5424-47-5|2-[3-(Dimethylamino)propionyl]thiophene Hydrochloride| Ambeed

Structure of 5424-47-5

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Quality Control of [ 5424-47-5 ] Purity: 98% SDS Specification

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Product Details of [ 5424-47-5 ]

CAS No. :	5424-47-5
Formula :	C₉H₁₄ClNOS
M.W :	219.73
SMILES Code :	O=C(C1=CC=CS1)CCN(C)C.[H]Cl
MDL No. :	MFCD00126349
InChI Key :	HPVHJPMLORARSR-UHFFFAOYSA-N
Pubchem ID :	2876891

Safety of [ 5424-47-5 ]

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

Computational Chemistry of [ 5424-47-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	5
Fraction Csp3	0.44
Num. rotatable bonds	4
Num. H-bond acceptors	2.0
Num. H-bond donors	0.0
Molar Refractivity	58.8
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	48.55 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	1.26
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	2.68
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.	1.13
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	2.59
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.53

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-2.02
Solubility	2.11 mg/ml ; 0.00962 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.	-1.88
Solubility	2.91 mg/ml ; 0.0132 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	-2.54
Solubility	0.64 mg/ml ; 0.00291 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.	-6.75 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)	2.13

Application In Synthesis of [ 5424-47-5 ]

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

Upstream synthesis route of [ 5424-47-5 ]
Downstream synthetic route of [ 5424-47-5 ]

[ 5424-47-5 ] Synthesis Path-Upstream 1~1

1
[ 5424-47-5 ]
[ 132335-47-8 ]

References: [1] Tetrahedron Letters, 1990, vol. 31, # 45, p. 7101 - 7104.
[2] Patent: WO2011/33366, 2011, A2, .

[ 5424-47-5 ] Synthesis Path-Downstream 1~35

1
[ 5424-47-5 ]
[ 98288-52-9 ]
[ 123760-40-7 ]

References: [1]Synthesis,1976,p. 1 - 24.

2
[ 5424-47-5 ]
[ 65867-28-9 ]
[ 70959-88-5 ]

References: [1]Archiv der Pharmazie,1979,vol. 312,p. 455 - 457.

3
[ 3406-02-8 ]
[ 5424-47-5 ]
[ 76283-81-3 ]

References: [1]Synthesis,1980,p. 565 - 566.

4
[ 26482-00-8 ]
[ 5424-47-5 ]
[ 123760-40-7 ]

References: [1]Journal of Organometallic Chemistry,1989,vol. 361,p. 277 - 282.
[2]European Journal of Inorganic Chemistry,2008,p. 1784 - 1794.

5
[ 16883-69-5 ]
[ 5424-47-5 ]
[ 144221-02-3 ]

References: [1]Journal of the Chemical Society, Dalton Transactions,1992,p. 2467 - 2474.

6
[ 42508-60-1 ]
[ 5424-47-5 ]
[ 29886-66-6 ]

References: [1]Synthesis,1991,p. 663 - 664.

7
[ 5424-47-5 ]
[ 81471-31-0 ]
[ 81471-45-6 ]

References: [1]Archiv der Pharmazie,1982,vol. 315,p. 199 - 207.

8
[ 5424-47-5 ]
[ 7465-65-8 ]
[ 35299-71-9 ]

References: [1]Journal of the Chemical Society, Dalton Transactions,1992,p. 2467 - 2474.

9
[ 5424-47-5 ]
[ 99764-97-3 ]
2-Benzenesulfinyl-1,5-di-thiophen-2-yl-pentane-1,5-dione [ No CAS ]

References: [1]Archiv der Pharmazie,1985,vol. 318,p. 1045 - 1048.

10
[ 5424-47-5 ]
[ 266338-29-8 ]
2-amino-6-(thiophen-2-yl)pyridine-3-carbonitrile [ No CAS ]

References: [1]Archiv der Pharmazie,1994,vol. 327,p. 33 - 40.

11
[ 5424-47-5 ]
[ 29481-22-9 ]

References: [1]Chemistry of Heterocyclic Compounds,1980,vol. 16,p. 339 - 344.
Khimiya Geterotsiklicheskikh Soedinenii,1980,vol. 16,p. 455 - 460.

12
[ 5424-47-5 ]
[ 132335-49-0 ]
[ 132335-44-5 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.
[2]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.

13
[ 5424-47-5 ]
cis,cis-1,3,5-Tri-(2-thenoyl)-cyclohexan [ No CAS ]

References: [1]Zeitschrift fur Naturforschung, Teil B: Anorganische Chemie, Organische Chemie,1985,vol. 40,p. 524 - 533.

14
[ 2170-09-4 ]
[ 5424-47-5 ]
2-(4-dimethylamino-2-hydroxy-2-thiophen-2-yl-butyl)-<i>N</i>-methyl-benzamide [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 3057 - 3068.

15
[ 5424-47-5 ]
[ 13196-35-5 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide; In water; at 20℃;	30% w/w NaOH (73 g, 0.55 mol) was added to a mixture of 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride (100 g, 0.46 mol) in water (150 ml), at room temperature, and the free base was extracted with toluene (170 ml).
	With sodium hydroxide; In water;pH 10;	1.2: Preparation of 3-dimethylamino-1-(thiophen-2-yl)-1-propanol 3-Dimethylamino-1-(2-thienyl)-1-acetone hydrochloride (30.8g, 0.14mol) was dissolved in 150 ml distilled water. The mixture was added dropwise with 2.5 M sodium hydroxide aqueous solution to reach a pH of about 10, extracted with ethyl acetate (100 mlx3). The organic phases were combined and washed with saturated sodium chloride anqueous solution twice, dried over anhydrous sodium sulfate, and distilled under a reduced pressure to remove ethyl acetate, thereby obtaining a yellow oily liquid. The liquid was dissolved in 30ml anhydrous tetrahydrofuran, the mixture was slowly added dropwise to the solution of LiAlH4 (7.8g, 0.21 mol) in 100 ml anhydrous tetrahydrofuran, and the reaction temperature was controlled at 0-5C in an ice bath. The ice bath was removed, and the reaction was performed at room temperature for 2h and stopped. The reaction liquid was added dropwise with anhydrous ethanol slowly, and the solids were removed by filtration under vacumm after the residual LiAlH4 was completed. Tetrahydrofuran was distilled out under a reduced pressure and the residue was extracted with dichloromethane (50 mlx3). The organic phases were combined, washed with saturated sodium chloride aqueous solution twice, dried over anhydrous sodium sulfate, and distilled to remove dichloromethane, to obtain 22.9g of 3-dimethylamino-1-(thiophen-2-yl)-1-propanol as a white solid in a yield of 88.3%. 1H-NMR delta (ppm, CD3COCD3-d6): 7.28-7.30(dd,1H,Ar-H); 6.92-6.96(m,2H,Ar-H); 5.06-5.09(t,1H,CHOH); 2.87(s,1H,OH); 2.55-2.62(m,1H,CH2N); 2.40-2.47 (m,1H, CH2N); 2.23(s,6H,N(CH3)2); 1.86-1.91(m,2H,CH2CH2N).

References: [1]Patent: EP1857451,2007,A1 .Location in patent: Page/Page column 4.
[2]Patent: EP2305669,2011,A1 .Location in patent: Page/Page column 6.

16
[ 5424-47-5 ]
3-(2-dimethylaminoethyl)-3-(2-thienyl)-isochroman-1-one hydrochloride [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry,2005,vol. 13,p. 3057 - 3068.

17
[ 5424-47-5 ]
[ 144221-05-6 ]

References: [1]Journal of the Chemical Society, Dalton Transactions,1992,p. 2467 - 2474.

18
[ 5424-47-5 ]
[ 144221-04-5 ]

References: [1]Journal of the Chemical Society, Dalton Transactions,1992,p. 2467 - 2474.

19
[ 5424-47-5 ]
[ 144221-03-4 ]

References: [1]Journal of the Chemical Society, Dalton Transactions,1992,p. 2467 - 2474.

20
[ 5424-47-5 ]
C₁₃H₁₂Cl₂NO₂PS [ No CAS ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1981,vol. 20,p. 414 - 415.

21
[ 5424-47-5 ]
[ 78994-00-0 ]

References: [1]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1984,vol. 23,p. 907 - 913.
[2]Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry,1981,vol. 20,p. 414 - 415.

22
[ 5424-47-5 ]
[ 132335-47-8 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.
[2]Patent: WO2011/33366,2011,A2 .

23
[ 5424-47-5 ]
[ 116539-60-7 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.

24
[ 5424-47-5 ]
[ 116539-58-3 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.
[2]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[3]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[4]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.

25
[ 5424-47-5 ]
[ 878757-08-5 ]

References: [1]Tetrahedron Letters,1990,vol. 31,p. 7101 - 7104.

26
[ 5424-47-5 ]
[ 4653-08-1 ]

References: [1]Journal of the Chemical Society,1947,p. 1196,1200.

27
[ 5424-47-5 ]
[ 145763-17-3 ]

References: [1]Journal of the Chemical Society,1947,p. 1196,1200.

28
[ 5424-47-5 ]
[ 91803-19-9 ]

References: [1]Journal of the American Chemical Society,1942,vol. 64,p. 451,453.

29
[ 5424-47-5 ]
[ 132335-44-5 ]

Yield	Reaction Conditions	Operation in experiment
92.1%	With glucose dehydrogenase; D-glucose; Rhodosporidium toruloides carbonyl reductase 9 from Escherichia coli; NADPH; sodium hydroxide; In aq. phosphate buffer; at 30℃; for 4h;pH 7;Enzymatic reaction;Kinetics;	In a 2-L bioreactor, 2a (1000mM), glucose (6000mM), NADP+ (0.75mM), and sonicated cells of co-expressing E. coli/RtSCR9-GDH (10gDCWL-1) were mixed in a total volume of 1L phosphate buffer (100mM, pH 7.0). The resulting mixture was stirred at 30C with 200rpm shaking for 240min. The pH was maintained at 7.0 with 2M NaOH during the reaction. After reaching completion, the pH was adjusted to 11-12 followed by extraction using ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated to give (S)- 3a. Yield: 92.1%. 1H NMR (500MHz, DMSO-d6): delta=7.36 (dd, J=4.9, 1.2Hz, 1H), 6.93 (m, 2H), 5.79 (s, 1H), 4.86 (m, 1H), 2.30 (qt, J=12.0, 7.1Hz, 2H), 2.12 (s, 6H), 1.79 (m, 2H). 13C NMR (126MHz, DMSO-d6): delta=150.72, 126.40, 123.79, 122.51, 67.39, 55.96, 45.15, 36.92. [alpha]25D=-4.9 (c=10mg/mL, ethyl acetate).
	With hydrogen; sodium hydrogencarbonate; (2R,4R)-4-(dicyclohexylphosphino)-2-(diphenylphosphino-methyl)-N-methyl-aminocarbonyl-pyrrolidine;di-mu-chloro-bis(1,5-cyclooctadiene)dirhodium; In methanol; water; at 30℃; under 75007.5 Torr; for 20h;	70 g (0.32 mol) of 1-(N,N-dimethylamino)-3-(2-thienyl)-propan-3-one-hydrochloride are suspended in 630 ml of methanol and 70 ml of water under nitrogen; 16.5 mg bis-(1.5-cyclooctadiene)-dirhodium(I)-dichloride, 34.9 mg (2R, 4R)-4-dicyclohexylphosphino)-2-(diphenylphosphino-methyl)-N-methyl-aminocarbonyl) pyrrolidine and 140 mg sodium hydrogen carbonate are added and the suspension is hydrogenated at 30 C. and 100 bar hydrogen pressure for about 20 hours. Then the reaction mixture is evaporated down and the residue obtained is divided between 350 ml of water and 250 ml organic solvent (toluene or dichloromethane). The pH is adjusted to 1.6 with 32% hydrochloric acid and the mixture is stirred for 10 minutes, then the aqueous phase is separated off. The organic phase is again combined with 250 ml of water, stirred and the aqueous phase is again separated off. The combined aqueous phases are adjusted to pH 9.0 with 400 ml organic solvent and 45% sodium hydroxide solution, stirred, and then the phases are separated. The aqueous phase is extracted again with 200 ml solvent and the combined organic phases are evaporated down at 60 C. and 5 mbar. The yield of crude product is 50.0 g (85% of theory), chemical purity >98% (NMR). The crude product is recrystallised from 150 ml n-heptane, washed with another 50 ml of n-heptane and dried overnight at 40 C. and 5 mbar. 46.8 g (79% of theory) of S-N, N-dimethyl-3-hydroxy-3-(2-thienyl)-propylamine are obtained as a white solid, purity >98% (NMR), enantiomeric purity 94% (HPLC), melting point 76-78 C.
		The duloxetine alkyl carbamate represented by the formula (Ib) was synthesized by a known method (steps 1 to 4 of the above scheme).Specifically, 2-acetylthiophene (63.1 g; 0.5 mol), dimethylamine hydrochloride (53.0 g; 0.65 mol), paraformaldehyde (19.8 g; 0.22 mol) and ethanol (80 ml) (1 ml) to give 3-dimethylamino-1- (2-thienyl) -1-propanone hydrochloride,Reduction with sodium borohydride, resolution with optically active mandelic acid yielded optically active (S) N, N-dimethyl-3- (2-thienyl) -3-hydroxypropylamine.Next, by reaction of 1-fluoronaphthalene with sodium hydride, N, N-dimethyl-duloxetine was obtained.Subsequently, the reaction with the corresponding alkyl chloroformate (4.6 ml; 48.5 mmol) gave the duloxetine alkyl carbamate represented by the above formula (Ib). The ethanol solution (10 mL) of the potassium hydrate (87% of purity, 2.16g;33.5mmol) was added to the toluene solution (10 mL) of the obtained duloxetine ethyl carbamate (Ib) and (2.5g;6.7mmol) at the room temperature. It heated until it flowed back at 85 to 90 degree C about mixed liquor, and the solvent was distilled off until the internal temperature became 100 degrees C from there. Repeating distilling off of a solvent furthermore, in the range of 95 to 100 degree C, temperature was maintained and it stirred for 2 hours. It cooled to the room temperature and washed the organic layer obtained by adding water (10 mL) and ethyl acetate (10 mL) with water (20 mL). With sodium sulfate, it dried, concentration drying was filtered and carried out, and the compound of the title was obtained at 1.96 g (yield: 98.4%, optical isomer:0.16%).[0054]1H-NMR(400-MHz, DMSO-d6):8.23-8.20 (m, 1H), 7.86-7.82 (m, 1H), 7.53-7.49 (m, 2H), 7.44-7.41 (m, 2H), 7.33 (t, 1H), 7.21 (dd, 1H), 7.05(d,1H),6.97(dd,1H),5.99(t,1H),2.62(2H,t)2.26(3H,s),2.36-2.29(m,1H),2.12-2.03(m,1H)

References: [1]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[2]Patent: US2005/197503,2005,A1 .Location in patent: Page/Page column 4.
[3]Organic Process Research and Development,2006,vol. 10,p. 905 - 913.
[4]Organic Process Research and Development,2006,vol. 10,p. 905 - 913.
[5]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[6]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[7]Patent: CN105566284,2016,A .
[8]Patent: JP2017/19727,2017,A .Location in patent: Paragraph 0053.
[9]Patent: CN104803968,2017,B .
[10]Patent: CN104829587,2017,B .
[11]Patent: CN104829587,2017,B .

30
[ 5424-47-5 ]
[ 74-89-5 ]
N-methyl-3-(thien-2-yl)-3-morpholino-propylamine hydrochloride [ No CAS ]

References: [1]Patent: WO2004/65376,2004,A1 .Location in patent: Page/Page column 3.

31
[ 88-15-3 ]
[ 506-59-2 ]
[ 5424-47-5 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrogenchloride; In isopropyl alcohol;	PREPARATION 1 (S)-(-)-N,N-dimethyl-3-hydroxy-3-(2-thienyl)-propanamine A mixture of 8.18 g of 2-acetylthiophene, 6.66 g of dimethylamine hydrochloride, 2.9 g of paraformaldahyde and 0.31 g of concentrated hydrochloric acid in 20 ml of isopropanol was heated to reflux and stirredfor 6 hours. The mixture was then cooled to 0 and stirred for one hour more. The slurry was then filtered, and the solid was washed with cold ethanol. The washed solid was dried for 16 hours at 50 to obtain 12.5 g of 2-thienyl 2-dimethylaminoethyl ketone hydrochloride, as awhite solid.
75.0 g (73%)	With hydrogenchloride; paraformaldehyde; In ethanol;	A. 3-Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride A mixture of 2-acetylthiophene (63.1 g, 0.5 mol), dimethyl-amine hydrochloride (53.0 g, 0.65 mol), paraformaldehyde (19.8 g, 0.22 mol), and 12N hydrochloric acid (1 ml) in ethanol (80 ml) was refluxed for one and one-half hours. The solution was diluted with ethanol (100 ml) and acetone (500 ml). The solution was chilled overnight and the resulting solid was collected by filtration to yield 75.0 g (73%) of 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride as a colorless crystalline solid. mp=182 C.-184 C. Analysis calculated for C9 H14 ClNOS Theory: C, 49.20; H, 6.42; N, 6.37; Found: C, 49.40; H, 6.21; N, 6.09.
3.391 kg (85.7%)	With hydrogenchloride; paraformaldehyde; In ethanol;	A. 3 -Dimethylamino-1-(2-thienyl)-1-propanone hydrochloride A mixture of 2-acetylthiophene 2.274 kg, 18.0 mol), dimethylamine hydrochloride (1.91 kg, 23.4 mol), paraformaldehyde (0.8108 kg, 9.0 mol), and 37.5 ml of concentrated hydrochloric acid in ethanol (5.6 L) is refluxed for twenty hours. The mixture is cooled to 35C slowly then chilled to 0-5C. The solid is collected by vacuum filtration, washed twice with 1 L of ethanol, and vacuum dried at room temperature for 49 hours to afford 3.391 kg (85.7%) of 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride. mp = 174-176C

References: [1]Patent: US5744474,1998,A .
[2]Patent: US4956388,1990,A .
[3]Patent: EP457559,1991,A2 .

32
[ 5424-47-5 ]
[ 13636-02-7 ]

Yield	Reaction Conditions	Operation in experiment
95%	With sodium tetrahydroborate; sodium hydroxide; In methanol; water; at 35 - 40℃; for 2h;	1 50 g of 3-dimethylamino- l -(2-thienyl)- l -propanone hydrochloride was taken in 300 ml methanol. To the resulting mixture, 300 ml water and sodium hydroxide solution (27.3g in 45ml water) was added and stirred for few minutes. To the resulting mixture, 1 5.5 g of sodium borohydride was added. The reaction mass was heated at 35-40C under stirring for 2 hour. After completion of reaction, methanol was distilled off and the reaction mass was cooled to room temperature. Dichloromethane was added and the reaction mass was stirred for 30 minutes. The layers were separated and the aqueous layer was extracted with dichloromethane. The organic layers were combined and washed with water. The organic layer was distilled under vacuum to obtain the title compound.Yield: 90-95%.
93.5%	With sodium tetrahydroborate; sodium hydroxide; In ethanol; water; at 20℃;pH 11 -Ca. 12;	0.38 mol) of 2-thiophene-2-dimethylaminomethylethanone hydrochloride, 260 ml of ethanol and 130 ml of water were mixed and stirred, and 13.9 g of NaOH was slowly added at room temperature. The pH was adjusted to 11 to 12, Sodium borohydride 14.5 g (0.37mol), thereaction was carried out at room temperature overnight. The reaction was completed. The reaction was quenched by the addition of 160 ml of acetone. The ethanol was evaporated under reduced pressure to precipitate as a white solid and filtered todryness to give 66.7 g of a white solid in 93.5% yield.
87%	With sodium tetrahydroborate; sodium hydroxide; In methanol; water; at 0 - 20℃; for 4h;Inert atmosphere;	General procedure: Under a nitrogen atmosphere, sodium hydroxide(4.0 g of a 50% aqueous solution) was added carefully to a mixture of 2a-2b (50 mmol) in methanol (30 mL) at0 oC. The solution was treated with sodium borohydride (0.57 g, 15mmol) in several portions with stirring at ambient temperature for 4 h. Acetone(10 mL) was added slowly for further 20 min before water (20 mL) was added. Themixture was concentrated in vacuum and the residue was extracted with ethyl acetate. The combined organic phases were concentratedto obtain racemic 3a-3b.

78%	With methanol; sodium tetrahydroborate; sodium hydroxide; In water; at 0℃; for 15h;pH 11 - 12;	DX-A 02 · HCl (70.0 g, 0.34 mol)Was dissolved in methanol (840 mL)And water (420 mL) at 0 C.,By gradually adding sodium hydroxide, The pH of this solution was raised to 11-12.Sodium borohydride (12.9 g, 0.34 mol) was added,The mixture was stirred at 0 C. for 15 h. next,Methanol was distilled off under reduced pressure,The remaining solution was diluted with water.This solution was extracted with diethyl ether,This solution was extracted with diethyl ether,Washed with saturated sodium chloride solution,Dried over anhydrous sodium sulfate solution and concentrated under reduced pressure to obtain colorless crystals.This crystal was recrystallized from hexane, alpha-[2-(dimethylamino)ethyl]-2-thiophenemethanol(DX-A 03, 49.2 g, 78%).
72%	With sodium tetrahydroborate; sodium hydroxide; In water; at 20℃; for 1.5h;pH 1 - 12;Inert atmosphere;	To a solution of NaBH4 (310 mg, 0.30 eq)In aqueous NaOH(30% w / w) was added portionwise over 30 minutes a solution of 3-dimethylamino-1-thiophen-2-yl-propan-1-one hydrochlorideSalt (5.95 g, 27.2 mmol). The cloudy mixture was stirred at room temperature. After one hour, add a second portionOf NaBH4 (310 mg, 0.30 eq.). The reaction mixture was stirred overnight at room temperature under nitrogen. In about 20 hours, The HPLC showed complete conversion, and the turbid mixture was cooled to 0 & lt; 0 & gt; C. The reaction mixture was carefully washed with 37%HCl (aqueous) to pH 1 while maintaining the temperature below 10 & lt; 0 & gt; C. The turbid mixture gradually turns homogeneous. With toluene(2 x 20 mL) was added to the reaction mixture. The aqueous layer was cooled to 0 & lt; 0 & gt; C and carefully added with 30% NaOH (water) to pH 12,While maintaining the temperature below 20 & lt; 0 & gt; C. Forming a white precipitate. The aqueous solution was extracted with warm toluene (45 [deg.] C, 3 x 80 mL).Toluene was removed under reduced pressure (bath temperature 45 C). This white solid was taken up in ethylcyclohexane (20 mL) and heated to70 & lt; 0 & gt; C until a clear homogeneous mixture is obtained. The solution was stirred at 70 & lt; 0 & gt; C for 2 hours. The solution was cooled to zeroLt; 0 & gt; C. After about 45 minutes at 0 & lt; 0 & gt; C, the white solid was filtered and washed with ice-cold ethylcyclohexane (2 x 15 mL)Line washing. The white solid was dried under vacuum at 40 & lt; 0 & gt; C for 18 hours to give 3.6 g (72%) of 2 as a racemicmixture.
49.24 g (78%)	With sodium hydroxide; sodium borohydrid; In methanol; water;	B. alpha-[2-(Dimethylamino)ethyl]-2-thiophene methanol To a solution of 3-dimethylamino-1-(2-thienyl)-1-propanone hydrochloride (70.0 g, 0.34 mol) in 840 ml of methanol and 420 ml of water at about 0 C. was added 5N sodium hydroxide until the solution was slightly basic. To the resulting solution was added sodium borohydride (12.9 g., 0.34 mol) in portions. The mixture was allowed to warm to room temperature overnight. The methanol was removed in vacuo and the remaining solution was diluted with water. The solution was extracted with diethyl ether, and the solution was washed with a saturated sodium chloride solution, dried over anhydrous sodium sulfate and concentrated in vacuo to provide 56.7 g of colorless crystals. Recrystallization of the crystals from hexanes gave 49.24 g (78%) of the title compound as colorless crystals mp=72 C.-74 C. Analysis calculated for C9 H15 NOS Theory: C, S8.34; H, 8.16; N, 7.56; Found: C, S8.62; H, 8.29; N, 7.68.
	With methanol; sodium hydroxide; sodium tetrahydroborate; water; at 0 - 30℃; for 11h;	Example-4:Preparation of 3-(dimethyIamino)-l-(thiophen-2-yl) propan-l-olAdded 50 liters of 20% sodium hydroxide solution to a cooled solution of 100 Kgs. of 3-(dimethylamino)-l-(thiophen-2-yl) propan-1-one hydrochloride, 100 liters of methanol and 25 liters of water at 0-50C. Added a solution of 10 Kgs. of sodium borohydride in 50 liters of 20% sodium hydroxide to the above reaction mixture slowly at 0-50C in 5 hours. Allowed the reaction mixture temperature to 25-300C. Stirred the reaction mixture for 6 hours at 25-3O0C. Extracted the reaction mixture with methylene chloride. Separated the organic and aqueous layers. Extracted the aqueous layer with methylene chloride. Washed the organic layer with 10% sodium chloride solution. Distilled the solvent completely under reduced pressure at below 400C. Added 25 liters of hexanes to the above reaction mixture. Distilled the solvent completely under reduced pressure at below 400C. Added 100 liters of hexanes to the above reaction mixture. Heated the reaction mixture to reflux. Stirred the reaction mixture for 60 minutes. Cooled the reaction mixture to 0-50C and stirred the reaction mixture for 3 hours. Filtered the precipitated solid and washed with chilled hexanes. Dried the material at 50-550C for 6 hours to get the title compound. Yield: 75 Kgs. MR: 70-800C.
		b) Preparation of 3-dimetbyami»theta~l-(24Meffiy.)~I-pr°paiithetal:; A solution of 1 N sodium hydroxide (460 mL) was added to a mixture of 2-thienyi~ 2-dimelhylaminoepsilonthyl ketone hydrochloride (100 g) in methanol (350 mL) at about 250C to the pH of 11. After cooling the reaction mixture to 10-150C, sodium borohydride <n="8"/>(8.5 g) was added in portion over a period of 30 minutes. The reaction mixture was stirred at about 25C for 2 h. After the completion of the reaction, excess sodium borohydride was decomposed by addition of acetone at about 25C. The mixture was stirred at about 25C for 30 minutes. After concentrating the reaction mixture under reduced pressure to about 1/3 of the initial volume, the concentrated reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2 x 400 raL). The ethyl acetate layer was washed with water and concentrated under reduced pressure, Hexanes (200 mL) were added to the residue and the mixture was stirred for at about 250C for 1 Ii and at 5-10C for a further hour. The solid was filtered and dried under vacuum at 40-450C for 4-6 h to provide the title compound as an off-white solid.Yield: 78 g
		Example 1; (S)- 3-(dimethylamino)-l-(2-thienyl)-l-propanol (5): <n="11"/>lambda mixture of 2-acetyl thiophene (250 g, 1.98 mol), dimethyl amine hydrochloride (21 O g, 2.57 mole), paraformaldehyde (78.44 g, 0.871 mole) and concentrated HCl (3.97 ml) in ethanol (317 ml) was refluxed for 4 h. The reaction mixture was cooled to the room temperature and water (700 ml) was added, followed by addition of methanol (1.6 L) at room temperature. The reaction mixture was cooled to 5-10 C and basified with aqueous sodium hydroxide solution to adjust the pH 7-8. Then sodium borohydride (81 g, 2.18 mole) was added in small lots at 5-10 C. After completion of addition of sodium borohydride, reaction mixture was stirred for 30 minutes at 5-10 C. Then it was stirred at room temperature for 12-15 h. The reaction mixture was concentrated to obtain oily residue. The residue was treated with ethyl acetate (3.0 L) and washed with water (3x500 ml) and brine solution (500 ml). The ethyl acetate layer was separated, dried over sodium sulphate, and concentrated to obtain oil which solidified on standing to white solid (210 g). This solid was taken in methyl tert butyl ether (3.15 L) and heated to 45-50 C and a solution of (S)-(+)-Mandelic acid (86.27 g. 0.567 mole) in ethanol (250 ml) was added in a dropwise manner. The reaction mixture was stirred for 45 minutes at 45-50 C and cooled to room temperature. The solid obtained was filtered and washed with methyl tert butyl ether to obtain Mandelate salt (112 g). This salt was crystallized using acetone to get pure Mandelate salt (96 g). The Mandelate salt was basified with sodium hydroxide followed by extraction with dichloromethane to obtain (S)- 3-(dimethylamino)-l-(2- thienyl)-l-propanol as oil which solidified on standing. Yield 50g.
		Example 4; (S)- 3-(dimcthylamino)-l-(2-thienyl)-l-propanol (5):A mixture of 2-acetyl thiophene (100 g, 0.793 mole), dimethylamine hydrochloride (81.5 g, 1 mole), paraformaldehyde (35.5 g, 0.394 mole) and concentrated HCl (4.0 ml) in isopropanol (IPA) (250 ml) was refluxed for 6 h. The reaction mixture was cooled to room temperature and IPA was removed by distillation. Water (600 ml) was added to the residue. A solution of sodium borohydride (15 g) in 10% aqueous sodium hydroxide solution (41 g, NaOH in 410 ml water) was slowly added to the reaction mixture at 30-350C. The reaction mixture was stirred at room temperature for 6 h. Then aqueous HCl (Cone HCl 150 ml in 300 ml water) was added to get a clear solution. The reaction' mass was then washed with toluene (2x300 ml) to remove organic impurities. The reaction mass was again basified by adding sodium hydroxide solution (75 g NaOH in 150 ml water). This basic solution was extracted with methyl tert butyl ether (3x300 ml). The ethereal layer was washed with water and dried over sodium sulphate. This organic layer was heated to 50-550C and a solution of (S)-(+)-Mandelic acid (44 g) in ethanol (44 ml) was added. The reaction mass was heated at this temperature for 1 h and cooled to rt and filtered to get chiral Mandelate salt. This crude salt was taken in acetone (900 ml) and the mixture was heated at reflux temperature for 3 h. Then reaction mixture was cooled and filtered to get the pure Mandelate salt of the compound 5 (84 g). The Mandelate salt was basified with sodium hydroxide and extracted with dichloromethane to obtain (S)- 3- (dimethylamino)-l-(2-thienyl)-l-propanol as oil, which solidified on standing. Yield 42 g. The mother liquor containing the unwanted isomer (8) was concentrated, basified and extracted with ethyl acetate to get the oily residue which solidified on standing. <n="14"/>Example 5(S)- 3-(dimethylamino)-l-(2-thienyl)-l-propanol (5)A mixture of 2-acetyl thiophene (100 g, 0.793 mole), dimethyl amine hydrochloride (81.5 g, 1 mole), paraformaldehyde (35.5 g, 0.394 mole) and concentrated HCl (4.0 ml) in isopropanol (250 ml) was refluxed for 6 h. The reaction mixture was cooled to 5-100C and filtered and washed with IPA to get a white colored solid. This solid (150 g) was dissolved in water (600 ml). A solution of sodium borohydride (12.5 g, 0.342 mole) in 10% aqueous sodium hydroxide solution (41 g, NaOH in 410 mL water) was slowly added to the reaction mixture at 30-350C. The reaction mixture was stirred at room temperature for 6 h. Then aqueous HCl (150 ml cone HCl in 300 ml water) was added to get a clear solution. The reaction mass was then washed with toluene (2x300 ml) to remove organic impurities. The reaction mass was then basified using sodium hydroxide solution (75 g NaOH in 150 ml water) and then extracted using methyl tert butyl ether. (3x300 ml). The ethereal layer was washed with water and dried over sodium sulphate. This organic layer was heated to 50-550C and a solution of (S)-(+)-Mandelic acid (44 g, 0.289 mole) in ethanol (44 ml) was added. The reaction mass was heated at this temperature for 1 h, cooled to rt and filtered to get crude Mandelate salt. This crude salt was taken in acetone (900 ml) and the mixture was heated at reflux temperature for 3 h. Then reaction mixture was cooled and filtered to get the pure Mandelate salt of the compound 5 (84 g). The Mandelate salt was basified with sodium hydroxide and extracted with dichloromethane to obtain (S)- 3-(dimethylamino)-l-(2-thienyl)-l- propanol as oil which solidified on standing. Yield 42 g.The mother liquor containing the unwanted isomer (8) was concentrated, basified and extracted with ethyl acetate to get the oily residue which solidified on standing.
	With sodium hydroxide; sodium tetrahydroborate; water; at 10 - 70℃; for 4h;	To a solution of sodium hydroxide (237 g), sodium borohydride (102.17 g) and demineralized water (3.55 It), was added N,N-dimethyl-3-oxo-3-(2-thienyl)-propanamine hydrochloride (1.185 kg) at 10- 15 0C. The solution was stirred for 3 hours at 20-25 0C, and then heated to 70 0C for one hour. The reaction mixture was cooled to 0 0C, and treated with concentrated hydrochloric acid (1.017 It) at 0- 10 0C, and washed with n-heptane (1x2.3 It; 2x1.2 It) at 30-35 0C. The aqueous layer was cooled to 10-15 0C, basified with aqueous sodium hydroxide solution (277 g in 277 ml demineralized water) at 10-15 0C and extracted with toluene at 30-35 0C (2x3.56 lt+ 1x2.3 It). Combined toluene layer was washed with water (1.18 It). Some of the solvent was distilled off followed by addition of anhydrous toluene (1.0 lt).The toluene solution thus obtained was used as such for the next stage.
		Example-2: Preparation of 3-(dimethylamino)-l-(2-thienyl) propan-1-olCharge D M Water (500 ml) into a flask. Charge Sodium hydroxide (21.84 g) to the flask. Stir the reaction mass to get clear solution. Add 3-(N, N- Dimethylamino)-l-(2-thienyl) propan-1-one hydrochloride (100 g) to the flask under stirring. Cool the reaction mass to 10-150C. Add Sodium borohydride (8.65 g) to the reaction mixture at 10-150C. Stir the reaction mixture. Add Sodium borohydride (1.75 g) to the reaction mixture. Stir the reaction mixture. After the completion of the reaction; add Acetone (5.0 ml) to the reaction mixture. Stir for 30-45 min at 20-250C. Filter the content at 20-250C. Wash with D M water. Dry it at 50-550C in hot air oven.
		Example 2 Preparation of Rac-AT-OL A solution of 90 g of AT-ONE from the previous example in 290 ml of methanol and 145 ml of water was cooled to 0 C. and 14 ml of NaOH [47%] were gradually added till pH 10. To the resulting solution was added portion added 12.1 g of sodium borohydride, and the mixture was allowed to warm to room temperature overnight. The methanol was evaporated under reduced pressure, and 250 ml were added, followed by the slow addition of concentrated HCl till pH 1.5, and stirred for an additional 20 minutes.
		b) Preparation of 3-dimethylamino-1-(2-thienyl)-1-propanolA solution of 1 N sodium hydroxide (460 mL) was added to a mixture of 2-thienyl-2-dimethylaminoethyl ketone hydrochloride (100 g) in methanol (350 mL) at about 25 C. to the pH of 11. After cooling the reaction mixture to 10-15 C., sodium borohydride (8.5 g) was added in portion over a period of 30 minutes. The reaction mixture was stirred at about 25 C. for 2 h. After the completion of the reaction, excess sodium borohydride was decomposed by addition of acetone at about 25 C. The mixture was stirred at about 25 C. for 30 minutes. After concentrating the reaction mixture under reduced pressure to about of the initial volume, the concentrated reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×400 mL). The ethyl acetate layer was washed with water and concentrated under reduced pressure. Hexanes (200 mL) were added to the residue and the mixture was stirred for at about 25 C. for 1 h and at 5-10 C. for a further hour. The solid was filtered and dried under vacuum at 40-45 C. for 4-6 h to provide the title compound as an off-white solid.Yield: 78 g
	With sodium tetrahydroborate; sodium hydroxide; In ethanol; water; at 10 - 20℃;pH 11 - 12;	In a 500 mL four-necked flask, 25 g was added <strong>[5424-47-5]2-thiophene-2-dimethylamine methyl ethyl ketone hydrochloride</strong>(0.114 mol), 150 mL of ethanol and 75 mL of water to dissolve all. After stirring at room temperature, 13.7 g of 30% NaOH solution was slowly added, adjusted to pH 11 to 12, and 3.0 g (0.08 mol) of sodium borohydride was added in portions at a temperature of less than 10 C and stirred overnight at room temperature. Add 5mL of acetone, After stirring for 20 min, ethanol was evaporated under reduced pressure and precipitated as a white solid. The residue was added to 150 ml of t-butyl methyl ether. The layers were stirred and extracted. After extraction with 50 ml of t-butyl methyl ether, the organic layers were combined,After brine washing, it was used directly in Example 2.

References: [1]Patent: WO2011/33366,2011,A2 .Location in patent: Page/Page column 19.
[2]Patent: CN104829587,2017,B .Location in patent: Paragraph 0053-0054.
[3]Organic Process Research and Development,2006,vol. 10,p. 905 - 913.
[4]Bioorganic Chemistry,2016,vol. 65,p. 82 - 89.
[5]Patent: JP2016/222628,2016,A .Location in patent: Paragraph 0063.
[6]Patent: CN105566284,2016,A .Location in patent: Paragraph 0245; 0251.
[7]Patent: US4956388,1990,A .
[8]Patent: WO2007/77580,2007,A2 .Location in patent: Page/Page column 15.
[9]Patent: WO2008/4191,2008,A2 .Location in patent: Page/Page column 6-7.
[10]Patent: WO2008/93360,2008,A2 .Location in patent: Page/Page column 9-10.
[11]Patent: WO2008/93360,2008,A2 .Location in patent: Page/Page column 12-13.
[12]Patent: WO2009/19719,2009,A2 .Location in patent: Page/Page column 16.
[13]Patent: WO2010/79404,2010,A2 .Location in patent: Page/Page column 7.
[14]Patent: US2007/281989,2007,A1 .Location in patent: Page/Page column 5.
[15]Patent: US2010/280093,2010,A1 .Location in patent: Page/Page column 3.
[16]Patent: EP2305669,2011,A1 .
[17]Patent: CN104803968,2017,B .Location in patent: Paragraph 0039; 0040.

33
[ 1003869-22-4 ]
[ 5424-47-5 ]
[ 1003869-34-8 ]

References: [1]Journal of Medicinal Chemistry,2008,vol. 51,p. 659 - 665.

34
[ 5424-47-5 ]
[ 13636-01-6 ]

Yield	Reaction Conditions	Operation in experiment
		Example 2; (S)- 3-(dimethylamino)-l-(2-thienyl)-l-propanol (5):lambda mixture of 2-acetyl thiophene (25Og, 1.98 mole), dimethyl amine hydrochloride (21 O g, 2.57 mole), paraformaldehyde (78.44 g, 0.871 mole) and concentrated HCl (3.97 ml) in ethanol (317 ml) was refluxed for 4 h. The reaction mixture was cooled to the room temperature and water (700 ml) was added followed by addition of methanol (1.6 L) at room temperature. The reaction mixture was cooled to 5-10 C and basified with aqueous sodium hydroxide solution to adjust pH 7-8. Then sodium borohydride (81 g, 2.18 mole) was added in small lots at 5-10 C. After completion of addition of sodium borohydride, reaction mixture was stirred for 30 minutes at 5-10 C. Then it was stirred at room <n="12"/>temperature for 12-15 h. After completion of reaction, acetone (240 ml) was added to quench the excess borohydride. The reaction mixture was concentrated to obtain oily residue. To this residue dilute aqueous HCl solution (250 ml cone HCl in 250 ml water) was added to form the hydrochloride salt. This aqueous solution was washed with toluene (2x200 ml) to remove organic impurities. Washed aqueous solution was basified with aqueous alkali solution to pH 10-11. This alkaline solution was then extracted with methyl tert butyl ether (3x750 ml). The organic layer was then washed with water and dried over sodium sulphate. The organic layer was heated to 45-50 C and a solution of (S)-(+)-Mandelic acid (86.27 g, 0.567 mole) in ethanol (250 ml.) was added in a dropwise manner. The reaction mixture was stirred for 45 minutes at 45-50 C and cooled to room temperature. The solid obtained was filtered and washed with acetone to obtain Mandelate salt. This salt was leached in acetone at reflux temperature to get pure Mandelate salt (98 g). The Mandelate salt was basified with sodium hydroxide followed by extraction with dichloromethane to obtain (S)- 3-(dimethylamino)-l-(2-thienyl)-l- propanol as oil which solidified on standing. Yield 52 g.

References: [1]Patent: WO2008/93360,2008,A2 .Location in patent: Page/Page column 10-11.

35
[ 52807-29-1 ]
[ 5424-47-5 ]
trans-1-[4-(benzoylamino)phenyl]-3-(2-thienyl)-1-propen-3-one [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2008,vol. 18,p. 1985 - 1989.

Historical Records

Technical Information

• Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chan-Lam Coupling Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Fischer Indole Synthesis • Grignard Reaction • Henry Nitroaldol Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Lawesson's Reagent • Leuckart-Wallach Reaction • Mannich Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Amines • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Ketenes • Specialized Acylation Reagents-Vilsmeier Reagent • Stobbe Condensation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Similar Product of
[ 5424-47-5 ]

A276757 [13196-35-5]

3-(Dimethylamino)-1-(thiophen-2-yl)propan-1-one

Reason: Free-Salt

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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

Physical hazards
Code	Phrase
H200	Unstable explosive
H201	Explosive; mass explosion hazard
H202	Explosive; severe projection hazard
H203	Explosive; fire, blast or projection hazard
H204	Fire or projection hazard
H205	May mass explode in fire
H220	Extremely flammable gas
H221	Flammable gas
H222	Extremely flammable aerosol
H223	Flammable aerosol
H224	Extremely flammable liquid and vapour
H225	Highly flammable liquid and vapour
H226	Flammable liquid and vapour
H227	Combustible liquid
H228	Flammable solid
H229	Pressurized container: may burst if heated
H230	May react explosively even in the absence of air
H231	May react explosively even in the absence of air at elevated pressure and/or temperature
H240	Heating may cause an explosion
H241	Heating may cause a fire or explosion
H242	Heating may cause a fire
H250	Catches fire spontaneously if exposed to air
H251	Self-heating; may catch fire
H252	Self-heating in large quantities; may catch fire
H260	In contact with water releases flammable gases which may ignite spontaneously
H261	In contact with water releases flammable gas
H270	May cause or intensify fire; oxidizer
H271	May cause fire or explosion; strong oxidizer
H272	May intensify fire; oxidizer
H280	Contains gas under pressure; may explode if heated
H281	Contains refrigerated gas; may cause cryogenic burns or injury
H290	May be corrosive to metals
Health hazards
Code	Phrase
H300	Fatal if swallowed
H301	Toxic if swallowed
H302	Harmful if swallowed
H303	May be harmful if swallowed
H304	May be fatal if swallowed and enters airways
H305	May be harmful if swallowed and enters airways
H310	Fatal in contact with skin
H311	Toxic in contact with skin
H312	Harmful in contact with skin
H313	May be harmful in contact with skin
H314	Causes severe skin burns and eye damage
H315	Causes skin irritation
H316	Causes mild skin irritation
H317	May cause an allergic skin reaction
H318	Causes serious eye damage
H319	Causes serious eye irritation
H320	Causes eye irritation
H330	Fatal if inhaled
H331	Toxic if inhaled
H332	Harmful if inhaled
H333	May be harmful if inhaled
H334	May cause allergy or asthma symptoms or breathing difficulties if inhaled
H335	May cause respiratory irritation
H336	May cause drowsiness or dizziness
H340	May cause genetic defects
H341	Suspected of causing genetic defects
H350	May cause cancer
H351	Suspected of causing cancer
H360	May damage fertility or the unborn child
H361	Suspected of damaging fertility or the unborn child
H361d	Suspected of damaging the unborn child
H362	May cause harm to breast-fed children
H370	Causes damage to organs
H371	May cause damage to organs
H372	Causes damage to organs through prolonged or repeated exposure
H373	May cause damage to organs through prolonged or repeated exposure
Environmental hazards
Code	Phrase
H400	Very toxic to aquatic life
H401	Toxic to aquatic life
H402	Harmful to aquatic life
H410	Very toxic to aquatic life with long-lasting effects
H411	Toxic to aquatic life with long-lasting effects
H412	Harmful to aquatic life with long-lasting effects
H413	May cause long-lasting harmful effects to aquatic life
H420	Harms public health and the environment by destroying ozone in the upper atmosphere

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CAS No.: 5424-47-5

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