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Chemical Structure| 4100-13-4 Chemical Structure| 4100-13-4

Structure of 4100-13-4

Chemical Structure| 4100-13-4

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Product Details of [ 4100-13-4 ]

CAS No. :4100-13-4
Formula : C3H2N2O2S
M.W : 130.13
SMILES Code : OC(=O)C1=CSN=N1
MDL No. :MFCD00052099
InChI Key :HJZYBDPHAHGHAZ-UHFFFAOYSA-N
Pubchem ID :351418

Safety of [ 4100-13-4 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P301+P312-P302+P352-P304+P340-P305+P351+P338

Computational Chemistry of [ 4100-13-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 8
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 4.0
Num. H-bond donors 1.0
Molar Refractivity 26.87
TPSA ?

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

91.32 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.58
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

0.3
Log Po/w (WLOGP)?

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

0.24
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.

-1.26
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

1.31
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.23

Water Solubility

Log S (ESOL):?

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

-1.23
Solubility 7.62 mg/ml ; 0.0586 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.

-1.78
Solubility 2.16 mg/ml ; 0.0166 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

-0.26
Solubility 71.8 mg/ml ; 0.552 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.

-6.88 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.

0.56

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)

2.5

Application In Synthesis of [ 4100-13-4 ]

* 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 [ 4100-13-4 ]

[ 4100-13-4 ] Synthesis Path-Downstream   1~34

  • 2
  • [ 58792-16-8 ]
  • [ 4100-13-4 ]
  • 3
  • [ 58792-16-8 ]
  • [ 4100-13-4 ]
  • [ 58792-17-9 ]
  • 4
  • 5-furan-2-yl-[1,2,3]thiadiazole-4-carboxylic acid [ No CAS ]
  • [ 4100-13-4 ]
  • 5
  • [ 67-56-1 ]
  • [ 4100-13-4 ]
  • [ 3989-35-3 ]
YieldReaction ConditionsOperation in experiment
99.9% With hydrogenchloride; at 65℃; for 16h; <strong>[4100-13-4]1,2,3-Thiadiazole-4-carboxylic acid</strong> (1.0, 1g, 7.7 mmol) was added to HCl (1.25 M in MeOH, 10 mL) and the reaction mixture was stirred at 65 C for 16 h. The solvent was removed under reduced pressure and the resulting crude mixture was purified (FCC, SiO2, 0-100 % EtOAc in DCM) to provide the title compound (1.1g, 99.9%). MS (ESI): mass calcd. for C4H4N2O2S, 144.0; m/z found, 145 [M+H]+.1H NMR (300 MHz, CDCl3) delta 9.27 (s, 1H), 4.07 (s, 3H).
  • 8
  • [ 4100-13-4 ]
  • [ 75-03-6 ]
  • [ 18212-34-5 ]
  • 9
  • [ 4100-13-4 ]
  • [ 4100-20-3 ]
  • 10
  • [ 4100-13-4 ]
  • [ 288-48-2 ]
  • 11
  • N'-[1-Hydroxy-2-oxo-prop-(Z)-ylidene]-hydrazinecarboxylic acid ethyl ester [ No CAS ]
  • [ 4100-13-4 ]
  • 12
  • [ 4100-13-4 ]
  • [ 35661-40-6 ]
  • [ 119831-72-0 ]
  • [ 135673-97-1 ]
  • [1,2,3]Thiadiazole-4-carboxylic acid {(S)-1-[(S)-1-((S)-1-carbamoyl-2-phenyl-ethylcarbamoyl)-4-guanidino-butylcarbamoyl]-2-cyclohexyl-ethyl}-amide [ No CAS ]
  • 14
  • 1.2.3-thiodiazole-dicarboxylic acid-(4.5) [ No CAS ]
  • [ 4100-13-4 ]
  • 15
  • [ 7719-09-7 ]
  • [ 58792-16-8 ]
  • [ 4100-13-4 ]
  • [ 58792-17-9 ]
  • 16
  • [ 4100-13-4 ]
  • 4-{2-[1-methyl-4-(1-methyl-4-(4-amino-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine dihydrochloride [ No CAS ]
  • 4-{2-[1-methyl-4-(1-methyl-4-(1-methyl-4-([1,2,3]thiadiazole-4-carboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido)-2-pyrrolecarboxamido]ethyl}morpholine [ No CAS ]
  • 17
  • [ 4100-13-4 ]
  • [ 320780-86-7 ]
  • [ 320781-63-3 ]
  • 18
  • [ 488-93-7 ]
  • [ 59-67-6 ]
  • [ 16874-33-2 ]
  • [ 88-14-2 ]
  • [ 98-97-5 ]
  • [ 21169-71-1 ]
  • [ 4100-13-4 ]
  • [ 3405-77-4 ]
  • [ 6973-60-0 ]
  • [ 5744-59-2 ]
  • [ 5521-55-1 ]
  • [ 636-44-2 ]
  • [ 13602-12-5 ]
  • C25H33N2O3Pol [ No CAS ]
  • C25H33N2O3Pol [ No CAS ]
  • [ 88-13-1 ]
  • [ 149-87-1 ]
  • furan-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-yl-methyl]-amide [ No CAS ]
  • furan-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • furan-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • furan-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • N-[4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-nicotin amide [ No CAS ]
  • pyrazine-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • isoxazole-5-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 1-methyl-1H-pyrrole-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • isoxazole-5-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • thiophene-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • N-[4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-nicotinamide [ No CAS ]
  • pyrazine-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • thiophene-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 1-methyl-1H-pyrrole-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • 5-methyl-isoxazole-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 5-methyl-isoxazole-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • 1,5-dimethyl-1H-pyrazole-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 5-oxo-pyrrolidine-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • [1,2,3]-thiadazole-4-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • N-[4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-1-hydroxyisonicotin amide N-oxide [ No CAS ]
  • tetrahydro-furan-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • tetrahydro-furan-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
  • 5-methyl-pyrazine-2-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 2,5-dimethyl-furan-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-3-ylmethyl]-amide [ No CAS ]
  • 2,5-dimethyl-furan-3-carboxylic acid [4'-(1,1-dimethyl-6-morpholin-4-yl-6-oxo-hexyl)-2'-hydroxy-biphenyl-2-ylmethyl]-amide [ No CAS ]
YieldReaction ConditionsOperation in experiment
Compounds 41-70 were part of a parallel set prepared in library plate format according to General Procedure L, outlined below. ; L. General Procedure for Plate Preparation-Amide Formation XXI: Resin bound deprotected biarylphenol XVII (prepared from intermediate XII, boronates XIVd and XIVe, following general procedures D-F) was distributed into a 96 well plate, 10 mg of resin (0.013 mmol) per well. To the resin 400 mul of dichloromethane was added, followed by 100 mul of DIEA, followed by 0.13 mmol (10 equiv) of heterocyclic carboxylic acid XXa-XXn was added followed by 61 mg (0.13 mmol, 10 equiv) of PyBrop. The plate was shaken at room temperature for 24 hours, then drained and washed with dichloromethane, methanol/dichloromethane, dimethylformamide, methanol/dichloromethane and dichloromethane. The compounds were cleaved with TFA/dichloromethane (600 mul, 1:1) into a 96 deep well plate and submitted for testing without further purification. (Mass spec results obtained are shown in Table 4). Carboxylic Acids Het-COOH XX:
  • 19
  • [ 4100-13-4 ]
  • [ 103922-89-0 ]
  • N-[4-(4-piperidinomethyl-pyridin-2-yloxy)-cis-2-butenyl]-1,2,3-thiadiazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
52% EXAMPLE 27 N-[4-(4-piperidinomethyl-2-pyridyloxy) -cis-2-butenyl]-1,2,3-thiadiazole-4-carboxamide Following a procedure similar to that described in Example 13, but using 4-(4-piperidinomethyl-2-pyridyloxy) -cis-2-butenylamine and <strong>[4100-13-4]1,2,3-thiadiazole-4-carboxylic acid</strong> as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained as colorless needles, melting at 70-72 C., in a 52% yield. Nuclear Magnetic Resonance Spectrum (CDCl3), delta ppm: 1.28-1.53 (2H, multiplet); 1.53-1.82 (4H, multiplet); 2.24-2.55 (4H, multiplet); 3.46 (2H, singlet); 4.35 (2H, triplet, J=6.3 Hz); 5.01 (2H, doublet, J=6.3 Hz); 5.75-5.87 (1H, multiplet); 5.87-6.00 (1H, multiplet); 6.77 (1H, singlet); 6.85-7.00 (1H, multiplet); 7.72-7.90 (1H, broad); 8.13 (1H, doublet, J=5.4 Hz); 9.23 (1H, singlet). Infrared Absorption Spectrum (CHCl3), numax cm-1: 3425, 2940, 1675, 1612, 1540, 1420, 1402, 1300, 1290, 1260, 1035.
  • 20
  • [ 4100-13-4 ]
  • [ 637336-01-7 ]
  • triphenylphosphine-polystyrene [ No CAS ]
  • [ 637336-45-9 ]
YieldReaction ConditionsOperation in experiment
24.7% With N-chloro-succinimide; triethylamine; In methanol; dichloromethane; Example 111 [1,2,3]Thiadiazole-4-carboxylic acid {4-[3-cyclopropylmethyl-1-(2-fluorobenzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide A mixture of <strong>[4100-13-4][1,2,3]thiadiazole-4-carboxylic acid</strong> (29 mg, 0.30 mmol) in dichloromethane (6 mL) at 25 C. was treated with triphenylphosphine-polystyrene 100-200 mesh (372 mg, 0.46 mmol). This mixture was cooled to 0 C. and then treated with N-chlorosuccinimide (49 mg, 0.37 mmol). This mixture was stirred at 0 C. for 15 min and at 25 C. for 15 min. At this time, the reaction was treated with 3-cyclopropylmethyl-1-(2-fluoro-benzyl)-8-(4-methylamino-benzyl)-3,7-dihydro-purine-2,6-dione (55 mg, 0.12mmol) and triethylamine (96 [IL, 0.69 mmol). The reaction was then stirred at 25 C. for 3 days. At this time, the reaction was filtered to remove solids and rinsed with dichloromethane. The filtrate was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1:99 methanol/dichloromethane) afforded <strong>[4100-13-4][1,2,3]thiadiazole-4-carboxylic acid</strong> {4-{3-cyclopropylmethyl-1-(2-fluoro-benzyl)-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-8-ylmethyl]-phenyl}-methyl-amide (17 mg, 24.7%): LR-MS for C27H24FN7O3S (M+H)+ at m/z=546.
  • 21
  • [ 4100-13-4 ]
  • [ 637336-01-7 ]
  • [ 637336-45-9 ]
YieldReaction ConditionsOperation in experiment
24.7% A mixture of [1, 2,3] thiadiazole-4-carboxylic acid (29 mg, 0.30 mmol) in dichloromethane (6 mL) at [25 oC] was treated with triphenylphosphine-polystyrene [100-200] mesh (372 mg, 0.46 mmol). This mixture was cooled to [0 oC] and then treated with N-chlorosuccinimide (49 mg, 0.37 mmol). This mixture was stirred at 0 oC for 15 min and at [25 oC] for 15 min. At this time, the reaction was treated with 3- [CYCLOPROPYLMETHYL-1- (2-FLUORO-BENZYL)-8- (4-METHYLAMINO-BENZYL)-3,] 7-dihydro-purine- 2,6-dione (55 mg, 0.12mmol) and triethylamine [(96] [. L,] 0.69 mmol). The reaction was then stirred at [25 oC] for 3 days. At this time, the reaction was filtered to remove solids and rinsed with dichloromethane. The filtrate was washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and [CONCENTRATED IN VACUO.] Flash chromatography (Merck Silica gel [60,] 230-400 mesh, 1: 99 methanol/ dichloromethane) afforded [[1,] 2,3] thiadiazole-4-carboxylic acid [14- [3-] [CYCLOPROPYLMETHYL-1-(2-FLUORO-BENZYL)-2,] 6-dioxo-2,3, 6, 7-tetrahydro-1H-purin-8- [YLMETHYL]-PHENYL}-METHYL-AMIDE] (17 mg, 24.7%)
  • 22
  • [ 4100-13-4 ]
  • [ 805322-20-7 ]
  • [ 1134816-55-9 ]
  • 23
  • [ 4100-13-4 ]
  • [ 914942-96-4 ]
  • C25H26N8O3S [ No CAS ]
  • 24
  • [ 4100-13-4 ]
  • 7-[6-(aminomethyl)-2-pyridinyl]-1,6-dihydro-N,1-dimethyl-imidazo[4,5-d]pyrrolo[2,3-b]pyridin-4-amine trihydrochloride [ No CAS ]
  • N-[[6-[1,6-dihydro-1-methyl-4-(methylamino)imidazo[4,5-d]pyrrolo[2,3-b]pyridin-7-yl]-2-pyridinyl]methyl]-1,2,3-thiadiazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
To an individual well in a Bohdan XT reactor was added 150 uL of a 0.25 M solution of either a carboxylic acid in dimethylformamide (DMF)(0.038 mmol; 1.25 eq), 37.5 uL of a 1 M solution of 1-hydroxybenzotriazol in DMF (0.038 mmol, 1.25 equiv) and 150 uL of a 0.25 M solution of N-(3-dimethylaminopropyl)-N- ethylcarbodiimide hychloride (0.038 mmol; 1.25 eq) or an isocyanate or sulfonylchloride reagent with pyridine in similar molar ratio to the carboxylic acid reagent. The reactor was agitated for 10 minutes via orbital shaker. Then 150 uL of a solution of 0.2 molar amine in DMF (0.03 mmol; 1 eq) and diisopropylethylamine (0.150; 5 eq) was added to each reactor well and the reactor was agitated for 16 hours at 650C. The library was dried via centrifugal evaporation and BOC groups were removed by adding 600 uL of a 30% by volume solution of trifluoroacetic acid (TFA) in dichloromethane (DCM) to each reactor (that had a BOC group) and the reactor was agitated for 2 hours. The library was dried via centrifugal evaporation and was EPO <DP n="168"/>dissolved in 600 uL of DMF and 600 uL of methanol (MeOH). The entire contents for each reactor were transferred to an STR plate was was purified by standard preparative HPLC-MS (H2O/MeOH/0.1% TFA, gradient 35-90% MeOH over 15 min, 2Ox 100mm 5mum YMC ODS-A column) utilizing mass-directed fractionation. The purified sample was reconstituted in l:l/MeOH:DCE, transferred to a tared 2.5 mL plastic microtube, dried via centrifugal evaporation and weighed. The final product was analyzed by HPLC-MS (H2O/MeOH/0.1% TFA). Compounds were isolated as trifluoroacetate salts. Examples prepared by this method are described in Table A8.
  • 25
  • [ 4100-13-4 ]
  • [ 1276676-40-4 ]
  • [ 1276676-42-6 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In N,N-dimethyl-formamide; at 20℃; for 18h; 5-[(15*,45)-2,5-diazabicyclo[2.2.1]hept-2-yl]-l-(2,2-dimethylpropyl)-3-methyl- l,3-dihydro-2H-imidazo[4,5-£]pyridin-2-one (29-2, 25 mg, 0.079 mmol) was added to anhydrous dimethylformamide (793 l,2,3-thiadiazole-4-carboxylic acid (11.4 mg, 0.087 mmol), EDC (15.19 mg, 0.079 mmol), EtaOmicronBetaTau (12.14 mg, 0.079 mmol) and triethylamine (22 pL, 0.159 mmol) were added sequentially and the resulting reaction mixture was allowed to stir at room temperature for 18 h. Following this duration, the contents were filtered and the resulting filtrate was purified via reverse-phase HPLC (5-95%, 0.1% TFA in H20:acetonitrile) to give 1- (2,2-dimethylpropyl)-3-methyl-5-[(15*,45)-5-(l,2,3-thiadiazol-4-ylcarbonyl)-2,5- diazabicyclo[2.2.1]hept-2-yl]-l,3-dihydro-2H-imidazo[4,5-¾]pyridin-2-one (29-3) as a white solid. MS m/z (Mu+Eta): calculated = 428.1863; observed = 428.1860.
  • 26
  • [ 4100-13-4 ]
  • [ 1276672-92-4 ]
  • 1-(2,2-dimethylpropyl)-3-methyl-2-oxo-5-(3-[(1,2,3-thiadiazol-4-ylcarbonyl)amino]methyl}piperidin-1-yl)-2,3-dihydro-1H-imidazo[4,5-b]pyridin-4-ium chloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1,4-dioxane; at 150℃; for 0.166667h; 5-[3-(Aminomethyl)piperidin- 1 -yl]- 1 -(2,2-dimethylpropyl)-3-methyl-l ,3- dihydro-2H-imidazo[4,5-£]pyridin-2-one (2-1, 131 mg, 0.397 mmol) was added to anhydrous 1,4-dioxane (2 mL). l,2,3-Thiadiazole-4-carboxylic acid (86 mg, 0.66 mmol), EDC (127 mg, 0.66 mmol) and EtaOmicronBetaTau (101 mg, 0.66 mmol) were added sequentially and the resulting reaction mixture was allowed to stir at 150 C for 10 min. Following this duration, the contents were filtered and the resulting filtrate was purified via reverse-phase HPLC (10-100%, 0.1% TFA in H20:acetonitrile) to give l-(2,2-dimethylpropyl)-3-methyl-2-oxo-5-(3-[(l,2,3-thiadiazol-4- ylcarbonyl)amino]methyl}piperidin- 1 -yl)-2,3-dihydro- lH-imidazo[4,5-b]pyridin-4-ium chloride (3-1) as a white solid. MS m/z (M+H): calculated = 444.2176; observed = 444.2166.
  • 27
  • [ 4100-13-4 ]
  • [ 1093254-29-5 ]
  • [ 1093255-42-5 ]
YieldReaction ConditionsOperation in experiment
46% With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; In a 1 dram vial, 3-[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5- chlorobenzonitrile (25 mg, 0.080 mmol), DIPEA (0.014 mL, 0.080 mmol) and 1 ,2,3- thiadiazole-4-carboxylic acid (10.46 mg, 0.080 mmol) were dissolved in DMF (1 mL). HATU was added (30.6 mg, 0.080 mmol) and the solution stirred overnight. The reaction mixture was diluted to 2 mL with MeOH. Purification was accomplished by Reverse-Phase HPLC (water/acetonitrile with 0.1 % TFA) to afford the title compound (0.016 g, 46%) as a white solid. 1H NMR (400 MHz, Acetone-d6): delta ppm 9.55 (s, 1 <n="110"/>H), 8.94 (br. s., 1 H), 7.63 (t, 1 H), 7.53 (t, 1 H), 7.41 - 7.46 (m, 1 H), 7.37 - 7.41 (m, 2 H), 4.79 (d, 2 H). LCMS m/z 422.8 (M+1 ).
  • 28
  • [ 4100-13-4 ]
  • [ 19348-53-9 ]
  • C17H9ClN4O3S [ No CAS ]
  • 29
  • [ 4100-13-4 ]
  • 5-((+/-)-2,5-diazabicyclo[2.2.2]octan-2-yl)-3-methyl-1-neopentyl-1H-imidazo[4,5-b]pyridin-2(3H)-one [ No CAS ]
  • C21H27N7O2S [ No CAS ]
  • 30
  • [ 4100-13-4 ]
  • [ 6610-29-3 ]
  • 4-methyl-5-(1,2,3-thiadiazol-4-yl)-4H-1,2,4-triazole-3-thiol [ No CAS ]
  • 31
  • [ 4100-13-4 ]
  • 3-amino-4-(4-(2,4-difluorophenoxy)piperidin-1-yl)benzonitrile [ No CAS ]
  • N-(5-cyano-2-(4-(2,4-difluorophenoxy)piperidin-1-yl)phenyl)-1,2,3-thiadiazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
3% Theta445] To a 4 mL scintillation vial equipped with a stir bar was charged l,2,3-thiadiazole-4- carboxylic acid (21,7 mg, 0.167 mmol), DMF (0.5 mL), 2,4,6-tripropyl- 1,3,5,2,4,6- trioxatriphosphinane 2,4,6-trioxide (0.186 mL, 0.304 mmol) and pyridine (0.05 mL, 0.607 mmol). The mixture was stirred for 5 minutes at ambient temperature and then a solution of 3- amino-4-(4-(2,4-difluorophenoxy)piperidin-l -yl)benzonitrile (50 mg, 0.152 mmol) in DMF (0.5 mL) was added in a single portion. The reaction mixture was stirred at 70C overnight, then cooled to ambient temperature, and diluted with water (2 mL), The mixture was sonicated and stirred until a residue was observed around the inside of the vessel. The liquids were decanted, leaving an oily residue to which was added MeOH (~1 mL). The mixture was heated until it became a translucent solution and was then sonicated and stirred at ambient temperature until a precipitate was observed. The material was filtered and the solids were washed with minimal MeOH, collected, and dried under vacuum to give the title compound as a white solid (2.1 mg, 3%). NMR (400 MHz, DMSO-ifc) delta pprn 1.98 - 2.07 (rn, 2 H), 2.20 - 2.26 (m, 2 H), 2.93 (ddd,.7=11.87, 8.34, 3.28 Hz, 2 H), 3.21 (ddd, J= 1.68, 7.01, 4.04 Hz, 2 H), 4.53 (dt,.7=7,77, 3.82 Hz, 1H), 6.86 - 6.95 (m, 1H), 7.02 (ddd, J=11.49, 8.72, 3.03 Hz, 1H), 7.18 (td,.7=9,22, 5.56 Hz,l H), 7.39 (d, J=8.34 Hz, 1 I I). 7.52 (dd,./ 8.2 1. 1.89 Hz, 1H), 8.78 (d, J=2.02 Hz, 1H), 9,51 (s, 1H), 10.39 (br s, 1 1 1): ESI-MS m/z | i H I 442.2.
  • 32
  • [ 4100-13-4 ]
  • [ 38875-53-5 ]
  • N-(2-amino-5-bromopyridin-3-yl)-1,2,3-thiadiazole-4-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
754 mg With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 10 - 35℃; A mixture of 5-bromopyridine-2,3-diamine (723 mg), <strong>[4100-13-4]1,2,3-thiadiazole-4-carboxylic acid</strong> (500 mg), HATU (2050 mg), Et3N (1.6 mL) and DMF (8 mL) was stirred overnight at room temperature. The mixture was diluted with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with a saturated brine, then dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (754 mg). The title compound was used for the subsequent reaction without being further purified. MS: [M+H]+ 299.9.
  • 33
  • [ 3989-36-4 ]
  • [ 4100-13-4 ]
  • 34
  • [ 4100-13-4 ]
  • [ 121-66-4 ]
  • C6H3N5O3S2 [ No CAS ]
 

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