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Structure of 2632-65-7

Chemical Structure| 2632-65-7

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Product Details of [ 2632-65-7 ]

CAS No. :2632-65-7
Formula : C10H14N2
M.W : 162.23
SMILES Code : NC1=CC=C(N2CCCC2)C=C1
MDL No. :MFCD00156245
InChI Key :URAARCWOADCWLA-UHFFFAOYSA-N
Pubchem ID :808841

Safety of [ 2632-65-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 2632-65-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 6
Fraction Csp3 0.4
Num. rotatable bonds 1
Num. H-bond acceptors 0.0
Num. H-bond donors 1.0
Molar Refractivity 55.49
TPSA ?

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

29.26 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.8
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

2.88
Log Po/w (WLOGP)?

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

1.5
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.

1.71
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

1.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.9

Water Solubility

Log S (ESOL):?

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

-2.96
Solubility 0.176 mg/ml ; 0.00109 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.

-3.15
Solubility 0.114 mg/ml ; 0.000701 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

-2.47
Solubility 0.546 mg/ml ; 0.00337 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

No
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.

-5.24 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.

2.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

1.0 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)

1.0

Application In Synthesis of [ 2632-65-7 ]

* 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 [ 2632-65-7 ]

[ 2632-65-7 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 2632-65-7 ]
  • [ 6727-73-7 ]
  • [ 855624-33-8 ]
  • 2
  • [ 2632-65-7 ]
  • [ 98-88-4 ]
  • benzoic acid-(4-pyrrolidino-anilide) [ No CAS ]
  • 3
  • [ 2632-65-7 ]
  • [ 95-48-7 ]
  • [ 109595-59-7 ]
  • 4
  • [ 2632-65-7 ]
  • 1-(4-imonio-cyclohexa-2,5-dienylidene)-pyrrolidinium; diperchlorate [ No CAS ]
  • 5
  • [ 10220-22-1 ]
  • [ 2632-65-7 ]
YieldReaction ConditionsOperation in experiment
85% With palladium 10% on activated carbon; hydrogen; In ethanol; at 20℃; for 9h;Inert atmosphere; Schlenk technique; General procedure: The nitrophenyl analogue 7a-7e (7.5 mmol) was dissolved in ethanol (50 mL), and to this solution was added 10% Pd/C (0.2 g). The reaction mixture was stirred at room temperature under an atmosphere of H2 for 9 h. After completion of the reaction, the resulting mixture was filtered through Celite. The filtrate was concentrated under high vacuum to afford the desired aniline derivatives 8a-8e.
80% With ammonium hydroxide; sodium dithionite; In water; for 0.25h;Reflux; General procedure: To a solution of 1-(substituted) 4-nitrobenzene IVa,b,e,f(0.01 mol) in NH4OH (20 mL, 30%), a solution of sodium dithionite(7 g, 0.04 mol) in water (30 mL) was quickly added, the reactionmixture was refluxed for 15 min. After cooling, the crude productwas filtered, washed and crystallized from methylene chloride toyield target compounds Va,b,e,f. 4-(Pyrrolidin-1-yl) aniline Vb Yield 80% as yellow oil, (as reported) [66] .
59.28% With iron; ammonium chloride; In ethanol; water; at 90℃; To a stirred solution of 580 1-(4-nitrophenyl)pyrrolidine (0.60 g, 3.121 mmol, 1.0 eq) in 6 EtOH (20 mL) was added Fe(0) (1.395 g, 24.971 mmol, 8.0 eq) and a solution of 67 NH4Cl (1.67 g, 31.210 mmol, 10.0 eq) at rt. The resulting mixture was heated at 90 C. for 60 min. The progress of reaction was monitored by LCMS. The reaction mixture was filtered through celite the residue was washed with EtOH (50 mL) the filtrate was concentrated and the residue was dissolved in 19 EtOAc (50 mL), washed with water (2×50 mL), dried over Na2SO4, and concentrated to afford 583 4-(pyrrolidin-1-yl)aniline (0.30 g, 59.28%) as brown viscous. (0608) LCMS: 163.3 [M+1]+
55% With sodium hydroxide;Pd on carbon; In ethanol; acetic acid; ethyl acetate; 2) 4-(Pyrrolidin-1-yl)-phenylamine (8). To a solution of 7 in ethanol (20 mL) was added 10 wt % Pd on carbon (Degussa) (25 mg, 23 mol). Glacial acetic acid (2-3 drops) was added to the reaction. The reaction was placed under a H2 atmosphere and stirred for 16 hours, after which the reaction mixture was filtered through a pad of celite. The filtrate was evaporated, and the residue then dissolved in ethyl acetate (20 mL) and washed with 2N HCl (aq. 15 mL). The aqueous phase was isolated and then basified by the addition of 2N NaOH (aq. 20 mL). The aqueous layer was extracted with ethyl acetate (20 mL*2). The ethyl acetate extracts were dried over anhydrous magnesium sulfate, filtered, and evaporated to give crude 8 as a yellow oil (642 mg, 55% for 2 steps).
With hydrogen; In ethyl acetate; at 50℃; under 7500.75 Torr; l-(4-nitrophenyl)pyrrolidine was dissolved in ethyl acetate (0.05 M) and reduced with H-cube at 50C, 10 bar. Reduction was completed in 2 cycles. The solvent was evaporated off in vacuo, and the crude purified using column chromatography to afford the product. 1H NMR (400 MHz, DMSO-d6) 6 (ppm): 6.49 (d, J=8.4 Hz, 2H), 6.34 (d, J-8.4 Hz), 4.24 (s, 2H), 3.07 (m, 4H), 1.87 (m, 4H). LC-MS: m/z 163 (M+H).
With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; General procedure: A suspension of 1.01 g (5 mmol) 1-bromo-4-nitrobenzene, 1.5 g K2CO3, 0.59 mL (6 mmol) piperidine in 10 mL of DMF was heated to reflux overnight. Upon cooling, the reaction mixture was dilute with water, extracted with EA, and the organic layer was washed with water, followed by saturated NaCl aqueous solution, dried over anhydrous Na2SO4 and purified by flash chromatography (PE : EA = 50:1, 30:1) to afford 902 mg (87%) yellow solid. The solid was dissolved in methanol, 90 mg Pd-C (10%) was added and stirred under hydrogen overnight at room temperature and then filtered through Celite and concentratedin vacuo. The crude product was purified by flash chromatography (PEEA = 5:1) to afford 4l? 0.706 g 99%.
With 5%-palladium/activated carbon; hydrogen; In ethanol; water; at 20℃; General procedure: The substituted nitro compound 11 (1 equiv in a mixture of EtOH-H2O, 95:5, 20mL) was treated with 10% Pd-carbon (5% w/w). The reaction was subjected to hydrogenation under hydrogen gas at room temperature and the reaction was monitored by TLC. After completion of the reaction, the mixture was filtered through a Celite bed and concentrated in a vacuum to afford product 12.

  • 6
  • 1-(4-nitroso-phenyl)-pyrrolidine; hydrochloride [ No CAS ]
  • [ 2632-65-7 ]
  • 7
  • [ 110-56-5 ]
  • [ 106-50-3 ]
  • [ 2632-65-7 ]
  • 8
  • [ 109-99-9 ]
  • [ 106-50-3 ]
  • [ 2632-65-7 ]
  • [ 50771-64-7 ]
  • 9
  • [ 2632-65-7 ]
  • [ 191880-48-5 ]
  • 5,17-bis(N-(4-(pyrrolidin-1-yl)phenyl)aminocarbonyl)-25,26,27,28-tetrapropoxycalix<4>arene [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% General procedure: To a flame-dried 25 mL round bottom flask was charged activated Mg (7.5 mmol, 1.5 eq.) and 5 mL anhydrous THF. To this suspension was added 2 drops of 1,2-dibromoethane. After 5 min, a solution of Aryl bromide (5 mmol, 1.0 eq.) in 5 mL anhydrous THF was slowly added to the suspension of Mg at room temperature. The reaction was mildly exothermic. The Grignard reagent was titrated and 1 mmol of this reagent was added to a flame-dried reaction vial. The solution was diluted with 3 mL anhydrous toluene and after cooling to the target temperature T, a solution of oxaziridine (1.2 mmol, 1.2 eq.) in 1 mL anhydrous toluene was added. The reaction was maintained at the targeted temperature T for time t before being quenched with saturated aqueous NH4Cl. (The actual temperature/reaction time is listed for each substrate.)
The following 4-substituted anilines were prepared: 4-azocan-1-ylphenylamine N-cyclohexyl-N-methylbenzene-1,4-diamine 4-pyrrolidin-1-ylphenylamine 4-(2,5-dimethylpyrrolidin-1-yl)phenylamine 4-(3,6-dihydro-2H-pyridin-1-yl)phenylamine ...
Representative examples of suitable p-phenylenediamine compounds are: 4-N,N-dimethylamino aniline, 4-N,N-diethylamino aniline, 4-(N-ethyl,N-hydroxyethyl)amino aniline, ... 2,6-dimethyl,4-(N,N-dihydroxyethyl)amino aniline, 2,3,5,6-tetramethyl-4-N,N-diethylamino aniline, 4-piperidino aniline, 4-morpholino aniline, 4-pyrrolidyl aniline, 4-imidazolo aniline.
Representative examples of suitable p-phenylenediamine compounds are: ... 2,6-dimethyl,4-(N,N-dihydroxyethyl)amino aniline, 2,3,5,6-tetramethyl-4-N,N-diethylamino aniline, 4-piperidino aniline, 4-morpholino aniline, 4-pyrrolidyl aniline, 4-imidazolo aniline.
With hydroxylamine hydrochloride; sodium hydroxide; In water; at 20 - 100℃; for 5h; General procedure: To a stirred solution of the corresponding 3-phenyl-3-oxopropanenitrile (1 equiv.) in water (0.7M) was added aqueous sodium hydroxide (2 equiv.) solution and hydroxylamine hydrochloride (1.1 equiv.) at room temperature. The resulting reaction mixture was stirred at 100 C for 5 h. After completion of starting material, the reaction mixture was cooled to room temperature and precipitated solid was collected by filtration and dried to give the desired product.

  • 13
  • [ 123-75-1 ]
  • [ 106-40-1 ]
  • [ 2632-65-7 ]
  • 14
  • [ 342801-20-1 ]
  • [ 2632-65-7 ]
  • (8-Isopropyl-7-methoxy-quinazolin-2-yl)-(4-pyrrolidin-1-yl-phenyl)-amine [ No CAS ]
  • 15
  • [ 342801-27-8 ]
  • [ 2632-65-7 ]
  • (8-Cyclopentyl-7-methoxy-quinazolin-2-yl)-(4-pyrrolidin-1-yl-phenyl)-amine [ No CAS ]
  • 16
  • 4-(1-oxy-pyrrolidin-1-yl)-phenylamine [ No CAS ]
  • [ 2632-65-7 ]
  • 17
  • [ 2632-65-7 ]
  • [ 7693-46-1 ]
  • [ 916646-21-4 ]
  • 19
  • [ 2632-65-7 ]
  • 4-{6-amino-5-[(2-methanesulfonylamino-ethoxyimino)-methyl]-pyrimidin-4-yl}-piperazine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide [ No CAS ]
  • 20
  • [ 2632-65-7 ]
  • 4-{6-amino-5-[(2-morpholin-4-yl-ethoxyimino)-methyl]-pyrimidin-4-yl}-piperazine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide [ No CAS ]
  • 21
  • [ 2632-65-7 ]
  • 4-{6-amino-5-[(2-morpholin-4-yl-2-oxo-ethoxyimino)-methyl]-pyrimidin-4-yl}-piperazine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide [ No CAS ]
  • 22
  • [ 2632-65-7 ]
  • 1-(4-pyrrolidino-phenyl)-hexahydro-azocin-5-one [ No CAS ]
  • 23
  • [ 2632-65-7 ]
  • 6-hydroxy-1-(4-pyrrolidino-phenyl)-octahydro-azonin-5-one [ No CAS ]
  • 24
  • [ 2632-65-7 ]
  • [ 854859-04-4 ]
  • 26
  • [ 898270-94-5 ]
  • [ 2632-65-7 ]
  • 2-tert-butyl-5-phenyl-4-[(4-pyrrolidin-1-ylphenyl)amino]isothiazol-3(2H)-one 1,1-dioxide [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With triethylamine; In N,N-dimethyl-formamide; acetonitrile; at 120℃; for 1h;Microwave irradiation; Example 16; 2-felambdaf-ButyI-5-phenyl-4-[(4-pyrrolidin-l-ylphenyl)amino]isothiazoI-3(2H)-one 1,1-dioxide; A mixture of 2-t°rt-butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (0.150g, 0.500mmol), (4-pyrrolidin-l-ylrhohenyl)amine (0.08 Ig, 0.500mmol) and TEA (0.070ml, 0.500mmol) in MeCN (2ml) and DMF (ImI) was heated in a microwave reactor at 120C for 45mins. TEA (0.070ml, 0.500mmol) was added and the mixture was heated at 120C for 5 15mins. The precipitate from the reaction mixture was isolated by filtration and washed with MeCN. The crude product was dissolved in MeOH and purified by silica gel column chromatography using 15-100% EtOAc in petroleum ether 40-60C as eluent, to give the title compound (0.146g, 69%).
  • 27
  • [ 2632-65-7 ]
  • [ 7693-46-1 ]
  • (4-Pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride [ No CAS ]
YieldReaction ConditionsOperation in experiment
In tetrahydrofuran; at 20℃; for 1h; a. (4-Pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
In tetrahydrofuran; at 20℃; for 1h; To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
In tetrahydrofuran; at 20℃; for 1h; a. (4-Pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)-.
In tetrahydrofuran; at 20℃; for 1h; To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
In tetrahydrofuran; at 20℃; for 1h; To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2*10 mL) and then with anhydrous DCM (3*10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
In tetrahydrofuran; at 20℃; for 1h; EXAMPLE 74; 4-{7-[2-(2-Oxo-pyrrolidin-1-yl)-ethoxy]-quinazolin-4-yl}-piperidine-1-carboxylic acid (4-pyrrolidin-1-yl-phenyl)-amide; a). (4-Pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride; To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2×10 mL) and then with anhydrous DCM (3×10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)+.
In tetrahydrofuran; at 20℃; for 1h; EXAMPLE NO. 49; 1-[1-(6,7-Dimethoxy-quinazolin-4-yl)-pyrrolidin-3-yl]-3-(4-pyrrolidin-1-yl-phenyl)-urea (Compound No. 49); a. (4-Pyrrolidin-1-yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochloride; To a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin-1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THF. After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2×10 mL) and then with anhydrous DCM (3×10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, 1H), 8.32 (d, 2H), 7.73 (d, 2H), 7.60 (d, 2H), 7.48 (d, 2H), 3.86-3.68 (bs, 4H), 2.35-2.24 (bs, 4H). LC/MS (ESI): 328 (MH)-.
In tetrahydrofuran; at 20℃; for 1h; Example 18; 4-[6-Amino-5-(methoxyimmo-methyl)-pyrimidin-4-yl]-piperazine-l-carboxylic acid (4-pyrrolidin- 1 -yl-phenyl)-amide; a. (4-Pyrrolidin- 1 -yl-phenyl)-carbamic acid 4-nitro-phenyl ester hydrochlorideTo a stirred solution of 4.9 g (30.4 mmol) of 4-pyrrolidin- 1-yl-phenylamine in 70 mL of anhydrous THF at room temperature, was added dropwise a solution of 6.4 g (32 mmol) of 4-nitrophenyl chloroformate in 16 mL of anhydrous THE After the addition was complete, the mixture was stirred for 1 h and then filtered. The precipitate was washed first with anhydrous THF (2 x 10 mL) and then with anhydrous DCM (3 x 10 mL) and dried in vacuo to yield 10 g of an off-white solid. 1H-NMR (300 MHz, CD3OD): 10.39 (s, IH), 8.32 (d, 2H), 7.73 (d, 2H), 7.60

  • 28
  • [ 643087-44-9 ]
  • [ 2632-65-7 ]
  • C22H24N6O [ No CAS ]
  • 29
  • [ 2632-65-7 ]
  • [ 348626-23-3 ]
YieldReaction ConditionsOperation in experiment
Example 18 5-Chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide The compound 5-chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide is obtained from 4-pyrrolidin-1-ylaniline (Reppe et al., Justus Liebigs Ann. Chem.; 596; 1955; 151) in analogy to Example 17. IC50=40 nM; M.p.: 216 C.; Rf (SiO2, toluene/ethyl acetate 1:1)=0.31 [precursor: 0.0].
Example 18 5-Chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide The compound 5-chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide is obtained from 4-pyrrolidin-1-ylaniline (Reppe et al., Justus Liebigs Ann. Chem.; 596; 1955; 151) in analogy to Example 17. IC50=40 nM; M.p.: 216 C.; Rf (SiO2, toluene/ethyl acetate 1:1)=0.31 [precursor: =0.0].
Example 18 5-Chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide Analogously to Example 17, starting from <strong>[2632-65-7]4-pyrrolidin-1-yl-aniline</strong> (Reppe et al., Justus Liebigs Ann. Chem.; 596; 1955; 151) the compound 5-chloro-N-({(5S)-2-oxo-3-[4-(1-pyrrolidinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide is obtained. IC50=40 nM; m.p.: 216 C.; Rf value (SiO2, toluene/ethyl acetate 1:1)=0.31 [starting material:=0.0].
  • 30
  • [ 2632-65-7 ]
  • [ 131543-46-9 ]
  • [ 1172626-91-3 ]
  • 31
  • [ 2632-65-7 ]
  • C20H20N6O2 [ No CAS ]
  • [ 1144072-79-6 ]
  • 32
  • [ 2632-65-7 ]
  • [ 1233178-95-4 ]
  • [ 1232398-54-7 ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; In 2-methoxy-ethanol; at 180℃; for 0.666667h;Microwave irradiation; 7-(3-Chloro-phenyl)-2-methanesulfmyl-pyrrolo[2,l-f][l,2,4]triazine (125.0 mg, 0.0004284 mol), N,N-Diisopropylethylamine (0.112 mL, 0.000643 mol) and 4-Pyrrolidin-l-yl- phenylamine (139 mg, 0.000857 mol) were dissolved in 2-Methoxyethanol (3.01 mL) and The reaction was microwaved on 300 watts , 1800C for 40 minutes or until HPLC showed consumption of starting material. The reaction mixture was then reduced en vacuo and the product was isolated and purified by Gilson prep HPLC to afford 26.91 mg of [7-(3- Chloro-phenyl)-pyrrolo[2, 1 -fj [ 1 ,2,4]triazin-2-yl]-(4-pyrrolidin- 1 -yl-phenyl)-amine as a lyophilized powder. (M+H)=390.09. 1H NMR (400 MHz, CDCl3) delta 9.63 (s, IH), 8.63 (s, IH), 8.32 (s, IH), 7.84 (m, IH), 7.76 (d, 2H, J = 8.93 Hz), 7.48 (m, 2H), 7.34 (d, 2H, J = 8.93 Hz), 7.21 (m, IH), 7.18 (m, IH), 3.66 (m, 4H), 2.25 (m, 4H).
  • 33
  • [ 2632-65-7 ]
  • [ 405175-13-5 ]
  • [ 1002158-46-4 ]
  • 34
  • [ 1258532-14-7 ]
  • [ 2632-65-7 ]
  • 35
  • [ 2018-66-8 ]
  • [ 2632-65-7 ]
  • [ 1286716-55-9 ]
 

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