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Chemical Structure| 61929-24-6 Chemical Structure| 61929-24-6

Structure of 61929-24-6

Chemical Structure| 61929-24-6

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Product Details of [ 61929-24-6 ]

CAS No. :61929-24-6
Formula : C2HBrN2S
M.W : 165.01
SMILES Code : BrC1=NN=CS1
MDL No. :MFCD04115375
InChI Key :DQBCRVIBTFHJLM-UHFFFAOYSA-N
Pubchem ID :2795198

Safety of [ 61929-24-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315
Precautionary Statements:P280

Computational Chemistry of [ 61929-24-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 6
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 27.61
TPSA ?

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

54.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.31
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

0.8
Log Po/w (WLOGP)?

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

1.3
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.

-0.02
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

3.01
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.28

Water Solubility

Log S (ESOL):?

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

-1.98
Solubility 1.71 mg/ml ; 0.0104 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.

-1.52
Solubility 5.03 mg/ml ; 0.0305 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

-1.76
Solubility 2.83 mg/ml ; 0.0172 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.

-6.74 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)

2.87

Application In Synthesis of [ 61929-24-6 ]

* 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 [ 61929-24-6 ]

[ 61929-24-6 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 61929-24-6 ]
  • [ 17356-08-0 ]
  • [ 18686-82-3 ]
  • 2
  • [ 61929-24-6 ]
  • [ 74-89-5 ]
  • [ 24854-43-1 ]
  • 3
  • [ 61929-24-6 ]
  • [ 289-06-5 ]
  • 4
  • [ 61929-24-6 ]
  • [ 5794-88-7 ]
  • [ 71860-11-2 ]
  • 5
  • [ 61929-24-6 ]
  • [ 30094-47-4 ]
  • 6
  • [ 61929-24-6 ]
  • [ 4506-71-2 ]
  • 6,7,8,9-tetrahydro-10H-<1>benzothieno<2,3-d><1,3,4>thiadiazolo<3,2-a>pyrimidin-10-one [ No CAS ]
  • 7
  • [ 61929-24-6 ]
  • [ 3111-52-2 ]
  • [ 3530-72-1 ]
  • 9
  • [ 61929-24-6 ]
  • ethanolic methylamine [ No CAS ]
  • [ 24854-43-1 ]
  • 10
  • [ 61929-24-6 ]
  • [ 32231-06-4 ]
  • [ 67869-86-7 ]
YieldReaction ConditionsOperation in experiment
In N-methyl-acetamide; ethanol; water; benzene; Second method A solution of 11.2 g (0.0678 mole) of <strong>[61929-24-6]2-bromo-1,3,4-thiadiazole</strong> and 29.8 g (0.136 mole) of 1-piperonyl piperazine (cf. French Patent No. 1,312,427) in 400 ml of anhydrous dimethylformamide was heated at 110 C. for 8 hours. Then, the solvent was evaporated off under reduced pressure and the oily residue was taken up in 200 ml of benzene and 400 ml of water. The organic layer was decanted off then concentrated under reduced pressure. There was obtained a crystalline residue which recrystallized from 60 ml of ethanol, gave 9.9 g of crystals of 1-piperonyl-4-(1,3,4-thiadiazol-2-yl)-piperazine, melting at 112-114 C.
  • 11
  • [ 61929-24-6 ]
  • [ 645-36-3 ]
  • (1,3,4-thiadiazol-2-yl)aminoacetaldehyde diethyl acetal [ No CAS ]
YieldReaction ConditionsOperation in experiment
In ethyl acetate; benzene; (a) Preparation of the starting compound A solution of <strong>[61929-24-6]2-bromo-1,3,4-thiadiazole</strong> (3.14 g.) and aminoacetaldehyde diethyl acetal (5.1 g.) in benzene (75 ml) was refluxed for 20 hours. After cooling, the insoluble material was filtered off. The filtrate was concentrated under reduced pressure to give oil (6.3 g.). The oil was purified by column chromatography on silica gel (120 g.) using benzene and then ethyl acetate as developing solvent to give (1,3,4-thiadiazol-2-yl)aminoacetaldehyde diethyl acetal (3.3 g.), mp 108 to 112 C. I.R. spectrum (Nujol) 3130, 2940, 1555, 1494 cm-1.
  • 12
  • [ 61929-24-6 ]
  • [ 940307-34-6 ]
  • [ 940307-26-6 ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 100℃; for 0.166667h;Irradiation; A lO mL microwave vessel was charged with a solution of 8-amino-l -(8-fhioro-2-phenyl-quinolin-7-yl)-2H-imidazo[l,5-a]pyrazine-3-thione (20 mg, 0.00005 mol), 2-brom.o- 1,3,4-thiadiazole (0.017 g, 0.00010 mol) and potassium carbonate (0.021 g, 0.00015 mol) in DMF (1.4 mL, 0.018 mol). The reaction mixture was heated in the microwave at 100 0C for 10 min. The reaction mixture was concentrated in vacuo and purification by Gilson HPLC eluting with 10?65% acetontrile: H2O afforded the title compound as a light yellow solid. 1H NMR (400 MHz, CDCl3): delta = 7.31 (d, /=5.05 Hz, IH), 7.47 -7.58 (m, 3H), 7.69 -7.80 (m, 3H), 8.05 <n="81"/>(d, ./=8.84 Hz, IH), 8.24 (dd, J =8.34, 1.52 Hz, 2H), 8.32 (dd, J=8.72, 1.39 Hz, IH), 9.07 (s, IH). MS(ES+): m/z 472.13 (10O)[MH+]. HPLC: tR = 2.9 min (Open Lynx polar_5min).
  • 13
  • [ 4005-51-0 ]
  • [ 144-55-8 ]
  • [ 61929-24-6 ]
YieldReaction ConditionsOperation in experiment
With aqueous HBr; sodium nitrite;copper(I) bromide; In water; ethyl acetate; Example 32 Compound 24 In a 200 mL round-bottom flask, 2-amino-1,3,4-thiadiazole (1.00 g, 9.89 mmol) was added to 10 mL of 48% aqueous HBr. Water (10 mL) was added to give a yellow solution in which most solids dissolved. The mixture was cooled to 0 C. and CuBr (142 mg, 0.989 mmol) was added to give an opaque brown solution with some precipitate. NaNO2 (682 mg, 9.89 mmol) was dissolved in 25 mL H2O and added dropwise over 45 minutes to the thiadiazole mixture. The mixture became dark green and opaque with the first drops of NaNO2 solution. Slowly, the solution became brownish yellow and brown gas evolved. The mixture was stirred for an additional 10 minutes at 0 C. from the time gas evolution began. The mixture was warmed to room temperature over 30 minutes. Saturated aqueous NaHCO3 was added dropwise until bubbling ceased and the pH was 8.5. To this was added 50 mL of EtOAc and the biphasic mixture stirred rapidly. The mixture was filtered through a pad of Celite to remove solids and then the layers were separated. The organics were washed with brine (2*). The aqueous layer was extracted with EtOAc and washed with brine (1*). The combined organic layers were dried over Na2SO4. The remaining aqueous material was extracted once more by vigorous stirring with EtOAc (50 mL) for 12 hours. This EtOAc layer was washed with brine and combined with the EtOAc that was already drying over Na2SO4. The solution was filtered and evaporated under vacuum to give 24 as a tan solid (1.22 g, 7.36 mmol), which was used without further purification.
  • 14
  • [ 61929-24-6 ]
  • platinum(II) bromde [ No CAS ]
  • [ 101332-70-1 ]
  • 15
  • [ 61929-24-6 ]
  • tetrabromopalladate(II)(2-) [ No CAS ]
  • [ 101332-67-6 ]
  • 16
  • [ 61929-24-6 ]
  • tetrachloropalladium anion [ No CAS ]
  • [ 101332-66-5 ]
  • 17
  • [ 61929-24-6 ]
  • tetrachloroplatinum(II) [ No CAS ]
  • [ 101332-69-8 ]
  • 18
  • [ 61929-24-6 ]
  • [ 109-07-9 ]
  • [ 943326-08-7 ]
YieldReaction ConditionsOperation in experiment
78% In butan-1-ol; at 120℃; for 0.333333h; a) Synthesis of 2-(3-methylpiperazine-1-yl)-1,3,4-thiadiazol 2.0 g (12.1 mmol) 2-bromine-[1,3,4]-thiadiazol and 7.2 g (72.7 mmol) 2-methylpiperazine were stirred in n-butanol (10 ml) for 20 min at 120 C. The mixture was subsequently concentrated in a vacuum. CC (SiO2, DCE/EtOH/conc. NH4OH 5:1:0.06) was performed with the residue, whereby 1.7 g (9.3 mmol, 78%) 2-(3-methylpiperazine-1-yl)-1,3,4-thiadiazol was obtained.
  • 19
  • [ 61929-24-6 ]
  • [ 109-81-9 ]
  • N1-methyl-N1-(1,3,4-thiadiazol-2-yl)ethane-1,2-diamine [ No CAS ]
YieldReaction ConditionsOperation in experiment
33% With copper; copper(l) chloride; In isopropyl alcohol; at 70℃; for 1h; a) Synthesis of N1-methyl-N1-(1,3,4-thiadiazol-2-yl)ethane-1,2-diamine 70 mg (1.1 mmol) copper and 328 mg (3.3 mmol) copper(I) chloride were added to a solution of 3.3 g (20.0 mmol) 2-bromothiadiazol and 10.6 ml (120.0 mmol) N-methyl-ethylene-diamine in isopropanol (114 ml). Heating was subsequently performed at 1 h to 70 C. After cooling to RT, filtration was performed through silica gel and the filtrate was concentrated in a vacuum. 1.05 g (6.6 mmol, 33%) N1-methyl-N1-(1,3,4-thiadiazol-2-yl)ethane-1,2-diamine was obtained by CC (DCE/EtOH/conc. aq. NH4OH sol. 4:4:0.25) with the residue.
  • 20
  • [ 61929-24-6 ]
  • [ 1036991-14-6 ]
  • [ 1036989-52-2 ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate;tetrakis(triphenylphosphine) palladium(0); In water; toluene; butan-1-ol; at 80℃;Heating / reflux; Procedure E3e; To a solution of 1-{3-[7-(4,4,5,5-tetramethyl-[1 ,3,2]dioxaborolan-2-yl)-imidazo[1 ,2-a]pyridin- 3-yl]-phenyl}-3-(2,2,2-trifluoro-ethyl)-urea (107mg, 0.23mmol) and 2-bromo- [1 ,3,4]thiadiazole (96mg, 0.58mmol) in a mixture of toluene (2ml), "butanol (2ml) and water (0.5ml) was added cesium carbonate (228mg, 0.7mmol). The reaction mixture was deoxygenated and tetrakis(triphenylphosphine)palladium (0) (81 mg, 0.07mmol) added. The reaction mixture was again degassed and heated at 80 0C overnight. The mixture was cooled, partitioned between EtOAc and H2O, the organic layer separated, dried (MgSO4), filtered and the solvent remove in vacuo. The crude product was purified by preparative HPLC to give the 18mg of product. MS: [M+H]+419.
  • 21
  • [ 61929-24-6 ]
  • [ 1097626-52-2 ]
  • [ 1097626-56-6 ]
YieldReaction ConditionsOperation in experiment
With copper(l) iodide; N-ethyl-N,N-diisopropylamine;bis-triphenylphosphine-palladium(II) chloride; In N,N-dimethyl-formamide; at 120℃; for 0.333333h;Microwave irradiation; To a stirred and degassed solution of 2-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-5-ethynyl-3,4 difluorobenzaldehyde (Intermediate 47, 0.35 mmol) in dry DMF (2 mL) was added DIPEA (1.5 mL), copper iodide (0.01 mmol), dichorobis(triphenylphosphine) palladium (0.01 mmol), and 2- bromo- 1,3, 4-thiadiazole (0.71 mg, 0.43 mmol), sequentially. The reaction mixture was heated at 120 0C for 20 minutes in a microwave reactor, cooled to room temperature, and concentrated. The residue was purified by flash chromatography over a silica gel column using a gradient of ethyl acetate in petroleum ether to give the title product. MS (ES) MH+: 364 for Ci7Hi5F2N3O2S.
  • 22
  • [ 61929-24-6 ]
  • [ 1105510-43-7 ]
  • [ 1105511-23-6 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tris-(dibenzylideneacetone)dipalladium(0); XPhos; In water; acetonitrile; at 90℃; for 12h; To a stirred and degassed solution of 2-((2S,6R)-2,6-dimethyl-morpholin-4-yl)-5-(4,4,5,5- tetramethyl[l,3,2 ]dioxaborolan-2-yl)-pyridine-3-carbaldehyde (Intermediate 36) (250 mg, 0.61 mmol) in 10 ml acetonitrile:water (4:1), was added sodium carbonate (65 mg, 0.61 mmol), 2- bromo-1,3,4 thiadiazole (120 mg, 0.73 mmol), 2-dicyclohexylphosphino 2'4'6'- <n="97"/>triisopropylbiphenyl (X-phos) (88 mg, 0.18 mmol) and tris(dibenzylideneacetone)dipalladium(0) (56 mg, 0.061 mmol), sequentially and the reaction mixture was heated to 90 0C for 12 hours. The reaction mixture was cooled to room temperature and concentrated. The residue thus obtained was purified over silica gel column using a gradient of ethyl acetate in pet. ether to give product as yellow solid. Yield: 230 mg. MS (ES) MH+: 305.2 for Ci4Hi6N4O2S.
  • 23
  • [ 61929-24-6 ]
  • [ 2150-47-2 ]
  • [ 1196474-79-9 ]
YieldReaction ConditionsOperation in experiment
16% With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h; A solution of 2,4-dihydroxy-benzoic acid methyl ester (1.0 g, 6 mmol), 5-bromothiadiazole (1.0 g, 6 mmol) and K2CO3 (1.25 g, 9 mmol) in DMF (15 mL) was heated at 80 C. for 16 hours. Water (25 mL) was added and the mixture extracted with EtOAc (2×10 mL). The organic extracts were washed with water (10 mL), dried and concentrated in vacuo. The residue was purified by silica gel flash column chromatography (hexane:EtOAc 80:20) to give 2-hydroxy-4-([1,3,4]thiadiazol-2-yloxy)-benzoic acid methyl ester (0.23 g, 16%). 1H NMR (400 MHz, CDCl3): delta 10.98 (s, 1H), 8.82 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 6.89 (dd, J=2.4, 12 Hz, 2H), 3.96 (s, 3H). MS (ESI) m/z=253 [M+H]+.
  • 24
  • [ 61929-24-6 ]
  • rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester [ No CAS ]
  • rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(1-[1,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
32% With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 150℃; for 0.583333h;Irradiation with microwave; To a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (100 mg, 0.20 mmol) in N-methylpyrrolidinone (1 mL) was added <strong>[61929-24-6]2-bromo-1,3,4-thiadiazole</strong> (50 mg, 0.30 mmol) and N,N-diisopropyl ethyl amine (69 mul, 0.40 mmol). The solution was irradiated in the microwave for 35 min at 150 C. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separated and washed with brine (15 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, ethyl acetate:methanol=100:0 to 80:20) afforded the title compound (37 mg, 32%) as an off-white foam. MS m/e: 578.1 [M]+.
32% With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 150℃; for 0.583333h;Microwave irradiation; Example 78 rac-[(3R,4S)-4-(3,4-Dichloro-phenyl)-l-(l-[l,3,4]thiadiazol-2-yl-piperidine-4-carbonyl)- pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl esterTo a solution of rac-[(3R,4S)-4-(3,4-dichloro-phenyl)-l-(piperidine-4-carbonyl)-pyrrolidin-3- yl]-methyl-carbamic acid 4-fluoro-phenyl ester (100 mg, 0.20 mmol) in N-methylpyrrolidinone (1 mL) was added 2-bromo-l,3,4-thiadiazole (50 mg, 0.30 mmol) and Nu,Nu-diisopropyl ethyl amine (69 mu, 0.40 mmol). The solution was irradiated in the microwave for 35 min at 150C. The reaction mixture was diluted with ethyl acetate (15 mL) and washed with an aqueous solution of sodium carbonate (1 M, 15 mL). The organic layer was separeted and washed with brine (15 mL) and the aqueous layers were extracted with ethyl acetate (20 mL). The combined organic layers were dried over sodium sulfate and concentrated. Purification by chromatography (Si02, ethyl acetate :methanol = 100:0 to 80:20) afforded the title compound (37 mg, 32%) as an off-white foam. MS m/e: 578.1 [M]+.
  • 25
  • [ 61929-24-6 ]
  • [ 4897-50-1 ]
  • [ 1222996-43-1 ]
  • 26
  • [ 61929-24-6 ]
  • [ 4746-97-8 ]
  • [ 1228652-78-5 ]
  • 27
  • [ 61929-24-6 ]
  • [ 101-79-1 ]
  • [ 1562690-58-7 ]
YieldReaction ConditionsOperation in experiment
28% With toluene-4-sulfonic acid; In isopropyl alcohol; at 60 - 80℃;Inert atmosphere; [0197] To a solution of Compound 7-A (1.35 g, 6.2 mmol) and compound 7-B (0.4 g,mmol) in isopropanol (25 mL) was added p-toluenesulfonic acid (1.16 g, 6.1 mmol). The resulting mixture was stirred overnight at about 60-80 C overnight under nitrogen. Monitoring by thin layer chromatography (petrol ether: ethyl acetate=2: 1 and Rf at 0.5) showed the reaction was complete. The mixture was diluted with saturated aqueous NaHCO3 (90 mL) and extracted with ethyl acetate (30 mL x 3). The organic layers were concentrated and purified by silica gel column (petrol ether: ethyl acetate= 15:1) to give the title compound (206 mg, 28%) as a solid. ?H NMR (400 MHz, DMSO) oe 6.97-6.95 (d, J=Hz, 1H), 7.06-7.04 (d, J= 8.4 Hz, 1H), 7.39-7.37 (d, J= 8.4 Hz, 1H), 7.67-7.65 (d, J=Hz, 1H), 8.87 (s, 1H), 10.39 (s, 1H). MS: 303.9 (M+lj.
  • 28
  • [ 61929-24-6 ]
  • [ 13065-93-5 ]
  • [ 1562690-62-3 ]
YieldReaction ConditionsOperation in experiment
With toluene-4-sulfonic acid; In isopropyl alcohol; at 120℃; for 1h;Microwave irradiation; Sealed tube; [0201] Step 3. To a solution of Compound 8-D (0.4 g, 1.8 mmol) and Compound 8-E(0.31 g, 1.8 mmol) in isopropanol (8 mL) was added p-toluenesulfonic acid (0.36 g, 1.9 mmol). The mixture was sealed and heated in microwave at 120 C for 1 hour. Monitoring by thin layer chromatography (petrol ether: ethyl acetate= 1:1 and Rf at 0.6) showed that Compound 8-E was consumed. The mixture was diluted with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (15 mL x 3). The organic layers were concentrated and the residue was purified by preparative HPLC to give the title compound (38 mg, 1.3%, combined with other 5 batches; purity 79% by HPLC) as a white solid. ?H NMR (400 MHz, DMSO) oe 6.94-6.96 (d, J= 8.4 Hz, 1H), 7.07-7.05 (d, J= 8.4 Hz, 1H), 7.17-7.19 (d, J = 8.8 Hz, 1H), 7.50-7.52 (d, J= 8.4 Hz, 1H), 8.14 (s, 1H), 8.80 (s, 1H), 10.19 (s, 1H). MS:302.9 (M+lj.
  • 29
  • [ 61929-24-6 ]
  • [ 4913-77-3 ]
  • [ 1562690-64-5 ]
YieldReaction ConditionsOperation in experiment
18% With toluene-4-sulfonic acid; In isopropyl alcohol; [0205] Step 3. To a solution of Compound 9-D (0.2 g, 0.86 mmol) in isopropanol (9 mL) was added Compound 9-E (0.14 g, 0.86 mmol) and p-toluenesulfonic acid (0.16 g, 0.86 mmol). Then the mixture was refluxed overnight. Monitoring by thin layer chromatography (petroleum ether/ethyl acetate=4: 1 and Rf at 0.2) showed the reaction was almost complete. The solvent was removed. The residue was purified by silica gel chromatography and preparative HPLC to give the title compound (181 mg, combined with other 2 batches, yield = 18 %) as a yellow solid. ?H NMR (400 MHz, DMSO) oe 8.64 (s, J= 8 Hz, 1H), 7.66-7.61 (m, 4H), 7.57-7.53 (m, 4H). MS: 316.0 (M+lj.
  • 30
  • [ 61929-24-6 ]
  • (R)-tert-butyl-(1-((5-methoxy-4-(oxazol-5-yl)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate [ No CAS ]
  • (R)-tert-butyl-(1-((5-methoxy-4-(oxazol-5-yl)-2-( 1,3,4-thiadiazol-2-yl)phenyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tetrakis(triphenylphosphine) palladium(0); caesium carbonate; In 1,4-dioxane; water;Inert atmosphere; Reflux; (R)-tert-Butyl (1 -((5 -methoxy-4-(oxazol-5 -yl)-2-(4,4,5 ,5 -tetramethyl- 1,3,2- dioxaborolan-2-yl)phenyl)amino)-4-methyl- 1 -oxopentan-2-yl)carbamate (400 mg, 0.75 6 mmol) was taken up in 1 ,4-dioxane (8 mL) and water (4 mL) and treated with<strong>[61929-24-6]2-bromo-1,3,4-thiadiazole</strong> (150 mg, 0.907 mmol), Cs2CO3 (738 mg, 2.267 mmol) and tetrakis(triphenylphosphine)palladium(0) (873 mg, 0.756 mmol). The resultantmixture was degassed for 5 mm and heated at reflux overnight. After the reaction was complete, the mixture was partitioned between water (10 mL) and ethyl acetate (3 x 10 mL). The combined organic layers were washed with brine (10 mL), dried (sodium sulfate), filtered, and concentrated under reduced pressure to give crude (R)tert-butyl (1 -((5 -methoxy-4-(oxazol-5 -yl)-2-( 1,3 ,4-thiadiazol-2-yl)phenyl)amino)-4-methyl-1-oxopentan-2-yl)carbamate (230 mg, 62% yield): LCMS (ESI) m/e 486.4 [(M), calcd for C23H28N505S, 486.2]; LC/MS retention time (method C): tp. = 2.09 mm.
  • 31
  • [ 61929-24-6 ]
  • [ 1185019-97-9 ]
  • 2-(2-methoxy-4-nitrophenyl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; caesium carbonate; In N,N-dimethyl-formamide; at 100℃; for 16h;Inert atmosphere; Prepared in a similar fashion as described in Example 22 except that the following conditions were used in Part B: 2-(2-methoxy-4-nitrophenyl)-4,4,5 ,5 -tetramethyl- 1,3 ,2-dioxaborolane (700 mg, 2.508 mmol), 2-bromo- 1,3 ,4-thiadiazole(414 mg, 2.508 mmol), cesium carbonate (1634 mg, 5.02 mmol), and DMF (12 mL)were combined. N2 was bubbled into the reaction mixture for 2 mi (1,1?-Bis(diphenylphosphino)ferrocene)-dichloropalladium(II) dichloromethane complex(206 mg, 0.25 1 mmol) was then added and the reaction mixture was stirred at 100 Cfor 16 h. The mixture was cooled to room temperature, and was filtered through apad of diatomaceous earth (Celite) with ethyl acetate rinsing. The filtrate was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (15 mL). The aqueous layer was extracted with ethyl acetate (3 x 15 mL). The combined organic layers were washed with brine (10 mL), dried over MgSO4,filtered, and concentrated. The residue was purified by column chromatography on silica gel (1% -* 3% MeOH in CH2C12) to afford 2-(2-methoxy-4-nitrophenyl)-1,3,4- thiadiazole (42 mg, 7% yield) as a light brown solid: LC/MS (ESI) m/e 238.2 ((M+H), calcd for C9H8N303S 238.0).
  • 32
  • [ 61929-24-6 ]
  • 6-(1-methylpyrazol-4-yl)-1-(1-tetrahydropyran-4-yl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-3-yl)-3,4-dihydro-2H-quinoline [ No CAS ]
  • 2-(3-(6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-1-(tetrahydro-2H-pyran-4-yl)-6,7-dihydro-1H-pyrazolo[4,3-c]pyridin-5(4H)-yl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
10% With dichloro[1,3-bis(2,6-di-3-pentylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II); sodium t-butanolate; In 1,4-dioxane; at 120℃; for 16h;Inert atmosphere; To a vial was added 6-( 1 -methylpyrazol-4-yl)- 1 -(1 -tetrahydropyran-4-yl-4,5 ,6,7- tetrahydropyrazolo[4,3 -cjpyridin-3 -yl)-3 ,4-dihydro-211-quinoline (Intermediate J, 18.8 mg, 0.0449 mmol), 2-bromo-l,3,4-thiadiazole (15.0 mg, 0.0898 mmol), dichloro[l,3-bis(2,6-di-3- pentylphenyl)imidazo1-2-ylidene(3 -chloropyridyl)palladium(II) (7.5 mg, 0.0090 mmol), tBuONa (8.6 mg, 0.090 mmol) and 1 ,4-dioxane (0.4 mL). The mixture was sparged with anargon ballon, and then heated to 120 C for 16 h under an argon atmosphere. Afier cooling the reaction to room temperature, DCM (1 mL) was added and the reaction was filtered through celite and concentrated in vacuo to give the crude product that was purified by reverse phase chromatography (acetonitrile 5-85% / 0.1% NH4OH in water) to give the title compound (2.5 mg, 10%) as a white solid. ?H NMR (400 MHz, DMSO-d6) 6 8.78 (s, 1H),7.91 (d,J0.8Hz, 1H), 7.68 (d,J 0.8 Hz, 111), 7.21 (d,J2.1 Hz, 1H), 7.12 (dd,J 8.4,2.2 Hz, IH), 6.45 (d,J= 8.4 Hz, IH), 4.37-4.25 (m, IH), 4.18 (s, 2H), 4.00-3.90 (m, 2H),3.85 (t, J 5.8 Hz, 2H), 3.82 (s, 311), 3.62-3.53 (m, 211), 3.45 (t, J 11.5 Hz, 211), 2.94 (t, J= 5.7 Hz, 211), 2.82 (t,J= 6,4 Hz, 2H), 2.05-1.92 (m, 4H), 1.81 (d,J 10.9 Hz, 2H). LCMSM/Z (M+H) 503.
  • 33
  • [ 61929-24-6 ]
  • (S)-1-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)piperazine dihydrochioride [ No CAS ]
  • (S)-2-(4-((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)methyl)piperazin-1-yl)-1,3,4-thiadiazole [ No CAS ]
YieldReaction ConditionsOperation in experiment
53 mg With N-ethyl-N,N-diisopropylamine; In 1-methyl-pyrrolidin-2-one; at 150℃; for 3h;Microwave irradiation; A Mixture of (5)-i -((2,3 -dihydrobenzo[b] [1,4] dioxin-2-yl)methyl)piperazine dihydrochloride(0.20 g, 0.65 mmol), 2-bromo-i,3,4-thiadiazole (0.16 g, 0.98 mmol), and DIPEA (0.45 ml,0.34 g, 2.60 mmol) in NMP (4 ml) was heated MW reactor for 3 h at 150 C. The reactionmixture was diluted with water and extracted with EtOAc. Combined organic phases werewashed with water and brine, dried and evaporated to dryness. The residue was purified byflash chromatography yielding 53 mg (5)-2-(4-((2,3 -dihydrobenzo[b] [1,4] dioxin-2- yl)methyl)piperazin- 1 -yl)- 1,3 ,4-thiadiazole.?H NMR (400 MHz, CDC13): 2.62-2.82 (6H, m), 3.52-3.67 (4H, m), 4.00-4.08 (1H, m), 4.27-4.39 (2H, m), 6.79-6.93 (4H, m), 8.46 (1H, s).
  • 34
  • [ 61929-24-6 ]
  • 2-(2-isopropylphenyl)-7-methyl-9-(piperidin-4-ylmethyl)-7,9-dihydro-8H-purin-8-one [ No CAS ]
  • 9-((1-(1,3,4-thiadiazol-2-yl)piperidin-4-yl)methyl)-2-(2-isopropylphenyl)-7-methyl-7,9-dihydro-8H-purin-8-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
With methanesulfonato(2-dicyclohexylphosphino-2?,6?-di-i-propoxy-1,1?-biphenyl)(2?-methylamino-1,1?-biphenyl-2-yl)palladium(II); caesium carbonate; In N,N-dimethyl-formamide; at 110℃; for 16h; Example 42: General Protocol for Amine Arylation (1984) (1985) B-80 (1986) [00518] A mixture of Intermediate B-80 (0.2M in DMF, 150 jiL, 30 mumol), heteroaryl bromide (A) (0.2M in DMF, 300 mu,, 60 muiotaetaomicron), cesium carbonate (48 mg, 150 muiotaetaomicron), and RuPhos Pd G3 (0.02M in DMF, 300 mu, 6 muiotaetaomicron) was heated for 16 h at 110 C. The reaction mixture was cooled to ambient temperature, concentrated and partitioned between IN NaOH (0.5 mL) and EtOAc (0.5 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc. The combined organic extracts were concentrated to afford the crude product, which was purified by mass-triggered preparatory FIPLC. The product-containing fractions were combined and concentrated in a Genevac to afford the desired product.
  • 35
  • [ 61929-24-6 ]
  • [ 4105-21-9 ]
  • 2-(2-phenylimidazo[1,2-a]pyridin-3-yl)-1,3,4-thiadiazole [ No CAS ]
 

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