Structure of 24188-74-7
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| 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 |
| 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 |
33.12 Ų |
| Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
1.44 |
| Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.71 |
| Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.59 |
| Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.16 |
| Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
2.6 |
| Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.3 |
| Log S (ESOL):? ESOL: Topological method implemented from |
-3.28 |
| Solubility | 0.0948 mg/ml ; 0.000528 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (Ali)? Ali: Topological method implemented from |
-3.06 |
| Solubility | 0.157 mg/ml ; 0.000873 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.74 |
| Solubility | 0.0327 mg/ml ; 0.000182 mol/l |
| Class? Solubility class: Log S scale |
Soluble |
| 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) |
No |
| CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
| CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
No |
| CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
| CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
| CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
| Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-5.47 cm/s |
| Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
| Ghose? Ghose filter: implemented from |
None |
| Veber? Veber (GSK) filter: implemented from |
0.0 |
| Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
| Muegge? Muegge (Bayer) filter: implemented from |
1.0 |
| Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
| PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
| Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
| Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
| Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.35 |
* 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.

| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 91% | With tetraphosphorus decasulfide In pyridine for 1.5h; Heating; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| 85% | With oxygen; 1,3-propanediol In 1,2-dimethoxyethane |
| Yield | Reaction Conditions | Operation 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. |

| Yield | Reaction Conditions | Operation 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). |
| Yield | Reaction Conditions | Operation 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). |
| Yield | Reaction Conditions | Operation 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. |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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℃; |
| Yield | Reaction Conditions | Operation in experiment |
|---|---|---|
| Multi-step reaction with 2 steps 1: N-Bromosuccinimide / acetonitrile / 3.5 h / Reflux; Inert atmosphere 2: trichlorophosphate / 5 h / Reflux; Inert atmosphere | ||
| Multi-step reaction with 2 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 |
| Yield | Reaction Conditions | Operation 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 |
| Yield | Reaction Conditions | Operation 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%; |
| Yield | Reaction Conditions | Operation 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%; |
| Yield | Reaction Conditions | Operation 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%; |

A336484 [950746-21-1]
6,8-Dichloro-2,7-naphthyridin-1(2H)-one
Similarity: 0.70