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Structure of 1203705-55-8

Chemical Structure| 1203705-55-8

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Product Details of [ 1203705-55-8 ]

CAS No. :1203705-55-8
Formula : C3H4BrN3
M.W : 161.99
SMILES Code : NC1=CC(Br)=NN1
MDL No. :MFCD18801156
InChI Key :VGBYIGUWAWHQOT-UHFFFAOYSA-N
Pubchem ID :46179974

Safety of [ 1203705-55-8 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H320-H335
Precautionary Statements:P261-P280-P301+P312-P302+P352-P305+P351+P338

Computational Chemistry of [ 1203705-55-8 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 1.0
Num. H-bond donors 2.0
Molar Refractivity 30.69
TPSA ?

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

54.7 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

0.89
Log Po/w (WLOGP)?

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

0.76
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.

0.21
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

1.23
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.73

Water Solubility

Log S (ESOL):?

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

-1.93
Solubility 1.89 mg/ml ; 0.0117 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.

-1.62
Solubility 3.86 mg/ml ; 0.0238 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

-1.72
Solubility 3.1 mg/ml ; 0.0191 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.

-6.66 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)

1.89

Application In Synthesis of [ 1203705-55-8 ]

* 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 [ 1203705-55-8 ]

[ 1203705-55-8 ] Synthesis Path-Downstream   1~13

  • 1
  • [ 1203705-55-8 ]
  • [ 87-13-8 ]
  • [ 1203705-56-9 ]
  • 2
  • [ 104599-37-3 ]
  • [ 1203705-55-8 ]
YieldReaction ConditionsOperation in experiment
32% With tin(II) chloride dihdyrate; In ethanol; ethyl acetate; at 110.0℃; for 0.75h; This intermediate, 3,4-dibromo-5-nitro-1H-pyrazole (69 g) was reduced by refluxing with Stannous chloride, dihydrate (135 g) in Ethyl acetate (600 mL) and Ethanol (300 mL) at 110 C. for 45 minutes. The yellow homogenous reaction solution was cooled to room temperature and slowly poured over a vigorously stirring solution of sodium bicarbonate (33 g) in water (200 mL) and ethyl acetate (800 mL). To the resultant slurry was added Celite (30 g), and this slurry was filtered through a bed of Celite. The filter cake was washed with additional ethyl acetate (600 mL). The organic solution was then washed with brine (200 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to give the crude product as an orange oil. The crude product was then purified by flash column chromatography (Biotage, Quad 25; Eluent: 6% EtOH in methylene chloride). This afforded the title compound as a light beige solid (13.2 g, 32%). 1HNMR (400 MHz, DMSO-d6) delta: 5.20, (m, 3H), 11.60, (br s, 1H).
  • 3
  • [ 10420-33-4 ]
  • [ 1203705-55-8 ]
  • [ 1364597-15-8 ]
YieldReaction ConditionsOperation in experiment
54.2% toluene-4-sulfonic acid; In xylene; for 8.0h;Reflux; Methyl 2-(2-bromo-7-hydroxy-5-methylpyrazolo / ,5-aj 'pyrimidin-6-y I) acetate.; To a solution of 3-bromo-lH-pyrazol-5-amine (0.2 g, 1.235 mmol) and dimethyl 2- acetylsuccinate (0.697 g, 3.70 mmol) in xylene (10 mL) was added -toluenesulfonic acid monohydrate (2 mg, 10.51 muiotaetaomicron). The reaction mixture was heated at reflux under a Dean-Stark trap for 8 h. The solid was filtered and washed with hexanes to afford the title compound (0.201 g, 54.2%). ¾ NMR (400 MHz, MeOD) delta ppm 2.37 (3 H, s), 3.65 (2 H, s), 3.71 (3 H, s), 6.20 (1 H, s).
54.2% With toluene-4-sulfonic acid; In 5,5-dimethyl-1,3-cyclohexadiene; for 8.0h;Reflux; Dean-Stark; Methyl 2-(2-bromo-7-hydroxy-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate To a solution of <strong>[1203705-55-8]3-bromo-1H-pyrazol-5-amine</strong> (0.2 g, 1.235 mmol) and dimethyl 2-acetylsuccinate (0.697 g, 3.70 mmol) in xylene (10 mL) was added p-toluenesulfonic acid monohydrate (2 mg, 10.51 mumol). The reaction mixture was heated at reflux under a Dean-Stark trap for 8 h. The solid was filtered and washed with hexanes to afford the title compound (0.201 g, 54.2%). 1H NMR (400 MHz, MeOD) delta 2.37 (3H, s), 3.65 (2H, s), 3.71 (3H, s), 6.20 (1H, s).
  • 4
  • [ 1203705-55-8 ]
  • [ 63458-98-0 ]
  • C15H11BrF3N3O2 [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% With acetic acid; at 80.0℃; for 1.0h; A mixture of 3-amino-5-bromopyrazole C-8 (3.24 g, 20 mmol) and diketone C-2 (5.52 g, 20 mmol) in Acetic acid (20 mL) was heated to 80 C. After 1 h, the reaction mixture was cooled to rt, and diluted with IPA. A yellow ppt formed in the mixture, which was collected by filtration. Upon standing, additional ppt was formed in the mother liquor. The combined crops were collected and dried under vacuum to afford 3.89 g of compound C-9 as a yellow solid (9.67 mmol, 48% yield). [0369] 1H NMR (400 MHz, CHLOROFORM-d) delta ppm 3.99 (s, 3H) 4.05 (s, 3H) 6.85 (s, 1H) 7.00 (d, J=8.47 Hz, 1H) 7.57 (s, 1H) 7.62 (dd, J=8.45, 2.16 Hz, 1H) 7.80 (d, J=2.14 Hz, 1H) [0370] MS (M+H+) 402.2
  • 5
  • [ 1203705-55-8 ]
  • 1-(1,3-dimethyl-1H-pyrazol-4-yl)-4,4,4-trifluoro-3-hydroxybut-2-en-1-one [ No CAS ]
  • 2-bromo-5-(1,3-dimethyl-1H-pyrazol-4-yl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine [ No CAS ]
YieldReaction ConditionsOperation in experiment
73.1% With acetic acid; at 120.0℃;Sealed tube; 1-(1,3-dimethyl-1H-pyrazol-4-yl)-4,4,4-trifluoro-3-hydroxybut-2-en-1-one (Preparation 5, 1.7 g) and <strong>[1203705-55-8]3-bromo-1H-pyrazol-5-amine</strong> (Preparation 6, 1.18 g) in Acetic acid (52.61 mL) was heated at 120 C. in a sealed tube overnight. The reaction solution was cooled to room temperature, and poured into ice water (500 mL) resulting in a white precipitate. The precipitate was filtered and washed with copious amounts of water. The precipitate was then collected and dried in vacuo to afford the title compound as a white powder (1.9 g, 73.1%). [0524] 1HNMR (400 MHz, DMSO-d6) delta: 2.47 (s, 3H), 3.79, (s, 3H), 6.95, (s, 1H), 7.73, (s, 1H), 8.67, (s, 1H).
  • 6
  • [ 406-87-1 ]
  • [ 1203705-55-8 ]
  • [ 614-16-4 ]
  • C16H12BrF3N4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In N,N-dimethyl-formamide; at 90.0℃; for 16.0h; General procedure: 1H-Pyrazol-5-amine 1 (1 equiv.), 3-oxopropanenitrile 2 (1 equiv.), benzaldehyde 3 (1 equiv.), and Et3N (2 equiv.) were stirred in DMF (1 M) at 90 C for 16 h. The volatiles were removed under reduced pressure (or positive N2 (g) pressure). Sodium nitrite (3 equiv.) and acetic acid (134 equiv.) were added to the crude material, and the reaction mixture was stirred for 10 min. The volatiles were removed under reduced pressure (or positive N2 (g) pressure), and the crude reaction mixture was subjected to silica gel column chromatography with ethyl acetate in hexanes.
  • 7
  • [ 1203705-55-8 ]
  • ethyl (3Z)-3-[(dimethylamino)methylidene]-4-oxopentanoate [ No CAS ]
  • ethyl 2-bromo-7-methylpyrazolo[1,5-a]pyrimidine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% In ethanol; for 2.0h;Reflux; Step 17A: Ethyl 2-bromo-7-methylpyrazolo[1.5-a]pyrimidine-6-carboxylate (0758) A solution of 3-bromo-lH-pyrazol-5-amine (4.2 g, 26 mmol, 1.0 eq) and ethyl (3Z)-3-[(dimethylamino)methylidene]-4-oxopentanoate (4.9 g, 26 mmol, 1.0 eq) in ethanol (300 mL) was prepared and heated to reflux for 2 hrs. The reaction mixture was concentrated. Silica gel column was loaded using methylene chloride and run using an increasing gradient of MeOH (0-5%) in methylene chloride over 20 min to provide ethyl 2-bromo-7-methylpyrazolo[l,5-a]pyrimidine-6-carboxylate 17a (6.0 g, 21 mmol, 81%) as a white solid.
  • 8
  • [ 1203705-55-8 ]
  • 4-amino-7-(tert-butyl)-7H-pyrrolo[2, 3-d]pyrimidine-5-carboxylic acid [ No CAS ]
  • 4-amino-N-(5-bromo-1H-pyrazol-3-yl)-7-(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
6.5 mg With N-ethyl-N,N-diisopropylamine; 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 20.0℃; 40 mg of 4-amino-7 -(tert-butyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylic acid obtained in step 5 of ReferenceExample 7 was suspended in 2 mL of DMF, and 33 mgof 3-bromo-lH-pyrazol-5-amine, 89 f.LL of diisopropylethylamine,and 78 mg ofHATU were added thereto, followedby stirring at room temperature overnight. 2 mL of anaqueous sodium hydroxide solution (1 mol/L) was added tothe reaction mixture, and the mixture was stirred at roomtemperature for 1 hour. Thereafter, the reaction mixture waspartitioned between ethyl acetate and water. The organiclayer was washed with water and a saturated aqueoussodium chloride solution, and dried over sodium sulfate.After concentration, the residue was purified by silica gelchromatography (ethyl acetate/methanol= I/O-'> 10/1 ),thereby obtaining 6.5 mg of the title compound as a whitesolid.
  • 9
  • [ 1203705-55-8 ]
  • [ 87-13-8 ]
  • ethyl 2-bromo-7-hydroxypyrazolo[1,5-a]pyrimidine-6-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
81% With acetic acid; for 20.0h;Reflux; To the solution of <strong>[1203705-55-8]5-amino-3-bromo-1H-pyrazole</strong> II (20.0 g, 121 mmol) in acetic acid (200 mL) diethyl ethoxymethylenemalonate III (25.9 mL, 127 mmol) was added. Reaction mixture was heated at reflux with stirring for 20 hours. Then the mixture was cooled to room temperature, precipitated solid was filtered, washed with ethanol and diethyl ether. Product was obtained as a creamy solid (27.9 g, 97.4 mmol), with the yield 81%. MS-ESI: (m/z) calculated for C9H7BrN303 [M-H]-= 284.0, found 284.0. 1H NMR (300 MHz, DMSO-d6) delta 8.37 (s, 1H), 6.15 (s, 1H), 4.50 (bs, 1H), 4.14 (q, J=7.1 Hz, 2H), 1.24 (t, 3=1.1 Hz, 3H).
  • 10
  • [ 1203705-55-8 ]
  • methyl 2-hydroxy-4-oxo-4-(pyridin-2-yl)but-2-enoate [ No CAS ]
  • methyl 2-bromo-7-(pyridin-2-yl)pyrazolo[1,5-a]pyrimidine-5-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
13% In methanol; for 18.0h;Reflux; A mixture of methyl 2-hydroxy-4-oxo-4-(pyridin-2-yl)but-2-enoate [1224740-13-9] (730 mg, 3.52 mmol) and 3-bromo-lH-pyrazol-5-amine [950739-21-6] (628 mg, 3.88 mmol) in MeOH (17 mL) was stirred under reflux for 18 h. The reaction mixture was cooled to rt and the precipitate was filtered off, rinsed with MeOH and dried. The residue (546 mg) was purified via achiral SFC (Stationary phase: Lux Cellulose-2 5 pm 250*30mm, mobile phase: 60% C02, 40% MeOH) to afford intermediate 1171 (147 mg, 13%) as a yellow solid.
  • 11
  • [ 874-14-6 ]
  • [ 1203705-55-8 ]
  • (2-bromopyrazolo[1,5-a]pyrimidin-5-yl)oxysodium [ No CAS ]
YieldReaction ConditionsOperation in experiment
38% With sodium; at 80.0℃; for 3.0h; To a solution of Na (7.10 g, 309 mmol) in EtOH (125 mL) was added <strong>[1203705-55-8]3-bromo-1H-pyrazol-5-amine</strong> (5.00 g, 30.9 mmol, CAS1203705-55-8) and 1,3-dimethylpyrimidine-2,4-dione (4.33 g, 30.9 mmol, CAS874-14-6). The reaction mixture was stirred at 80 C. for 3 hours. On completion, the mixture was cooled to 0-5 C., then filtered. The filter cake was washed with cold EtOH, and dried in vacuo to give the title compound (2.80 g, 38% yield) as a yellow solid. 1H NMR (400 MHz, D2O) delta 8.02 (d, J=7.6 Hz, 1H), 5.98 (d, J=7.6 Hz, 1H), 5.85 (s, 1H).
  • 12
  • [ 1001-26-9 ]
  • [ 1203705-55-8 ]
  • 2-bromopyrazolo[1,5-a]pyrimidin-5-ol [ No CAS ]
YieldReaction ConditionsOperation in experiment
2 g With caesium carbonate; In N,N-dimethyl-formamide; at 125.0℃; for 2.0h; To a solution of <strong>[1203705-55-8]3-bromo-1H-pyrazol-5-amine</strong> (3.2 g, 20.0 mmol) in DMF (60 mL) were added Cs 2CO 3 (13.0 g, 40.0 mmol) and ethyl-3-ethoxyacrylate (8.6 g, 60.0 mmol), the reaction mixture was stirred at 125 C for about 2 h. The reaction mixture was cooled to ambient temperature, poured into H 2O (200 mL), acidified by 1N HCl acid solution, extracted with EA (100 mL 3). The combined organic layers were washed with H 2O (100 mL), concentrated and purified by chromatography on silica gel (eluent: DCM/MeOH = 10/1) to afford the desired compound as a yellow solid (2.0 g). MS (ESI, m/e) [M+1] + 213.9, 214.9.
  • 13
  • [ 1203705-55-8 ]
  • [ 10078-54-3 ]
  • C15H14BrN3O3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
91.1% With acetic acid;Reflux; 1.0 g of compound II was dissolved in 15 mL of acetic acid, and 0.61 g of <strong>[1203705-55-8]3-bromo-1H-pyrazole-5-amine</strong> was added to the above solution, heated under reflux, and monitored by thin layer chromatography. After the reaction was completed, the mixture was extracted with ethyl acetate-water. The ethyl acetate layer was dried over anhydrous sodium sulfate, and the solution was concentrated. Column chromatography of dichloromethane-methanol 100: 3 gave 1.25 g of compound III. Yield: 91.1%.
 

Historical Records

Technical Information

Categories

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[ 1203705-55-8 ]

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