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Chemical Structure| 86123-95-7 Chemical Structure| 86123-95-7

Structure of Boc-D-Ser(Me)-OH
CAS No.: 86123-95-7

Chemical Structure| 86123-95-7

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Product Details of [ 86123-95-7 ]

CAS No. :86123-95-7
Formula : C9H17NO5
M.W : 219.24
SMILES Code : COC[C@@H](NC(=O)OC(C)(C)C)C(O)=O
MDL No. :MFCD08063987
InChI Key :RFGMSGRWQUMJIR-ZCFIWIBFSA-N
Pubchem ID :27281801

Safety of [ 86123-95-7 ]

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

Computational Chemistry of [ 86123-95-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 0
Fraction Csp3 0.78
Num. rotatable bonds 7
Num. H-bond acceptors 5.0
Num. H-bond donors 2.0
Molar Refractivity 52.75
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.

1.88
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

0.41
Log Po/w (WLOGP)?

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

0.61
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.

0.01
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

-0.14
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.55

Water Solubility

Log S (ESOL):?

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

-1.0
Solubility 22.1 mg/ml ; 0.101 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.

-1.76
Solubility 3.82 mg/ml ; 0.0174 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

-0.79
Solubility 35.2 mg/ml ; 0.161 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.

-7.35 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)

2.97

Application In Synthesis of [ 86123-95-7 ]

* 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 [ 86123-95-7 ]

[ 86123-95-7 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 100-46-9 ]
  • [ 86123-95-7 ]
  • [ 880468-89-3 ]
YieldReaction ConditionsOperation in experiment
90% To a solution of acid (R)-9 (0.7 g, 3.2 mmol) in dry THF was added N-methylmorpholine (0.43 mL, 3.8 mmol) at -78 °C under an argon atmosphere. After 5 min, isobutyl chloroformate (0.5 mL, 3.8 mmol) was added and stirred for another 5 min. To this reaction mixture benzylamine (0.4 mL, 3.8 mmol) was added at -78 °C after which the reaction mixture was stirred at room temperature for 1 h. After completion of the reaction, the reaction mixture was filtered, and washed with ethylacetate. The solvent was removed under reduced pressure and the crude product was subjected to column chromatography (silica gel, petroleum ether/acetone, 85:15) to yield (R)-10 as a colorless solid (0.9 g, 90percent); mp 63-64 °C; (c 0.9, CHCl3); IR (CHCl3, cm-1): numax 3683, 3431, 3020, 2931, 2401, 1714, 1523, 1496, 1368, 1165, 1119, 928, 758, 669; 1H NMR (200 MHz, CDCl3): deltaH 1.43 (s, 9H), 3.37 (s, 3H), 3.47-3.54 (dd, J = 9.2, 6.1 Hz, 1H), 3.82 (dd, J = 9.3, 3.7 Hz, 1H), 4.27 (m, 1H), 4.47 (d, J = 5.1 Hz, 1H), 5.41 (br s, 1H), 6.77 (m, 1H), 7.22-7.37 (m, 5H); 13C NMR (50 MHz, CDCl3): deltaC 170.3 (CO), 155.5 (CO), 137.9 (C), 128.7 (CH, 2 carbons), 127.5 (CH, 3 carbons), 80.4 (C), 72.1 (CH2), 59.1 (CH3), 54.0 (CH), 43.5 (CH2), 28.3 (CH3, 3 carbons); MS: m/z 331 [M+Na]+.
90% With 4-methyl-morpholine; isobutyl chloroformate; In tetrahydrofuran; at -78 - 30℃; for 1h;Inert atmosphere; Example-5 Synthesis of (R)-tert-butyl 1-(benzylamino)-3-methoxy-1-oxopropan-2-ylcarbamate (R)-9 To a solution of acid (R)-8 (0.7 g, 3.2 mmol) in dry THF was added N-methylmorpholine (0.43 mL, 3.8 mmol) at -78° C. under argon atmosphere. After 5 min, isobutyl chloroformate (0.5 mL, 3.8 mmol) was added and stirred the content for another 5 min. To this reaction mixture benzylamine (0.4 mL, 3.8 mmol) was added at -78° C. and allowed the reaction mixture to stir at 30° C. for 1 h. After completion of the reaction, reaction mixture was filtered, washed with ethylacetate. The solvent was removed under reduced pressure and the crude product was subjected to column chromatography (silica gel, petroleum ether/acetone, 85:15) to yield (R)-9 as colorless solid (0.9 g, 90percent). m.p 63-64° C.; [alpha]25D=-20.5 (c 0.9, CHCl3); IR (CHCl3, cm-1): vmax 3683, 3431, 3020, 2931, 2401, 1714, 1523, 1496, 1368, 1165, 1119, 928, 758, 669; 1H NMR (200 MHz, CDCl3): deltaH 1.43 (s, 9H), 3.37 (s, 3H), 3.47-3.54 (dd, J=9.2, 6.1 Hz, 1H), 3.82 (dd, J=9.3, 3.7 Hz, 1H), 4.27 (m, 1H), 4.47 (d, J=5.1 Hz, 1H), 5.41 (bs, 1H), 6.77 (m, 1H), 7.22-7.37 (m, 5H); 13C NMR (50 MHz, CDCl3): deltaC 170.3 (CO), 155.5 (CO), 137.9 (C), 128.7 (CH, 2 carbons), 127.5 (CH, 3 carbons), 80.4 (C), 72.1 (CH2), 59.1 (CH3), 54.0 (CH), 43.5 (CH2), 28.3 (CH3, 3 carbons); MS: m/z 331 [M+Na]+.
90% To a solution of acid 5 (0.985 g, 4.49 mmol) in dry THF (10ml) was added N-methylmorpholine (0.6 mL, 5.39 mmol) at -78 °C under an argon atmosphere.After 5 min, isobutyl chloroformate (0.7 mL, 5.39 mmol)was added and stirred for another 5 min. To this reaction mixture benzyl amine (0.6 mL, 5.39 mmol) was added at -78 °C andthe reaction mixture was allowed to come up to room temperature and stirred foranother 1 h. After completion of the reaction (TLC), the reaction mixture wasfiltered through a pad of celite, and washed with ethyl acetate (20 mL). Thesolvent was removed under reduced pressure and the crude reaction mixture wassubjected to flash chromatography (CombiFlash Rf 200i, Teledyne Isco) using RediSep silica gel column (12 g) eluting with petroleum ether?EtOAc (3:2,isocratic) to yield 6as a white solid (1.24 g, 90percent); Rf0.35 (40percent EtOAc inpetroleum ether); mp 63-64 °C [Lit.63-64 °C3]; [alpha]D26 -24.3 (c 1.04, CHCl3) [Lit. [alpha]D26-20.5 (c 0.9, CHCl3)3]; IR (CHCl3) umax:3428, 3345, 3017, 2933, 2405, 1708, 1671, 1493, 1365, 1220, 1167, 1116, 1075,1025, 922, 860, 762, 668 cm-1; 1H NMR (200 MHz, CDCl3) delta: 7.40-7.19 (m, 5H), 6.78 (brs, 1H),5.55-5.33 (m, 1H), 4.48 (d, J = 4.3 Hz, 2H), 4.27 (brs, 1H), 3.84 (dd, J= 3.9, 9.2 Hz, 1H), 3.50 (dd, J = 6.2, 9.1 Hz, 1H), 3.36 (s, 3H), 1.43(s, 9H); 13C NMR (50 MHz,CDCl3) delta: 170.3,155.5, 138.0, 128.7, 127.5, 80.4, 72.1, 59.1, 43.5, 28.3; HRMS (ESI): m/z calcdfor C16H24N2O4Na [M + Na]+331.1628; found: 331.1612.
46.4% With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 2h;Cooling with ice; Synthesis of (R)-N-Benzyl-2-Boc-amino-3-methoxypropionamide[0157] (R)-2-N-Boc-amino-3-methoxypropanoic acid (15.0 g, 68.4 mmol), phenylmethanamine (7.33 g, 68.4 mmol), and DMAP (4.17 g, 34.2 mmol) were dissolved in DCM (150 mL). The solution was cooled in an ice-bath and EDC (21 .21 g, 137 mmol) was added dropwise to the solution. Once addition was complete, the reaction mixture stirred at warmed to room temperature and stirred for two hours. Then DCM (200 ml) was added to the mixture. The DCM organic phase was washed with H20 (200 mL x 1 ), 0.5 N HC1 (200 mL x 2), 5percent sodium bicarbonate (200 mL chi 2) and water (200 mL x 2). The organic phase was dried over sodium sulfate, filtered, and solvent removed under reduced pressure. The desired product was obtained as a colorless semi-solid with a purity >95percent (9.8 g, 46.4percent). NMR (500 MHz, CDC13) delta 1.46 (s, 9H), 3.38 (s, 3H), 3.51 (m, 1H), 3.86 (d, 1 H), 4.30 (br., 1H), 4.50 (s, 2H), 5.42 (br., 1H), 6.74 (br., 1H), 7.28 (m, 3H), 7.35 (m, 2H). LC-MS (m/z) , calculated. 308.2, found 309.1 [M + H]+, 331.1 [M + Naf.
The C936 solution prepared as above in example 2 was cooled to <-10°C and isobutyl chloroformate (14.2ml, 0.107mol) at <-5°C. N-methylmorpholine (11.8ml, 0.17mol) was added at<-5°C and the mixture aged for 30 minutes at <-5O. A solution of benzylamine (12.2ml, 0.11mol) in methylene chloride was added at <-5°C and the mixture warmed to room temperature. After aging for 1 hour the mixture was washed with water (44ml), 1N HCI (44ml), 8percent sodium bicarbonate (44ml) and water (44ml) to yield a C937 solution in methylene chloride.
Example-32: Preparation of (R)-2-tert-butyl l-(benzylamino)-3-methoxy-l- oxopropan-2-yl carbonate compound of formuIa-18:; Ethylchoroformate (49.3 g) followed by N-methylmorpholine (46 g) was added to a pre-cooled reaction mass of (R)-2-(tert-butoxycarbonylamino)-3-methoxy propionic acid (280 ml) obtained in example-31 at -10 to -15°C and stirred for 15 min at -15°C. Benzylamine (49 g) was added to the reaction mixture slowly at -10 to -15 °C and stirred for 1.5 hours. Reaction temperature was raised to 20-25°C and stirred for 1.5 hours. The reaction mixture was washed with dilute hydrochloric acid (100 ml), and further the organic layer was washed with sodium bicarbonate solution followed by washed with water. The reaction mixture containing title compound was directly used for next stage without any isolation and purification.
Preparation of (R)-N-benzyl-2-((tert-butoxy)carbonylamino)-3- methoxypropionamide(R)-2-((Tert-butoxy)carbonylamino)-3-methoxypropanoic acid (92.5 gm) as obtained in example 2 was dissolved in methylene chloride (925 ml) and then cooled to - 10°C. To the solution was added isobutyl chloroformate (57 ml) and then added 4- methylmorpholine (46.5 ml). The reaction mass was maintained for 30 minutes at -5°C and then added a solution of benzyl amine (46 ml) in methylene chloride (46 ml). The temperature of the reaction mass was raised to room temperature and then added water (140 ml). The separated organic layer was dried with sodium sulfate and the solvent was distilled off to obtain a residual mass. To the residual mass was added n-hexane (1200 ml) and stirred for 2 hours at room temperature. The solid obtained was collected by filtration and dried to obtain 116 gm of (R)-N-benzyl-2-((tert-butoxy)carbonylamino)-3- methoxypropionamide.

  • 2
  • [ 86123-95-7 ]
  • [ 880468-89-3 ]
  • 3
  • [ 100-46-9 ]
  • [ 86123-95-7 ]
  • [ 880468-89-3 ]
  • [ 1253790-58-7 ]
  • [ 69805-82-9 ]
  • C16H24N2O4 [ No CAS ]
  • C19H23N3O3 [ No CAS ]
  • C17H26N2O4 [ No CAS ]
 

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