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[ CAS No. 1125-60-6 ] {[proInfo.proName]}

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Chemical Structure| 1125-60-6
Chemical Structure| 1125-60-6
Structure of 1125-60-6 * Storage: {[proInfo.prStorage]}
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Product Details of [ 1125-60-6 ]

CAS No. :1125-60-6 MDL No. :MFCD00006907
Formula : C9H8N2 Boiling Point : -
Linear Structure Formula :- InChI Key :DTVYNUOOZIKEEX-UHFFFAOYSA-N
M.W :144.17 Pubchem ID :70766
Synonyms :

Calculated chemistry of [ 1125-60-6 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 10
Fraction Csp3 : 0.0
Num. rotatable bonds : 0
Num. H-bond acceptors : 1.0
Num. H-bond donors : 1.0
Molar Refractivity : 46.15
TPSA : 38.91 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) : -6.17 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.27
Log Po/w (XLOGP3) : 1.42
Log Po/w (WLOGP) : 1.82
Log Po/w (MLOGP) : 0.92
Log Po/w (SILICOS-IT) : 1.77
Consensus Log Po/w : 1.44

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -2.3
Solubility : 0.721 mg/ml ; 0.005 mol/l
Class : Soluble
Log S (Ali) : -1.84
Solubility : 2.08 mg/ml ; 0.0144 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -3.32
Solubility : 0.0693 mg/ml ; 0.000481 mol/l
Class : Soluble

Medicinal Chemistry

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

Safety of [ 1125-60-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 1125-60-6 ]

* 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.

  • Upstream synthesis route of [ 1125-60-6 ]
  • Downstream synthetic route of [ 1125-60-6 ]

[ 1125-60-6 ] Synthesis Path-Upstream   1~12

  • 1
  • [ 1125-60-6 ]
  • [ 2439-04-5 ]
Reference: [1] Journal fuer Praktische Chemie (Leipzig), 1895, vol. <2> 52, p. 10
[2] Journal fuer Praktische Chemie (Leipzig), 1895, vol. <2> 52, p. 10
[3] Yakugaku Zasshi, 1953, vol. 73, p. 666[4] Chem.Abstr., 1954, p. 7014
  • 2
  • [ 1125-60-6 ]
  • [ 23687-27-6 ]
Reference: [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 740 - 743
[2] Patent: WO2009/130481, 2009, A1,
  • 3
  • [ 1125-60-6 ]
  • [ 5430-45-5 ]
Reference: [1] Journal of Medicinal Chemistry, 2005, vol. 48, # 15, p. 4972 - 4982
  • 4
  • [ 1125-60-6 ]
  • [ 34784-04-8 ]
YieldReaction ConditionsOperation in experiment
53%
Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃; for 0.5 h;
Stage #2: With hydrogen bromide; copper(I) bromide In water at 0 - 20℃;
A solution of sodium nitrite (2.15 g, 31.21 mmol) in water (2 mL) was added to a solution of isoquinolin-5-ylamine (3.0 g, 20.80 mmol) in aqueous 46percent hydrogen bromide (9.98 g, 124.84 mmol) at 0 °C. The mixture was stirred at 0 0C for 30 min then a solution of cuprous bromide (3.58 g, 24.96 mmol) in aqueous 46percent hydrogen bromide (9.98 g, 124.84 mmol) was added and the reaction was allowed to warm to ambient temperature and stirred for 2 h. The resulting mixture was basified with aqueous ammonium and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulphate and concentrated to afford the crude compound. Purification by column chromatography over silica gel (100-200 mesh) with 20percent ethyl acetate in petroleum ether as eluent afforded 5-bromoisoquinoline (2.3 g, 53percent) as a pale yellow solid.
50%
Stage #1: With hydrogen bromide; sodium nitrite In HBr; water at 0℃; for 0.333333 h;
Stage #2: With copper(I) bromide In water at 0 - 20℃; for 1 h;
Stage #3: With sodium hydroxide In water
Example 78A
5-Bromoisoquinoline
To a solution of 5-aminoisoquinoline (2.0 g, 13.8 mmol) and 48percent HBr (6 mL) in 20 mL water cooled to 0° C. was added a solution of sodium nitrite (0.95 g, 13.8 mmol) in 6 mL water.
The solution was stirred at 0° C. for 20 minutes.
The solution, while kept at 0° C., was added to a solution of CuBr (2.11 g, 15.9 mmol) in 48percent HBr (4.77 mL) and water (10 mL).
The reaction was stirred at room temperature for an additional 1 hr.
The reaction was neutralized with NaOH (50percent) and extracted with ethyl acetate (3*).
The combined organic layer was concentrated in vacuo and chromatographed using 1:1 hexanes/ethyl acetate to yield 1.4 g product (50percent).
36%
Stage #1: With hydrogen bromide; sodium nitrite In water at 0℃;
Stage #2: With hydrogen bromide; copper(I) bromide In water at 20 - 75℃;
Stage #3: With sodium hydroxide In water at 0℃;
PREPARATION 40; (Isoquinolin-5-yl) oxoacetic acid methyl ester; 5-Aminoisoquinoline (20 g, 139 mmol) is dissolved in hydrobromic acid (48percent, 100 mL) in a 500 mL round bottom flask, and then a solution of sodium nitrite (9.6g, 139 mmol) in water (50 mL) added cautiously at 0°C. The white slurry turns bright red upon complete addition of the salt, and then this solution is transferred to another 500 mL vessel containing CuBr (25g, 174 mmol) stirring in hydrobromic acid (48percent, 200 mL) at 75°C. This transfer is performed slowly and carefully. After complete addition, the mixture is allowed to stir at 75°C for one hour, then cooled to room temperature, and kept stirring overnight. The mixture is then placed onto an ice bath and some ice added to the solution, then basified using sodium hydroxide aqueous solution (20percent, 250 mL) solution. The slurry is filtered and then filtrate is extracted with diethyl ether. The solid and the extract are then combined and sonicated for one hour in chloroform. This sludge is filtered through a plug of Celite, and the chloroform removed by rotovap. The final compound is obtained in pure form by column chromatography in chloroform with 36percent yield, 10.4g (50 mmol) of 5-Bromo-isoquinoline. MS (ES, m/z): 208.0 (M+ (79Br) +l), 210.0 (M+(81Br)+1).
50% With sodium nitrite In water; hydrogen bromide Example 78A
5-Bromoisoquinoline
To a solution of 5-aminoisoquinoline (2.0 g, 13.8 mmol) and 48percent HBr (6 mL) in 20 mL water cooled to 0° C. was added a solution of sodium nitrite (0.95 g, 13.8 mmol) in 6 mL water.
The solution was stirred at 0° C. for 20 minutes.
The solution, while kept at 0° C., was added to a solution of CuBr (2.11 g, 15.9 mmol) in 48percent HBr (4.77 mL) and water (10 mL).
The reaction was stirred at room temperature for an additional 1 hr.
The reaction was neutralized with NaOH (50percent) and extracted with ethyl acetate (3*).
The combined organic layer was concentrated in vacuo and chromatographed using 1:1 hexanes/ethyl acetate to yield 1.4 g product (50percent).

Reference: [1] Canadian Journal of Chemistry, 2005, vol. 83, # 3, p. 213 - 219
[2] Patent: WO2009/130481, 2009, A1, . Location in patent: Page/Page column 142
[3] Patent: US2003/199511, 2003, A1, . Location in patent: Page/Page column 34
[4] Patent: WO2003/76398, 2003, A2, . Location in patent: Page/Page column 27
[5] Patent: US2004/180874, 2004, A1, . Location in patent: Page/Page column 18-19
[6] Patent: WO2003/76442, 2003, A1, . Location in patent: Page/Page column 40
[7] Patent: US2003/187026, 2003, A1,
  • 5
  • [ 1125-60-6 ]
  • [ 12775-96-1 ]
  • [ 34784-04-8 ]
YieldReaction ConditionsOperation in experiment
53% With aqueous HBr; sodium nitrite In water Step 1
5-Aminoisoquinoline (5.0 g, 34.7 mmol) was mixed with 48percent aqueous HBr (65 mL) at -78° C. for 15 min.
Sodium nitrite (3.1 g, 45 mmol) in water (6 mL) was then added dropwise.
After stirring for 15 min at -78° C., the mixture was warmed to 0° C. Copper powder (0.3 g) was added very slowly to avoid excessive foaming.
After addition was completed, the reaction vessel was fitted with a reflux condensor and the mixture was heated to 100° C. for 4 h.
The mixture was poured onto ice (ca. 200 g) and was made basic (pH=10) with KOH.
The aqueous mixture was extracted with ethyl acetate, the combined organic layers were washed with brine, were dried (MgSO4), were filtered, and were concentrated in vacuo.
Purification by silica gel chromatography (10:1 hexanes-ethyl acetate) afforded 3.8 g (53percent yield) of 5-bromoisoquinoline; 1H NMR (400 MHz, CD3OD) δ 9.25 (s, 1H), 8.57 (d, J=6.2 Hz, 1H), 8.1 (m, 3H), 7.60 (m, 1H); MS (AP/CI): 208.0, 210.0 (M+H)+.
53% With aqueous HBr; sodium nitrite In water Step 1
5-Aminoisoquinoline (5.0 g, 34.7 mmol) was mixed with 48percent aqueous HBr (65 mL) at -78° C. for 15 min.
Sodium nitrite (3.1 g, 45 mmol) in water (6 mL) was then added dropwise.
After stirring for 15 min at -78° C., the mixture was warmed to 0° C. Copper powder (0.3 g) was added very slowly to avoid excessive foaming.
After addition was completed, the reaction vessel was fitted with a reflux condensor and the mixture was heated to 100° C. for 4 h.
The mixture was poured onto ice (ca. 200 g) and was made basic (pH=10) with KOH.
The aqueous mixture was extracted with ethyl acetate, the combined organic layers were washed with brine, were dried (MgSO4), were filtered, and were concentrated in vacuo.
Purification by silica gel chromatography (10:1 hexanes-ethyl acetate) afforded 3.8 g (53percent yield) of 5-bromoisoquinoline; 1H NMR (400 MHz, CD3OD) δ9.25 (s, 1H), 8.57 (d, J=6.2 Hz, 1H), 8.1 (m, 3H), 7.60 (m, 1H); MS (AP/CI): 208.0, 210.0 (M+H)+.
Reference: [1] Patent: US2003/83352, 2003, A1,
[2] Patent: US2002/119963, 2002, A1,
  • 6
  • [ 1336-21-6 ]
  • [ 1125-60-6 ]
  • [ 34784-04-8 ]
YieldReaction ConditionsOperation in experiment
86% With sodium nitrite In hexane; water; hydrogen bromide; ethyl acetate EXAMPLE 57
5-Bromoisoquinoline
The procedure described by Osborn AR, et al, J Chem Soc 1956:4191 was used. 5-Aminoisoquinoline (43.6 g, 0.302 mol) was dissolved in 300 ml 48percent HBr and 200 mL water and cooled in an ice bath. NaNO2 (21.21 g, 0.307 mol) in 130 mL of water was added dropwise to the HBr solution and the reaction stirred for 1 hour. CuBr (52 g, 0.363 mol) in 500 mL of 48percent HBr was heated to 85° C., the diazonium solution added dropwise from an ice-cooled jacketed-addition funnel, and the reaction stirred overnight at 50° C.
The reaction mixture was cooled in an ice bath and the acid neutralized by dropwise addition of concentrated NH4OH solution.
The solid precipitates were filtered off, washed with concentrated NH4OH until colorless, and then water.
The solid was dissolved in ethyl acetate, washed with brine (2*), and dried over magnesium sulfate, filtered, and evaporated.
The reside was chromatographed on silica gel (30percent ethyl acetate in hexane as eluant) to give 53.7 g (86percent) of the product as an off-white solid.
Reference: [1] Patent: US2003/114422, 2003, A1,
  • 7
  • [ 1125-60-6 ]
  • [ 58142-99-7 ]
YieldReaction ConditionsOperation in experiment
6.5 g With hydrogenchloride; potassium iodide; sodium nitrite In water at 0℃; for 1 h; Reflux Step A - Preparation of Int Int 58-1 To a solution of 5-aminoisoquinoline (14 g, 97.2 mmol) in HCI/H2O (40 mL/ 40 mL) was added a 02 (8 g, 1 16 mmol) by portions at 0°C. The mixture was stirred at 0°C for 1 hour then Kl (32 g, 194 mmol) was added slowly and the mixture was refluxed overnight. After cooling to room temperature, the mixture was poured into NH4OH (40 mL) and extracted with DCM (50 mL x 3). The combined organic layers were washed with brine (40 mL), dried and concentrated. The residue was purified by column chromatography (EtOAc : Petroleum Ether = 1 : 10) to give Int 58-1 (6.5 g). MS (ESI): m/z (M+H)+ 256.
6.5 g
Stage #1: With hydrogenchloride; sodium nitrite In water at 0℃; for 1 h;
Stage #2: With potassium iodide In water at 0℃; Reflux
Step A - Preparation of Int 58-1 Int 58-1 To a solution of 5-aminoisoquinoline (14 g, 97.2 mmol) in HC1/H20 (40 mL/ 40 mL) was added NaN02 (8 g, 116 mmol) by portions at 0°C. The mixture was stirred at 0°C for 1 hour then KI (32 g, 194 mmol) was added slowly and the mixture was refluxed overnight. After cooling to room temperature, the mixture was poured into NH4OH (40 mL) and extracted with DCM (50 mL x 3). The combined organic layers were washed with brine (40 mL), dried and concentrated. The residue was purified by column chromatography (EtOAc : Petroleum Ether = 1 : 10) to give Int 58-1 (6.5 g). MS (ESI): m/z (M+H)+ 256.
Reference: [1] Journal of Medicinal Chemistry, 2002, vol. 45, # 3, p. 740 - 743
[2] Patent: US2002/19527, 2002, A1,
[3] Patent: WO2015/73308, 2015, A1, . Location in patent: Page/Page column 79
[4] Patent: WO2015/70366, 2015, A1, . Location in patent: Page/Page column 78-79
  • 8
  • [ 1125-60-6 ]
  • [ 115955-90-3 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 8, p. 2085 - 2094
[2] Patent: US5580872, 1996, A,
[3] Patent: US4812573, 1989, A,
[4] Patent: WO2014/160668, 2014, A1, . Location in patent: Page/Page column 357
[5] Applied Catalysis A: General, 2018, vol. 560, p. 37 - 41
  • 9
  • [ 57554-78-6 ]
  • [ 1125-60-6 ]
  • [ 115955-90-3 ]
Reference: [1] Yakugaku Zasshi, 1953, vol. 73, p. 666[2] Chem.Abstr., 1954, p. 7014
  • 10
  • [ 1125-60-6 ]
  • [ 63927-23-1 ]
Reference: [1] Patent: WO2009/130481, 2009, A1,
  • 11
  • [ 1125-60-6 ]
  • [ 90721-34-9 ]
YieldReaction ConditionsOperation in experiment
35%
Stage #1: at 80℃; for 4 h;
Stage #2: With sodium hydroxide In waterAlkaline aqueous solution
EXAMPLE 73A
8-bromoisoquinolin-5-amine
5-Aminoisoquinoline (5.50 g, 38.1 mmol) and aluminium trichloride (15.1 g, 113 mmol) were combined and heated at 80° C. in a 3-necked flask equipped with a dropping funnel, stirrer bar, needle and sintered glass tube.
Bromine (3.04 g, 19.05 mmol) was dripped onto the sintered glass funnel and the vapour diffused onto the complex over a period of 2 hours.
Heating was continued for 2 hours.
The suspension was added portionwise to crushed ice and the solution basified with concentrated NaOH solution.
The aqueous layer was extracted with ethyl acetate (4*100 mL) and the layers were separated.
The organic layers were combined, dried (Na2SO4), filtered and the filtrate was concentrated to give a grey solid.
The grey solid was subjected to column chromatography (hexanes:ethyl acetate, 3:1) to provide the title compound (2.96 g, 35percent). MS (ESI+) m/z 225 (M+H)+; MS (ESI-) m/z 223 (M-H)-; 1H NMR (CDCl3, 300 MHz) δ 4.22 (br s, 2H), 6.83 (d, J 8.1, 1H), 7.25 (s, 1H), 7.54 (d, J 5.8, 1H), 7.61 (d, J 8.1, 1H), 8.59 (d, J 5.8, 1H), 9.56 (s, 1H).
Reference: [1] Patent: US2003/158188, 2003, A1,
[2] Patent: US6933311, 2005, B2,
[3] Patent: US2005/113576, 2005, A1, . Location in patent: Page/Page column 34
[4] Patent: US2004/157849, 2004, A1,
  • 12
  • [ 1125-60-6 ]
  • [ 201150-73-4 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2000, vol. 8, # 8, p. 2085 - 2094
[2] Patent: WO2014/160668, 2014, A1,
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