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(5-Bromothiophen-2-yl)methanamine hydrochloride

(5-Bromothiophen-2-yl)methanamine hydrochloride

(5-Bromothiophen-2-yl)methanamine hydrochloride

CAS No.: 1001414-56-7

Category Products

Cat.NO.:A270417 Purity:97%

Product Details of [ 1001414-56-7 ]

CAS No. :	1001414-56-7
Formula :	C₅H₇BrClNS
M.W :	228.54
SMILES Code :	NCC1=CC=C(Br)S1.[H]Cl
MDL No. :	MFCD08752581
InChI Key :	DWYVWUCEDHIAMH-UHFFFAOYSA-N
Pubchem ID :	42888202

Safety of [ 1001414-56-7 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H335
Precautionary Statements:	P261-P305+P351+P338

Computational Chemistry of [ 1001414-56-7 ] Show Less

Physicochemical Properties

Num. heavy atoms	9
Num. arom. heavy atoms	5
Fraction Csp3	0.2
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	1.0
Molar Refractivity	46.66
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	54.26 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
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	2.32
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.62
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.	1.63
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	2.83
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.88

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-3.06
Solubility	0.197 mg/ml ; 0.000864 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.	-3.1
Solubility	0.182 mg/ml ; 0.000798 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	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	-2.57
Solubility	0.619 mg/ml ; 0.00271 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.	-6.05 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.	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)	2.24

Application In Synthesis of [ 1001414-56-7 ]

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

Downstream synthetic route of [ 1001414-56-7 ]

[ 1001414-56-7 ] Synthesis Path-Downstream 1~7

1
[ 215183-27-0 ]
[ 1001414-56-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With hydrogenchloride; In ethyl acetate; for 2.0h;	Reactamt (8.322 g, 0.0285 mmol) was dissolved in 150 ml of anhydrous ethyl acetate. The dried HCl was induced continuously for two hours and a large amount of precipitate formed. The solvent was removed and the residue was washed with anhydrous ethyl acetate (3 x 50 ml), ether (3 x 50 ml) in turn to give the product 01-0034-1 (5.862 g), yield: 95%.

References: [1]Patent: WO2008/5457,2008,A2 .Location in patent: Page/Page column 185.

2
[ 1001414-56-7 ]
[ 1035346-03-2 ]
[ 1035346-67-8 ]

Yield	Reaction Conditions	Operation in experiment
	With N-ethyl-N,N-diisopropylamine; HATU; In ISOPROPYLAMIDE; at 20.0℃; for 24.0h;	21H. 4-(Aminomethv?-N-((5-bromothiophen-2-v?methv?-l-(7H-pyrrolor2.3- dlpyrimidin-4-yl)piperidine-4-carboxamide; <n=”133″/>HATU (419 mg, 1.10 mmol) was added in one portion to 4-((diphenylmethylene- amino)methyl)- 1 -(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (440mg, 1.00 mmol), <strong>[1001414-56-7](5-bromothiophen-2-yl)methanamine hydrochloride</strong> (229 mg, 1.00 mmol) and DIPEA (0.699 mL, 4.00 mmol) in DMA (5 ml) at 2O0C under nitrogen. The resulting solution was stirred at 20 0C for 24 hours. The reaction mixture was diluted with EtOAc (100 mL), and washed sequentially with water (2 x 100 mL) and saturated brine (50 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% MeOH in DCM. Pure fractions were evaporated to dryness to afford N-((5-bromothiophen- 2-yl)methyl)-4-((diphenylmethyleneamino)methyl)-l-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)piperidine-4-carboxamide. The product was dissolved in IPA (5.00 ml), water (1 ml) and hydrogen chloride 6N in isopropanol (1.669 ml, 10.01 mmol). The solution was stirred at 20 0C for 24 hours. The crude product was purified by ion exchange chromatography, using an SCX column. The desired product was eluted from the column using 7MNH3/MeOH and pure fractions were evaporated to dryness. The crude gum was triturated with Et20 to give a solid which was collected by filtration and dried under vacuum to give 4-(aminomethyl)-N-((5-bromothiophen-2-yl)methyl)-l-(7H-pyrrolo[2,3-d]pyrimidin-4- yl)piperidine-4-carboxamide (134 mg, 29.8 %) as a white solid. IH NMR (400.13 MHz, DMSO-d6) delta 1.44 – 1.51 (2H, m), 1.79 (2H, s), 2.07 – 2.10 (2H, m), 2.66 (2H, s), 3.40 (2H, d), 4.28 (2H, q), 4.42 (2H, d), 6.56 (IH, d), 6.82 (IH, d), 7.03 (IH, d), 7.15 (IH, d), 8.12 (IH, s), 8.71 (IH, t), 11.62 (IH, s) MS m/e MH+ 451

References: [1]Patent: WO2008/75110,2008,A1 .Location in patent: Page/Page column 130-131.

3
[ 1001414-56-7 ]
[ 1939-99-7 ]
[ 1445720-39-7 ]

Yield	Reaction Conditions	Operation in experiment
84%	With N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20.0℃; for 16.0h;	Step 1 : N-((5-Bromothiophen-2-yl)methyl)-l-phenylmethanesulfonamide To a suspension of <strong>[1001414-56-7](5-bromo-2-thienyl)methanamine hydrochloride</strong> (2 g, 8.75 mmol) in dichloromethane (30 mL) was added N,N-diisopropylethylamine (3.2 mL, 18.4 mmol) and the reaction was stirred until complete dissolution. Phenylmethanesulfonyl chloride (1.75 g, 9.18 mmol) was then added and the reaction was stirred at ambient temperature for 16 hours. The reaction was diluted with dichloromethane and washed with water and brine, dried with MgS04, concentrated and purified by silica gel column chromatography (0-100% EtOAc in heptane) to give N-[(5-bromo-2-thienyl)methyl]-l-phenyl-methanesulfonamide (2.55 g, 84% yield). LCMS (m/z) ES+ 364 [M+18]+.

References: [1]Patent: WO2013/92939,2013,A1 .Location in patent: Page/Page column 31-32.

4
[ 27757-85-3 ]
[ 1001414-56-7 ]

References: [1]Patent: WO2008/5457,2008,A2 .

5
[ 401485-19-6 ]
[ 1001414-56-7 ]

References: [1]Patent: WO2008/5457,2008,A2 .

6
[ 1001414-56-7 ]
[ 1445720-16-0 ]

References: [1]Patent: WO2013/92939,2013,A1 .

7
[ 1001414-56-7 ]
[ 1445720-40-0 ]

References: [1]Patent: WO2013/92939,2013,A1 .

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