5), 4.54 (s, 2H, 7-CH2), 4.29 (q, J = 7.1 Hz, 2H, CH2CH3), 3.87 (s, 2H, CH2Ph), 3.68 (m, 2H, 5-CH2), 2.90 (m, 2H, 4-CH2), 1.53 (s, 9H, Boc), 1.37 (t, J = 7.2 Hz, 3H, CH2CH3). ESI-MS m/z 445.3 [M + H]+.

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7089 - 7093.

28
[ 193537-14-3 ]
[ 1351512-20-3 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7089 - 7093.

29
[ 193537-14-3 ]
[ 921091-23-8 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7089 - 7093.

30
[ 193537-14-3 ]
[ 1351512-23-6 ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2011,vol. 21,p. 7089 - 7093.

31
[ 75-36-5 ]
[ 193537-14-3 ]
[ 874801-58-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.
[2]Organic and Biomolecular Chemistry,2016,vol. 14,p. 6119 - 6133.

32
[ 193537-14-3 ]
[ 1369966-94-8 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.

33
[ 193537-14-3 ]
[ 1369966-95-9 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.

34
[ 193537-14-3 ]
[ 1369966-96-0 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.

35
[ 193537-14-3 ]
[ 1369966-97-1 ]

References: [1]Journal of Medicinal Chemistry,2012,vol. 55,p. 3101 - 3112.

Historical Records

Technical Information

• Acyl Group Substitution • Bouveault-Blanc Reduction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Catalytic Hydrogenation • Chan-Lam Coupling Reaction • Complex Metal Hydride Reductions • Ester Cleavage • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • Petasis Reaction • Preparation of Amines • Reactions of Amines • Reactions with Organometallic Reagents • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Ugi Reaction

Related Functional Groups of
[ 193537-14-3 ]

Amides

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Esters

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Amines

A388367 [25913-34-2]

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Related Parent Nucleus of
[ 193537-14-3 ]

Other Aromatic Heterocycles

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CAS No.: 193537-14-3

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