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Chemical Structure| 24188-74-7 Chemical Structure| 24188-74-7

Structure of 24188-74-7

Chemical Structure| 24188-74-7

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Product Details of [ 24188-74-7 ]

CAS No. :24188-74-7
Formula : C9H6ClNO
M.W : 179.60
SMILES Code : OC1=NC=CC2=C1C=C(Cl)C=C2
English Name :7-Chloroisoquinolin-1-ol
MDL No. :MFCD08436984
InChI Key :YWUCOQGBXQHOJM-UHFFFAOYSA-N
Pubchem ID :10012505

Safety of [ 24188-74-7 ]

Computational Chemistry of [ 24188-74-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 48.78
TPSA ?

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

33.12 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.44
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

2.71
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.59
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.

2.16
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

2.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.3

Water Solubility

Log S (ESOL):?

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

-3.28
Solubility 0.0948 mg/ml ; 0.000528 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.

-3.06
Solubility 0.157 mg/ml ; 0.000873 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-3.74
Solubility 0.0327 mg/ml ; 0.000182 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.

-5.47 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)

1.35

Application In Synthesis of [ 24188-74-7 ]

* 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.

  • Downstream synthetic route of [ 24188-74-7 ]

[ 24188-74-7 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 24188-74-7 ]
  • [ 130874-99-6 ]
YieldReaction ConditionsOperation in experiment
91% With tetraphosphorus decasulfide In pyridine for 1.5h; Heating;
  • 2
  • [ 131002-05-6 ]
  • [ 24188-74-7 ]
YieldReaction ConditionsOperation in experiment
85% With oxygen; 1,3-propanediol In 1,2-dimethoxyethane
  • 3
  • [ 24188-74-7 ]
  • [ 1028252-13-2 ]
YieldReaction ConditionsOperation in experiment
90% With N-Bromosuccinimide In acetonitrile for 3.5h; Reflux; Inert atmosphere;
With N-Bromosuccinimide In acetonitrile for 3.5h; Reflux; 6.1.5 A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258 (M++H).
With N-Bromosuccinimide In acetonitrile at 20℃; Reflux; 2.5 Step 5: A slurry of the product of Step 4, Example 2 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification. 1H NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27(d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-d6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258.
With N-Bromosuccinimide In acetonitrile at 20℃; for 6.5h; Heating / reflux; 22.5 Step 5:; A slurry of the product of Step 4 and NBS (39.747 g, 223.3 mmol) in MeCN (500 mL, anhydrous) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h (This reaction can be monitored by LC/MS). The reaction mixture was then slowly cooled to room temperature over a period of 3 h and the observed solid was removed by simple filtration. The collected solid was washed with MeCN (100 mL×3) to provide 47 g of the desired product. This material was used in the next step without further purification.1H NMR (400 MHz, CD3OD) δ ppm 7.46 (s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.27 (d, J=2.00 Hz, 1H); 13C NMR (100 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC-MS, MS m/z 258.

  • 4
  • [ 67-56-1 ]
  • [ 24188-74-7 ]
  • [ 630423-35-7 ]
YieldReaction ConditionsOperation in experiment
85% With methanesulfonic acid; [bis(acetoxy)iodo]benzene Inert atmosphere; Cooling with ice; Reflux; 3 To a 500 ml, 3-neck round-bottom flask (Flask A) equipped with overhead stirring, nitrogen inlet, heating mantle and temperature probe were charged the following reagents respectively: 1) starting isocarbostyril 2) Methanol (10 ml/g-bulk-LR) 3) Methanesulfonic acid Cooled Flask A via ice bath to 0° C.In a separate 250 ml, 3-neck round-bottom flask (Flask B) equipped with stir bar, nitrogen inlet, temperature probe and heating mantle was dissolved the oxidant in methanol (10 ml/g-bulk-LR) at 30° C.The completely homogeneous oxidant solution was then transferred to an addition funnel and added dropwise to the contents of Flask A, which resulted in a homogeneous solution.The ice bath was removed and the reaction was allowed to age at room temperature for 1 hour prior to heating to reflux.The reaction was then aged at reflux until complete conversion was observed (3-5 hours).Upon complete conversion the reaction volume was then reduced via atmospheric distillation (collected 92 ml distillate).The reaction was then cooled to room temperature and the resulting slurry was aged (at) rt overnight.The following morning, a total of 45 ml of H2O was slowly added dropwise via addition funnel as anti-solvent.The resulting slurry was aged 1 hour at room temperature prior to filtering.The resulting cake was washed with 100 ml 50:50 H2O/MeOH, then 2×100 ml H2O.The solids were dried on the frit under vacuum for several hours prior to being transferred to the vac oven were they continued to dry (at) 50° C. and 30 Hg over the weekend. Typical results range from 75-85% isolated yield with 97 LCAP (250 nm wavelength).
  • 5
  • [ 1028252-12-1 ]
  • [ 24188-74-7 ]
YieldReaction ConditionsOperation in experiment
Stage #1: C11H13ClN2O With potassium 2-methylbutan-2-olate In toluene at 85℃; Heating; Stage #2: With hydrogenchloride In 1-methyl-pyrrolidin-2-one; water Inert atmosphere; 2 The above solution of 5-chloro-2-methylbenzamide was atmospherically solvent switched to toluene.The resulting solution was then cooled to 50° C.DMF/DMA was charged to the reaction solution.Heated to reflux.The solution was allowed to reflux for 3 hrs in order to convert all of the 5-Cl-2-methyl benzamide to the desired amidine intermediate.Removal of the methanol byproduct was then performed by distillation.The resulting warm, homogeneous solution was then inversely added to a separate reactor that contained 25 wt % potassium t-amylate/toluene solution pre-heated to 85° C. Addition rate was maintained 12 L/min on scale.Upon complete addition, heating was maintained of the now heterogeneous solution until complete conversion of the amidine intermediate was observed.The reaction was then cooled to 50° C.Methanol was added, the solution remained heterogeneous.Began vacuum distillation (volume reduction involves removing 2-methyl-2-butanol and toluene) to an approximate concentration of 10 ml/g.Temperature was reduced to room temperature, then n-heptane was added to the heterogeneous solution.A pre-made solution of 50:50 NMP/H2O was then quickly added via addition funnel.The resulting bi-phasic solution was then stirred for 10 minutes prior to transferring to a separatory funnel.The layers separated quickly and cleanly.The aqueous NMP layer was cut and transferred to a separate IL 3-neck round-bottom equipped with a mechanical stirrer, nitrogen inlet and temperature probe.While stirring, acid was added via addition funnel in order to neutralize the reaction and subsequently precipitate desired product from solution.A total of 100 ml H2O was then added dropwise to the resulting slurry.The heterogeneous solution was stirred at room temperature for one hour prior to filtering.The resulting cake was washed with 100 ml of 20% NMP/H2O, then 3×100 ml H2O.The cake was dried on the frit for several hours under vacuum prior to being transferred to the vacuum oven to continue drying overnight (at) 30 Hg and 50° C. Typical results provide 89% isolated yield with 98% LCAP (250 nm wavelength).
  • 6
  • [ 940-62-5 ]
  • [ 26386-88-9 ]
  • [ 24188-74-7 ]
YieldReaction ConditionsOperation in experiment
53% Stage #1: 3-(4-chlorophenyl)prop-2-enoic acid; diphenyl phosphoryl azide With triethylamine In benzene for 2h; Stage #2: In Diphenylmethane at 90℃; for 3.5h; Reflux; 1001.1 Step 1To a solution of (is)-3-(4-chlorophenyl)acrylic acid (18.3 g, 0.1 mol) and Et3 (20.2 g, 0.2 mol) in benzene (100 mL) was added dropwise DPPA (27.5 g, 0.1 mol). After stirring for 2 h, the solution was concentrated and purified by chromatography (Biotage, mobile phase 20/80 EtOAc/hexanes) to give 16 g of an intermediate azide as a solid. This intermediate was dissolved in 100 mL of PI12CH2 and the resulting mixture was slowly heated to 90 °C over a 30 min time period. The reaction mixture was heated to reflux and maintained at this temperature for 3h. After cooling to RT, a solid precipitated which was collected by filtration and washed with toluene to provide 9.5 g of 7-chloroisoquinolin-l(2H)-one (53%). XH NMR (400 MHz, CD3OD) δ ppm 6.66 (d, J=7.05 Hz, 1 H), 7.18 (d, J=7.05 Hz, 1 H), 7.66 (s, 1 H) 7.67 (d, J=2.01 Hz, 1 H), 8.24 (d, J=2.27 Hz, 1 H); 13C NMR (101 MHz, DMSO-D6) δ ppm 104.05, 125.62, 127.21, 128.54, 129.52, 130.77, 132.43, 136.55, 160.72; LC/MS, MS m/z (M+H)+ 180.
  • 7
  • [ 24188-74-7 ]
  • [ 630423-36-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / acetonitrile / Reflux 2.1: trichlorophosphate / 5 h / Reflux 2.2: -35 °C / pH 8 3.1: n-butyllithium; Triisopropyl borate / hexane; tetrahydrofuran / 0.75 h / -78 - -65 °C 3.2: 1.17 h / -60 - 20 °C 3.3: 0 °C / pH 6 4.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C
  • 8
  • [ 24188-74-7 ]
  • [ 953421-74-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide / acetonitrile / Reflux 2.1: trichlorophosphate / 5 h / Reflux 2.2: -35 °C / pH 8
  • 9
  • [ 24188-74-7 ]
  • [ 1028252-13-2 ]
YieldReaction ConditionsOperation in experiment
With N-Bromosuccinimide In acetonitrile Reflux; 1001.2 Step 2A slurry of the product of Step 1, Example 1001, 7-chloroisoquinolin-l(2H)- one (36.33 g, 203 mmol) and N-bromosuccinimide (39.74 g, 223.3 mmol) in anhydrous CH3CN (500 mL) was slowly heated to a gentle reflux over a period of approximately 2 h and maintained at a gentle reflux for 1.5 h. The reaction was monitored by LC/MS and, when complete, the slurry, was slowly cooled to room temperature over a period of 3 h. The precipitated solid was collected by filtration and washed with CH3CN (100 mL x 3) to provide 47 g (90%) of 4-bromo-7- chloroisoquinolin-l(2H)-one. This material was used in the next step without further purification. ¾ NMR (400 MHz, CD3OD) δ ppm 7.46(s, 1H), 7.81 (dd, J=8.40, 2.00 Hz, 1 H), 7.88 (d, J=8.8 Hz, 1 H), 8.27(d, J=2.00 Hz, 1 H); 13C NMR (101 MHz, DMSO-D6) δ ppm 96.68, 126.34, 127.58, 127.71, 130.73, 132.20, 133.47, 134.46, 159.88; LC/MS, MS m/z (M+H)+ 258.
With N-Bromosuccinimide In N,N-dimethyl-formamide at 20℃;
  • 11
  • [ 24188-74-7 ]
  • [ 630423-36-8 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / acetonitrile / 3.5 h / Reflux; Inert atmosphere 2.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 3.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 3.2: 0.75 h / 65 °C / Inert atmosphere 3.3: 0.5 h / -60 - -40 °C 4.1: diazomethyl-trimethyl-silane / hexane; acetonitrile / 14 h / 0 - 20 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / acetonitrile / 3.5 h / Reflux; Inert atmosphere 2.1: trichlorophosphate / 5 h / Reflux; Inert atmosphere 3.1: n-butyllithium / hexane; tetrahydrofuran / 0.75 h / 65 °C / Inert atmosphere 3.2: 0.75 h / 65 °C / Inert atmosphere 3.3: 0.5 h / -60 - -40 °C 4.1: sodium hydride / N,N-dimethyl-formamide; mineral oil / 1 h / 4 °C / Inert atmosphere
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide / acetonitrile / 6.5 h / 20 °C / Heating / reflux 2.1: trichlorophosphate / 5 h / Heating / reflux 2.2: -35 °C / pH 8 3.1: n-butyllithium / tetrahydrofuran; hexanes / 0.75 h / -78 - -65 °C 3.2: 0.67 h / -78 - -65 °C 4.1: methanol; hexanes; acetonitrile / 14 h / 0 - 20 °C
References: [1]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[2]Scola, Paul M.; Sun, Li-Qiang; Wang, Alan Xiangdong; Chen, Jie; Sin, Ny; Venables, Brian L.; Sit, Sing-Yuen; Chen, Yan; Cocuzza, Anthony; Bilder, Donna M.; D'Andrea, Stanley V.; Zheng, Barbara; Hewawasam, Piyasena; Tu, Yong; Friborg, Jacques; Falk, Paul; Hernandez, Dennis; Levine, Steven; Chen, Chaoqun; Yu, Fei; Sheaffer, Amy K.; Zhai, Guangzhi; Barry, Diana; Knipe, Jay O.; Han, Yong-Hae; Schartman, Richard; Donoso, Maria; Mosure, Kathy; Sinz, Michael W.; Zvyaga, Tatyana; Good, Andrew C.; Rajamani, Ramkumar; Kish, Kevin; Tredup, Jeffrey; Klei, Herbert E.; Gao, Qi; Mueller, Luciano; Colonno, Richard J.; Grasela, Dennis M.; Adams, Stephen P.; Loy, James; Levesque, Paul C.; Sun, Huabin; Shi, Hong; Sun, Lucy; Warner, William; Li, Danshi; Zhu, Jialong; Meanwell, Nicholas A.; McPhee, Fiona [Journal of Medicinal Chemistry, 2014, vol. 57, # 5, p. 1730 - 1752].
[3]Current Patent Assignee: BRISTOL MYERS SQUIBB - US2008/119461, 2008, A1.
  • 12
  • [ 24188-74-7 ]
  • [ 103-19-5 ]
  • [ 2238818-70-5 ]
YieldReaction ConditionsOperation in experiment
95% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 8h;
95% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 90℃; for 10h; High pressure; 19 Example 19 7-chloroisoquinolin-1 (2Η)-one (12 mmol), bis(4-methylphenyl) disulfide (10 mmol), hexafluoride was sequentially added to a pressure-resistant reaction tube at room temperature. Silver acetate (10 mmol) and dichloroethene (6 mL). The reaction mixture was then reacted at 90 ° C for 10 hours. The reaction was stopped, concentrated under reduced pressure to give a crude material, which was washed with a mixture of petroleum ether and ethyl acetate. 4-(4-Methylphenylthio)-7-chloroisoquinolin-1 (2H)-one. Yield 95%;
  • 13
  • [ 24188-74-7 ]
  • [ 5335-87-5 ]
  • [ 2238818-72-7 ]
YieldReaction ConditionsOperation in experiment
90% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 8h;
90% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 105℃; for 10h; High pressure; 21 Example 21 7-chloroisoquinolin-1 (2Η)-one (12 mmol), bis(4-methoxyphenyldisulfide (15 mmol), hexafluoroantimonic acid was sequentially added to a pressure-resistant reaction tube at room temperature. Silver (10 mmol) and dichloroethane (10 mL). The reaction mixture was then at 105 ° C. The reaction was carried out for 10 hours. The reaction was quenched and concentrated under reduced pressure to give a crude material which was washed with a mixture of petroleum ether and ethyl acetate. Fast column chromatography to obtain the corresponding product 4-(4-Methoxyphenylthio)-7-chloroisoquinolin-1 (2H)-one. Yield 90%;
  • 14
  • [ 24188-74-7 ]
  • [ 882-33-7 ]
  • [ 2238818-71-6 ]
YieldReaction ConditionsOperation in experiment
95% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 110℃; for 8h;
95% With silver hexafluoroantimonate In 1,2-dichloro-ethane at 100℃; for 10h; High pressure; 20 Example 20 7-chloroisoquinolin-1 (2Η)-one (12 mmol), diphenyl disulfide (10 mmol), silver hexafluoroantimonate (15 mmol) and, in a pressure-resistant reaction tube, were sequentially added at room temperature. Dichloroethane (6 mL). The reaction mixture was then reacted at 100 ° C for 10 hours. The reaction was stopped, concentrated under reduced pressure to give a crude material, which was washed with a mixture of petroleum ether and ethyl acetate. 4-phenylsulfur-7-chloroisoquinolin-1 (2H)-one. Yield 95%;
 

Historical Records

Technical Information

• Alkyl Halide Occurrence • Appel Reaction • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Bucherer-Bergs Reaction • Buchwald-Hartwig C-N Bond and C-O Bond Formation Reactions • Chugaev Reaction • Clemmensen Reduction • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Corey-Kim Oxidation • Dess-Martin Oxidation • Fischer Indole Synthesis • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Jones Oxidation • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • Martin's Sulfurane Dehydrating Reagent • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Mitsunobu Reaction • Moffatt Oxidation • Oxidation of Alcohols by DMSO • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Alcohols • Preparation of Aldehydes and Ketones • Preparation of Amines • Prins Reaction • Reactions of Alcohols • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions with Organometallic Reagents • Reformatsky Reaction • Ritter Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Sharpless Olefin Synthesis • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Swern Oxidation • Tebbe Olefination • Ugi Reaction • Wittig Reaction • Wolff-Kishner Reduction

Categories

Pharmaceutical Intermediates of
[ 24188-74-7 ]

Asunaprevir Related Intermediates

Chemical Structure| 159622-10-3

[159622-10-3]

(1R,2S)-1-((tert-Butoxycarbonyl)amino)-2-vinylcyclopropanecarboxylic acid

Chemical Structure| 630423-36-8

[630423-36-8]

1,7-Dichloro-4-methoxyisoquinoline

Chemical Structure| 13726-69-7

[13726-69-7]

Boc-Hyp-OH

Chemical Structure| 940-62-5

[940-62-5]

(E)-3-(4-Chlorophenyl)acrylic acid

Chemical Structure| 259217-95-3

[259217-95-3]

(1R,2S)-Ethyl 1-((tert-butoxycarbonyl)amino)-2-vinylcyclopropanecarboxylate

Related Functional Groups of
[ 24188-74-7 ]

Chlorides

Chemical Structure| 58498-61-6

A222565 [58498-61-6]

5-Chloro-3-methylpyridin-2-ol

Similarity: 0.77

Chemical Structure| 34784-06-0

A204259 [34784-06-0]

7-Chloroisoquinoline

Similarity: 0.76

Chemical Structure| 62882-02-4

A224530 [62882-02-4]

6-Chloroisoquinoline

Similarity: 0.76

Chemical Structure| 886364-92-7

A135906 [886364-92-7]

5-Chloro-4-methylpyridin-2-ol

Similarity: 0.73

Chemical Structure| 193624-86-1

A138761 [193624-86-1]

4-Chlorofuro[2,3-b]pyridine

Similarity: 0.71

Alcohols

Chemical Structure| 58498-61-6

A222565 [58498-61-6]

5-Chloro-3-methylpyridin-2-ol

Similarity: 0.77

Chemical Structure| 24228-13-5

A121442 [24228-13-5]

3-Phenylpyridin-2-ol

Similarity: 0.75

Chemical Structure| 886364-92-7

A135906 [886364-92-7]

5-Chloro-4-methylpyridin-2-ol

Similarity: 0.73

Chemical Structure| 950746-21-1

A336484 [950746-21-1]

6,8-Dichloro-2,7-naphthyridin-1(2H)-one

Similarity: 0.70

Chemical Structure| 223671-15-6

A105736 [223671-15-6]

7-Bromoisoquinolin-1-ol

Similarity: 0.70

Related Parent Nucleus of
[ 24188-74-7 ]

Isoquinolines

Chemical Structure| 34784-06-0

A204259 [34784-06-0]

7-Chloroisoquinoline

Similarity: 0.76

Chemical Structure| 62882-02-4

A224530 [62882-02-4]

6-Chloroisoquinoline

Similarity: 0.76

Chemical Structure| 34784-07-1

A144432 [34784-07-1]

8-Chloroisoquinoline

Similarity: 0.70

Chemical Structure| 5430-45-5

A493591 [5430-45-5]

5-Chloroisoquinoline

Similarity: 0.70

Chemical Structure| 223671-15-6

A105736 [223671-15-6]

7-Bromoisoquinolin-1-ol

Similarity: 0.70