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Chemical Structure| 97308-23-1 Chemical Structure| 97308-23-1
Chemical Structure| 97308-23-1

tert-Butyl aziridine-1-carboxylate

CAS No.: 97308-23-1

4.5 *For Research Use Only !

Cat. No.: A330357 Purity: 95%

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Product Citations

Product Citations

Sherwood, Alexander M. ; Burkhartzmeyer, Elise K. ; Williamson, Samuel E. ; Faley, Michael T. ;

Abstract: A divergent two-step process has provided access to optically pure enantiomers of MDMA and MDA, clin. relevant phenylisopropylamine entactogens. Target compounds were synthesized from com. available alanine-derived aziridines. Critical process parameters were identified, and the reactions were optimized to avoid chromatog. purifications toward gram-scale isolations, providing (R)-(-)-MDMA, (S)-(+)-MDMA, (R)-(-)-MDA, and (S)-(+)-MDA each in greater than 98% purity by UPLC, >99% enantiomeric excess, and net yields between 50 and 60% for the complete process.

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Product Details of [ 97308-23-1 ]

CAS No. :97308-23-1
Formula : C7H13NO2
M.W : 143.18
SMILES Code : O=C(N1CC1)OC(C)(C)C
MDL No. :MFCD16036961
InChI Key :VBYPJHLRWKGNAI-UHFFFAOYSA-N
Pubchem ID :15933185

Safety of [ 97308-23-1 ]

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H315-H319-H225
Precautionary Statements:P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235
Class:3
UN#:1993
Packing Group:

Calculated chemistry of [ 97308-23-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 10
Num. arom. heavy atoms 0
Fraction Csp3 0.86
Num. rotatable bonds 3
Num. H-bond acceptors 2.0
Num. H-bond donors 0.0
Molar Refractivity 42.17
TPSA ?

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

29.31 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.34
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

0.89
Log Po/w (WLOGP)?

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

0.86
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.

0.76
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

0.52
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.07

Water Solubility

Log S (ESOL):?

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

-1.09
Solubility 11.6 mg/ml ; 0.0812 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.

-1.09
Solubility 11.6 mg/ml ; 0.0812 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

-0.64
Solubility 32.7 mg/ml ; 0.228 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.

-6.54 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

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)

1.75

Application In Synthesis of [ 97308-23-1 ]

* 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.

  • Upstream synthesis route of [ 97308-23-1 ]
  • Downstream synthetic route of [ 97308-23-1 ]

[ 97308-23-1 ] Synthesis Path-Upstream   1~9

  • 1
  • [ 151-56-4 ]
  • [ 24424-99-5 ]
  • [ 97308-23-1 ]
YieldReaction ConditionsOperation in experiment
88% With dmap; triethylamine In dichloromethane; ethyl acetate Example 47
N-Boc aziridine 166:
Boc anhydride (113 mg, 0.52 mmol) was added to a solution of aziridine 165 (125 mg, 0.49 mmol), triethylamine (70 μL), DMAP (cat. amount) in dichloromethane (7 mL).
After 1 h the reaction was concentrated and the residue subjected to flash chromatography (40percent EtOAc in hexanes) to give 154 mg (88percent) of the N Boc aziridine 166 as a pale oil. 1 H NMR (CDCl3, 300 MHz): δ 6.82 (m, 1H); 4.47 (br m, 1H); 4.23 (t, 2H, J=4.7 Hz); 3.81 (t, 2H, J=4.7 Hz); 3.75 (s, 3H); 3.00 (br d, 1H, J=18.0 Hz); 2.90-2.85 (m, 2H); 2.65-2.55 (m, 1H); 2.10 (s, 3H); 1.44 (s, 9H).
88% With dmap; triethylamine In dichloromethane; ethyl acetate Example 47
N-Boc aziridine 166:
Boc anhydride (113 mg, 0.52 mmol) was added to a solution of aziridine 165 (125 mg, 0.49 mmol), triethylamine (70 μL), DMAP (cat. amount) in dichloromethane (7 mL).
After 1 h the reaction was concentrated and the residue subjected to flash chromatography (40percent EtOAc in hexanes) to give 154 mg (88percent) of the N Boc aziridine 166 as a pale oil.
1 H NMR (CDCl3, 300 MHz): δ6.82 (m, 1H); 4.47 (br m, 1H); 4.23 (t, 2H, J=4.7 Hz); 3.81 (t, 2H, J=4.7 Hz); 3.75 (s, 3H); 3.00 (br d, 1H, J=18.0 Hz); 2.90-2.85 (m, 2H); 2.65-2.55 (m, 1H); 2.10 (s, 3H); 1.44 (s, 9H).
88% With dmap; triethylamine In dichloromethane Example 47
N-Boc aziridine 166:
Boc anhydride (113 mg, 0.52 mmol) was added to a solution of aziridine 165 (125 mg, 0.49 mmol), triethylamine (70 μL), DMAP (cat. amount) in dichloromethane (7 mL).
After 1 h the reaction was concentrated and the residue subjected to flash chromatography (40percent EtoAc in hexanes) to give 154 mg (88percent) of the N Boc aziridine 166 as a pale oil. 1H NMR (CDCl3, 300 MHz): δ 6.82 (m, 1H); 4.47 (br m, 1H); 4.23 (t, 2H, J=4.7 Hz); 3.81 (t, 2H, J=4.7 Hz); 3.75 (s, 3H); 3.00 (br d, 1H, J=18.0 Hz); 2.90-2.85 (m, 2H); 2.65-2.55 (m, 1H); 2.10 (s, 3H); 1.44 (s, 9H).
15% With triethylamine In dichloromethane; water Preparation of t-Boc aziridine
Di-t-butyl-dicarbonate (22.0 g, 0.1 mol) in dichloromethane (20 mL) was added dropwise to a stirred solution of aziridine (4.3 g, 0.1 mol, Example 1(A)) and triethylamine (15.0 g, 0.15 mol) in dichloromethane (10 mL).
After 2 h at room temperature, the reaction mixture was concentrated to ~10 mL by rotary evaporation at room temperature, then treated with water (100 mL).
The organic layer was separated and thoroughly washed with water (5*50 mL).
Removal of the solvent yielded the title product, which was used in the next step without further purification. Yield: 2.1 g (15percent).
1 H NMR (CDCl3): δ 1.5 (s, 9H, C--Me) and 2.15 (s, 4H, N--CH2).

References: [1] Chemical Communications, 1998, # 2, p. 253 - 254.
[2] Patent: US6534037, 2003, B1, .
[3] Patent: US5952375, 1999, A, .
[4] Patent: US5763483, 1998, A, .
[5] Patent: US2004/53999, 2004, A1, .
[6] Patent: US2008/318957, 2008, A1, . Location in patent: Page/Page column 63.
[7] Patent: US5608110, 1997, A, .
  • 2
  • [ 158690-56-3 ]
  • [ 97308-23-1 ]
References: [1] Organic Letters, 2013, vol. 15, # 8, p. 1946 - 1949.
[2] Angewandte Chemie - International Edition, 2018, vol. 57, # 34, p. 10980 - 10984[3] Angew. Chem., 2018, vol. 130, # 34, p. 11146 - 11150,5.
  • 3
  • [ 26690-80-2 ]
  • [ 97308-23-1 ]
References: [1] Heterocycles, 1997, vol. 45, # 2, p. 231 - 234.
[2] European Journal of Medicinal Chemistry, 2010, vol. 45, # 11, p. 5370 - 5383.
[3] Angewandte Chemie - International Edition, 2018, vol. 57, # 34, p. 10980 - 10984[4] Angew. Chem., 2018, vol. 130, # 34, p. 11146 - 11150,5.
  • 4
  • [ 96628-67-0 ]
  • [ 117861-38-8 ]
  • [ 97308-23-1 ]
References: [1] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 6, p. 1492 - 1498.
  • 5
  • [ 39684-80-5 ]
  • [ 97308-23-1 ]
References: [1] Organic Letters, 2018, vol. 20, # 2, p. 337 - 340.
  • 6
  • [ 71999-74-1 ]
  • [ 97308-23-1 ]
References: [1] Organic Letters, 2018, vol. 20, # 2, p. 337 - 340.
  • 7
  • [ 122234-46-2 ]
  • [ 97308-23-1 ]
References: [1] Organic Letters, 2018, vol. 20, # 2, p. 337 - 340.
  • 8
  • [ 371-41-5 ]
  • [ 26690-80-2 ]
  • [ 263409-78-5 ]
  • [ 97308-23-1 ]
References: [1] Tetrahedron Letters, 2006, vol. 47, # 27, p. 4591 - 4595.
  • 9
  • [ 24424-99-5 ]
  • [ 97308-23-1 ]
References: [1] Heterocycles, 1997, vol. 45, # 2, p. 231 - 234.
 

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Technical Information

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