Home Cart 0 Sign in  
X

[ CAS No. 78686-79-0 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 78686-79-0
Chemical Structure| 78686-79-0
Chemical Structure| 78686-79-0
Structure of 78686-79-0 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 78686-79-0 ]

Related Doc. of [ 78686-79-0 ]

Alternatived Products of [ 78686-79-0 ]

Product Details of [ 78686-79-0 ]

CAS No. :78686-79-0 MDL No. :MFCD03844848
Formula : C7H5BrClNO2 Boiling Point : -
Linear Structure Formula :- InChI Key :MOMQDEDQGJAKII-UHFFFAOYSA-N
M.W : 250.48 Pubchem ID :2763343
Synonyms :

Calculated chemistry of [ 78686-79-0 ]

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.14
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 48.23
TPSA : 39.19 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.15 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.19
Log Po/w (XLOGP3) : 2.36
Log Po/w (WLOGP) : 2.28
Log Po/w (MLOGP) : 1.67
Log Po/w (SILICOS-IT) : 2.53
Consensus Log Po/w : 2.21

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -3.12
Solubility : 0.191 mg/ml ; 0.000763 mol/l
Class : Soluble
Log S (Ali) : -2.82
Solubility : 0.376 mg/ml ; 0.0015 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.58
Solubility : 0.0666 mg/ml ; 0.000266 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 1.82

Safety of [ 78686-79-0 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 78686-79-0 ]

* 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 [ 78686-79-0 ]
  • Downstream synthetic route of [ 78686-79-0 ]

[ 78686-79-0 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 13061-96-6 ]
  • [ 78686-79-0 ]
  • [ 65169-43-9 ]
YieldReaction ConditionsOperation in experiment
87% With potassium phosphate In water; toluene at 100℃; INTERMEDIATE 31Methyl 2-chloro-5-methylnicotinate; To a solution of methyl 5-bromo-2-chloronicotinate (1.05g, 4.19mmol), K3PO4 (2.95g, 13.90mmol), methylboronic acid (0.32g, 5.26mmol) and tricyclohexylphosphine (0.11g, 0.39mmol) in toluene/water (16ml/0.8ml) under nitrogen atmosphere was added Pd(OAc)2 (0.04g, 0.18mmol). The mixture was heated at 1000C overnight under nitrogen atmosphere. The reaction mixture was then cooled to room temperature and concentrated in vacuum. Ethyl acetate was added to the residue and this organic layer was washed with water, brine, dried over MgSO4, filtered and the solvent evaporated under vacuum to yield the desired product as a yellow oil. Yield=87percent LRMS: m/z 186 (M+1 )+ Retention time: 4.84min
Reference: [1] Patent: WO2008/77639, 2008, A1, . Location in patent: Page/Page column 26
  • 2
  • [ 67-56-1 ]
  • [ 29241-65-4 ]
  • [ 78686-79-0 ]
YieldReaction ConditionsOperation in experiment
100%
Stage #1: at 60℃; for 36 h;
Stage #2: With sodium hydrogencarbonate In water
To 0.5 L flask charged with 5-Bromo-2-chloronicotinic acid (25.0 g, 106.4 mmol) in MeOH (250 mL) was added H2SO4 (5 mL). The mixture was heated to 60° C., stirred for 1.5 day. LC-MS indicated full conversion of starting material at this time. The reaction was cooled to RT and the volatile components removed in vacuo. The crude residue was dissolved in EtOAc (300 mL), quenched with sat. aqueous Na(HCO3)2 (200 mL). The organic layer was separated, washed with brine, dried over MgSO4 and concentrated to afford the compound, methyl-5-bromo-2-chloronicotinate, as a while solid (quantitative yield). LC-MS (M+H)=250.1.
89% for 15 h; Reflux Sulfuric acid (2 mL, 52.1 mmol) was added to the suspension of 5-bromo-2-chloronicotinic acid (1) (12.3 g, 52 mmol) was in methanol (100 mL). The mixture was stirred and refluxed for 15 hours. The solvent was evaporated and the residue was neutralized with saturated aqueous NaHC03(aq.). The result suspension was filtered and the solid was washed by water and dried by pump. Methyl 5-bromo-2-chloronicotinate (2) (11.6 g, 89 percent yield) was afforded. NMR (400 MHz, CDCL) δ 8.53 (d, J = 2.4 Hz, 1H), 8.25 (d, J = 2.4 Hz, 1H), 3.93 (s, 3H). 13C NMR (101 MHz, CDCL) δ 163.58, 152.75, 148.61, 142.49, 127.64, 118.57, 53.10. ESI-MS m/z: 251.9 (M+H+).
85% at 90℃; for 12 h; To a solution of 5-bromo-2-chloronicotinic acid (50 g, 211 mmol) in MeOH (200 mL) was added H2SO4 (20.7 g, 211.46 mmol) at 25 °C. The mixture heated to 90 °C and stirred for 12 hours. LCMS showed that the reaction was complete. The reaction was neutralized with Na2CO3 to pH = 7-8 and concentrated under reduced pressure to remove MeOH. The residue was extracted with EtOAc (300 mL x 3). The combined organic layer was concentrated under reduced pressure to give methyl 5-bromo-2-chloronicotinate (45 g, 180 mmol, 85percent yield) as a brown solid. ESI-MS (m/z): 249.9 (M+H)+
Reference: [1] Patent: US2012/172391, 2012, A1, . Location in patent: Page/Page column 79
[2] Journal of Agricultural and Food Chemistry, 2016, vol. 64, # 18, p. 3533 - 3537
[3] Patent: WO2014/186398, 2014, A1, . Location in patent: Page/Page column 49; 50; 51
[4] Patent: WO2017/120429, 2017, A1, . Location in patent: Page/Page column 263
[5] Patent: US2012/178776, 2012, A1, . Location in patent: Page/Page column 42-43
  • 3
  • [ 67-56-1 ]
  • [ 78686-79-0 ]
YieldReaction ConditionsOperation in experiment
95%
Stage #1: at 80℃; for 2 h;
Stage #2: for 1 h;
Example 18; 2-(4-(1H-Pyrrolo[2,3-b]pyridin-4-yloxy)-3-fluorophenylamino)-5-bromo-N-(2,4-difluorophenyl)nicotinamide, dihydrochloride salt; A) Methyl 5-bromo-2-chloronicotinate; To a suspension of 5-bromo-2-hydroxynicotinic acid (4.34 g, 20 mmol) in 20 mL of SOCl2 at room temperature was added 1 mL of DMF slowly. The solution was then heated at 80° C. for 2 h. The solvent was removed under reduced pressure and the residue was dissolved in 50 mL of DCM. To the mixture was added 10 mL of MeOH and the stirring continued for 1 h. The solution was concentrated in vacuo and the residue was dissolved in 200 mL of EtOAc. The mixture was then washed with brine and dried over MgSO4. After filtration and concentration in vacuo, the desired product (5.0 g, >95percent yield) was obtained. MS (ESI) m/z 250.04, 252.05, 254.05 (M+H)+.
Reference: [1] Patent: US2007/78140, 2007, A1, . Location in patent: Page/Page column 35
  • 4
  • [ 67-56-1 ]
  • [ 104612-36-4 ]
  • [ 78686-79-0 ]
YieldReaction ConditionsOperation in experiment
74%
Stage #1: at 95℃; for 16 h; Cooling with ice
Stage #2: at 20℃; for 2 h; Cooling
POCl3 (50 mL) was added slowly through an addition funnel to ice-cooled 5-bromo- 2-hydroxynicotinic acid (10 g, 45.9 mmol). The reaction mixture was heated to 95°C and stirred at the same temperature for 16 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure to remove POCh. To the residue was added toluene (100ml), and the mixture evaporated under reduced pressure to remove residual POCb . The obtained residue was diluted with DCM (100 mL) and cooled. MeOH (50 mL) was added slowly through an addition funnel to the mixture under nitrogen. The resulting mixture was then stirred at room temperature for 2 hr. After completion of the reaction, the reaction mixture was concentrated under reduced pressure. The residue thus obtained was diluted with water, neutralized by using saturated aq.Na2C03 solution, and extracted with EtOAc (50ml x3). The combined organic layers were washed with brine, dried over Na2S04, filtered and concentrated under reduced pressure. The crude product was purified via Combiflash column chromatography using a 40g silica gel column with 7percent EtOAc in pet. ether as an eluent to afford methyl 5-bromo-2-chloronicotinate as a white solid. Yield: 8.5 g, (74 percent). 1H MR (400 MHz, CDCh) δ ppm = 8.57 (d, J= 2.4 Hz, 1 H), 8.29 (d, J= 2.4 Hz, 1 H), 3.91 (s, 3H). LCMS: (ES+) m/z observed = 252.1 (M+H)+, Column- Acquity BEH CI 8 (2.1 x 50 mm) 1.7 urn, Buffer : lOmM AmmoniumAcetate pH-5 adjusted with HCOOH, Mobile phase A: Buffer : MeCN (95:5), Mobile phase B: Buffer : MeCN (5:95), Flow: 0.8 ml/min. Rt: 0.86 min, wavelength: 220nm.
Reference: [1] Patent: WO2016/137832, 2016, A1, . Location in patent: Page/Page column 32
[2] Patent: EP1593673, 2005, A1, . Location in patent: Page/Page column 95
  • 5
  • [ 120034-05-1 ]
  • [ 78686-79-0 ]
YieldReaction ConditionsOperation in experiment
94.15% at 0 - 80℃; for 12.5 h; Inert atmosphere Example 30 - Preparation of Intermediate 7 [ 00261] The synthesis of Intermediate 7 followed General Procedure 8 following. General Procedure 8 Intermediate 5 Intermediate 7 [ 00262 ] To a round-bottomed flask charged with methyl 5-bromo-2-oxo- l,2-dihydropyridine-3-carboxylate (Intermediate 5, 50.0 g, 0.2154 mol, 1.0 eq) at 0 C under N2 atmosphere was added POCl3 (100 mL) dropwise. After 30 minutes the reaction mixture was warmed to 80 C and stirred for 12-15 hours. After completion of the reaction, the reaction mixture was cooled to room temperature and poured slowly into ice cold water. It was stirred for 30 min, at which point the product precipitated out as a white solid. The solid product was filtered and vacuum dried to give desired Intermediate 7 (40.0 g, yield-94.15percent). m/z 252.12 [M+2]+ 1H NMR (DMSO-de, 400 MHz) δ 8.78 (d, J = 2.5 Hz, 1H), 8.50 (d, J = 2.5 Hz, 1H), 3.89 (s, 3H) ppm.
Reference: [1] Patent: WO2016/44662, 2016, A1, . Location in patent: Paragraph 00261-00262
[2] Journal of Organic Chemistry, 1989, vol. 54, # 15, p. 3618 - 3624
  • 6
  • [ 29241-65-4 ]
  • [ 18107-18-1 ]
  • [ 78686-79-0 ]
YieldReaction ConditionsOperation in experiment
69% at 0℃; for 1 h; Example 24; A. Methyl 5-bromo-2-chloropyridine-3-carboxylate; To a solution of S-bromo-l-chloropyridine-S-carboxylic acid (1.0 g, 4.2 mmol) in methanol :benzene (1 :1, 50 mL) was added trimethylsilyldiazomethane (3.2 mL, 6.5 mmol) at 0 0C. The reaction mixture was then stirred at 0 0C for 60 min. The reaction mixture was concentrated under reduced pressure. The residue was diluted with ethyl acetate (40 mL), washed with water (10 mL x 2). The aqueous layer was extracted with ethyl acetate (50 mL x 2). The combined organic layers were washed with brine solution (50 mL), dried over anhydrous MgSO4 and evaporated under reduced pressure to provide the crude product. The crude product was purified through a filter column (Silica gel, 100-200 mesh) to provide methyl 5-bromo-2-chloropyridine-3-carboxylate as an off- white solid (0.72 g, 69percent). LC-MS: [M+H] + 251 1H NMR (400 MHz, CDCl3) δ: ppm 8.59 (s, IH) 8.35 (s, IH), 3.99 (s, 3H).
Reference: [1] Patent: WO2010/100475, 2010, A1, . Location in patent: Page/Page column 87-88
  • 7
  • [ 10128-91-3 ]
  • [ 78686-79-0 ]
Reference: [1] Journal of Organic Chemistry, 1989, vol. 54, # 15, p. 3618 - 3624
  • 8
  • [ 609-71-2 ]
  • [ 78686-79-0 ]
Reference: [1] Journal of Organic Chemistry, 1989, vol. 54, # 15, p. 3618 - 3624
  • 9
  • [ 186581-53-3 ]
  • [ 29241-65-4 ]
  • [ 78686-79-0 ]
Reference: [1] Journal of Chemical & Engineering Data, 1981, vol. 26, # 3, p. 332 - 333
  • 10
  • [ 29241-65-4 ]
  • [ 78686-79-0 ]
Reference: [1] Journal of Chemical & Engineering Data, 1981, vol. 26, # 3, p. 332 - 333
  • 11
  • [ 609-71-2 ]
  • [ 78686-79-0 ]
Reference: [1] Patent: WO2016/137832, 2016, A1,
  • 12
  • [ 67-56-1 ]
  • [ 78686-86-9 ]
  • [ 78686-79-0 ]
Reference: [1] Journal of Chemical & Engineering Data, 1981, vol. 26, # 3, p. 332 - 333
  • 13
  • [ 78686-79-0 ]
  • [ 228251-24-9 ]
YieldReaction ConditionsOperation in experiment
74% With diisobutylaluminium hydride In dichloromethane at -78℃; for 2 h; To a (-78eC) cooled and stirred solution of methyl 5-bromo-2-chloronicotinate (10.0 g, 39.9 mmol) in DCM (100 mL) was added diBAL-H (43.9 mL, 43.9 mmol, 1.6 M in hexane) dropwise and then stirred for 2h at the same temperature. Reaction was quenched with 2M aqueous HCI (50 mL) and stirred for 30 min at room temperature. Reaction mixture was filtered through the celite. The layers were separated and the aqueous layer was extracted with ethyl acetate (2/1,100 mL). The combined organic layer was washed with brine (100 mL), dried (Na2S04) and filtered. The filtrate was concentrated under vacuum and the crude product was purified by flash column chromatography (silica gel, 20-30percent EtOAc in hexane system as eluent) to afford 6.50 g (74percent) of the titled compound. 1HNMR (400 MHz, DMSO- d6) U10.19 (s, 1H), 8.86 (brs, 1H), 8.40 (brs, 1H); GCMS (m/z) 218.94(M)\
Reference: [1] Patent: WO2018/20474, 2018, A1, . Location in patent: Page/Page column 157
[2] Patent: WO2011/103202, 2011, A2,
[3] Patent: WO2015/181747, 2015, A1,
  • 14
  • [ 78686-79-0 ]
  • [ 931105-37-2 ]
YieldReaction ConditionsOperation in experiment
57% With cesium fluoride In dimethyl sulfoxide at 20 - 60℃; for 52 h; B) Methyl 5-bromo-2-fluoronicotinate; To a solution of methyl 5-bromo-2-chloronicotinate (170 mg, 0.68 mmol) in 3 mL of DMSO was added CsF (152 mg, 1.0 mmol). The solution was stirred at room temperature for 2 d and then heated at 60° C. for 4 h. After cooling, the mixture was diluted with 30 mL of H2O. The aqueous solution was extracted with EtOAc and the combined organic layers were washed with brine, and dried over MgSO4. After filtration and concentration in vacuo, the residue was purified by silica gel flash chromatography to give the desired product (90 mg, 57percent yield). MS (ESI+) m/z 234.06, 236.09 (M+H)+.
Reference: [1] Patent: US2007/78140, 2007, A1, . Location in patent: Page/Page column 35-36
Same Skeleton Products
Historical Records

Related Functional Groups of
[ 78686-79-0 ]

Bromides

Chemical Structure| 29241-65-4

[ 29241-65-4 ]

5-Bromo-2-chloronicotinic acid

Similarity: 0.95

Chemical Structure| 1256809-64-9

[ 1256809-64-9 ]

5-Bromo-2-chloro-6-methylnicotinic acid

Similarity: 0.89

Chemical Structure| 29681-44-5

[ 29681-44-5 ]

Methyl 5-bromonicotinate

Similarity: 0.82

Chemical Structure| 886365-31-7

[ 886365-31-7 ]

5-Bromo-2-chloroisonicotinic acid

Similarity: 0.78

Chemical Structure| 20826-04-4

[ 20826-04-4 ]

3-Bromo-5-pyridine carboxylic acid

Similarity: 0.76

Chlorides

Chemical Structure| 29241-65-4

[ 29241-65-4 ]

5-Bromo-2-chloronicotinic acid

Similarity: 0.95

Chemical Structure| 1256809-64-9

[ 1256809-64-9 ]

5-Bromo-2-chloro-6-methylnicotinic acid

Similarity: 0.89

Chemical Structure| 40134-18-7

[ 40134-18-7 ]

Methyl 2-chloronicotinate

Similarity: 0.86

Chemical Structure| 53277-47-7

[ 53277-47-7 ]

Methyl 2-chloro-6-methylnicotinate

Similarity: 0.85

Chemical Structure| 65169-43-9

[ 65169-43-9 ]

Methyl 2-chloro-5-methylnicotinate

Similarity: 0.83

Esters

Chemical Structure| 40134-18-7

[ 40134-18-7 ]

Methyl 2-chloronicotinate

Similarity: 0.86

Chemical Structure| 53277-47-7

[ 53277-47-7 ]

Methyl 2-chloro-6-methylnicotinate

Similarity: 0.85

Chemical Structure| 1452-94-4

[ 1452-94-4 ]

Ethyl 2-chloropyridine-3-carboxylate

Similarity: 0.83

Chemical Structure| 65169-43-9

[ 65169-43-9 ]

Methyl 2-chloro-5-methylnicotinate

Similarity: 0.83

Chemical Structure| 29681-44-5

[ 29681-44-5 ]

Methyl 5-bromonicotinate

Similarity: 0.82

Related Parent Nucleus of
[ 78686-79-0 ]

Pyridines

Chemical Structure| 29241-65-4

[ 29241-65-4 ]

5-Bromo-2-chloronicotinic acid

Similarity: 0.95

Chemical Structure| 1256809-64-9

[ 1256809-64-9 ]

5-Bromo-2-chloro-6-methylnicotinic acid

Similarity: 0.89

Chemical Structure| 40134-18-7

[ 40134-18-7 ]

Methyl 2-chloronicotinate

Similarity: 0.86

Chemical Structure| 53277-47-7

[ 53277-47-7 ]

Methyl 2-chloro-6-methylnicotinate

Similarity: 0.85

Chemical Structure| 65169-43-9

[ 65169-43-9 ]

Methyl 2-chloro-5-methylnicotinate

Similarity: 0.83