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Chemical Structure| 248921-66-6 Chemical Structure| 248921-66-6

Structure of Boc-D-Ser(tBu)-OH
CAS No.: 248921-66-6

Chemical Structure| 248921-66-6

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Product Details of [ 248921-66-6 ]

CAS No. :248921-66-6
Formula : C12H23NO5
M.W : 261.31
SMILES Code : O=C(O)[C@H](NC(OC(C)(C)C)=O)COC(C)(C)C
MDL No. :MFCD09751020
InChI Key :BPYLRGKEIUPMRJ-MRVPVSSYSA-N
Pubchem ID :6992546

Safety of [ 248921-66-6 ]

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

Computational Chemistry of [ 248921-66-6 ] Show Less

Physicochemical Properties

Num. heavy atoms 18
Num. arom. heavy atoms 0
Fraction Csp3 0.83
Num. rotatable bonds 8
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 67.21
TPSA ?

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

84.86 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

2.65
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

1.39
Log Po/w (WLOGP)?

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

1.78
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.

0.89
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

0.77
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.5

Water Solubility

Log S (ESOL):?

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

-1.81
Solubility 4.07 mg/ml ; 0.0156 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.

-2.78
Solubility 0.438 mg/ml ; 0.00168 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

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

-1.61
Solubility 6.37 mg/ml ; 0.0244 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.

-6.91 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.

0.56

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)

3.35

Application In Synthesis of [ 248921-66-6 ]

* 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 [ 248921-66-6 ]

[ 248921-66-6 ] Synthesis Path-Downstream   1~9

  • 1
  • [ 248921-66-6 ]
  • [ 56602-33-6 ]
  • [ 86499-35-6 ]
  • [ 77-92-9 ]
  • [ 145486-02-8 ]
YieldReaction ConditionsOperation in experiment
480 mg (100%) With triethylamine; In dichloromethane; ethyl acetate; Step A: 2(R)-t-Butoxycarbonylamino-3-(t-butoxy)-N-[2,3,4,5-tetrahydro-2-oxo-1H-1-benzazepin-3(R)-yl]propanamide To a solution of 200 mg (1.13 mmol) of 3(R)-amino-2,3,4,5-tetrahydro-1H-1-benzazepin-2-one (Example 1, Step B) in 8 mL of dry methylene chloride was added 0.206 mL (1.48 mmol) of triethylamine, 553 mg (1.25 mmol) of <strong>[248921-66-6]BOC-D-serine t-butyl ether</strong> followed by 602 mg (1.36 mmol) of benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate. The reaction mixture was stirred at room temperature for 2 hours then diluted with 100 mL of ethyl acetate, washed with 25 mL of 5% aqueous citric acid, 25 mL of saturated sodium bicarbonate and 25 mL of brine. The organic layer was dried over magnesium sulfate, filtered and the solvents removed under vacuum. The residue was purified by flash chromatography on silica gel, eluding with ethyl acetate/hexane (55:45) to afford 480 mg (100%) of the product as a white foam. 1 H NMR (200 MHz,CDCl3): 1.20 (s,9H), 1.47 (s,9H), 1.92 (m,1H), 2.55-3.02 (m,3H), 3.38 (t,8 Hz,1H), 3.78 (m,1H), 4.15 (m,1H), 4.52 (m,1H), 5.45 (s,1H), 7.00 (m,1H), 7.10-7.35 (m,3H), 7.68 (d,4 Hz,1H), 8.05 (s,1H). FAB-MS: calculated for C22 H33 N3 O5 419; found 420 (M+H,20%), 426 (M+Li,40%).
  • 2
  • [ 110-91-8 ]
  • [ 248921-66-6 ]
  • [ 935878-01-6 ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; N-(3-dimethylaminopropyl)-N-ethylcarbodiimide; triethylamine; In dichloromethane; at 0 - 20℃; STEP A: (l-fe/t-Butoxymethyl-2-morpholin-4-yl-2-oxo-ethyl)-(J?)-carbamic acid fert-butyl ester To an ice cooled solution of morpholine (0.6 mL, 6.9 mmol) , <strong>[248921-66-6]Boc-D-Ser(tBu)-OH</strong> (3 g, 6.8 mmol) and HOBT (1.2 g, 9 mmol) in CH2Cl2 (50 mL), TEA (1.9 mL) was added followed by addition of 1,3-dimethylamino propyl-3-ethylcarbodiimide (EDC, 1.7 g, 8.6 mmol). The reaction mixture was allowed to warm to room temperature and was then stirred overnight. EtOAc (200 mL) was added to the reaction mixture. This resulting solution was washed with dilute HCl solution, NaHCO3 (aq.) solution, and NaCl (aq.) solution. The organic <n="109"/>layer was dried over MgSO4, filtered, and evaporated to yield (l-tert-butoxymethyl-2- morpholin-4-yl-2-oxo-ethyl)-(/?J-carbamic acid tert-butyl ester as a crude oil. MH+ 331.2
  • 3
  • [ 248921-66-6 ]
  • [ 1137085-16-5 ]
  • C32H46N6O12 [ No CAS ]
  • 4
  • [ 248921-66-6 ]
  • [ 74-88-4 ]
  • [ 1126450-26-7 ]
  • 5
  • [ 24424-99-5 ]
  • [ 18783-53-4 ]
  • [ 248921-66-6 ]
  • 7
  • [ 248921-66-6 ]
  • [ 1212336-73-6 ]
  • 8
  • Fmoc-gly-wang resin [ No CAS ]
  • [ 248921-66-6 ]
  • [ 21394-04-7 ]
  • [ 1429504-34-6 ]
  • [ 1429504-44-8 ]
  • [ 71989-14-5 ]
  • [ 35661-38-2 ]
  • [ 109425-55-0 ]
  • (R)-2-(9H-Fluoren-9-ylmethoxycarbonylamino)-N-trityl-succinamic acid [ No CAS ]
  • C122H173N17O32 [ No CAS ]
  • 9
  • [ 248921-66-6 ]
  • [ 1367454-32-7 ]
  • [ 1367455-21-7 ]
YieldReaction ConditionsOperation in experiment
79% 2-[2-Amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionate (?A93?) [0808] 954 mg of dicyclohexylcarbodiimide are added to a solution of 2.4 g of <strong>[248921-66-6](R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionic acid</strong> in 50 ml of dichloromethane, and the mixture is stirred at 25 C. for 1 h. The precipitate is filtered off, and the filtrate is added to a solution of 1 g of [2-amino-6-(4,5-difluoro-2-hydroxymethylphenyl)quinazolin-4-yl]-(1,3-dihydroisoindol-2-yl)methanone and 14 mg of 4-(dimethylamino)pyridine (DMAP) in 50 ml of tetrahydrofuran. The mixture is stirred at 25 C. for 48 h, undissolved material is filtered off, and the filtrate is evaporated to dryness. The residue is purified by normal-phase chromatography. [0809] Yield: 1.2 g (79%) of 2-[2-amino-4-(1,3-dihydroisoindole-2-carbonyl)quinazolin-6-yl]-4,5-difluorobenzyl (R)-3-tert-butoxy-2-tert-butoxycarbonylaminopropionate; LC-MS retention time: 2.79 min.
 

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