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Product Details of [ 147804-30-6 ]

CAS No. :147804-30-6
Formula : C11H19NO3
M.W : 213.27
SMILES Code : O=C(N(CC1)CCC21CO2)OC(C)(C)C
MDL No. :MFCD07779385
Boiling Point : No data available
InChI Key :ULSBMKGFFFMGOI-UHFFFAOYSA-N
Pubchem ID :22135564

Safety of [ 147804-30-6 ]

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

Computational Chemistry of [ 147804-30-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.91
Num. rotatable bonds 3
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 60.41
TPSA ?

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

42.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.85
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

1.11
Log Po/w (WLOGP)?

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

1.41
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.

1.15
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

1.62
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.63

Water Solubility

Log S (ESOL):?

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

-1.66
Solubility 4.63 mg/ml ; 0.0217 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.

-1.59
Solubility 5.53 mg/ml ; 0.0259 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

-1.51
Solubility 6.56 mg/ml ; 0.0308 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

Yes
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.

-6.81 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

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)

2.62

Application In Synthesis of [ 147804-30-6 ]

* 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 [ 147804-30-6 ]

[ 147804-30-6 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 147804-30-6 ]
  • [ 392331-66-7 ]
YieldReaction ConditionsOperation in experiment
95% With ammonium hydroxide; In methanol; at 80℃; for 16h;Sealed tube; A 100-mL sealed tube fitted with a magnetic stir bar was charged with tert-Butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (300 mg, 1.28 mmol) and a solution of ammonium hydroxide in methanol (20 mL, 7M). The solution was stirred for 16 h at 80 C. in an oil bath and cooled to room temperature. The mixture was concentrated under vacuum to afford tert-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate (350 mg, >95%) used without further purification. LCMS (ESI) m/z 231 [M+H].
86% With ammonia; In methanol; at 20℃; for 12h; To a stirred solution of tert-butyl 1-oxa-6-aza-spiro[2.5]octane-6-carboxylate (0.64 grams, 3.0 mmol, obtained in the above step) in methanol (4 mL) at room temperature, a solution of ammonia (NH3) in methanol (7M, 8 mL) was added and the reaction was stirred for12 hours. The volatiles were removed under reduced pressure to obtain the crude mass which was triturated with hexanes and ether which yielded the above titled compound (0.6 gram). Yield: 86 %.?H - NMR CDCI3 (6 ppm): 1.45 (9H, s), 1.35 - 1.60 (4H, m), 2.63 (2H, s), 3.10 - 3.25 (2H, m), 3.80 - 3.95 (2H, m).Mass (m/z): 231.5 (M+H)4.
86% With ammonia; In methanol; at 20℃; for 12h; To a stirred solution of N-tert butyloxycarbonyl1-oxa-6-aza-spiro[2.5]octane 21 (0.64 g, 3.0 mmols) in methanol(4.0 mL) at r.t., a solution of ammonia (NH3)in methanol (7M, 8.0 mL) was added and the reaction was stirred for 12 hours.The volatiles were removed under reduced pressure to obtain the crude masswhich was triturated with hexanes and ether which yielded the above titledcompound 22c (0.6 g) in 86% yield.1H - NMR CDCl3 (CDCl3): d 3.95 - 3.80 (m, 2H), 3.25 -3.10 (m, 2H), 2.63 (s, 2H), 1.35 - 1.60 (m, 4H), 1.45 (s, 9H). Mass (m/z): 231.5 (M+H)+. Anal. (C11H22N2O3) C, H, N
76% With ammonia; In methanol; at 25 - 40℃; for 40h; tert-Butyl l-Oxa-6-aza-spiro[2.5]octane-6-carboxylate (0.5 grams, 2.34 mmole) was added to methanolic ammonia solution (20 mL, 14.83 % w/v) at room temperature. Then reaction mass was stirred for 40 hours at room temperature in a closed vessel. The progress of the reaction was monitored by TLC. After completion of the reaction (TLC), the reaction mass was concentrated on rotavacuum to obtain the title compound. Yield: 0.41 gram (76%). 'H-NMR(8 ppm): 1.35 - 1.69 (16H, m), 2.61 (2H, s), 3.10 - 3.20 (2H, m), 3.81 -3.90(2H, m); Mass (m/z): 231.3 (M+H)+.
76% With ammonia; In methanol; at 20℃; for 40h; tert-Butyl l-oxa-6-azaspiro[2.5]octane-6-carboxylate (0.5 grams, 2.34 mmole, obtained in the step (i) of preparation 5) was added to methanolic ammonia solution (20 mL, 14.83 % w/v) at RT. Then reaction mass was stirred for 40 hours at RT in a closed vessel. The reaction mass was concentrated under vacuum to obtain the title compound. Weight: 0.41 gram (Yield: 76 %). (0385) - NMR (delta ppm): 1.35 - 1.69 (16H, m), 2.61 - 2.69 (2H, m), 3.10 - 3.20 (2H, m), 3.81 - 3.90 (2H, m); (0386) Mass (m/z): 231.3 (M+H)+ .
69% With ammonia; In methanol; at 20℃; Intermediate 2M: tert-butyl 4-(amiriomethyl)-4-hydroxypiperidine-1 -carboxylate A mixture of intermediate 1A (10.0 g, 46.9 mmol) and ammonia solution (201 mL, 7 M solution in methanol, 1.4 mol) was stirred at r.t. overnight. The solvent was removedunder vacuum and the residue was purified by flash chromatography, silica gel, gradient dichioromethane to methanol:dichloromethane (1:4) to give the title compound (7.4 g, 69% yield) as a white solid. HPLC retention time: 2.15 mm; MS:131 (M+H-100).
69% With ammonia; In methanol; at 20℃; A solution of intermediate 1A (10.0 g, 46.9 mmol) in ammonia (201 ml_, 7 M solution in methanol, 1.4 mol) was stirred at r.t. overnight. The solvent was removed under vacuum and the residue was purified by flash chromatography, silica gel, gradient dichloromethane to methanokdichloromethane (1 :4) to give the title compound (7.4 g, 69% yield) as a white solid. HPLC retention time: 2.15 min; MS: 131 (M+H-100).
69% With ammonia; In methanol; at 20℃; Intermediate 2A: fert-butyl 4-(aminomethyl)-4-hydroxypiperidine-1-carboxylate A mixture of intermediate 1A (10.0 g, 46.9 mmol) and ammonia solution (201 mL, 7 M solution in methanol, 1.4 mol) was stirred at r.t. overnight. The solvent was removed under vacuum and the residue was purified by flash chromatography, silica gel, gradient dichloromethane to methanokdichloromethane (1 :4) to give the title compound (7.4 g, 69% yield) as a white solid. HPLC retention time: 2.15 min; MS: 131 (M+H-100).
60.5% With ammonia; In ethanol; water;Inert atmosphere; A stirred solution of 1-oxa-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (9.0 g, 42.2 mmol) in ethanol (60 ml) was added with ammonia (100 ml). The resulting mixture was stirred under a nitrogen atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was added with water (50 ml) and extracted with ethyl acetate (150 ml*3). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane:methanol (20:1) as eluents to give 4-aminomethyl-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (5.87 g, 60.5%) as a white solid. MS m/z (ESI): 231 [M+1]
60.5% With ammonia; In ethanol; A stirred solution of l-oxa-6-aza-spiro [2.5] octane-6-carboxylic acid tert-butyl ester (9.0 g, 42.2 mmol) in ethanol(60 ml) was added with ammonia (100 ml). The resulting mixture was stirred under a nitrogen atmosphere overnight. The mixture was concentrated under reduced pressure. The residue was added with water (50 ml) and extracted with ethyl acetate (150 ml><3). The combined organic extracts were dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with dichloromethane: methanol (20:1) as eluents to give 4-aminomethyl-4-hydroxy-piperidine-l-carboxylic acid tert-butyl ester (5.87 g, 60.5%) as a white solid. MS m/z (ESI): 231[M+1] ,
With ammonia; In methanol; water; at 0 - 20℃; for 7h; 4-Aminomethyl-4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester is prepared from 1-oxa-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (Bourrain et al Bioorg. Med. Chem. Lett. 9(23):3369-3374 (1999)). Concentrated aqueous NH4OH (6 mL) is added to a solution of 1-oxa-6-aza-spiro[2.5]octane-6-carboxylic acid tert-butyl ester (0.50 g, 2.3 mmol) in MeOH (4 mL) at 0 C. The reaction mixture is removed from the cooling and allowed to warm to room temperature. After 7 hours, the reaction mixture is concentrated under reduced pressure to afford desired product as a white solid.
With ammonium hydroxide; In methanol; at 0 - 20℃; for 16h; aqueous ammonia (6mL)was added to a solution of tert-butyl 1-oxa-6-azaspiro[2.5]octan-6-carboxylate (500mg, 2mmol) in methanol (4mL) at0C. The reaction solution warmed to room temperature and was stirred for 16 hours, then concentrated under reduced pressure to give a colorless oil (530mg, 2.3mmol) with a yield of 100%, which was used directly in the next step withoutpurification.

  • 3
  • [ 19181-54-5 ]
  • [ 147804-30-6 ]
  • tert-butyl 4-hydroxy-4-((8-methyl-4-oxoquinazolin-3(4H)-yl)methyl)piperidine-1-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With caesium carbonate; In N,N-dimethyl-formamide; at 80℃; for 16h; To a solution of <strong>[19181-54-5]8-methylquinazolin-4(3H)-one</strong> (20 mg, 0.125 mmol) and tert-butyl 1-oxa-6-azaspiro[2.5]octane-6-carboxylate (33 mg, 0.156 mmol) in DMF (0.625 mL) was added cesium carbonate (122 mg, 0.375 mmol). The reaction mixture was stirred at 80 C. for 16 h, then cooled to room temperature, diluted with ethyl acetate (0.5 mL) and washed with water (0.5 mL). The organic layer was concentrated under reduced pressure to afford tert-butyl 4-hydroxy-4-((8-methyl-4-oxoquinazolin-3(4H)-yl)methyl)piperidine-1-carboxylate, which was used without further purification. LCMS: (ESI) m/z 396.29 [M+Na].
  • 4
  • [ 403-01-0 ]
  • [ 147804-30-6 ]
  • C19H26FNO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
63% With lithium perchlorate; In acetonitrile; at 80℃; (2)Compound j (8 g, 1.0 eq), compound k (1.5 eq), lithium perchlorate (1.7 eq) and acetonitrile (50 ml) were added to a three-necked flask, and the mixture was heated to 80 ° C to stir the reaction for 12-18 h.Cool down to room temperature,Diluted with 200 ml of ethyl acetate.Wash with saturated brine and dry over anhydrous sodium sulfate.Concentrate the organic phase to dryness, over the fast column,Obtaining 9.06 g of compound l,Yield: 63percent.
  • 5
  • [ 20872-93-9 ]
  • [ 147804-30-6 ]
  • C19H24N4O6 [ No CAS ]
  • 6
  • [ 403-01-0 ]
  • [ 147804-30-6 ]
  • C19H25NO6 [ No CAS ]
YieldReaction ConditionsOperation in experiment
6.37 g (2) Compound j (8 g, 1.0 eq), compound k (1.5 eq), lithium perchlorate (1.7 eq) and acetonitrile (50 ml) were added to a three-necked flask, heated to 80 ° C and stirred for 12-18 h. After completion, the mixture was cooled to room temperature, diluted with 200 ml of ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfateObtaining 9.06 g of compound l,Yield: 63percent. (3) Compound l (8g, 1.0 eq), cesium carbonate (1.5 eq) and acetonitrile (50 ml) were added to a three-necked flask, heated to 60 ° C and stirred for 6-8 h. After the reaction was completed, the temperature was lowered to room temperature, and 200 ml was added. Diluted with ethyl acetate, washed with saturated brine, dried over anhydrous sodium sulfate6.37 g of compound m was obtained in a yield: 84percent.
  • 7
  • [ 171178-33-9 ]
  • [ 147804-30-6 ]
  • C18H23ClN4O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With potassium carbonate; In N,N-dimethyl-formamide; at 70℃; for 48h; 6-Chloro-3/7-pyrido[3,2-i/]pyrimidin-4-onc (1.242 g, 6.67 mmol), tert- butyl l-oxa-6- azaspiro[2.5]octane-6-carboxylate (2.34 g, 11 mmol) and K2CO3 (2.76 g, 19.9 mmol) were stirred in DMF (20 ml) at 70 C for 48 hours. The reaction mixture was filtered, and the resulted filtrate was purified by preparative LC (on C-18 Gemini-NX 5 pm column, 5 mM aqueous NH4HC03-MeCN, gradient), to give tert- butyl 4-[(6-chloro-4-oxo-quinazolin-3- yl)methyl]-4-hydroxy-piperidine- 1 -carboxylate.
  • 8
  • [ 171178-33-9 ]
  • [ 147804-30-6 ]
  • C26H33N5O5 [ No CAS ]
 

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