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Structure of 53332-78-8

Chemical Structure| 53332-78-8

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Product Details of [ 53332-78-8 ]

CAS No. :53332-78-8
Formula : C4H8Cl2N2S
M.W : 187.09
SMILES Code : Cl.Cl.NCC1=NC=CS1
MDL No. :MFCD09817422
InChI Key :SXOAJLQMTFZXKM-UHFFFAOYSA-N
Pubchem ID :44890709

Safety of [ 53332-78-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Computational Chemistry of [ 53332-78-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 5
Fraction Csp3 0.25
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 43.72
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

67.15 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

0.0
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

1.45
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.05
Log Po/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.

-0.09
Log Po/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

1.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.04

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.26
Solubility 1.03 mg/ml ; 0.00551 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.

-2.47
Solubility 0.64 mg/ml ; 0.00342 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

-1.28
Solubility 9.75 mg/ml ; 0.0521 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.

-6.41 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

2.0
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)

2.26

Application In Synthesis of [ 53332-78-8 ]

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

  • Downstream synthetic route of [ 53332-78-8 ]

[ 53332-78-8 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 53332-78-8 ]
  • [ 153538-13-7 ]
  • 2-<N-<4-<N-<<3,4-dihydro-2,7-dimethyl-4-oxo-3-(pivaloyloxymethyl)-6-quinazolinyl>methyl>-N-prop-2-ynylamino>-2-fluorobenzoyl>aminomethyl>thiazole [ No CAS ]
  • 2
  • 5-bromo-3-(pyrrolidin-1-ylsulfonyl)-1H-indole-2-carboxylic acid [ No CAS ]
  • [ 53332-78-8 ]
  • 5-bromo-3-(pyrrolidin-1-ylsulfonyl)-N-(1,3-thiazol-2-ylmethyl)-1H-indole-2-carboxamide trifluoroacetate [ No CAS ]
YieldReaction ConditionsOperation in experiment
A mixture of 5-bromo-3-(pyrrolidin-l-ylsulfonyl)-lH-indole-2-carboxylic acid (37 mg,0.1 mmol), PS-DCC (170 mg, 0.20 mmol) and EtaOBt (14 mg, 0.1 mmol), (l,3-thiazol-2-ylmethyl)amine (dihydrochloride salt, 39 mg, 0.2 mmol), and DIEA (100 uL) in TEtaF/DCM (1:1, 2 mL) was shaken for 16 hours at room temperature. After this time, the resin was filtered and washed with DCM/MeOEta (1:1, 4 x 1.5 mL). The combined organic solution was concentrated and the residue was purified by LCMS to give the title product (TFA salt) as slightly yellow solidAnalytical LCMS: single peak (214 nm), 3.254 min, ES MS (M+l) = 469; lEta NuMR (500 MHz, d6-DMSO) delta 13.02 (br, IH), 9.61 (t, J= 6.1 Hz, IH),8.12 (d, J= 1.8 Hz, IH), 7.77 (d, J= 3.2 Hz, IH), 7.70 (d, J= 3.2 Hz, IH), 7.53 (d, J= 8.7 Hz, IH), 7.48 (dd, J= 8.7, 1.8 Hz, IH), 4.88 (d, J= 6.1 Hz, IH ), 3.16-3.12 (m, 4H), 1.67-1.63 (m, 4H); HRMS, calc'd for Ci7HisBrNu4theta3S2 (M+H), 468.9998; found 469.0015.
  • 3
  • [ 1001915-87-2 ]
  • [ 53332-78-8 ]
  • [ 1001915-93-0 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In NMP (1-methylpyrrolidin-2-one); at 180℃; for 1.5h; Example 6 1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-(1,3-thiazol-2-ylmethyl)methanesulfonamide (Compound 6-1) N-Methyl-2-pyrrolidinone (13.3 ml) was added to N-methyl-1-[3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-7-yl]-N-phenylmethanesulfonamide (627 mg, 1.33 mmol) and 2-aminomethylthiazole dichloride (1004 mg, 6.66 mmol) in a vial. Triethylamine (1.86 mL, 13.3 mmol) was added and the vial was sealed, the resulting solution was heated to 180 C. with stirring. After 1.5 h., the reaction was cooled to room temperature and diluted in DMSO and water. The resulting solution was purified by preparative HPLC Reverse phase (C-18), eluding with Acetonitrile/Water+0.05% TFA, to afford the title compound as a yellow solid. 1H NMR (600 MHz, DMSO-D6) delta 9.22 (d, 1H); 8.54 (d, 1H); 8.48 (s, 1H); 8.16 (m, 3H); 7.81 (d, 1H); 7.78 (dd, 1H); 7.71 (d, 1H); 7.63 (d, 1H); 7.41 (d, 1H); 7.33 (d, 1H); 4.67 (s, 2H); 4.43 (d, 2H); 3.88 (s, 3H). LRMS (APCI) calculated for C24H19N5O3S [M+H]+, 478.1; found 478.0.
  • 4
  • [ 53332-78-8 ]
  • [ 109-94-4 ]
  • [ 93714-84-2 ]
YieldReaction ConditionsOperation in experiment
24% With triethylamine; at 20℃; To 2-thiazole methylamine dihydrochloride(1.0 g, 5.4 mmol) were added ethyl formate (5 mL) and Et3N (1.7 mL,11.2 mmol). The mixture was stirred at rt for overnight.The mixture was diluted by EA, washed by 10% citric acid, extracted by EA (5x25 mL), dried over Na2SO4,and concentrated under reduced pressure to get 2-(isocyanomethyl)thiazoleas dark oil (180 mg, 1.3 mmol, 24% yield), which was used directly for nextstep.2-(isocyanomethyl)thiazole (180 mg, 1.3mmol) in 2 mL of anhydrous DCM was added by NMM (343 muL, 3.1 mmol). Whenthe mixture was cooled to -45 oC, triphosgene (140 mg, 0.47 mmol) in2 mL of anhydrous DCM was added dropwise. Then the temperature was slowlywarmed up to rt over 1 h. The mixture was quenched carefully by adding it to 2M of Na2CO3 under 0 oC and organic layer wascollected, dried and purified by silica gel chromatography (PE/DCM = 1/1) togive the product as reddish oil (100 mg, 62% yield).
24% With triethylamine; at 22℃; To 2-thiazole methylamine dihydrochloride (1.0 g, 5.4 mmol) were added ethyl formate (5 mL) and Et3N (1.7 mL, 11.2 mmol). The mixture was stirred at rt for overnight. The mixture was diluted by EA, washed by 10% citric acid, extracted by EA (5*25 mL), dried over Na2SO4, and concentrated under reduced pressure to get 2-(isocyanomethyl)thiazole as dark oil (180 mg, 1.3 mmol, 24% yield), which was used directly for next step.
  • 5
  • [ 53332-78-8 ]
  • [ 78706-26-0 ]
  • 5-chloro-N-(thiazol-2-ylmethyl)-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine; In 1,4-dioxane; at 25℃;Inert atmosphere; General procedure: Example 7. General Procedure G A mixture of the desired chlorotriazolopyrimidines i-G (1 equiv), desired aminomethyl heterocycle or benzylamine ii-G (1.2 equiv), and triethylamine (NEt3) (1.5- 3.5 equiv) in 1,4-dioxane (~0.2 M) was stirred at room temperature until the reaction was complete by LC-MS and/or TLC analysis. The crude reaction mixture was directly purified by silica gel chromatography (typical eluents included either a mixture of hexanes and EtOAc or a mixture of CH2Cl2 and MeOH or an 80:18:2 mixture of CH2Cl2/CH3OH/concentrated NH4OH) to afford the desired product iii-G. The product structures prepared according to General Procedure G were confirmed by 1H NMR and/or by mass analysis.
  • 6
  • [ 57473-32-2 ]
  • [ 53332-78-8 ]
  • 7-chloro-N-(thiazol-2-ylmethyl)imidazo[1,2-a]pyrimidin-5-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With triethylamine; In 1,4-dioxane; at 70℃;Inert atmosphere; General procedure: Example 8. General Procedure H A mixture of the desired chloroimidazopyrimidines i-H (1 equiv), desired aminomethyl heterocycle or benzylamine ii-H (1.2 equiv), and triethylamine (NEt3) (1.5-3.5 equiv) in 1,4-dioxane (~0.1 M) was stirred at 70 C until the reaction was complete by LC-MS and/or TLC analysis. The crude reaction mixture was directly purified by silica gel chromatography (typical eluents included, for example, a mixture of hexanes and EtOAc, or a mixture of CH2Cl2 and MeOH, or an 80:18:2 mixture of CH2Cl2/CH3OH/concentrated NH4OH) to afford the desired product iii-H. The product structures prepared according to General Procedure H were confirmed by 1H NMR and/or by mass analysis.
  • 7
  • [ 2273-93-0 ]
  • [ 53332-78-8 ]
  • 2-chloro-7-methyl-N-(thiazol-2-ylmethyl)-7H-purin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
58% With triethylamine; In 1,4-dioxane; at 75℃;Inert atmosphere; Example 19.2-Chloro-7-methyl-N-(thiazol-2-ylmethyl)-7H-purin-6-amine A mixture of 2,6-dichloro-7-methyl-7H-purine (60 mg, 0.30 mmol), thiazol-2- ylmethanamine dihydrochloride (67 mg, 0.36 mmol) and triethylamine (0.15 mL, 1.05 mmol) in 1,4-dioxane (2 mL) was stirred at 75 C overnight. After this time the mixture was concentrated and the residue purified by column chromatography (silica gel, 0-6% MeOH in CH2Cl2) to afford the title compound as a white solid (48 mg, 58%): ESI MS (M+H) m/z 281; 1H NMR (300 MHz, DMSO-d6) G 8.27 (br s, 2H), 7.75 (d, J = 3.3 Hz, 1H), 7.63 (d, J = 3.3 Hz, 1H), 4.95 (d, J = 5.7 Hz, 2H), 4.03 (s, 3H).
  • 8
  • 2,6-dichloro-7-methyl-8-propoxy-7H-purine [ No CAS ]
  • [ 53332-78-8 ]
  • 2-chloro-7-methyl-8-propoxy-N-(thiazol-2-ylmethyl)-7H-purin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; In dimethyl sulfoxide; at 60℃; for 2h;Inert atmosphere; Example 24.2-Chloro-7-methyl-8-propoxy-N-(thiazol-2-ylmethyl)-7H-purin-6- amine A mixture of 2,6-dichloro-7-methyl-8-propoxy-7H-purine (28 mg, 0.11 mmol), <strong>[53332-78-8]thiazol-2-ylmethanamine dihydrochloride</strong> (70 mg, 0.37 mmol) and triethylamine (0.16 mL, 1.14 mmol) in DMSO (1.5 mL) was stirred at 60 C for 2 h. After this time the mixture was cooled to room temperature, diluted with EtOAc and washed with water and brine. The organic layer was concentrated and the resulting residue was purified by column chromatography (silica, 0-5% MeOH in CH2Cl2) to provide 2-chloro-7-methyl- 8-propoxy-N-(thiazol-2-ylmethyl)-7H-purin-6-amine (21 mg, 56%): ESI MS (M+H) 339; 1H NMR (500 MHz, DMSO-d6) G 7.93 (s, 1H), 7.73 (d, J = 3.3 Hz, 1H), 7.61 (d, J = 3.3 Hz, 1H), 4.90 (s, 2H), 4.44 (t, J = 6.5 Hz, 2H), 3.73 (s, 3H), 1.84-1.76 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H).
  • 9
  • 2-bromo-5,7-dichlorothiazolo[5,4-d]pyrimidine [ No CAS ]
  • [ 53332-78-8 ]
  • 2-bromo-5-chloro-N-(thiazol-2-ylmethyl)thiazolo[5,4-d]pyrimidin-7-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dimethyl sulfoxide; at 50℃; for 2h;Inert atmosphere; Step 1.2-Bromo-5-chloro-N-(thiazol-2-ylmethyl)thiazolo[5,4-d]pyrimidin-7-amine A mixture of 2-bromo-5,7-dichlorothiazolo[5,4-d]pyrimidine (50 mg, 0.18 mmol), <strong>[53332-78-8]thiazol-2-ylmethanamine dihydrochloride</strong> (100 mg, 0.53 mmol) and triethylamine (0.23 mL, 1.65 mmol) in DMSO (3 mL) was stirred at 50 C for 2 h. After this time the mixture was cooled to room temperature, diluted with EtOAc and washed with water and brine. The organic layer was dried over sodium sulfate, filtered and concentrated to obtain 2-bromo-5-chloro-N-(thiazol-2-ylmethyl)thiazolo[5,4-d]pyrimidin-7-amine (69 mg), which was used in the next step without further purification: ESI MS (M+H) 362; 1H NMR (500 MHz, DMSO-d6) G 9.65 (t, J = 5.8 Hz, 1H), 7.75 (d, J = 3.2 Hz, 1H), 7.64 (d, J = 3.2 Hz, 1H), 4.93 (d, J = 6.0 Hz, 2H).
  • 10
  • [ 867032-28-8 ]
  • [ 53332-78-8 ]
  • 8-bromo-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-N-(thiazol-2-ylmethyl)-9H-purin-6-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
In 1,4-dioxane; at 25℃;Alkaline conditions; Inert atmosphere; Step 3a.8-bromo-2-chloro-9-(tetrahydro-2H-pyran-2-yl)-N-(thiazol-2-ylmethyl)-9H- purin-6-amine 8-Bromo-2,6-dichloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (1 equiv), 2- (aminomethyl)thiazole dihydrochloride (1.1 equiv) and triethylamine or DIPEA (3 equiv) in 1,4-dioxane (~0.4 M) were stirred at room temperature overnight. The reaction mixture was then concentrated under reduced pressure and purified by silica gel chromatography (EtOAc/hexanes) to afford the title compound (iv-D(a)) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) G 9.29 (s, 1H), 7.73 (d, J = 3.5 Hz, 1H), 7.60 (d, J = 3.0 Hz, 1H), 5.58 (dd, J = 11.0, 2.0 Hz, 1H), 4.89 (d, J = 6.0 Hz, 2H), 4.06 (s, 1H), 3.66 (td, J = 11.5, 3.5 Hz, 1H), 2.87-2.78 (m, 1H), 2.00 (s, 1H), 1.90-1.85 (m, 1H), 1.74-1.55 (m, 3 H).
  • 11
  • [ 53332-78-8 ]
  • [ 42754-96-1 ]
  • 6-chloro-N-(thiazol-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
60% With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 125℃; for 3h;Sealed tube; Inert atmosphere; Example 16.6-Chloro-N-(thiazol-2-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine A mixture of 4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine (53.6 mg, 0.284 mmol), <strong>[53332-78-8]2-(aminomethyl)thiazole dihydrochloride</strong> (75.4 mg, 0.403 mmol) and DIPEA (0.30 mL, 1.72 mmol) in 1,4-dioxane (1.2 mL) was heated in a sealed tube at 125 C for 3 h, then cooled to room temperature. The solvents were removed by rotary evaporation, and the crude residue was purified by chromatography on silica gel (gradient 0-10% MeOH in dichloromethane). The product isolated from chromatography was dissolved in acetonitrile/water, frozen and lyophilized, then dried under vacuum at 75 C for 16 h to afford the title compound (45.5 mg, 60%) as an off-white solid: ESI MS [M+H]+ m/z 267; 1H NMR (300 MHz, DMSO-d6) G 13.63 (br s, 1H), 9.52 (t, J = 5.9 Hz, 1H), 8.17 (s, 1H), 7.77 (d, J = 3.2 Hz, 1H), 7.66 (d, J = 3.3 Hz, 1H), 4.98 (d, J = 6.0 Hz, 2H).
  • 12
  • 5-(methylthio)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-yl trifluoromethanesulfonate [ No CAS ]
  • [ 53332-78-8 ]
  • 5-(methylthio)-N-(thiazol-2-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-amine [ No CAS ]
YieldReaction ConditionsOperation in experiment
22 mg With N-ethyl-N,N-diisopropylamine; In 1,4-dioxane; at 25℃; for 16.5h;Inert atmosphere; Step 2.5-(methylthio)-N-(thiazol-2-ylmethyl)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7- amine A mixture of crude 5-(methylthio)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-7-yl trifluoromethanesulfonate (130 mg, 0.43 mmol), <strong>[53332-78-8]2-(aminomethyl)thiazole dihydrochloride</strong> (99 mg, 0.529 mmol) and DIPEA (0.33 mL, 1.89 mmol) in 1,4-dioxane (2.0 mL) was stirred at room temperature 16.5 h. All volatiles were removed by rotary evaporation, and the crude residue was purified by chromatography on silica gel (gradient 0-20% methanol in DCM) to afford the title compound (22 mg, 18% over 2 steps) as an off-white solid: ESI MS m/z 280 [M + H]+; 1H NMR (500 MHz, DMSO-d6) G 9.99 (t, J = 6.0 Hz, 1H), 8.45 (s, 1H), 7.76 (d, J = 3.3 Hz, 1H), 7.67 (d, J = 3.3 Hz, 1H), 4.97 (d, J = 6.1 Hz, 2H), 2.50 (s, 3H).
  • 13
  • C12H13Cl2NO4S [ No CAS ]
  • [ 53332-78-8 ]
  • C16H17Cl2N3O3S2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
General procedure: A mixture of the intermediate obtained from step 2 (1.00 g; 2.96 mmol), HATU (1.24 g; 3.25 mmol), DMF (2.50 mL) and DIPEA (0.56 mL; 3.25 mmol) is stirred at r.t. for 20 min. The amine 4-cyanobenzylamine (0.36 mL, 2.96 mmol) is added and the resulting mixture is stirred at r.t. for 2 h. A molar surplus of aq. NaHCOs solution is added with stirring and the precipitate is filtered off and dried at 50 C to yield the title compound. C20H19CI2N3O3S ESI pos.+neg. (Loop-Inj.): [M+H]+ 452 m/z (0129) HPLC (RT): 0.70 min (HPLC method A)
 

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Technical Information

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