Structure of 180869-38-9
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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. : | 180869-38-9 |
Formula : | C8H13N3O2 |
M.W : | 183.21 |
SMILES Code : | CNC1=NC=CC(C(OC)OC)=N1 |
MDL No. : | MFCD10566061 |
InChI Key : | GVTZVNRRGNBOJF-UHFFFAOYSA-N |
Pubchem ID : | 17840014 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 13 |
Num. arom. heavy atoms | 6 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 4 |
Num. H-bond acceptors | 4.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 48.09 |
TPSA ? Topological Polar Surface Area: Calculated from |
56.27 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.09 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
0.19 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
0.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
-0.26 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
0.54 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
0.57 |
Log S (ESOL):? ESOL: Topological method implemented from |
-1.17 |
Solubility | 12.3 mg/ml ; 0.0671 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (Ali)? Ali: Topological method implemented from |
-0.93 |
Solubility | 21.5 mg/ml ; 0.117 mol/l |
Class? Solubility class: Log S scale |
Very soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-2.4 |
Solubility | 0.738 mg/ml ; 0.00403 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 |
No |
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 |
-7.28 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 |
1.0 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) |
2.24 |
* 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 |
---|---|---|
With hydrogenchloride; In water; at 48℃; for 17h; | Step [B] : Preparation of 2-methylamino-pyrimidine-4- carbaldehyde (4-Dimethoxymethyl-pyrimidin-2-yl) -methylamine (Step A, 3.60 g, 19.6 mmol) and 3 N HCl (14.4 mL, 43.2 mmol) were combined and stirred at [48 C] for 17 h. After cooling to RT, 4.3 g of [NAHC03] was added in portions. The mixture was extracted with EtOAc, the combined organic portions were dried over [MGSO4,] filtered, and condensed to give the titled compound as a yellow solid. MS [(ES+)] : 138.3 (M+H) +. Calc'd for [C6H7N30-137.] 14. | |
With hydrogenchloride; at 60℃; for 2h; | To the 2M solution of methylamine in THF (3 mL) 232 mg 4-(dimethoxymethyl)-2- methylsulfonyl-pyriinidine (Preparation 9a3, 1.00 mmol) was added and it was stirred at room temperature for lh. The reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. To the residue 3 mE 2N HC1 was added and it was stilTed at 60C for 2h. Than it was cooled to 0C, the pH was adjusted to 9 using 2N NaOH solution, and then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for lh. The reaction mixture was extracted with EtOAc, thecombined organic layers were dried over MgSO4 and concentrated under reduced pressure to give the title product.MS: (M+2H) 141.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In isopropyl alcohol; for 20h;Heating / reflux; | Example 125 [N- (4, 4-DIMETHYL-1,] 2,3, [4-TETRAHYDRO-ISOQUINOLIN-7-YL)-2-[(2-] [ METHYLAMINO-PYRIMIDIN-4-YLMETHYL)-AMINO]-BENZAMIDE] Step A: Preparation of [(4-DIMETHOXYMETHYL-PYRIMIDIN-2-YL)-] methyl-amine A mixture of 1, 1-dimethoxy-4-dimethylaminobut-3-en-2- one (4.06 g, 22.3 mmol) (Lipinski; J. Het. Chem. (1995), 22, 1723), 1-methylguanidine hydrochloride (2.50 g, 22.3 mmol) and NaOH (0.89 g, 22.3 mmol) in 20 mL of IpOH and was stirred at reflux for 20 h. The mixture was cooled to RT, diluted with MeOH, and the solids were removed by filtration. The filtrate was condensed, and the crude compound was purified by flash column chromatography [(5%] to 40% of EtOAc in [CH2CL2).] The titled compound was obtained as a light yellowish oil. MS (ES+) : 184.2 [(M+H) +. CAL'D] for [CGH13N302-183.] 21. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Procedure J: Intermediate 8 (1-10) - 2-Methylaminopyrimidine-4- carboxaldehyde dimethyl acetal; [0097] A solution of 5.5 mL (41 mmol, 1.0 eq.) of dimethylformamide dimethyl acetal and 5.0 mL (41 mmol, 1.0 eq.) of pyruvic aldehyde dimethyl acetal was heated at 100 0C for 16 h. Methanol was removed in vacuo to afford a brown oil. To a solution of 15 mL of sodium ethoxide (21% in ethanol, 41 mmol, 1.0 eq.) was added 4.5 g (41 mmol, 1.0 eq.) of methyl guanidine HCl. The mixture was stirred for 10 min before a solution of the above described oil in 15 mL anhydrous ethanol was added. The mixture was heated to reflux for 24 h, allowed to cool to room <n="39"/>temperature and filtered. The solvent was removed in vacuo to afford 2- methylaminopyrimidine-4-carboxaldehyde dimethyl acetal (I- 10) as a dark brown oil which was used in the next step without further purification |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 20℃; for 1h; | To the 2M solution of methylamine in THF (3 mL) 232 mg 4-(dimethoxymethyl)-2- methylsulfonyl-pyriinidine (Preparation 9a3, 1.00 mmol) was added and it was stirred at room temperature for lh. The reaction mixture was concentrated under reduced pressure, the residue was diluted with EtOAc and washed with brine. The organic layer was dried over MgSO4 and concentrated under reduced pressure. To the residue 3 mE 2N HC1 was added and it was stilTed at 60C for 2h. Than it was cooled to 0C, the pH was adjusted to 9 using 2N NaOH solution, and then 76 mg sodium borohydride (2.0 mmol) was added and the mixture was stirred for lh. The reaction mixture was extracted with EtOAc, thecombined organic layers were dried over MgSO4 and concentrated under reduced pressure to give the title product.MS: (M+2H) 141.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In tetrahydrofuran; water; at 40℃; | Aqueous 4 M HCI (2 ml) was added to a solution of 4-(dimethoxymethyl)-A/- methylpyrimidin-2-amine (0.060 g, 0.33 mmol) in THF (1 ml). The resulting mixture was heated to 40 C overnight and then cooled to room temperature. The reaction mixture containing the hydrochloride salt of the aldehyde was used directly in the next step without isolation. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In acetone; at 70℃;Inert atmosphere; | Compounds 4-(dimethoxymethyl)pyrimidin-2-amine 68 8b (1.00 g, 5.65 mmol), 70 iodomethane (2.80 g, 19.77 mmol) and 71 acetone (30 mL) were mixed. This mixture were stirred for 16 h at 70 C., cooled to room temperature, and filtered. The solid was mixed with 10% 67 sodium hydroxide (8 mL), stirred for 0.5 h at 80 C., and cooled to room temperature. This mixture was quenched with 250 mL of 72 ice water, extracted with dichloromethane (50 mL×2), and the organic phase was washed with saturated brine (50 mL×2). The organic phase was dried over anhydrous sodium sulfate, filtered to remove the drying agent, and subjected to exsolution under reduced pressure, to obtain the target 73 product 8c 4-(dimethoxymethyl)-N-methylpyrimidin-2-amine 8c (0.70 g, yellow oil), at a yield of 67%. (0175) MS m/z (ESI): 184 [M+1] (0176) 1H NMR (400 MHz, CDCl3) delta 8.37 (d, J=4.8 Hz, 1H), 6.77 (d, J=5.2 Hz, 1H), 5.18 (brs, 1H), 5.13 (s, 1H), 3.42 (s, 6H), 3.03 (d, J=5.2 Hz, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12% | With lithium hexamethyldisilazane; In tetrahydrofuran; at 0℃; for 2h;Inert atmosphere; | Compounds <strong>[180869-38-9]4-(dimethoxymethyl)-N-methylpyrimidin-2-amine</strong> 73 8c (0.20 g, 1.09 mmol), 25 diphenyl carbonate (0.47 g, 2.19 mmol), 26 lithium hexamethyldisilazide (1.5 mL, 1.51 mmol, 1 M solution in 27 tetrahydrofuran) and tetrahydrofuran (5 mL) were mixed and stirred for 2 h at 0 C. This mixture was quenched with 10 mL of a saturated ammonium chloride solution, extracted with ethyl acetate (20 mL×2), and the organic phase was washed with saturated brine (20 mL×2). The organic phase was dried over anhydrous sodium sulfate, and filtered to remove the drying agent. The residuals were purified through a preparative silica gel plate (dichloromethane/methanol 50:1), to obtain the target product phenyl (76 4-(dimethoxymethyl)pyrimidin-2-yl)(methyl) aminocarboxylate 8 d (40 mg, white solid), at a yield of 12%. (0178) MS m/z (ESI): 304 [M+1]. |
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