Structure of 79815-20-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 79815-20-6 |
Formula : | C9H9NO2 |
M.W : | 163.17 |
SMILES Code : | N2C1=CC=CC=C1C[C@H]2C(=O)O |
MDL No. : | MFCD00070578 |
InChI Key : | QNRXNRGSOJZINA-QMMMGPOBSA-N |
Pubchem ID : | 2733920 |
GHS Pictogram: |
![]() ![]() |
Signal Word: | Warning |
Hazard Statements: | H373-H317-H361 |
Precautionary Statements: | P260-P201-P280-P308+P313-P362+P364-P333+P313 |
Num. heavy atoms | 12 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.22 |
Num. rotatable bonds | 1 |
Num. H-bond acceptors | 2.0 |
Num. H-bond donors | 2.0 |
Molar Refractivity | 48.11 |
TPSA ? Topological Polar Surface Area: Calculated from |
49.33 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
0.93 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
1.57 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.54 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-1.24 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.11 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.58 |
Log S (ESOL):? ESOL: Topological method implemented from |
-2.14 |
Solubility | 1.17 mg/ml ; 0.00717 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-2.22 |
Solubility | 0.992 mg/ml ; 0.00608 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.13 |
Solubility | 1.2 mg/ml ; 0.00736 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) |
No |
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 |
-6.18 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 |
0.56 |
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) |
1.9 |
* 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 |
---|---|---|
95.9% | With potassium carbonate;copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 80 - 100℃; for 3.5 - 4h;Product distribution / selectivity; | Example 1 (S)-2,3-dihydro-1 H-indole-2-carboxylic acid: Conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> with 2 molpercent CuCl in NMP at 100°C A flask was charged successively with 366 mg (1.5 mmol) <strong>[42538-40-9](S)-2-bromophenylalanine</strong>, 217 mg (1.6 mmol) K2CO3, 3.2 mg (0.03 mmol) CuCl and 3.2 g NMP. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 100°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 4 hours, full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The yield (measured in solution) of (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was 95.9 percent, ee > 98.6percent.; Example 2 (S)-2,3-dihydro-1H-indole-2-carboxylic acid: Conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> with 1 molpercent CuCl in NMP at 80°C A flask was charged successively with 9.76 g (40.0 mmol) <strong>[42538-40-9](S)-2-bromophenylalanine</strong>, 5.80 g (42.0 mmol) K2CO3, 40 mg (0.4 mmol) CuCl and 40 g NMP. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 80°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 3.5 h full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C and then 40 mL H2O and 50 mL aqueous EtOAc were added. The pH of this mixture was adjusted to 3.3 with 3.5 g 37percent aqueous HCl. The phases were separated. The H2O phase was extracted with 2 x 50 mL aqueous EtOAc. The combined organic layers were washed with 25 mL sat aqueous NaCl. Then the organic phase was concentrated. The residu was dissolved in 16 mL 5N aqueous HCl, followed by pH adjustment to 2.1 with 9.4 g 32percent aqueous NaOH. The precipitated (S)-2,3-dihydro-1H-indole-2-carboxylic acid was isolated by filtration and washed with 2 x 10 mL H2O. 3.24 g (19.8 mmol) (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was found after drying. Yield 49.5percent, ee >99percent. |
95.6% | With potassium carbonate; In water; at 95℃; for 22h;Product distribution / selectivity; | A flask was charged successively with 366 mg (1.5 mmol) <strong>[42538-40-9](S)-2-bromophenylalanine</strong>, 217 mg (1.6 mmmol) K2CO3 and 3 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 5h hour the conversion was approximately 37percent. After 22h full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C and analyzed by HPLC. The yield in solution of (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was 95.6 percent, ee > 99percent. |
81.1% | With potassium carbonate;copper(l) chloride; In water; at 95℃; for 2 - 4h;Product distribution / selectivity; | Example 3 (S)-2,3-dihydro-1 H-indole-2-carboxylic acid: Conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> with 2 molpercent CuCl in water at 95°C A flask was charged successively with 366 mg (1.5 mmol) <strong>[42538-40-9](S)-2-bromophenylalanine</strong>, 217 mg (1.6 mmol) K2CO3, 3 mg (0.03 mmol) CuCl and 3.4 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 2 hour full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C and analyzed by HPLC. The yield in solution of (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was 81.1 percent, ee > 99percent.; Example 4 (S)-2,3-dihydro-1 H-indole-2-carboxylic acid: Conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> with 0.01 molpercent CuCl in water at 95°C A flask was charged successively with 4.89 g (20.0 mmol) <strong>[42538-40-9](S)-2-bromophenylalanine</strong>, 2.93 g (21.2 mmol) K2CO3, 0.2 mg CuCl (2.9 mmol) and 39.7 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 4h hour full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C. Then the reaction mixture was acidified with 4.47 g 5M aqueous HCI until pH = 4.4. The precipitated (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was isolated by filtration and washed with 2 x 10 mL H2O. Found after drying 2.24 g (13.7 mmol) (S)-2,3-dihydro-1 H-indole-2-carboxylic acid. Yield 69percent, ee >99percent. |
69% | Example 4; (S)-2,3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 0.01 molpercent CuCI in water at 95°C EPO <DP n="30"/>; A flask was charged successively with 4.89 g (20.0 mmol) (S)-2- bromophenylalanine, 2.93 g (21.2 mmol) K2CO3, 0.2 mg CuCI (2.9 mmol) and 39.7 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 4h hour full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C. Then the reaction mixture was acidified with 4.47 g 5M aqueous HCI until pH = 4.4. The precipitated (S)-2,3-dihydro-1H-indole-2-carboxylic acid was isolated by filtration and washed with 2 x 10 ml_ H2O. Found after drying 2.24 g (13.7 mmol) (S)-2,3-dihydro-1H- indole-2-carboxylic acid. Yield 69percent, ee >99percent. | |
49.5% | Example 2; (S)-2,3-dihydro-1H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 1 molpercent CuCI in NMP at 800C; A flask was charged successively with 9.76 g (40.0 mmol) (S)-2- bromophenylalanine, 5.80 g (42.0 mmol) K2CO3, 40 mg (0.4 mmol) CuCI and 40 g NMP. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 800C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 3.5 h full conversion of (S)- 2-bromophenylalanine was found. The reaction mixture was cooled to 25°C and then 40 ml_ H2O and 50 mL aqueous EtOAc were added. The pH of this mixture was adjusted to 3.3 with 3.5 g 37percent aqueous HCI. The phases were separated. The H2O phase was extracted with 2 x 50 mL aqueous EtOAc. The combined organic layers were washed with 25 mL sat aqueous NaCI. Then the organic phase was concentrated. The residu was dissolved in 16 mL 5N HCI, followed by pH adjustment to 2.1 with 9.4 g 32percent aqueous NaOH. The precipitated (S)-2,3-dihydro-1H-indole-2- carboxylic acid was isolated by filtration and washed with 2 x 10 mL H2O. 3.24 g (19.8 mmol) (S)-2,3-dihydro-1 H-indole-2-carboxylic acid was found after drying. Yield 49.5percent, ee >99percent. | |
95.9%Chromat. | With potassium carbonate; copper(l) chloride; In 1-methyl-pyrrolidin-2-one; at 100℃; for 4h;Product distribution / selectivity; | Examplei; (S)-2,3-dihydro-1H-indole-2-carboxylic acid: Conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> with 2 molpercent CuCI in NMP at 1000C; A flask was charged successively with 366 mg (1.5 mmol) (S)-2- bromophenylalanine, 217 mg (1.6 mmol) K2CO3, 3.2 mg (0.03 mmol) CuCI and 3.2 g NMP. The reactor was flushed with argon and then kept under a slow stream of argon.The reaction mixture was stirred and heated until 1000C and kept at this temperature.Samples were taken regularly and analyzed by HPLC. After 4 hours, full conversion of<strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The yield (measured in solution) of (S)-2,3- dihydro-1 H-indole-2-carboxylic acid was 95.9 percent, ee > 98.6percent. |
81.1%Chromat. | With potassium carbonate; copper(l) chloride; In water; at 95℃; for 2h;Product distribution / selectivity; | Example 3; (S)-2,3-dihydro-1 H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine with 2 molpercent CuCI in water at 95°C; A flask was charged successively with 366 mg (1.5 mmol) (S)-2- bromophenylalanine, 217 mg (1.6 mmol) K2CO3, 3 mg (0.03 mmol) CuCI and 3.4 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 2 hour full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C and analyzed by HPLC. The yield in solution of (S)-2,3-dihydro-1H-indole-2-carboxylic acid was 81.1 percent, ee > 99percent. |
95.6%Chromat. | With potassium carbonate; In water; at 95℃; for 22h;Product distribution / selectivity; | Example 5; (S)-2,3-dihydro-1H-indole-2-carboxylic acid: Conversion of (S)-2- bromophenylalanine without CuCI in water at 95°C; A flask was charged successively with 366 mg (1.5 mmol) (S)-2- bromophenylalanine, 217 mg (1.6 mmmol) K2CO3 and 3 g H2O. The reactor was flushed with argon and then kept under a slow stream of argon. The reaction mixture was stirred and heated until 95°C and kept at this temperature. Samples were taken regularly and analyzed by HPLC. After 5h hour the conversion was approximately 37percent. After 22h full conversion of <strong>[42538-40-9](S)-2-bromophenylalanine</strong> was found. The reaction mixture was cooled to 25°C and analyzed by HPLC. The yield in solution of (S)-2,3-dihydro-1 H- indole-2-carboxylic acid was 95.6 percent, ee > 99percent. |
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