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Structure of 127199-54-6

Chemical Structure| 127199-54-6

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Product Details of [ 127199-54-6 ]

CAS No. :127199-54-6
Formula : C10H20N2O2
M.W : 200.28
SMILES Code : O=C(OC(C)(C)C)N[C@@H]1CNC[C@@H]1C
MDL No. :MFCD18432662
InChI Key :BKITXDSDJGOXPN-JGVFFNPUSA-N
Pubchem ID :11138119

Safety of [ 127199-54-6 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 127199-54-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 14
Num. arom. heavy atoms 0
Fraction Csp3 0.9
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 2.0
Molar Refractivity 59.3
TPSA ?

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

50.36 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.4
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

1.13
Log Po/w (WLOGP)?

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

0.74
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.

0.86
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

0.64
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.15

Water Solubility

Log S (ESOL):?

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

-1.53
Solubility 5.92 mg/ml ; 0.0295 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-1.78
Solubility 3.31 mg/ml ; 0.0165 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Very 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

-1.92
Solubility 2.39 mg/ml ; 0.0119 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.

-6.72 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

0.0
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.

0.0 alert
Brenk?

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

0.0 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)

2.97

Application In Synthesis of [ 127199-54-6 ]

* 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 [ 127199-54-6 ]

[ 127199-54-6 ] Synthesis Path-Downstream   1~19

  • 1
  • [ 127199-52-4 ]
  • [ 127199-54-6 ]
YieldReaction ConditionsOperation in experiment
palladium on charcoal; In methanol; hydrogen; (3S,4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidine A mixture of 60.0 g of (3S,4S)-1-benzyl-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidine, 6.00 g of 5% palladium on charcoal, and 500 ml of methanol was hydrogenated in an autoclave under 5 kgf/cm2 hydrogen pressure at 40 C. for 3 hours. The catalyst was removed by filtration, and then the filtrate was concentrated under reduced pressure. The product was recrystallized from n-hexane to give 38.0 g of colorless needles, m.p. 83-85 C. NMR spectrum delta(CDCl3) ppm: 0.97 (3H, d, J=7 Hz), 1.45 (9H, s), 2.20-2.30 (1H, m), 2.44-2.53 (1H, m), 2.70 (1H, dd, J=11.5, 4.5 Hz), 3.15 (1H, dd, J=11, 7.5 Hz), 3.20-3.30 (1H, m), 4.05-4.20 (1H, m), 4.62 (1H, br-s)
With potassium hydroxide; ammonium formate;palladium charcoal; In methanol; water; Example 29 Synthesis of 3(S)-[(t-butoxycarbonyl)amino]-4(S)-methylpyrrolidine Into 60 ml of methanol were dissolved 5.27 g of 1-benzyl-3(S)-[(t-butoxycarbonyl)amino]-4(S)-methylpyrrolidine, and, after 12 ml of water containing 0.28 g of suspended 10% palladium charcoal and 4.57 g of dissolved ammonium formate was added, the mixture was refluxed for 1 hour at 80C. The catalyst in reaction liquor was filtered off and the filtrate was concentrated. After 12.0 g of potassium hydroxide was added to the residue, water and ether were added to extract. The ether layer was separated, washed with saturated saline solution, dried over anhydrous Glauber's salt, and then concentrated. The residue thus obtained was recrystallized from n-hexane to obtain 3.19 g of aimed product as white needle-like crystals. Melting point: 84-85C Specific rotation: [alpha] [20/D ] = +18.9 (c=1.47, chloroform)
  • 2
  • [ 127199-54-6 ]
  • [ 167888-38-2 ]
  • [ 181216-53-5 ]
  • 3
  • [ 847233-56-1 ]
  • [ 127199-54-6 ]
  • 7-((3S,4S)-3-tert-Butoxycarbonylamino-4-methyl-pyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]
  • 4
  • [ 127199-54-6 ]
  • [ 215999-32-9 ]
  • 7-((3S,4S)-3-tert-Butoxycarbonylamino-4-methyl-pyrrolidin-1-yl)-6-fluoro-1-((1R,2S)-2-fluoro-cyclopropyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]
  • 5
  • [ 127199-54-6 ]
  • [ 767306-94-5 ]
  • 7-((3S,4S)-3-tert-Butoxycarbonylamino-4-methyl-pyrrolidin-1-yl)-6-fluoro-1-(4-hydroxy-phenyl)-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid [ No CAS ]
  • 6
  • [ 127199-54-6 ]
  • [ 103995-00-2 ]
  • 7-((3S,4S)-3-tert-Butoxycarbonylamino-4-methyl-pyrrolidin-1-yl)-6-fluoro-1-(4-hydroxy-phenyl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]
  • 7
  • [ 127199-54-6 ]
  • C19H12BF4NO5 [ No CAS ]
  • 7-((3S,4S)-3-tert-Butoxycarbonylamino-4-methyl-pyrrolidin-1-yl)-6-fluoro-1-(4-hydroxy-phenyl)-8-methoxy-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid [ No CAS ]
  • 8
  • [ 127199-54-6 ]
  • 7-[3(S)-amino-4(S)-methyl-1-pyrrolidinyl]-6-fluoro-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid [ No CAS ]
  • 9
  • [ 127199-54-6 ]
  • 7-[3(S)-amino-4(S)-methyl-1-pyrrolidinyl]-6-fluoro-1-[2(S)-fluoro-1(R)-cyclopropyl]-1,4-dihydro-8-methoxy-4-oxoquinoline-3-carboxylic acid [ No CAS ]
  • 10
  • [ 127199-54-6 ]
  • 5-amino-7-((3S,4S)-3-amino-4-methyl-1-pyrrolidinyl)-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid [ No CAS ]
  • 11
  • [ 24424-99-5 ]
  • [ 127199-54-6 ]
  • 12
  • [ 178899-79-1 ]
  • [ 127199-54-6 ]
  • 13
  • [ 149598-21-0 ]
  • [ 127199-54-6 ]
  • 14
  • [ 149598-23-2 ]
  • [ 127199-54-6 ]
  • 15
  • [ 178755-12-9 ]
  • [ 127199-54-6 ]
  • 16
  • ›5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid-O3,O4!difluoroborate [ No CAS ]
  • [ 107-06-2 ]
  • [ 127199-54-6 ]
  • [ 181216-53-5 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; N-ethyl-N,N-diisopropylamine; In methanol; water; dimethyl sulfoxide; 5-Amino-7-[(3S,4S)-3-tert-butoxycarbonylamino-4-methyl-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid A mixture of 1.01 g of ?5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid-O3,O4!difluoroborate, 0.71 g of (3S,4S)-3-tert-butoxycarbonylamino-4-methylpyrrolidine, 0.51 ml of N,N-diisopropylethylamine, and 4.04 ml of dimethylsulfoxide was stirred at outer temperature of 30 C. for 64 hours. Water was added to the reaction mixture under ice cooling, and the mixture was extracted with methylene chloride. The methylene chloride layer was washed successively with water and brine, and then dried and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel, methylene chloride: methanol=100:1), and crystals obtained were washed with diethyl ether to give 0.58 g of yellowish orange crystals. A mixture of 0.58 g of the crystals obtained, 0.58 ml of triethylamine, 11.6 ml of methanol, and 5.8 ml of 1,2-dichloroethane was heated under reflux for 3 hours. The reaction mixture was concentrated under reduced pressure, and then, the residue was added with water and crystals precipitated were collected by filtration. The crystals were washed with water to give 0.52 g of yellow crystals. The crystals were recrystallized from acetone-diisopropyl ether to give yellow crystals, m.p. 178.5-180 C. Specific rotation [alpha]D20 -141.9 (c=0.1, CHCl3)
  • 17
  • [ 127199-54-6 ]
  • [ 112811-72-0 ]
  • 7-[3(S)-[(t-butoxycarbonyl)amino]-4(R)-methyl-l-pyrrolidinyl]-l-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 1,8-diazabicyclo[5.4.0]undec-7-ene; citric acid; In chloroform; water; acetonitrile; Example 34 Synthesis of 7-[3(S)amino-4(S)-methyl-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxyic acid hydrochloride To 20 ml of acetonitrile were added 2.00 g of 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid, 2.15 g of 3(S)-[(t-butoxycarbonyl)amino]-4(S)-methyl-pyrrolidine and 1.09 g of DBU, and the mixture was refluxed for 7 hours at 100C. The reaction liquor was concentrated and the residue was dissolved into 100 ml of chloroform, which was washed with 10% aqueous solution of citric acid, water and saturated saline solution in this order, dried over anhydrous Glauber's salt, and then concentrated. The residue was purified through silica gel column (elution solvent, chloroform:methanol: concentrated aqueous ammonia=20:5:1) to obtain 3.06 g of 7-[3(S)-[(t-butoxycarbonyl)amino]-4(S)-methyl-l-pyrrolidinyl]-l-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylic acid.
  • 18
  • [ 174637-91-3 ]
  • [ 127199-54-6 ]
  • [ 869956-22-9 ]
YieldReaction ConditionsOperation in experiment
70.2% [Referential Example 25] Ethyl 4-[(3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidin-1-yl]-2,5-difluoro-3-methylbenzoate A solution of (3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidine (1.80 g, 8.97 mmol), ethyl 3-methyl-2,4,5-trifluorobenzoate (2.18 g, 10.0 mmol), and 1,8-diazabicyclo[5.4.0]undeca-7-ene (DBU) (2.24 mL, 15 mmol) in dimethyl sulfoxide (20 mL) was stirred under a nitrogen atmosphere at an external temperature of 60C for 70 hours. The temperature of the mixture was cooled to room temperature. The resultant mixture was poured to a 10% aqueous citric acid solution, followed by extraction with ethyl acetate (200 mL * 3), washing by water (200 mL), saturated aqueous sodium hydrogencarbonate (150 mL), and saturated brine (150 mL), and dried over anhydrous sodium magnesium. After filtration, the filtrate was concentrated under reduced pressure. The obtained residue was purified through silica gel column chromatography (n-hexane: ethyl acetate = 6:1), to thereby yield the title compound as colorless crystals (2.51 g, 70.2%). 1H-NMR(400MHz, CDCl3)delta ppm:1.07(3H,d, J=7.0Hz),1.38(3H,t, J=7.OHz),1.47(9H,s),2.20(3H, d,J=2.5Hz),2.50-2.57(1H,m),3.06-3.12(1H,m), 3.16(1H,dd,J=3.0,10.0Hz),3.39-3.44(1H,m),3.73-3.77(1H,m), 4.27-4.33(1H,m),9.36(2H,q,J=7.0Hz), 4.71(1H,br),7.42(1H,dd,J=7.0,13.0Hz). MS (ESI)m/z:399 (M++1).
  • 19
  • [ 869956-21-8 ]
  • [ 127199-54-6 ]
YieldReaction ConditionsOperation in experiment
72.1% [Referential Example 22] (3S,4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidine A suspension of (3S,4S)-1-benzyloxycarbonyl-3-(tert-butoxycarbonyl)amino-4-(phenylsulfanil)methylpyrrolidine (7.97 g, 18.01 mmol) and Raney nickel (R100) (50 mL) in ethanol (150 mL) was stirred in a hydrogen atmosphere under an ordinary pressure at an external temperature of 50C for 18 hours. The temperature of the resultant mixture was cooled to room temperature. Thereafter, insoluble matter was removed through filtration by use of Celite, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in ethanol (100 mL), and a 10% palladium carbon catalyst (2.0 g) was added to the solution, followed by stirring in a hydrogen atmosphere under an ordinary pressure at room temperature for 3 hours. After insoluble matter was removed through filtration by use of Celite, the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in diethyl ether. The solution was washed by a 1 mol/L aqueous sodium hydroxide solution, dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and dried under reduced pressure, to thereby yield the title compound as colorless crystals (2.602 g, 72.1%). 1H-NMR(400MHz,CDCl3)delta ppm:0.97(3H,d,J=7.0Hz),1.45(9H,s),1.79(1H,br),2.21-2.28(1H,m),2.48(1H,dd,J=8.5,10.5),2.70(1H,dd,J=4.5,11.0Hz),3. 15(1H,dd,J=8.0,10.5Hz),3.25(1H,dd,J=6.5,11.0Hz),4.10(1H,br),4.63(1H,br). IR(ATR)nu cm-1:3365,3217,2956,1678,1520,1365,1244,1167, 1061,906,627. MS(FAB)m/z(%):201(93,M++1),145(100,M+-55),101(8,M+-99). HRMS(FAB)m/z:Calcd for C10H21O2N2:201.1603.Found:201.1602.
 

Historical Records

Technical Information

Categories

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[ 127199-54-6 ]

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[ 127199-54-6 ]

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