Home Cart 0 Sign in  

[ CAS No. 65-49-6 ]

{[proInfo.proName]} (Synonyms:PAS) ,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
2D
Chemical Structure| 65-49-6
Chemical Structure| 65-49-6
Structure of 65-49-6 *Storage: {[proInfo.prStorage]}

Quality Control of [ 65-49-6 ]

Related Doc. of [ 65-49-6 ]

SDS
Alternatived Products of [ 65-49-6 ]
Alternatived Products of [ 65-49-6 ]

Product Details of [ 65-49-6 ]

CAS No. :65-49-6MDL No. :MFCD00007789
Formula : C7H7NO3 Boiling Point : -
Linear Structure Formula :-InChI Key :N/A
M.W :153.14Pubchem ID :4649
Synonyms :

1. 4-Aminosalicylic Acid

Computed Properties of [ 65-49-6 ]

TPSA : 83.6 H-Bond Acceptor Count : 4
XLogP3 : - H-Bond Donor Count : 3
SP3 : 0.00 Rotatable Bond Count : 1

Safety of [ 65-49-6 ]

Signal Word:WarningClass:N/A
Precautionary Statements:P305+P351+P338UN#:N/A
Hazard Statements:H319Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 65-49-6 ]

  • Upstream synthesis route of [ 65-49-6 ]
  • Downstream synthetic route of [ 65-49-6 ]

[ 65-49-6 ] Synthesis Path-Upstream   1~8

  • 1
  • [ 65-49-6 ]
  • [ 18107-18-1 ]
  • [ 18179-39-0 ]
Reference: [1] Patent: WO2007/37187, 2007, A1, . Location in patent: Page/Page column 132
  • 2
  • [ 65-49-6 ]
  • [ 18179-39-0 ]
Reference: [1] Patent: US2014/81044, 2014, A1,
[2] Patent: WO2014/45135, 2014, A1,
[3] Patent: US2016/2269, 2016, A1,
  • 3
  • [ 65-49-6 ]
  • [ 1666-28-0 ]
YieldReaction ConditionsOperation in experiment
73%
Stage #1: With hydrogen bromide In water
Stage #2: With sodium nitrite In water at 0℃; for 0.5 h;
Stage #3: at 0℃; for 1 h;
Reference Example 51
4-Bromosalicylic acid
4-Aminosalicylic acid (15.0 g, 98 mmol) and hydrobromic acid (47 percent, 100 ml) were mixed with water (100 ml)..
A solution of sodium nitrite (6.8 g, 98 mmol) in water (50 ml) was added dropwise to the mixture at 0 °C, and the mixture was stirred at the same temperature for 30 minutes..
A mixture of cuprous bromide (16.9 g, 117 mmol) and hydrobromic acid (47percent, 45 ml) was added dropwise to the mixture at 0 °C, and the mixture was stirred at the same temperature for 1 hr..
The reaction mixture was combined with ethyl acetate and extracted..
The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate..
The solvent was evaporated to give the titled compound (15.5 g, 73 percent) as a gray solid.1H-NMR (DMSO-d6) δ: 7.09 (1H, dd, J = 0.9, 8.4 Hz), 7.19 (1H, d, J = 0.9 Hz), 7.69 (1H, d, J = 8.4 Hz), 10.33 (1H, br s).
35% With tert.-butylnitrite; copper(ll) bromide In acetonitrile at 0℃; for 2.5 h; t-Butyl nitrite (5.10 g, 49.5 mmol) was added to a suspension of copper(II) bromide (8.80 g, 39.4 mmol) in CH3CN (50 mL), and the reaction mixture was cooled to 0°C in an ice bath. 4- Aminosalicylic acid (5.00 g, 32.7 mmol) was added in small portions over 30 min. Additional CH3CN (20 mL) was added, and the reaction mixture was allowed to stir at 00C for 2 h. The reaction mixture was poured into 20percent HCl (200 mL) and extracted with Et2O (2 x 200 mL). The combined organic phases were washed with 20percent HCl (2 x 100 mL), dried over MgSO4, filtered, and concentrated in vacuo. The residue was dissolved in Et2O (300 mL) and extracted with 15percent NaOH (2 x 150 mL). The combined aqueous layers were washed with Et2O (100 mL), brought to pH ~1 with 20percent HCl, and extracted with Et2O (3 x 200 mL). The combined organic phases were dried over MgSO4, filtered, and concentrated in vacuo. The resulting solid was triturated with CHCl3 and collected by filtration, yielding 2.5 g (35percent) of the title compound as a crystalline solid. The material was used without further characterization or purification.
Reference: [1] Patent: EP1424336, 2004, A1, . Location in patent: Page 136
[2] Patent: WO2006/44775, 2006, A2, . Location in patent: Page/Page column 16
[3] Nippon Kagaku Zasshi, 1957, vol. 78, p. 1608,1612[4] Chem.Abstr., 1959, p. 21342
[5] Journal of Medicinal Chemistry, 1992, vol. 35, # 4, p. 734 - 740
[6] Journal of Chemical Research, Miniprint, 1989, # 12, p. 2826 - 2851
[7] Organic Letters, 2009, vol. 11, # 14, p. 2972 - 2975
[8] Patent: EP1445249, 2004, A1, . Location in patent: Page 128
[9] Patent: EP1577302, 2005, A1, . Location in patent: Page/Page column 113
  • 4
  • [ 65-49-6 ]
  • [ 222986-83-6 ]
  • [ 1666-28-0 ]
YieldReaction ConditionsOperation in experiment
21% With hydrogen bromide; copper(I) bromide; sodium nitrite In water; ethyl acetate Referential Example 38
2-Hydroxy-4-(4-pyridyl)benzoic acid
In water (22.5 ml) and a 47percent aqueous solution of hydrobromic acid (22.5 ml), 4-amino-2-hydroxybenzoic acid (5.04 g) was dissolved.
While the resulting solution mixture was maintained at 5° C. or lower, an aqueous solution (water: 15.0 ml) of sodium nitrite (2.26 g) was added dropwise thereto, followed by stirring for 30 minutes under ice cooling.
The reaction mixture was added, in portions, to a solution of cuprous bromide (5.63 g) dissolved in a 47percent aqueous solution of hydrobromic acid (15 ml) under ice cooling.
The resulting mixture was stirred at room temperature for 150 minutes.
Ethyl acetate was added to the reaction mixture for extraction.
The organic layer so obtained was washed with water and then dried over anhydrous sodium sulfate.
The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (dichloromethane~10percent methanol-dichloromethane), whereby 4-bromo-2-hydroxybenzoic acid (5.51 g) was obtained as a crudely purified product.
The crudely purified product (298 mg) was reacted as in Referential Example 6, whereby the title compound (70 mg, 21percent) was obtained.
1H-NMR (DMSO-d6) δ: 7.30-7.40(2H,m), 7.78(2H,d,J=4.4 Hz), 7.92(1H,d,J=6.3 Hz), 8.69(2H,d,J=5.9 Hz).
MS (FAB) m/z: 216 (M+H)+.
21% With hydrogen bromide; copper(I) bromide; sodium nitrite In water; ethyl acetate [Referential Example 38] 2-Hydroxy-4-(4-pyridyl)benzoic acid
In water (22.5 ml) and a 47percent aqueous solution of hydrobromic acid (22.5 ml), 4-amino-2-hydroxybenzoic acid (5.04 g) was dissolved.
While the resulting solution mixture was maintained at 5°C or lower, an aqueous solution (water: 15.0 ml) of sodium nitrite (2.26 g) was added dropwise thereto, followed by stirring for 30 minutes under ice cooling.
The reaction mixture was added, in portions, to a solution of cuprous bromide (5.63 g) dissolved in a 47percent aqueous solution of hydrobromic acid (15 ml) under ice cooling.
The resulting mixture was stirred at room temperaturefor 150 minutes.
Ethyl acetate was added to the reaction mixture for extraction.
The organic layer so obtained was washed with water and then dried over anhydrous sodium sulfate.
The residue obtained by distilling off the solvent under reduced pressure was purified by chromatography on a silica gel column (dichloromethane ~ 10percent methanol - dichloromethane), whereby 4-bromo-2-hydroxybenzoic acid (5.51 g) was obtained as a crudely purified product.
The crudely purified product (298 mg) was reacted as in Referential Example 6, whereby the title compound (70 mg, 21percent) was obtained.
1H-NMR (DMSO-d6) δ: 7.30-7.40(2H,m), 7.78(2H,d,J=4.4Hz), 7.92(1H,d,J=6.3Hz), 8.69(2H,d,J=5.9Hz).
MS (FAB) m/z: 216 (M+H)+.
Reference: [1] Patent: US6525042, 2003, B1,
[2] Patent: EP1104754, 2001, A1,
  • 5
  • [ 65-49-6 ]
  • [ 22717-56-2 ]
Reference: [1] Patent: EP1424336, 2004, A1,
  • 6
  • [ 65-49-6 ]
  • [ 108282-38-8 ]
Reference: [1] Letters in Drug Design and Discovery, 2012, vol. 9, # 5, p. 489 - 493
  • 7
  • [ 65-49-6 ]
  • [ 205448-66-4 ]
Reference: [1] Patent: CN107629001, 2018, A,
  • 8
  • [ 65-49-6 ]
  • [ 1334493-07-0 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 18, p. 5605 - 5609
[2] ACS Medicinal Chemistry Letters, 2013, vol. 4, # 11, p. 1102 - 1107
Historical Records