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Structure of 15910-91-5

Chemical Structure| 15910-91-5

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Product Details of [ 15910-91-5 ]

CAS No. :15910-91-5
Formula : C5H9NO
M.W : 99.13
SMILES Code : O=C(C1(C)CC1)N
MDL No. :MFCD11845570
InChI Key :HLCXNVMIINTAOG-UHFFFAOYSA-N
Pubchem ID :13002936

Safety of [ 15910-91-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P261-P280-P305+P351+P338

Computational Chemistry of [ 15910-91-5 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 26.68
TPSA ?

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

43.09 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.13
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

-0.04
Log Po/w (WLOGP)?

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

0.21
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.

0.1
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

0.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.4

Water Solubility

Log S (ESOL):?

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

-0.36
Solubility 42.9 mg/ml ; 0.433 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.

-0.41
Solubility 38.2 mg/ml ; 0.385 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

-0.59
Solubility 25.2 mg/ml ; 0.254 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

No
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.

-6.93 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.

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)

1.0

Application In Synthesis of [ 15910-91-5 ]

* 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 [ 15910-91-5 ]

[ 15910-91-5 ] Synthesis Path-Downstream   1~23

  • 1
  • [ 71441-76-4 ]
  • [ 15910-91-5 ]
  • 2
  • [ 6914-76-7 ]
  • [ 15910-91-5 ]
YieldReaction ConditionsOperation in experiment
119.4 g (84%) With ammonium hydroxide; thionyl chloride; In water; toluene; Preparation of 1-Methylcyclopropanecarboxamide A 77.7 weight percent solution of 1-methylcyclopropanecarboxylic acid in toluene (185.66 g of solution; about 144.24 g; 1.44 moles) prepared as described above and toluene (42 mL) were added to a 1-L, 4-necked flask equipped with a magnetic stirrer, an addition funnel, and a nitrogen T inlet linked to a water scrubber. The solution was heated to 45 C. and thionyl chloride (116 mL; 1.58 moles; 1.1 equiv.) was added over 1 hour. The addition was accompanied by gas evolution and a mild endotherm. After the addition was complete the reaction mixture was heated to 80 C. for 5 hours at which point no 1-methylcyclopropanecarboxylic acid was present according to GC analysis. Ammonium hydroxide (28% NH3; 390 mL; 5.76 moles; 4 equiv.) was added to a 2-L, 3-necked flask equipped with a mechanical stirrer and an addition funnel. The contents of the thionyl chloride reaction were placed into the addition funnel and washed in with a little toluene. The ammonium hydroxide was cooled in an ice-acetone bath and the contents of the addition funnel were added over 1 hour such that the reaction mixture was maintained below 25 C. Once the addition was complete the mixture was cooled to 0-5 C. in an ice-water bath for 1 hour. The precipitated 1-methylcycpropanecarboxamide was collected by filtration, washed with ice-cold water, and air-dried to afford 119.4 g (84%) of 1-methylcycpropanecarboxamide as a white solid, mp 144-145 C. 1H NMR (DMSO) delta7.03 (bs, 1H); 6.83 (bs, 1H); 1.19 (s, 3H); 0.89 (m, 2H); 0.45 (m, 2H)
C-(1-Methylcyclopropyl)methylamine A mixture of 1-methylcyclopropanecarboxylic acid (3.0 g) was heated with thionyl chloride (3.6 g) to reflux for 3 hours. The cooled reaction mixture was poured into a concentrated aqueous ammonia solution. Extraction with diethyl ether gave an organic phase, which was dried over sodium sulfate and concentrated. The residue was treated with lithium aluminum hydride according to method I. In an analogous manner, it is also possible to prepare C-(1-ethylcyclopropyl)methylamine.
Example B20 A solution of 1-methylcyclopropane-1-carboxylic acid (1.24 g, 12.39 mmol) and HOBt (2.47 g, 16.1 mmol) in MeCN (31 mL) was treated portion-wise with EDC (3.09 g, 16.1 mmol), stirred at RT for 2 h, treated with NH4OH (15M, 2.4 mL, 36 mmol) and stirred at RT overnight. The mixture was treated with 50% satd. brine, then solid NaHCO3 until saturated, and extracted with EtOAc (3×). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 1-methylcyclopropanecarboxamide (1.35 g, 110%) which was used without further purification. 1H NMR (400 MHz, DMSO-d6): delta 7.01 (br s, 1H), 6.81 (br s, 1H), 1.20 (s, 3H), 0.92-0.88 (m, 2H), 0.47-0.43 (m, 2H).
  • 3
  • [ 600-18-0 ]
  • [ 15910-91-5 ]
  • (Z)-2-[(1-Methyl-cyclopropanecarbonyl)-amino]-but-2-enoic acid [ No CAS ]
  • 4
  • [ 15910-91-5 ]
  • [ 119111-67-0 ]
YieldReaction ConditionsOperation in experiment
With potassium hydroxide; bromine; In water; at 25℃; for 1h; Step 2: N-bromo-<strong>[15910-91-5]1-methylcyclopropanecarboxamide</strong>; /COIH2 v CONHBrI? - AA solution of l-methylcyclopropanecarboxamide (1.082g; 10.92mmol) in water was treated with bromine (0.57mL; l l.OImmol). Solid KOH (850mg; 15.15mmol) was added. After stirring at 250C for lhr, the now heterogenous mixture was extracted with CH2CI2. The organic was dried over magnesium sulfate, filtered and evaporated to give the title compound as an orange yellow-solid.
  • 5
  • [ 16480-05-0 ]
  • [ 15910-91-5 ]
YieldReaction ConditionsOperation in experiment
With ammonia; In methanol; dichloromethane; at 5 - 20℃; The solvent and excess oxalyl chloride were removed by evaporation, the residuedissolved in DCM and added to a solution of ammonia (excess) in MeOH cooled at 5 C. The mixture was allowed to warm to ambient temperature and the volatiles removed by evaporation to give the title compound. NMR: 0.29 (q, 2H), 0.71 (q, 2H), 1.02 (s, 3H), 6.62 (s, 1H), 6.85 (s, 1H).
With ammonia; In chloroform; (ii) Preparation of 1-methylcyclopropanecarboxamide. A solution of 1-methylcyclopropanecarboxylic acid chloride (49 g) in chloroform (300 cm3) was added gradually to a concentrated aqueous solution of ammonia (300 cm3), previously cooled to 0 C. by external cooling. The reaction mixture warmed spontaneously to 20 C. and a white solid precipitate was formed; the precipitate was redissolved by further addition of chloroform. The organic layer was separated, dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure. The residual solid was recrystallized from a mixture of chloroform and n-hexane to give 1-methylcyclopropanecarboxamide (17.6 g) as colourless crystal. Melting point: 148 C. Infra red (paraffin mull): 3390, 3200, 1660, 1615, 1405, 1245, 1110, 880 cm-1
With ammonia; In chloroform; (ii) Preparation of 1-methylcyclopropanecarboxamide. A solution of 1-methylcyclopropanecarboxylic acid chloride (49 g) in chloroform (300 cm3) was added gradually to a concentrated aqueous solution of ammonia (300 cm3), previously cooled to 0 C. by external cooling. The reaction mixture warmed spontaneously to 20 C. and a white solid precipitate was formed; the precipitate was redissolved by further addition of chloroform. The organic layer was separated, dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure. The residual solid was recrystallized from a mixture of chloroform and n-hexane to give 1-methylcyclopropanecarboxamide (17.6g) as colourless crystals. Melting point: 148 C. Infra red (paraffin mull): 3390, 3200, 1660, 1615, 1405, 1245, 1110, 880 cm-1.
With ammonia; In chloroform; (ii) Preparation of 1-methylcyclopropanecarboxamide A solution of 1-methylcyclopropanecarboxylic acid chloride (49g) in chloroform (300 cm3) was added gradually to a concentrated aqueous solution of ammonia (300 cm3), previously cooled to 0C by external cooling. The reaction mixture warmed spontaneously to 20C and a white solid precipitate was formed; the precipitate was redissolved by further addition of chloroform. The organic layer was separated, dried over anhydrous magnesium sulphate and the solvent evaporated under reduced pressure. The residual solid was recrystallized from a mixture of chloroform and n -hexane to give 1-methylcyclopropanecarboxamide (17.6g) as colourless crystal. Melting point: 148C. Infra red (paraffin mull): 3390, 3200, 1660, 1615, 1405, 1245, 1110, 880 cmmin1.
With ammonia; In chloroform-d1; Example 19.34: Preparation of 6-{ r-[3-(dimethylamino)-l,2,4-thiadiazol-5-yl]-4,4'-bipiperidin-l-yl}-N- ( 1 -methylcyclopropyOnicotinamide; Step 1: 1-methylcyclopropanecarboxamide; <n="121"/>v CO2H v CONH2I? I?A solution of 1-methylcyclopropane carboxylic acid (2.01g; 20.08mmol) in CDCI3 (4OmL) was treated with oxalyl chloride (2.29mL; 26.1mmol). The solution was stirred at 25AC for 48hr (progress followed by NMR). The reaction was permeated with excess gaseous ammonia. The mixture was filtered and the filtrate evaporated to give the title compound as a white solid.

  • 9
  • [ 15910-91-5 ]
  • [ 22936-83-0 ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; bromine; In water; at 0 - 80℃; for 28.5h; Bromine (2. 87mol, 0. 056mol) was added to a solution of sodium hydroxide (13. 5g, 0. 338mol) in water (100ml) at 0-5 C. A slurry of 1- (1-methylcyclopropane) carboxamide (Method 51 ; 5.70g 0. 056mol) in water (sol) was then added and reaction mixture stirred at 5 C for 2 hours, then left to stand at ambient temperature for 24 hours. The mixture was then heated at 80 C for 2.5 hours, allowed to cool and mixture distilled to give the title compound (bp 75-80 C). NMR : 0.2 (q, 2H), 0.14 (q, 2H), 0.96 (s, 3H), 1.42 (s, 2H).
  • 10
  • [ 15910-91-5 ]
  • [ 78104-88-8 ]
YieldReaction ConditionsOperation in experiment
To a solution of <strong>[15910-91-5]1-methylcyclopropanecarboxylic acid amide</strong> (1.50g, 15.13mmol) in THF (225mL), cooled to 0C, was added pyridine (2.5mL, 30.26mmol) and the reaction was stirred at this temperature for 1 h. TFAA (10.5mL, 75.66mmol) was then added to the mixture, in one portion, and the reaction continued to stir at 0C for 15 min. Sat. NaHC03 solution was added, until pH 8 was reached, and then the mixture was diluted with DCM. The organic phase was separated, and the aqueous phase was extracted with DCM (x 2). Organic fractions were combined, dried (Na2S04) and the solvent removed in vacuo to afford the intermediate product 1-methylcyclopropanecarbonitrile.
With trifluoroacetic anhydride; In tetrahydrofuran; at 60℃; for 12h;Sealed tube; 1-Methylcyclopropane-1-carbonitrile In a 30-mL sealed tube, <strong>[15910-91-5]1-methylcyclopropane-1-carboxamide</strong> (800 mg, 8.07 mmol, 1.00 equiv) was dissolved in tetrahydrofuran (20 mL), to which was added TFAA (8.4 g, 39.99 mmol, 4.96 equiv) at room temperature. The resulting solution was then stirred for 12 h at 60 C. After the reaction was done, the reaction mixture was concentrated under reduced pressure and the residue was dissolved in 5 mL water. The pH value of the resulting mixture was adjusted to 8 using sat. sodium bicarbonate solution and the mixture was extracted with dichloromethane (3*30 mL). The organic layers were combined, dried over sodium sulfate and concentrated under reduced pressure to afford 1-methylcyclopropane-1-carbonitrile (2 g, crude) as yellow oil.
  • 11
  • [ 15910-91-5 ]
  • [ 1351342-98-7 ]
  • 12
  • [ 57933-83-2 ]
  • [ 15910-91-5 ]
  • prop-1-en-2-yl (1-methylcyclopropanecarbonyl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
2.9 g A -78 C. solution of <strong>[15910-91-5]1-methylcyclopropanecarboxamide</strong> (1.35 g, 13.6 mmol) in THF (30 mL) was treated drop-wise with lithium bis(trimethylsilyl)amide (1M THF, 17.7 mL, 17.7 mmol), stirred for 0.5 h, treated drop-wise with a solution of isopropenyl chloroformate (1.94 mL, 17.7 mmol) in THF (5 mL), stirred at -78 C. for 1 h, then allowed to warm to RT and stirred for 1 h. The mixture was quenched with satd. NaHCO3, extracted with EtOAc (3*) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford crude prop-1-en-2-yl (1-methylcyclopropanecarbonyl)carbamate (2.9 g, 116%) which was used without further purification.
A -78 C. solution of <strong>[15910-91-5]1-methylcyclopropanecarboxamide</strong> (1.35 g, 13.62 mmol) in THF (30 mL) was treated drop-wise with lithium bis(trimethylsilyl)amide (1 M THF, 17.7 mL, 17.7 mmol), stirred for 0.5 h, treated drop-wise with a solution of isopropenyl chloroformate (1.94 mL, 17.7 mmol) in THF (5 mL), stirred at -78 C. for 1 h, then allowed to warm to RT and stirred for 1 h. The mixture was quenched with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4 and concentrated to dryness to afford crude prop-1-en-2-yl (1-methylcyclopropanecarbonyl)carbamate (2.9 g, 116%) which was used without further purification.
  • 13
  • [ 2868-37-3 ]
  • [ 15910-91-5 ]
YieldReaction ConditionsOperation in experiment
1.35 g Example B4 A solution of methylcyclopropyl carboxylic acid (1.24 g, 12.39 mmol) and HOBt (2.466 g, 16.10 mmol) were in MeCN (31 mL) was treated portion-wise with EDC (3.09 g, 16.10 mmol), stirred at RT for 2 h, treated with NH4OH (?15M, 2.4 mL, -36 mmol) and stirred at RT overnight. The mixture was treated with 50% satd. brine, then solid NaHCO3 until saturated and extracted with EtOAc (3*). The combined organics were dried over Na2SO4 and concentrated to dryness to afford 1-methylcyclopropanecarboxamide (1.35 g, 110%) which was used without further purification. 1H NMR (400 MHz, DMSO-d6): delta 7.01 (br s, 1H), 6.81 (br s, 1H), 1.20 (s, 3H), 0.92-0.88 (m, 2H), 0.47-0.43 (m, 2H).
  • 14
  • [ 15910-91-5 ]
  • N-((5-((2-(cyclopropanecarboxamido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-1-methylcyclopropanecarboxamide [ No CAS ]
  • 15
  • [ 15910-91-5 ]
  • N-((5-((2-(3,3-dimethylureido)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)-1-methylcyclopropanecarboxamide [ No CAS ]
  • 16
  • [ 15910-91-5 ]
  • 1-methyl-N-((5-((6'-methyl-[2,3'-bipyridin]-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclopropanecarboxamide [ No CAS ]
  • 17
  • [ 15910-91-5 ]
  • 1-methyl-N-((5-((2-(2-methylthiazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)carbamoyl)cyclopropanecarboxamide [ No CAS ]
  • 18
  • [ 15910-91-5 ]
  • 1,1,1-trifluoro-N-((1-methylcyclopropyl)methyl)methanesulfonamide [ No CAS ]
  • 19
  • [ 15910-91-5 ]
  • 1,1,1-trifluoro-N-((1-methyl-2-(p-tolyl)cyclopropyl)methyl)methanesulfonamide [ No CAS ]
  • 20
  • [ 15910-91-5 ]
  • C5H11N*ClH [ No CAS ]
  • 21
  • [ 15910-91-5 ]
  • (Z)-N-hydroxy-1-methylcycloprop-1-carboximidamide [ No CAS ]
  • 22
  • [ 15910-91-5 ]
  • methyl 3-(1-methylcyclopropyl)-1,2,4-oxadiazole-5-carboxylate [ No CAS ]
  • 23
  • [ 15910-91-5 ]
  • [ 6914-76-7 ]
YieldReaction ConditionsOperation in experiment
86% With sodium hydroxide; for 3h;Reflux; To a 500 ml three-neck round bottom flask equipped with a mechanical stirrer,19.8 g,<strong>[15910-91-5]1-methylcyclopropylcarboxamide</strong> (0.2 mol),50 ml of 30% sodium hydroxide solution.With stirring,After heating under reflux for 3 hours,cool down,40 ml of concentrated hydrochloric acid was added dropwise to pH = 1 with stirring,Stir for another half hour.Extracted with methylene chloride,dry,The solvent was removed by evaporation,To give 17.2 g of 1-methylcyclopropylcarboxylic acid,The yield was 86.%Purity> 95% (GC normalization method).
 

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Technical Information

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