Home Cart Sign in  
Chemical Structure| 1346697-39-9 Chemical Structure| 1346697-39-9

Structure of 1346697-39-9

Chemical Structure| 1346697-39-9
Product Citations

Alternative Products

Product Details of [ 1346697-39-9 ]

CAS No. :1346697-39-9
Formula : C7H7BrN2
M.W : 199.05
SMILES Code : BrC1=CN=CN=C1C2CC2
MDL No. :MFCD19688785
InChI Key :AJHZEZBUHSHXIR-UHFFFAOYSA-N
Pubchem ID :53645907

Safety of [ 1346697-39-9 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 1346697-39-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 6
Fraction Csp3 0.43
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 42.2
TPSA ?

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

25.78 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.01
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

1.47
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.

1.39
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

2.61
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.91

Water Solubility

Log S (ESOL):?

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

-2.38
Solubility 0.833 mg/ml ; 0.00419 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.

-1.62
Solubility 4.8 mg/ml ; 0.0241 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

-3.11
Solubility 0.155 mg/ml ; 0.00078 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

Yes
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.

-6.47 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.78

Application In Synthesis of [ 1346697-39-9 ]

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

  • Upstream synthesis route of [ 1346697-39-9 ]

[ 1346697-39-9 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 4595-59-9 ]
  • [ 23719-80-4 ]
  • [ 1346697-39-9 ]
YieldReaction ConditionsOperation in experiment
41% With 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran at 20℃; for 17 h; 5-Bromopyrimidine (8 g, 50.3 mmol) was taken in anhydrous THF (160 mL) followed by the addition of cyclopropylmagnesium bromide (106 mL, 52.8 mmol, 0.5 M solution in THF) at 0 °C. The reaction mixture was stirred at room temperature for 1 hour, and then treated with a solution of 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (1 1.42 g, 50.3 mmol) in THF (26 mL). The resultant brown mixture was allowed to stir at room temperature for 16 hours and then evaporated under reduced pressure. The brown solid was suspended in water and extracted with dichloromethane (3x50 mL). The combined organics were washed with a IN aqueous solution of sodium hydroxide (2x15 mL), water, and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography using 160 g BIOTAGE.(R). column eluting with hexanes/EtOAc (9: 1) to provide Intermediate 61 as a pale yellow solid (4.1 g, 41 percent yield). MS (ES): m/z=199.05 [M+H]+. Intermediate 61 was used in the synthesis of Example 214.
20% at 0 - 20℃; for 1 h; Inert atmosphere To a solution of 5-bromopyrimidine (3 g, 18.87 mmol) in Et20 (120 mL) and THF (20ml) was added cyclopropylmagnesium bromide (39.6 mL, 19.81 mmol) at 0°C. The resulting white suspension was stirred at rt for lh and quenched with water (0.340 mL, 18.87 mmol) followed by addition of DDQ (4.28 g, 18.87 mmol) in THF (10ml). The resulting black mixture was stirred at room temperature overnight. The reaction mixture was extracted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layer was washed with NaOH (IN) and brine. The crude product was purified by Biotage (0-15percent EtOAc/hexanes, 1.2L) to afford the title compound (700 mg, 20percent) as a yellow solid. XH NMR (500 MHz, CC13D) δ ppm 8.87 (1 H, s), 8.66 (1 H, s), 2.40-2.56 (1 H, m), 1.13-1.32 (4 H, m).
20%
Stage #1: at 0 - 20℃;
Stage #2: With water; 2,3-dicyano-5,6-dichloro-p-benzoquinone In tetrahydrofuran; diethyl ether at 20℃;
Preparation 11 A: 5-Bromo-4-cyclopropylpyrimidine [00148] To a solution of 5-bromopyrimidine (3 g, 18.87 mmol) in Et20 (120 mL) and THF (20ml) was added cyclopropylmagnesium bromide (39.6 mL, 19.81 mmol) at 0 °C. The resulting white suspension was stirred at room temperature for lh and quenched with water (0.340 mL, 18.87 mmol) followed by addition of DDQ (4.28 g, 18.87 mmol) inTHF (10ml). The resulting black mixture was stirred at room temperature overnight. The reaction mixture was extracted with EtOAc. The aqueous layer was extracted with EtOAc and the combined organic layer was washed with NaOH (IN) and brine. The crude product was purified by BIOTAGE® (0-15percent EtOAc/hexanes, 1.2L) to afford the title compound (700 mg, 20percent) as a yellow solid. XH NMR (500 MHz, chloroform-d) δ ppm 8.87 (1 hr, s), 8.66 (1 hr, s), 2.40-2.56 (1 hr, m), 1.13-1.32 (4 hr, m).
References: [1] Patent: WO2012/15723, 2012, A1, . Location in patent: Page/Page column 107; 108.
[2] Patent: WO2012/9510, 2012, A1, . Location in patent: Page/Page column 54; 55.
[3] Patent: WO2013/49263, 2013, A1, . Location in patent: Paragraph 00147; 00148.
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 1346697-39-9 ]

Bromides

Chemical Structure| 1439-08-3

A162355 [1439-08-3]

5-Bromo-4-(tert-butyl)pyrimidine

Similarity: 0.92

Chemical Structure| 951884-36-9

A158021 [951884-36-9]

5-Bromo-4-ethylpyrimidine

Similarity: 0.88

Chemical Structure| 1439-09-4

A189946 [1439-09-4]

5-Bromo-4-methylpyrimidine

Similarity: 0.81

Chemical Structure| 17321-93-6

A198566 [17321-93-6]

2-Amino-5-bromo-4-methylpyrimidine

Similarity: 0.72

Chemical Structure| 114969-66-3

A355391 [114969-66-3]

5-Bromo-4-cyanopyrimidine

Similarity: 0.72

Related Parent Nucleus of
[ 1346697-39-9 ]

Pyrimidines

Chemical Structure| 1439-08-3

A162355 [1439-08-3]

5-Bromo-4-(tert-butyl)pyrimidine

Similarity: 0.92

Chemical Structure| 951884-36-9

A158021 [951884-36-9]

5-Bromo-4-ethylpyrimidine

Similarity: 0.88

Chemical Structure| 1439-09-4

A189946 [1439-09-4]

5-Bromo-4-methylpyrimidine

Similarity: 0.81

Chemical Structure| 17321-93-6

A198566 [17321-93-6]

2-Amino-5-bromo-4-methylpyrimidine

Similarity: 0.72

Chemical Structure| 114969-66-3

A355391 [114969-66-3]

5-Bromo-4-cyanopyrimidine

Similarity: 0.72