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Product Details of [ 157942-12-6 ]

CAS No. :157942-12-6 MDL No. :MFCD06203960
Formula : C8H7IO3 Boiling Point : -
Linear Structure Formula :- InChI Key :LXCQVWRESZDFGW-UHFFFAOYSA-N
M.W : 278.04 Pubchem ID :10378812
Synonyms :

Calculated chemistry of [ 157942-12-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 12
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.12
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 52.46
TPSA : 46.53 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.53 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.11
Log Po/w (XLOGP3) : 2.07
Log Po/w (WLOGP) : 1.78
Log Po/w (MLOGP) : 2.21
Log Po/w (SILICOS-IT) : 2.18
Consensus Log Po/w : 2.07

Druglikeness

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

Water Solubility

Log S (ESOL) : -3.11
Solubility : 0.218 mg/ml ; 0.000783 mol/l
Class : Soluble
Log S (Ali) : -2.68
Solubility : 0.586 mg/ml ; 0.00211 mol/l
Class : Soluble
Log S (SILICOS-IT) : -2.85
Solubility : 0.395 mg/ml ; 0.00142 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 1.91

Safety of [ 157942-12-6 ]

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 [ 157942-12-6 ]

* 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 [ 157942-12-6 ]
  • Downstream synthetic route of [ 157942-12-6 ]

[ 157942-12-6 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 157942-12-6 ]
  • [ 24589-98-8 ]
Reference: [1] Journal of Medicinal Chemistry, 2014, vol. 57, # 6, p. 2334 - 2356
  • 2
  • [ 63435-16-5 ]
  • [ 157942-12-6 ]
YieldReaction ConditionsOperation in experiment
48%
Stage #1: With hydrogenchloride; sodium nitrite In tetrahydrofuran; water at 0℃; for 0.516667 h;
Stage #2: With potassium iodide In tetrahydrofuran; water for 0.25 h;
A solution of the product from Step 35.a. (24.5g, 146mmol) in THF (77ml) was diluted with 3N HCl (232ml) and cooled in an ice bath to 8°C when a precipitate formed. NaNO2 (11.1g, 161mmol) in H2O (75ml) was added over 6 minutes at ice bath temperature. Continue stirring 25 minutes and then add a solution of KI (97.1g, 585mmol) in H2O (75ml) in one portion, and stir 15minutes. Add EtOAc (550ml) and separate layers. Wash the EtOAc layer with H2O (500ml) and brine (400ml), dry over Na2SO4, filter and concentrate to black solid. The crude product was purified by silica gel chromatography using CH2Cl2 as eluant to yield 19.7g (48percent) of an off-white solid. NMR (300MHZ, DMSO-d6, 30°C) 10.6-10.8 (1H, s), 7.8-7.9 (1H, d), 7.4-7.5 (1H, m), 7.1-7.2 (1H, m), 3.75-3.85 (3H, s).
8.1 g
Stage #1: With hydrogenchloride In water; acetonitrile at 0℃; for 0.5 h;
Stage #2: With sodium nitrite In water; acetonitrile at 0℃; for 0.5 h;
Stage #3: With potassium iodide In water; acetonitrile at 0℃; for 1 h;
[0467] 2 M hydrochloric acid (90 mL) was added to a solution of methyl 4-amino-3-hydroxybenzoate (6.00 g) in acetonitrile (30 mL), and the resultant was stirred for 30 minutes at 0°C. An aqueous solution (15 mL) of sodium nitrite (2.97 g) was added thereto, and the resultant was stirred for 30 minutes at 0°C. An aqueous solution of potassium iodide (23.8 g) was added to the reaction mixture, the resultant was stirred for 1 hour at 0°C, and then extraction thereof was performed using ethyl acetate. The obtained organic layer was washed with an aqueous saturated sodium carbonate solution and an aqueous saturated sodium tMosulfate solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by a silica gel column chromatography (hexane/ethyl acetate), thereby obtaining the title compound (8.10 g). 1H NMR (400 MHz, DMSO-de) δ 3.82 (3H, s), 7.14 (1H, dd, J = 8.0, 1.6 Hz), 7.43 (1H, d, J = 1.6 Hz), 7.83 (1H, d, J = 8.2 Hz), 10.80 (1H, tars).
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 9, p. 1269 - 1273
[2] Patent: EP1382607, 2004, A2, . Location in patent: Page 43
[3] Journal of Organic Chemistry, 2003, vol. 68, # 24, p. 9423 - 9432
[4] Bioorganic and Medicinal Chemistry, 2009, vol. 17, # 18, p. 6567 - 6582
[5] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 10, p. 1257 - 1260
[6] Patent: US6387903, 2002, B1,
[7] Patent: US6297239, 2001, B1,
[8] Patent: US5939439, 1999, A,
[9] Journal of Medicinal Chemistry, 2009, vol. 52, # 8, p. 2289 - 2310
[10] Patent: WO2014/142363, 2014, A1, . Location in patent: Paragraph 0467
  • 3
  • [ 67-56-1 ]
  • [ 58123-77-6 ]
  • [ 157942-12-6 ]
YieldReaction ConditionsOperation in experiment
76% at 70℃; for 48 h; Overall, 61.31 g of 3-hydroxy-4-iodobenzoic acid are obtained in the form of a white solid. 47 g (150 mmol) of this 3-hydroxy-4-iodobenzoic acid are placed in 300 mL of methanol and 6.13 g (35.6 mmol) of para-toluenesulfonic acid are added. The reaction mixture is heated at 70° C. for 48 hours.- The reaction is stopped by addition of 11 of water. The precipitated product is filtered off and rinsed with water to neutral pH. 37.4 g (76percent) of methyl 3-hydroxy-4-iodobenzoate are obtained in the form of a beige-colored powder.
70% at 20℃; for 20 h; Heating / reflux 3-Hydroxy-4-iodobenzoic acid (12.55 g, 47.5 mmol) is dissolved in MeOH (200 mL), treated slowly drop-wise with thionyl chloride (32.3 mL, 443 mmol) at RT, then heated to reflux for 20 h. The mixture is concentrated to dryness and partitioned between CH2Cl2 (100 mL) and saturated NaHCO3 (50 mL). Not all of the residue dissolves, so the mixture is filtered and the solid is washed with a small amount of CH2Cl2 in MeOH. The original filtrate and the organic washes are combined, concentrated to dryness, dissolved in 10percent MeOH/CH2Cl2 (200 mL), diluted with water (50 mL) and the layers separated. The organics are washed with saturated NaHCO3 (2.x.50 mL), then water (50 mL), dried (Na2SO4) and concentrated to a tan solid. This solid is triturated with CH2Cl2 (50 mL) and filtered. The two solids are combined to afford 9.4 g (70percent) of methyl 3-hydroxy-4-iodobenzoate as a beige solid. HRMS (FAB) calcd for C8H7IO3+H: 278.9520, found 278.9521 (M+H)+.
70% for 144 h; Heating / reflux 59 ml (1.10 mol, 2.4 eq.) of sulphuric acid are added to a solution of 121 g (0.458 mol, 1 eq.) of 3-hydroxy-4-iodobenzoic acid in 700 ml of methanol. The reaction mixture is heated at reflux for 6 days. The methanol is evaporated and then the reaction medium is poured into water and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulphate. The solvent is concentrated and the solid obtained is filtered off and dried. 88.56 g of methyl 3-hydroxy-4-iodobenzoate are obtained in the form of white crystals. Yield = 70percent
70% for 144 h; Heating / reflux 59 ml (1.10 mol, 2.4 eq) of sulphuric acid are added to a solution of 121 g (0.458 mol, 1 eq) of methyl 3-hydroxy-4-iodobenzoic acid in 700 ml of methanol. Thereaction mixture is refluxed for 6 days. The methanol is evaporated off and the reaction medium is then poured into water and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is concentrated and the solid obtained is filtered off and dried. 88.56 g of methyl 3-hydroxy-4-iodobenzoate are obtained in the form of white crystals. Yield = 70percent

Reference: [1] Chemical Communications (Cambridge, United Kingdom), 2012, vol. 48, # 83, p. 10328 - 10330,3
[2] Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry (1972-1999), 1995, # 9, p. 1103 - 1114
[3] Patent: US2009/12129, 2009, A1, . Location in patent: Page/Page column 21
[4] Patent: US2003/232853, 2003, A1, . Location in patent: Page 38
[5] Patent: WO2006/18325, 2006, A1, . Location in patent: Page/Page column 26
[6] Patent: WO2006/18326, 2006, A1, . Location in patent: Page/Page column 78; 79
[7] Journal of Medicinal Chemistry, 2005, vol. 48, # 9, p. 3290 - 3312
[8] Patent: EP2017263, 2009, A1, . Location in patent: Page/Page column 173
[9] Patent: EP1217000, 2002, A1, . Location in patent: Page 60
[10] Journal of Medicinal Chemistry, 2009, vol. 52, # 18, p. 5685 - 5702
[11] Patent: US2010/286430, 2010, A1, . Location in patent: Page/Page column title page; 1
[12] Synthesis (Germany), 2012, vol. 44, # 23, p. 3598 - 3602
[13] Chemical Communications, 2017, vol. 53, # 53, p. 7222 - 7225
  • 4
  • [ 19438-10-9 ]
  • [ 157942-12-6 ]
YieldReaction ConditionsOperation in experiment
76% With iodine; iodic acid In ethanol; water at 80℃; for 1 h; Inert atmosphere To a stirred solution of benzoate 4a (1.52 g, 10 ramol) in EtOH (4 mL) was added I2 ( 1.02 g, 4 mmol) in one portion. The reaction was heated to reflux before an aqueous solution (2 mL) of HIO3 (352 mg, 2 mmol) was added. The mixture was refluxed for 1 hour before it was cooled to RT. The product was recovered by filtration and washed with water to give compound 4b as a w hite solid. (2.11 g, 76percent yield). 1H NMR (400 MHz, CDCI3) δ 7.75 (d, 7=8.2 Hz, 1H), 7.47 (d, 7=1.9 Hz, 1H), 7.24 (dd, 7=8.2, 1.9 Hz, 1H), 3.88 (s, 3H). 13C NMR (101 MHz, CDC13) δ 167.34, 156.30, 139.41, 131.76, 122.61, 115.64, 91.51, 52.74. MS (ES-): m/z calc. for C8H7C1IC>3:277.9; found: 276.9 [M- H]-.
Reference: [1] Patent: WO2017/130191, 2017, A1, . Location in patent: Paragraph 00133; 00135
  • 5
  • [ 58123-77-6 ]
  • [ 104-15-4 ]
  • [ 157942-12-6 ]
YieldReaction ConditionsOperation in experiment
76% at 70℃; for 48 h; 6.1 g (35.6 mmol) of paratoluene sulfonic acid is added to a solution of 47 g (150 mmol) of 3-hydroxy-4-iodobenzoic acid in 300 ml of methanol. The reaction mixture is heated at 70° C. for 48 hours. After adding 1000 ml of water, the precipitate is filtered, and rinsed with water to neutral pH. 37.4 g (76percent) of methyl 3-hydroxy-4-iodobenzoate is obtained in the form of a beige powder.
Reference: [1] Patent: US2010/144884, 2010, A1, . Location in patent: Page/Page column 9
[2] Patent: US2010/158843, 2010, A1,
  • 6
  • [ 106291-80-9 ]
  • [ 157942-12-6 ]
Reference: [1] Synlett, 2016, vol. 27, # 12, p. 1794 - 1797
  • 7
  • [ 58123-77-6 ]
  • [ 157942-12-6 ]
YieldReaction ConditionsOperation in experiment
70% With thionyl chloride In methanol; dichloromethane 3-Hydroxy-4-iodobenzoic acid (12.55 g, 47.5 mmol) is dissolved in MeOH (200 mL), treated slowly dropwise with thionyl chloride (32.3 mL, 442.9 mmol) at rt, then heated to reflux for 20 h.
The mixture is concentrated to dryness and partitioned between CH2Cl2 (100 mL) and saturated NaHCO3 (50 mL).
Not all of the residue is solubilized, so the mixture is filtered and the solid is washed with a small amount of CH2Cl2 and MeOH.
The original filtrate and the organic washes are combined, concentrated to dryness, dissolved in 10percent MeOH/CH2Cl2 (200 mL), diluted with water (50 mL) and the layers separated.
The organics are washed with saturated NaHCO3 (2*50 mL), then water (50 mL), dried over anhydrous Na2SO4 and concentrated to a tan solid.
This solid is triturated with CH2Cl2 (50 mL) and filtered.
The two solids are combined to afford 9.4 g (70percent) of methyl 3-hydroxy-4-iodobenzoate as a beige solid. HRMS (FAB) calcd for C8H7IO3+H1: 278.9520, found 278.9521.
70% With thionyl chloride In methanol; dichloromethane 3-Hydroxy-4-iodobenzoic acid (12.55 g, 47.5 mmol) is dissolved in CH3OH (200 mL), treated slowly dropwise with thionyl chloride (32.3 mL, 442.9 mmol) at RT, then heated to reflux for 20 h.
The mixture is concentrated to dryness and partitioned between CH2Cl2 (100 mL) and saturated NaHCO3 (50 mL).
Not all of the residue is solubilized, so the mixture is filtered and the solid is washed with a small amount of CH2Cl2 and CH3OH.
The original filtrate and the organic washes are combined, concentrated to dryness, dissolved in 10percent CH3OH/CH2Cl2 (200 mL), diluted with water (50 mL) and the layers separated.
The organics are washed with saturated NaHCO3 (2*50 mL), then water (50 mL), dried over Na2SO4 and concentrated to a tan solid.
This solid is triturated with CH2Cl2 (50 mL) and filtered.
The two solids are combined to afford 9.4 g (70percent) of methyl 3-hydroxy-4-iodobenzoate as a beige solid. HRMS (FAB) calcd for C8H7IO3+H: 278.9520, found 278.9521 (M+H)+.
Reference: [1] Patent: US2003/73707, 2003, A1,
[2] Patent: US2003/105089, 2003, A1,
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  • [ 58123-77-6 ]
  • [ 18107-18-1 ]
  • [ 157942-12-6 ]
Reference: [1] Patent: WO2014/176142, 2014, A1, . Location in patent: Page/Page column 53-54
  • 9
  • [ 99-06-9 ]
  • [ 157942-12-6 ]
Reference: [1] Chemical Communications (Cambridge, United Kingdom), 2012, vol. 48, # 83, p. 10328 - 10330,3
[2] Chemical Communications, 2017, vol. 53, # 53, p. 7222 - 7225
  • 10
  • [ 2374-03-0 ]
  • [ 157942-12-6 ]
Reference: [1] Bioorganic and Medicinal Chemistry Letters, 2002, vol. 12, # 9, p. 1269 - 1273
[2] Bioorganic and Medicinal Chemistry Letters, 2001, vol. 11, # 10, p. 1257 - 1260
  • 11
  • [ 157942-12-6 ]
  • [ 588703-29-1 ]
Reference: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436
  • 12
  • [ 157942-12-6 ]
  • [ 1066-54-2 ]
  • [ 478169-68-5 ]
YieldReaction ConditionsOperation in experiment
91% With copper(l) iodide; triethylamine In tetrahydrofuran at 50℃; for 4 h; Methyl 3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL)/CHCl3 (40 mL) in a dry flask, under nitrogen. Triethylamine (8.14 mL, 58.4 mmol) is added and the mixture is heated to 50° C. for 4 h. The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2.x.40 mL), dried (MgSO4) and concentrated to a brown oily-solid (8.31 g). The crude material is chromatographed over a standard 90 g Biotage column, eluting with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L). The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3SI+H: 249.0947, found 249.0947 (M+H)+.
91% With triethanolamine; copper(I) iodide In tetrahydrofuran; hexane; chloroform; ethyl acetate Methyl 3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL) CHCl3 (40 mL) in a dry flask, under nitrogen. TEA (8.14 mL<58.4 mmol) is added and the mixture is heated to 50° C. for 4 h.
The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2*40 mL), dried over anhydrous MgSO4 and concentrated to a brown paste (8.31 g).
The crude material is chromatographed over a standard 90 g Biotage column, eluding with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L).
The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3SI+H1: 249.0947, found 249.0947.
91% With triethanolamine; copper(I) iodide In tetrahydrofuran; hexane; chloroform; ethyl acetate Methyl-3-hydroxy-4-iodobenzoate (5.22 g, 18.8 mmol) is combined with trimethylsilylacetylene (3.71 mL, 26.3 mmol), bis(triphenylphosphine)palladium dichloride (386 mg, 0.55 mmol) and cuprous iodide (54 mg, 0.28 mmol) in THF (20 mL)/CHCl3 (40 mL) in a dry flask under nitrogen. TEA (8.14 mL<58.4 mmol) is added and the mixture is heated to 50° C. for 4 h.
The mixture is diluted with CHCl3 (60 mL), washed with 5percent HCl (2*40 mL), dried over MgSO4 and concentrated to a brown oily-solid (8.31 g).
The crude material is chromatographed over a standard 90 g Biotage column, eluding with 10percent EtOAc/hexane (1 L) followed by 15percent EtOAc/hexane (1 L).
The appropriate fractions are combined and concentrated to afford 4.22 g (91percent) of methyl 3-hydroxy-4-[(trimethylsilyl)ethynyl]benzoate as a yellow solid. HRMS (FAB) calcd for C13H16O3Si+H: 249.0947, found 249.0947 (M+H)+.
Reference: [1] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436
[2] Patent: US2003/232853, 2003, A1, . Location in patent: Page 38
[3] Patent: US2003/73707, 2003, A1,
[4] Patent: US2003/105089, 2003, A1,
  • 13
  • [ 157942-12-6 ]
  • [ 162401-62-9 ]
Reference: [1] Synthesis (Germany), 2012, vol. 44, # 23, p. 3598 - 3602
[2] Synthesis (Germany), 2012, vol. 44, # 23, p. 3598 - 3602
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  • [ 157942-12-6 ]
  • [ 1243391-44-7 ]
Reference: [1] Synthesis (Germany), 2012, vol. 44, # 23, p. 3598 - 3602
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