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Chemical Structure| 103883-30-3 Chemical Structure| 103883-30-3
Chemical Structure| 103883-30-3

(R)-(2,2-Dimethyl-1,3-dioxolan-4-yl)methanamine

CAS No.: 103883-30-3

4.5 *For Research Use Only !

Cat. No.: A166755 Purity: 97%

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Product Details of [ 103883-30-3 ]

CAS No. :103883-30-3
Formula : C6H13NO2
M.W : 131.17
SMILES Code : NC[C@H]1OC(C)(C)OC1
MDL No. :MFCD02262087
InChI Key :HXOYWCSTHVTLOW-RXMQYKEDSA-N
Pubchem ID :10154073

Safety of [ 103883-30-3 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H314
Precautionary Statements:P280-P305+P351+P338-P310
Class:8
UN#:3259
Packing Group:

Calculated chemistry of [ 103883-30-3 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 1.0
Num. rotatable bonds 1
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 33.76
TPSA ?

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

44.48 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.85
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

-0.45
Log Po/w (WLOGP)?

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

0.1
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.

-0.26
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

0.6
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.37

Water Solubility

Log S (ESOL):?

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

-0.3
Solubility 65.2 mg/ml ; 0.497 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.

-0.02
Solubility 126.0 mg/ml ; 0.959 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

-0.73
Solubility 24.3 mg/ml ; 0.185 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.

-7.42 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)

2.88

Application In Synthesis of [ 103883-30-3 ]

* 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 [ 103883-30-3 ]

[ 103883-30-3 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 723280-98-6 ]
  • [ 103883-30-3 ]
  • [ 723284-02-4 ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In dichloromethane; Part A; To a solution of <strong>[723280-98-6]7-bromo-4-chloro-3-nitroquinoline</strong> (22.00 g, 76.52 mmol) indichloromethane (250 mL) was added triethylamine (16.0 mL, 115 mmol) followed by thedropwise addition of a solution of 4/?-(-)-(2,2-dimethyl)-l,3-dioxolane-4-methananiine(1 1 .04 g, 84.16 mmol) in dichloromethane (200 mL). The reaction was monitored byTLC, and after the starting material was consumed, the reaction mixture was transferred toa separatory funnel and washed with water (200 mL) and brine (200 mL), dried overNa2SC>4, filtered, and concentrated. The resulting yellow residue was triturated with water(200 mL) and the solid was collected by filtration and dried. The solid was sonicated indiethyl ether (100 mL) and isolated by filtration. The solid was dried under vacuum at 40°C to yield 7-bromo-A^-[(4JR)-2,2-dimethyl-l,3-dioxolan-4-yl]methyl}-3-nitroquinolin-4-amine (25.84 g) as a yellow solid, mp 136-137 °C.
  • 2
  • [ 103883-30-3 ]
  • 3-[(2R,4R)-4-([1-(2,2-difluoro-1,3-benzodioxol-5-yl)cyclopropyl]carbonyl}amino)-7-methyl-3,4-dihydro-2H-chromen-2-yl]benzoic acid [ No CAS ]
  • 3-((2R,4R)-4-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-7-methylchroman-2-yl)-N-(((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl acetamide; at 20.0℃; Example 48A 3-((2i?,4i?)-4-(l-(2,2-difluorobenzo[d][l,3]dioxol-5-yl)cyclopropanecarboxamido)-7- methylchroman-2-yl)-N-(((i?)-2,2-dimethyl-l,3-dioxolan-4-yl)methyl)benzamide In a 4 mL vial, 300 of a stock solution containing the product from Example 16 (0.13 M, 0.039 mmol, 1.0 equivalent) and diispropylethylamine (0.39 M, 0.12 mmol, 3.0 equivalents) in dimethyl acetamide was added to a stock solution containing 2-(3H-[l,2,3]triazolo[4,5- b]pyridin-3-yl)-l,l,3,3-tetramethylisouronium hexafluorophosphate(V) (0.15 M in dimethyl acetamide, 300 mu, 0.046 mmol, 1.2 equivalents). A stock solution of (i?)-(2,2-dimethyl-l,3- dioxolan-4-yl)methanamine (0.40 M in dimethyl acetamide, 145 mu, 0.058 mmol, 1.5 equivalents) was added and the reaction was stirred at room temperature until complete as determined by LC. The material was loaded directly into a Gilson GX-271 autosampler and purified using preparative LC method TFA8 to provide the title compound.
  • 3
  • [ 103883-30-3 ]
  • [ 327-92-4 ]
  • N-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-fluoro-2,4-dinitroaniline [ No CAS ]
YieldReaction ConditionsOperation in experiment
82% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; at 20.0℃; for 1.0h; Example 137A N-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-fluoro-2,4-dinitroaniline A solution of 1,5-difluoro-2,4-dinitrobenzene (0.778 g, 3.81 mmol) and N,N-diisopropylethylamine (0.732 mL, 4.19 mmol) in tetrahydrofuran (38 mL) was treated dropwise with a solution of <strong>[103883-30-3](R)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine</strong> (0.500 g, 3.81 mmol) in tetrahydrofuran (38 mL). The reaction was stirred at room temperature for 1 hour. Volatiles were then removed in vacuo, and the crude material was then partitioned between ethyl acetate (150 mL) and water (100 mL). The organic layer was washed with water (2*50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (10 to 70percent ethyl acetate-heptanes, eluent) to afford the title compound as a yellow oil (0.989 g, 82percent). 1H NMR (400 MHz, CDCl3) delta 9.15 (d, J=8.0 Hz, 1H), 8.78 (s, 1H), 6.67 (d, J=13.3 Hz, 1H), 4.48 (qd, J=5.8, 3.7 Hz, 1H), 4.24-4.07 (m, 1H), 3.81 (dd, J=8.7, 5.7 Hz, 1H), 3.58 (ddd, J=13.4, 4.9, 3.8 Hz, 1H), 3.42 (dt, J=13.3, 5.5 Hz, 1H), 1.52 (s, 3H), 1.40 (s, 3H). MS (DCI+) m/z 333.0 (M+H).
  • 4
  • [ 103883-30-3 ]
  • N1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-5-fluorobenzene-1,2,4-triamine [ No CAS ]
  • 5
  • [ 103883-30-3 ]
  • 2-[1-(benzyloxy)-2-methylpropan-2-yl]-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-6-fluoro-1H-benzimidazol-5-amine [ No CAS ]
  • 6
  • [ 103883-30-3 ]
  • (7R)-N-(2-[1-(benzyloxy)-2-methylpropan-2-yl]-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}-6-fluoro-1H-benzimidazol-5-yl)-2,2-difluoro-7-methyl-6,7-dihydro-2H-furo[2,3-f][1,3]benzodioxole-7-carboxamide [ No CAS ]
  • 7
  • [ 103883-30-3 ]
  • (R)-2-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropane-1-carboxamido)-3-mercapto-3-methylbutanoic acid [ No CAS ]
  • 1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)-N-((R)-1-((((R)2,2-dimethyl-1,3-dioxolan-4-yl)methyl)amino)-3-mercapto-3-methyl-1-oxobutan-2-yl)cyclopropane-1-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
56% With triethylamine; N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate; In N,N-dimethyl-formamide; at 20.0℃; for 16.0h; 10300] In a typical run, (R)-2-amino-3-mercapto-3-meth- ylbutanoic acid (0.25 g, 1.68 mmol, 1 eq) and 1-(2,2- difluorobenzo[d] [1 ,3]dioxol-5-yl)cyclopropane-1 -carboxylic acid (0.45 g, 1.85 mmol, 1.1 eq) were taken up in DMF (10 mE) and HATU (0.83 g, 2.18 mmol, 1.3 eq) was added, followed by Et3N (0.508 g, 5.03 mmol, 3 eq). The resulting reaction mixture was stirred at room temperature for 16 hours. The following morning, the reaction mixture was extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by preparative HPEC afford (R)-2-(1 -(2,2- difluorobenzo[d] [1 ,3]dioxol-5-yl)cyclopropane-1 -carboxamido)-3-mercapto-3-methylbutanoic acid (0.368 g, 59percentyield) as a white solid. This material (0.368 g, 0.987 mmol, 1 eq) and (R)-(2,2-dimethyl-1 ,3-dioxolan-4-yl)methan- amine (0.155 g, 1.2 mmol, 1.1 eq) were taken up in DMF (5 mE) and HATU (0.487 g, 1.28 mmol, 1.3 eq) was added, followed by Et3N (0.299 g, 2.96 mmol, 3 eq). The resulting reaction mixture was stirred at room temperature for 16 hours. The following morning, the reaction mixture was extracted with EtOAc. The combined organic layers were washed with water, brine, dried over anhydrous Na2SO4 and concentrated and concentrated under reduced pressure. The resulting residue was purified by preparative HPEC to afford 1 -(2,2-difluorobenzo[d] [1 ,3]dioxol-5-yl)-N-((R)- 1 -((((R)2,2-dimethyl- 1 ,3-dioxolan-4-yl)methyl)amino)-3-mercapto-3-methyl-i -oxobutan-2-yl)cyclopropane-1 -carboxamide(0.27 g, 56percent yield) as a colorless oil. This material (0.27 g, 0.556 mmol, 1 eq) was taken up in DMF (2 mE) along with tert-butyl N-((4Z,7Z, 1 OZ, 1 3Z, 1 6Z, 1 9Z)-docosa-4,7, 10,13, 16,1 9-hexaenoyl)-S-(pyridin-2-ylthio)-E-cysteinate (0.365 g, 0.611 mmol, 1.1 eq) and methanol (2 mE) was added. tert-butyl N-((4Z,7Z, 1 OZ, 13Z, 1 6Z, 1 9Z)-Docosa-4,7, 10,13, 16,1 9-hexaenoyl)-S-(pyridin-2-ylthio)-E-cysteinate, in turn, was prepared according to the procedures outlined in example 3. The resulting reaction mixture was stirred at room temperature for 16 hours and then concentrated under reduced pressure. The resulting residue was purified by preparative HPEC to afford tert-butyl S?(((R)-3-(i-(2,2- difluorobenzo[d] [1 ,3]dioxol-5-yl)cyclopropane-i -carboxamido)-4-((((R)-2,2-dimethyl-i ,3-dioxolan-4-yl)methyl) amino)-2-methyl-4-oxobutan-2-yl)thio)-N-((4Z,7Z, 1 OZ, 1 3Z, 1 6Z, 1 9Z)-docosa-4,7, 10,13,16,1 9-hexaenoyl)-E-cysteinate (0.22 g, 40.8percent yield) as a colorless oil. This material (0.22 g, 0.467 mmol, 1 eq) was taken up in CH2C12 (5 mE) and TFA (1 mE) was added. The resulting reaction mixture was stirred at room temperature for 4 hour and then concentrated under reduced pressure. The resulting residue was purified by preparative HPEC to afford S?(()-3-(i -(2,2-difluorobenzo[d] [1 ,3]dioxol-5-yl)cyclopropane- 1-car- boxamido)-4-(((R)-2,3-dihydroxypropyl)amino)-2-methyl- 4-oxobutan-2-yl)thio)-N-((4Z,7Z, 1 OZ, 13Z, 1 6Z, 1 9Z)- docosa-4,7, 10,13,16,1 9-hexaenoyl)-E-cysteine (0.02 g, 10percent yield) as a colorless oil. MS, calculated for CH59F2N3O9S2: 875.37; found 876 [M+H].
  • 8
  • [ 103883-30-3 ]
  • 2-((2-fluoro-4-iodophenyl)amino)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carbonyl chloride [ No CAS ]
  • (R)-N-((2,2-dimethyl-1,3-dioxolan-4-yl)methyl)-2-((2-fluoro-4-iodophenyl)amino)-1-methyl-1H-pyrrolo[2,3-b]pyridine-3-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
38.5% With N-ethyl-N,N-diisopropylamine; In tetrahydrofuran; for 18.0h;Inert atmosphere; Cooling with ice; A solution of 2-((2-fluoro-4-iodophenyl)amino)- 1-methyl- 1H-pyrrolo[2,3 - b]pyridine-3-carbonyl chloride (See Example 2, 937 mg, 2.18 mmol) in dry THF (4 mL) under N2 was cooled in an ice-water bath while stirring. The reaction mixture was treated with a solution of <strong>[103883-30-3](R)-(-)-(2,2-dimethyl-1,3-dioxolan-4-yl)methanamine</strong> (256 mg, 1.95 mmol) and diisopropylethylamine (0.33 mL, 1.95 mmol) in dry THF (5 mL) and stirred for 18 h. Reaction mixture was concentrated in vacuo and the crude residue was purified by flash column chromatography (Silica 40 g, 20-80percent EtOAc in hexane) to give the product (442 mg, 3 8.5percent) as an off-white solid which was used in subsequent steps without further purification. UPLC-MS (Acidic Method, 2 mm): rt 1.10 mi m/z 525.0 [M+H]t ?HNIVIR (400 IVIHz, DMSO-d6) ppm 8.83 (s, 1H), 8.32 - 8.36 (m, 1H), 8.27 - 8.32 (m, 1H), 7.62 - 7.68 (m, 1H), 7.55 -7.62 (m, 1H), 7.31 -7.37 (m, 1H), 7.21 -7.27 (m, 1H), 6.40 -6.47 (m, 1H), 4.05 -4.09 (m, 1H), 3.84 - 3.89 (m, 1H), 3.57 - 3.62 (m, 1H), 3.54 (s, 3H), 3.37 - 3.38 (m, 2H), 1.26 (s, 3H), 1.22 (s, 3H).
 

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Technical Information

Categories

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