Structure of 1211443-61-6
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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. : | 1211443-61-6 |
Formula : | C14H17ClN4O |
M.W : | 292.76 |
SMILES Code : | O=C(C1=CC2=CN=C(Cl)N=C2N1C3CCCC3)N(C)C |
MDL No. : | MFCD20527881 |
InChI Key : | PMDDQOHZLBZUSO-UHFFFAOYSA-N |
Pubchem ID : | 58315432 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H317-H412 |
Precautionary Statements: | P273-P280 |
Num. heavy atoms | 20 |
Num. arom. heavy atoms | 9 |
Fraction Csp3 | 0.5 |
Num. rotatable bonds | 3 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 0.0 |
Molar Refractivity | 78.81 |
TPSA ? Topological Polar Surface Area: Calculated from |
51.02 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.98 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.54 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.9 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
2.01 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
1.94 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.47 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.39 |
Solubility | 0.119 mg/ml ; 0.000407 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.26 |
Solubility | 0.161 mg/ml ; 0.000552 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-3.54 |
Solubility | 0.0846 mg/ml ; 0.000289 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) |
Yes |
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) |
Yes |
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) |
Yes |
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 |
-6.28 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 |
0.0 |
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<0.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
2.26 |
* 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 |
---|---|---|
96.4% | Toluene (500 mL) and 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine- 6-carboxylic acid (lOO.Og, 0.377 moles) were charged into 2L 4N RB flask under CaCb guard tube condition, and stirred of 5-10 min to get cream colored suspension. Added N,N-dimethylformamide (10.0 mL) and stirred for 5-10 min. Charged thionyl chloride (67.2g, 0.566 moles) to the reaction mass and stir for 5-l0min. at 25-35C to get pale brown colored suspension. Reaction mass was heated to 75-80C and stirred for 3-4h. After completion of reaction (by HPLC), cooled to 0-5C to become brown colored suspension. Mixture of 2M solution of dimethylamine in THF (470.0 mL, 0.942 moles) and triethylamine (l22.0g, 1.20 moles) added dropwise to the reaction mass through addition funnel by maintaining the mass temperature at 0-10C and then stirred for 5-10 min. Reaction mass temperature was raised to 25-35 C and stirred for 1 -2h. After completion of reaction (by HPLC) solvent was distilled off under vacuum on rotavapor at 60-65 C to yield brown colored crude. The resulting crude was dispersed in DM water (1000.0 mL) and stirred for lh at 25-35C to get cream colored suspension. Product was filtered under suction with the help of DM water (500 mL). The wet product was dried in hot air oven at 60-65 C for 6h to afford the title compound. Wt. of the product l06.0g (96.4% by theory). Purity by HPLC > 99.0%. | |
92% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 0 - 25℃; | A three-necked flask was charged with 5 (26.57 g, 100 mmol)And N, N-dimethylformamide (133 mL) were added, the mixture was cooled to 0-5 C while stirring, EDCI (23.00 g, 120 mmol) was added,A solution of dimethylamine in tetrahydrofuran (2.0 M, 75 mL, 150 mmol) was added. Triethylamine (20.24 g, 200 mmol) was added dropwise and the mixture was stirred at 20-25 C for 6-8 hours.The reaction mixture was extracted with ethyl acetate (133 mL) three times and the combined organic phases washed twice with brine (133 mL), dried over anhydrous sodium sulfate and concentrated. Compound A was isolated by column chromatography on a mixture of dichloromethane and methanol (26.93 g , 92%). |
92% | With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In tetrahydrofuran; N,N-dimethyl-formamide; at 0 - 25℃; | <strong>[1211443-58-1]2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid</strong> (26.57 g, 100 mmol) and N,N-dimethylformamide (133 mL) were added to a three-neck flask. stir well, then cool to 0 ~ 5 C, add EDCI (23.00g, 120mmol), A solution of dimethylamine tetrahydrofuran (2.0 M, 75 mL, 150 mmol) was added, and triethylamine (20.24 g, 200 mmol) was added dropwise, and the mixture was reacted at 20 to 25 C for 6 to 8 hours. The reaction was extracted with ethyl acetate (133 mL) three times.The organic phase was washed twice with saturated brine (133 mL).After concentration, it was beaten with isopropyl alcohol and water, and the solid was separated by filtration. drying in vacuo to gave 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (26.93 g, 92%). |
79% | With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In ethanol; N,N-dimethyl-formamide; for 0.5h; | 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxylic acid (1.07g, 4.03mmol), HBTU (1.53g, 4.03mmol) and diisopropylethylamine (2mL, 12.1mmol) are dissolves in dimethylformamide (20 mL). 2 M solution of dimethylamine in ethanol (2.4mL, 4.8 mmol) is added and the mixture is stirred for 30 minutes to achieve complete conversion. The reaction mixture is diluted with ethyl acetate and washed with saturated aqueous sodium hydrogen carbonate, water, then brine. The organic phase is dried (Na2SC^), filtered and concentrated. Purification by chromatography on silicagel(ethyl acetate :heptane) provides 2-Chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6- carboxylic acid dimethylamide (927mg,79% yield) MS(ESI) m/z 293.1 (M+H)+ |
78.1% | Compound VII (719.1 g, 2.70 mol, 1.0 e.q.) was added to 6 L DMF in a 10 L four-necked flask.At 0 C, DIPEA (1399.2 g, 10.83 mol, 4.0 e.q.) was added at -20 C.HATU (2566.6g, 6.75mol, 2.5e.q.) was added in batches, and the reaction was stirred for 0.5 h.At 5 C, dimethylamine methanol solution (2.5 M) 1.62 L was added dropwise, and the reaction was stirred for 1 h.LC-MS showed the reaction was completed.The reaction solution was poured into 12 L of ice water, stirred, and extracted with ethyl acetate.Wash with saturated aqueous sodium carbonate solution, wash with water, wash with dilute hydrochloric acid, and dry.The solvent was distilled off under reduced pressure, petroleum ether was filtered to obtain compound VIII as a yellow solid 617.4g,The yield was 78.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | A stirring solution of 6-chloro-l-cyclopentyl-l,5,7-triaza-lH-indene-2-carboxylic acid (199 mg, 0.75 mmol) and triethylamine (631 L, 4.5 mmol) in DMF (4 mL) was treated with HBTU (427 mg, 1.13 mmol) in one portion. The resulting mixture was stirred at room temperature for 30 minutes. Dimethylamine hydrochloride salt (122 mg, 1.50 mmol) was added in one portion and the resulting solution was stirred at room temperature overnight. Next morning, LCMS analysis indicated clean conversion to product (m/z = 293.4). The reaction mixture was diluted with EtOAc, transferred to a separatory funnel and washed with 0.1 N HC1 aqueous and brine. The organics were dried over anhydrous MgS04, filtered and concentrated to yield the crude product. This was purified on a S1O2 column using a hexanes/EtOAc gradient eluent. The fractions containing the product were concentrated to yield 215 mg (0.74 mmol, 99 %). LC/MS - HPLC (254 nm) - Rt 2.90 min. MS (ESI) m/z 293.4 [M+ + H+]. |
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