106092-11-9|(R)-4,5,6,7-Tetrahydro-benzothiazole-2,6-diamine| Ambeed

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 [ 106092-11-9 ] Purity: 97% 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 [ 106092-11-9 ]

CAS No. :	106092-11-9
Formula :	C₇H₁₁N₃S
M.W :	169.25
SMILES Code :	NC1=NC2=C(S1)C[C@@H](CC2)N
MDL No. :	MFCD07369986
InChI Key :	DRRYZHHKWSHHFT-SCSAIBSYSA-N
Pubchem ID :	16743100

Safety of [ 106092-11-9 ]

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

Computational Chemistry of [ 106092-11-9 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	5
Fraction Csp3	0.57
Num. rotatable bonds	0
Num. H-bond acceptors	2.0
Num. H-bond donors	2.0
Molar Refractivity	46.66
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	93.17 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.32
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	0.45
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	0.55
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.	0.06
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	1.64
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.8

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.51
Solubility	5.24 mg/ml ; 0.031 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.	-1.97
Solubility	1.79 mg/ml ; 0.0106 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	-1.45
Solubility	6.03 mg/ml ; 0.0356 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	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.	-7.01 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)	3.16

Application In Synthesis of [ 106092-11-9 ]

* 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 [ 106092-11-9 ]

[ 106092-11-9 ] Synthesis Path-Downstream 1~31

1
[ 123-62-6 ]
[ 106092-11-9 ]
[ 106006-85-3 ]

References: [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 494 - 498.

2
[ 106006-83-1 ]
[ 106092-11-9 ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 5501 - 5521.
[2]Journal of Medicinal Chemistry,1987,vol. 30,p. 494 - 498.

3
[ 106006-83-1 ]
[ 106092-11-9 ]
[ 106092-09-5 ]

Yield	Reaction Conditions	Operation in experiment
	Resolution of racemate;Purification / work up;	Example 4; Preparation of 2-amino-6-(alkyl)amino-4,5,6,7-tetrahydrobenzothiazole Compounds of Formulas (9a) and (9b)Under Polar Organic Conditions on a Chiralpak AD Column; [0066] The resolution of the compound of formula (9) was completed asfollows. A sample solution was prepared by dissolving 100 mg of a compound offormula (9) in 100 mL of ACN with 0.2percent DBA. The sample solution was loadedonto the Chiralpak AD column (50 mm x 500 mm) using ACN with 0.2percent DEA asmobile phase. The first enantiomer was observed from 38-50 minutes while thesecond one eluted from 91-110 minutes. Both components were collected andconcentrated to dryness using a rotary evaporator with a bath temperature of 30-35°C. The recovered material was dried under vacuum for at least 12 h to removeresidual solvents.Example 5 Preparation of 2-amino-6-(alkyl)amino-4,5,6,7-tetrahydrobenzothiazole Compounds of Formulas (9a) and (9b)Under Polar Organic Conditions on a Chiralpak AD Column[0067] The resolution of the compound of formula (9) was completed asfollows. A sample solution was prepared by dissolving 100 mg of a compound offormula (9) in 100 mL of 5:95 IPA/ACN with 0.2percent DEA. The sample solutionwas loaded onto the Chiralpak AD column (50 mm x 500 mm) using 5:95IPA/ACN with 0.2percent DEA as mobile phase. The first component of the mixturewas observed from 28-35 minutes while the second one eluted from 56-70minutes. Both components were collected upon elution and processed asdescribed above. These conditions are preferred for the resolution of large scalebatches.Example 6 Preparation of Chirally Pure 2-amino-6-(alkyl)amino-4,5,6,7-tetrahydrobenzothiazole Compounds of Formulas (9a) and (9b)Under Polar Organic Conditions on a Chiralpak AD Column[0068] The resolution of the compound of formula (9) was completed asfollows. A sample solution was prepared by dissolving 100 mg of a compound offormula (9) in 100 mL of 10:90 IPA/ACN with 0.2percent DBA. The sample solutionwas loaded onto the Chiralpak AD column (50 mm x 500 mm) using 10:90IP A/ACN with 0.2percent DEA as mobile phase. The first enantiomer was observedfrom 13-18 minutes while the second one eluted from 20-30 minutes. Bothcomponents were collected and processed as described previously.[0069] Samples of the resolved material from Examples 4-6 (1 mg each)were dissolved at 1 mg/mL in ACN and analyzed by HPLC. The chiral purity ofboth fractions was greater than 99percent, while the weight recovery was greater than90percent.

References: [1]Bioorganic and medicinal chemistry letters,2004,vol. 14,p. 3251 - 3256.
[2]Patent: WO2006/12276,2006,A1 .Location in patent: Page/Page column 16-17.

4
[ 106092-11-9 ]
[ 179523-60-5 ]
N-(2-amino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-2-(6-methyl-2-oxo-3-phenylmethanesulfonylamino-2H-pyridin-1-yl)-acetamide [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2004,vol. 14,p. 3251 - 3256.

5
[ 106092-11-9 ]
[ 729612-88-8 ]
N-(2-amino-4,5,6,7-tetrahydro-benzothiazol-6-yl)-2-[3-(4-fluoro-phenylmethanesulfonylamino)-6-methyl-2-oxo-2H-pyridin-1-yl]-acetamide [ No CAS ]

References: [1]Bioorganic and medicinal chemistry letters,2004,vol. 14,p. 3251 - 3256.

6
[ 867023-86-7 ]
[ 106092-11-9 ]
N-((6R)-2-amino-4,5,6,7-tetrahydro-1,3-benzothiazol-6-yl)-2-[6-chloro-2-oxo-3-[2-(2-pyridinyl)ethyl]amino}-1(2H)-pyrazinyl]acetamide [ No CAS ]

References: [1]European Journal of Medicinal Chemistry,2005,vol. 40,p. 782 - 791.

7
[ 106092-11-9 ]
[ 104632-28-2 ]

References: [1]Journal of Medicinal Chemistry,1987,vol. 30,p. 494 - 498.
[2]Patent: WO2013/96816,2013,A1 .

8
[ 599-91-7 ]
[ 106092-11-9 ]
(R)-pramipexole p-tosylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
56%	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 65℃; for 7h;Product distribution / selectivity;	[00250) EXAMPLE 7 - Preparation of (R)-pramipexole p-TSA salt: Condition C:A 12 L, three necked flask was equipped with an overhead stirrer, a temperature probe, a heating mantle, a claisen joint, a condenser, and a 500 ml addition funnel. The flask was charged with 250 grams of R(+)-2,6 diamino-4,5,6,7-tetrahydro-benzothiazole (R(+) diamine), followed by 2 L of dimethyl formamide (DMF). Under continuous stirring, the mixture was heated to a temperature of 65C. The addition funnel was charged with a solution of 386.6 grams <strong>[599-91-7]propyl tosylate</strong> (1.25 molar equivalents) and 322 ml diisopropylethyleamine (1.25 molar equivalents) in 500 ml DMF. This solution was added to the 12 L flask dropwise over a period of 2.0 hours. The reaction was monitored by analysis on HPLC.[00251] The reaction was continued at 65C for an additional 5 hours, after which the solution was gradually cooled to room temperature and stirred overnight. The solution was diluted with 2 L MTBE and stirred for an additional 0.5 hours. The precipitated material was collected by filtration and washed with 500 ml MTBE, followed by 3 washes of 500 ml each reagent alcohol. The washed precipitated cake was dried under high vacuum.[00252] The final weight of the dried product was 317.6 grams, representing a 56percent yield. HPLC was used to determine the chemical purity of the R(+)-2,6-diamino-4,5,6,7- tetrahydro-benzothiazole ((S)-pramipexole) as 98.4percent and the chiral purity as greater than 99.8percent. 1H NMR and 13C NMR was used to confirm the structure: 1H NMR (300 MHz, DMSO-rf6) delta 8.5 (br.s, 2H), 7.5 (d, 2H), 71.2 (d, 1H), 6.8 (s, 2H), 3.4 (m, 1H), 2.95 (m, 3H), 2.6 (m, 2H, merged with DMSO peak), 2.3 (s, 3H), 2.15 (m, 1H), 1.8 (m, I H), 1.55 (m, 2H), 0.9 (t, 3H); 13C NMR (300 MHz, DMSO-</6) delta 167.0, 145.5, 144.6, 138.4, 128.6, 125.8, 1 10.7, 53.9, 46.5, 25.8, 25.6, 24.5, 21.2, 19.6, 1 1.3.

References: [1]Patent: WO2010/22140,2010,A1 .Location in patent: Page/Page column 97.

9
[ 106092-11-9 ]
[ 104632-27-1 ]

References: [1]Patent: WO2013/96816,2013,A1 .

10
[ 599-91-7 ]
[ 106092-11-9 ]
[ 1332723-78-0 ]

Yield	Reaction Conditions	Operation in experiment
83.9%	With N-ethyl-N,N-diisopropylamine; In water; acetonitrile; at 20 - 80℃;Inert atmosphere;	Example 1 : (R)-(+)-2-amino-4,5,6,7-tetrahvdro-6-(n- [00132] Method 1: [00133] Compound 2 (100 g, 590.9 mmol, 98.8percent ee) was charged in a 1 L reactor equipped with nitrogen inlet, condenser, thermometer and overhead stirrer at room temperature. Acetonitrile (487.5 mL, 4.875 Volumes) was added to the reactor and agitation was started. Water (12.5 mL, 0.125 Volumes) was then added to the reactor, followed by DIPEA (38.2 g, 295 mmol). n-Propyl p-toluenesulfonate (189.9 g, 886 mmol) was then added to the reactor and the reaction mixture was heated to about 75 to 80 °C with stirring. The reaction stirred at about 75 to 80 °C for 6-16 hours, until complete (typically about 8-10 hours). The batch was then cooled to room temperature over 2-3 hours and aged at room temperature for additional 1 hour. The reaction mixture was filtered at room temperature, and the wet cake was washed with acetonitrile (250 mL) twice and dried to a constant weight to provide the product in 83.9percent yield (190.1 g), 98.2percent purity (determined by achiral HPLC), and about 100percent ee.

References: [1]Patent: WO2013/96816,2013,A1 .Location in patent: Paragraph 00131-00133.

11
[ 106092-11-9 ]
[ 1426335-37-6 ]