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Chemical Structure| 179474-79-4 Chemical Structure| 179474-79-4

Structure of 179474-79-4

Chemical Structure| 179474-79-4

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Product Details of [ 179474-79-4 ]

CAS No. :179474-79-4
Formula : C9H20N2O
M.W : 172.27
SMILES Code : COCCCN1CCC(N)CC1
MDL No. :MFCD11104531
InChI Key :HIXAJGFVNMKLML-UHFFFAOYSA-N
Pubchem ID :12088093

Safety of [ 179474-79-4 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H302-H312-H412-H314
Precautionary Statements:P260-P264-P270-P273-P280-P301+P330+P331-P302+P352-P303+P361+P353-P304+P340-P305+P351+P338-P310-P363-P405-P501
Class:8
UN#:2735
Packing Group:

Computational Chemistry of [ 179474-79-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 4
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 53.87
TPSA ?

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

38.49 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.2
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

0.09
Log Po/w (WLOGP)?

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

0.07
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.

0.34
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

0.73
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.68

Water Solubility

Log S (ESOL):?

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

-0.7
Solubility 34.3 mg/ml ; 0.199 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.

-0.45
Solubility 60.7 mg/ml ; 0.352 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

-1.35
Solubility 7.66 mg/ml ; 0.0445 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.

-7.29 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)

1.51

Application In Synthesis of [ 179474-79-4 ]

* 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 [ 179474-79-4 ]

[ 179474-79-4 ] Synthesis Path-Downstream   1~14

  • 1
  • [ 179474-79-4 ]
  • [ 519147-79-6 ]
YieldReaction ConditionsOperation in experiment
Example 6 5-AMINO-6-CHLORO-2-METHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE The title compound was prepared according to the procedure described in the step 3 of EXAMPLE 5 using 1-[3-(methoxy)propyl]-4-piperidinamine instead of 1-(1-butyl-4-piperidinyl)methanamine. MS (EI) m/z: 379 (M+). m.p.: 190 C. IR (KBr) nu: 3477, 3304, 3148, 2932, 2808, 1636, 1601, 1560, 1545, 1512, 1439, 1381, 1319,1234,1119 cm-1. 1H-NMR (DMSO-d6) delta: 1.56-1.45 (2H, m), 1.66 (2H, quint, J=6.9 Hz), 1.92-1.88 (2H, m), 2.21-2.14 (2H, m), 2.34 (2H, t, J=7.4 Hz), 2.38 (3H, s), 2.75-2.65 (2H, m), 3.22 (3H, s), 3.37-3.32 (2H, m), 3.91-3.86 (1H, m), 7.58 (2H, br s), 7.84 (1H, s), 7.87 (1H, d, J=0.9 Hz), 9.99 (1H, d, J=8.1 Hz). Anal. Calcd. for C18H26ClN5O2: C, 56.91; H, 6.90; N, 18.44. Found: C, 56.87; H, 6.92; N, 18.40.
  • 2
  • [ 519147-96-7 ]
  • [ 179474-79-4 ]
  • [ 519148-35-7 ]
YieldReaction ConditionsOperation in experiment
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo; Example 14 5-AMINO-6-CHLORO-2-ETHYL-N-{1-[3-(METHOXY)PROPYL]-4-PIPERIDINYL}IMIDAZO[1,2-a]PYRIDINE-8-CARBOXAMIDE The title compound was prepared according to the procedure described in the step 3 in EXAMPLE 5 using 5-amino-6-chloro-2-ethylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 10, Step 2) and 1-[3-(methyloxy)propyl]-4-piperidinamine (EXAMPLE 3). MS (EI) m/z: 393 (M+). m.p.: 179 C. IR (KBr) nu: 3329, 3169, 3055, 2938, 1653, 1630, 1583, 1540, 1513, 1427, 1337, 1324, 1122,745 cm-1. 1H-NMR (DMSO-d6) delta: 1.31 (3H, t, J=7.5 Hz), 1.40-1.55 (2H, m), 1.66 (2H, quint, J=6.9 Hz), 1.87-1.92 (2H, m), 2.16-2.28 (2H, m), 2.33 (2H, t, J=7.4 Hz), 2.66-2.71 (2H, m), 2.74 (2H, q, J=7.5 Hz), 3.22 (3H, s), 3.33-3.42 (2H, m), 3.88-3.95 (1H, m), 7.84 (1H, s), 7.90 (1H, s), 10.07 (1H, d, J=7.5 Hz). Anal. Calcd. for C19H28ClN5O2.0.1C4H10O: C, 58.06; H, 7.28; N, 17.45. Found: C, 58.08; H, 7.51; N, 17.08.
  • 3
  • [ 179474-79-4 ]
  • [ 519148-01-7 ]
  • [ 519148-03-9 ]
YieldReaction ConditionsOperation in experiment
In 5-Amino-N-[(1-butyl-4-piperidinyl)methyl]-6-chloro-2-methylimidazo; Step 1, 5-amino-6-chloro-2-propyl-N-{1-[3-(methoxy)propyl]-4-piperidinyl}imidazo[1,2-a]pyridine-8-carboxamide The title compound was prepared according to the procedure described in the step 3 in EXAMPLE 5 using 5-amino-6-chloro-2-propylimidazo[1,2-a]pyridine-8-carboxylic acid (EXAMPLE 16, Step 2) and 1-[3-(methyloxy)propyl]-4-piperidinamine (EXAMPLE 3). MS (EI) m/z: 407 (M+). 1H-NMR (DMSO-d6) delta: 0.99 (3H, t, J=7.4 Hz), 1.43-1.57 (2H, m), 1.61-1.80 (4H, m), 1.82-1.96 (2H, m), 2.17-2.37 (4H, m), 2.59-2.72 (2H, m), 2.70 (2H, t, J=7.2 Hz), 3.22 (3H, s), 3.27-3.48 (2H, m), 3.85-4.01 (1H, m), 7.57 (2H, br s), 7.84 (1H, s), 7.90 (1H, s), 10.10 (1H, br).
  • 4
  • [ 179474-79-4 ]
  • [ 872171-59-0 ]
  • [ 1254308-91-2 ]
  • 5
  • [ 179474-79-4 ]
  • 8-chloro-3-methyl-1,7-naphthyridin-2(1H)-one [ No CAS ]
  • C18H26N4O2 [ No CAS ]
  • 6
  • [ 1249604-45-2 ]
  • [ 179474-79-4 ]
  • 7
  • [ 519147-89-8 ]
  • [ 179474-79-4 ]
YieldReaction ConditionsOperation in experiment
83% With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; potassium hydroxide; In water; acetonitrile; at 5 - 25℃; for 13h; A solution of 4-formamide-1- (3-methoxypropyl) -piperidine (III) (229 g, 1.14 mol), water (2.06 L) and acetonitrile (571.9 g)After adding KOH (287.3 g, 5.13 mol), the reaction was carried out at a temperature of not higher than 5 C by adding dibromohydantoin (180.2 g, 0.63 mol) and the temperature was raised to 15-25 C for 13 hours to stop the reaction.The reaction solution was concentrated under reduced pressure at 55 C to recover acetonitrile.The residue was extracted with DCM and the organic layer was dried over anhydrous sodium sulfate,And the organic phase was concentrated under reduced pressure at 50 C to give 178.2 g of a pale yellow liquid,The yield was 95% (in terms of II-1) and the GC purity was 98.6%.The product was placed in a distillation flask, the pump was decompressed (with a thorned distillation column)External temperature gradient temperature (5 / times),When the internal temperature rose to 72 ~ 73 ,The fractions were collected to give 148 g of colorless transparent liquid,The distillation yield was 83%
  • 8
  • [ 179474-79-4 ]
  • prucalopride succinic acid [ No CAS ]
  • 9
  • [ 179474-79-4 ]
  • [ 123654-26-2 ]
  • [ 179474-81-8 ]
YieldReaction ConditionsOperation in experiment
85% THF, 4-amino-5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid (1.0 g), a small amount of CDI was added, stirred for 25 min,(0.8 g, GC & gt; 98%) was added dropwise to a solution of 1- (3-methoxypropyl) -4-piperidinamine (I) at 45 C for 4 h, (30g), precipitate a large amount of solid, stirring at 25 for 1h; pumping, 20g of water rinse, collecting filter cake, drying, diclofenac 1.5g , Yield 85% (mp = 91-92 C).To the reaction flask was added paclitaxel (1.0 g) and 75% ethanol (5 mL), heated to 40 C, and succinic acid (0.35 g) was added with stirring and stirred for 3 h. The filter cake was recrystallized from 75% ethanol and dried to give 1.17 g of white granular crystals in 93% yield
  • 10
  • methyl-1-(3-methoxypropyl)piperidine-4-carboxylate [ No CAS ]
  • [ 179474-79-4 ]
  • 11
  • [ 13035-19-3 ]
  • [ 179474-79-4 ]
  • 12
  • C22H28N2O [ No CAS ]
  • [ 179474-79-4 ]
YieldReaction ConditionsOperation in experiment
81% With hydrogenchloride; In water; at 0 - 20℃;pH 1 - 2; Under nitrogen protection, the intermediate (26.4 g, 0.1 mol) was dissolved in 120 mL of anhydrous tetrahydrofuran in a 500 mL three-necked flask equipped with a temperature and dropping funnel.The reaction solution was cooled to 0 C, and 60% sodium hydride solid (6.0 g, 0.15 mol) was added in 3-5 batches,After the addition was complete, the incubation was maintained at 0 C for 30 minutes.Then will be3-Methoxybromopropane (16.8 g, 0.11 mol) was dissolved in 30 mL of tetrahydrofuran slowly dropwise to the reaction system,After completion of the dropwise addition, the reaction solution was spontaneously stirred at room temperature for 3 hours, and the TLC reaction was terminated.The reaction system was cooled to 0 C and about 2.0% by weight of 10% hydrochloric acid was added dropwise. The temperature was not more than 20 C during the dropwise addition,Followed by incubation until the TLC detection of protective groups removed, this time measuring system PH = 1-2,After adding 80mL of ethyl acetate, the organic layer was dried,After addition of n-heptane, 16.7 g of benzophenone was obtained and the recovery was 92%.Water layer by adding 1 M sodium hydroxide adjusted PH = 13-14, dichloromethane 100mL extraction twice,Anhydrous Na2SO4 dried, filtered,The organic layer was dried to give 13.9 g of 1- (3-methoxypropyl) piperidin-4-amine in 81% yield, GC: 97.2%.
  • 13
  • [ 179474-79-4 ]
  • 4-amino-5-chloro-7-aldehyde-2,3-dihydrobenzofuran [ No CAS ]
  • [ 179474-81-8 ]
YieldReaction ConditionsOperation in experiment
36.5 g With tert.-butylhydroperoxide; calcium carbonate pentahydrate; In acetonitrile; at 80℃; for 8h; Taking 4-amino-5-chloro-7-aldehyde-2,3-dihydrobenzofuran 19.7 g,1-(3-methoxypropyl)-4-piperidinamine 18.5 g, dissolved in 100 mL of acetonitrile,Add 54g of t-butyl hydroperoxide (TBHP), 20g of calcium carbonate,3g3gCuSO4·5H2O, reacted at 80 C for 8 h, after the reaction is over,Add 30 g of sodium sulfite and 100 mL of water, extract with ethyl acetate, and wash with water.The organic layer is dried over anhydrous sodium sulfate.The filtrate was filtered under reduced pressure to give a white solid (36.5 g).
  • 14
  • [ 179474-79-4 ]
  • 4-amino-5-chloro-7-hydroxymethyl-2,3-dihydrobenzofuran [ No CAS ]
  • [ 179474-81-8 ]
YieldReaction ConditionsOperation in experiment
33.6 g With tert.-butylhydroperoxide; zinc(II) iodide; In acetonitrile; at 70℃; for 5h; Take 19.9 g of 4-amino-5-chloro-7-hydroxymethyl-2,3-dihydrobenzofuran, 18.5 g of 1-(3-methoxypropyl)-4-piperidinamine, dissolved in In 70 mL of acetonitrile, 54 g of t-butyl hydroperoxide (TBHP) was added, and 1.6 g of zinc iodide was reacted at 70 C for 5 h. After the reaction was completed, 30 g of sodium sulfite and 100 mL of water were added, and the mixture was extracted with ethyl acetate. After drying, the filtrate was filtered under reduced pressure to give a white solid (36.5 g).
 

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Technical Information

Categories

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[ 179474-79-4 ]

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