H-Ser(tBu)-OMe·HCl | C-protective Amino Acid

CAS No. :	17114-97-5
Formula :	C₈H₁₈ClNO₃
M.W :	211.69
SMILES Code :	O=C(OC)[C@@H](N)COC(C)(C)C.[H]Cl
Synonyms :	H-Ser(tBu)-OMe.HCl
MDL No. :	MFCD00077108
InChI Key :	PCIABNBULSRKSU-RGMNGODLSA-N
Pubchem ID :	16218549

Safety of [ 17114-97-5 ]

GHS Pictogram:
Signal Word:	Warning
Hazard Statements:	H302-H315-H319-H332-H335
Precautionary Statements:	P261-P280-P305+P351+P338

Computational Chemistry of [ 17114-97-5 ] Show Less

Physicochemical Properties

Num. heavy atoms	13
Num. arom. heavy atoms	0
Fraction Csp3	0.88
Num. rotatable bonds	5
Num. H-bond acceptors	4.0
Num. H-bond donors	1.0
Molar Refractivity	52.65
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	61.55 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.0
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	0.88
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.1
Log P_o/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.	0.55
Log P_o/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	0.29
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	0.56

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.38
Solubility	8.89 mg/ml ; 0.042 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	3.7 mg/ml ; 0.0175 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	-1.0
Solubility	21.3 mg/ml ; 0.1 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.	-6.97 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	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)	2.45

Application In Synthesis of [ 17114-97-5 ]

* 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 [ 17114-97-5 ]

[ 17114-97-5 ] Synthesis Path-Downstream 1~54

1
[ 75-44-5 ]
[ 17114-97-5 ]
[ 145080-94-0 ]

References: [1]Journal of Organic Chemistry,1992,vol. 57,p. 7364 - 7366.

2
[ 2389-60-8 ]
[ 17114-97-5 ]
N^α-Benzyloxycarbonyl-N^ε-tert-butyloxycarbonyl-L-lysyl-O-tert-butyl-L-serin-methylester [ No CAS ]

References: [1]Liebigs Annalen der Chemie,1993,p. 237 - 240.

3
[ 116939-86-7 ]
[ 17114-97-5 ]
[ 138541-20-5 ]

References: [1]Liebigs Annalen der Chemie,1992,p. 361 - 370.

4
[ 17114-97-5 ]
[ 114-25-0 ]
[ 109203-68-1 ]

References: [1]Monatshefte fur Chemie,1986,vol. 117,p. 1205 - 1217.

5
[ 129288-48-8 ]
[ 17114-97-5 ]
Z-D-Ala-Ser(OtBu)-OMe [ No CAS ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 807 - 810.

6
[ 17114-97-5 ]
Z-L-Ala-NCA [ No CAS ]
Z-Ala-Ser(OtBu)-OMe [ No CAS ]

References: [1]Tetrahedron Letters,1995,vol. 36,p. 807 - 810.

7
[ 2650-64-8 ]
[ 17114-97-5 ]
Z-Gln-Ser(OtBu)-OH [ No CAS ]

References: [1]Hoppe-Seyler's Zeitschrift fur Physiologische Chemie,1976,vol. 357,p. 1223 - 1227.

8
[ 453-71-4 ]
[ 17114-97-5 ]
4-[(S)-(2,2-Dimethyl-propoxy)-methoxycarbonyl-methyl]-amino}-3-nitro-benzoic acid [ No CAS ]
4-[(R)-(2,2-Dimethyl-propoxy)-methoxycarbonyl-methyl]-amino}-3-nitro-benzoic acid [ No CAS ]

References: [1]Journal of Organic Chemistry,1998,vol. 63,p. 1172 - 1177.

9
[ 17114-97-5 ]
3-Trimethylsilanylethynyl-pyridine-2-carboxylic acid [ No CAS ]
[ 219623-07-1 ]

References: [1]Acta Chemica Scandinavica,1998,vol. 52,p. 1327 - 1332.

10
[ 17114-97-5 ]
[ 219623-06-0 ]
(S)-O-tert-butyl-N-(3-phenylethynylpyridine-2-carbonyl)serine methyl ester [ No CAS ]

References: [1]Acta Chemica Scandinavica,1998,vol. 52,p. 1327 - 1332.

12
[ 17114-97-5 ]
[ 340714-55-8 ]
3-tert-butoxy-2-(2-tert-butoxycarbonylamino-5,5,5-trifluoro-4-trifluoromethyl-pentanoylamino)-propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
87%	With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine; In DMF (N,N-dimethyl-formamide); at 20℃; for 0.666667h;	To a stirred solution of 5 (11 mg, 0.03 mmol) in anhydrous DMF (1 mL) was added diisopropyl ethyl amine (13 mg, 0.1 mmol), HBTU (13 mg, 0.03 mmol), and H-Ser(t-Bu)-OMe HCl (14 mg, 0.065 mmol) sequentially. The mixture was stirred at room temperature for 40 min before 6 mL of H2O was added. The reaction mixture was extracted with ether (15 ml) and the organic layer was futher washed with 1 N HCl (5 mL.x.2) and 5percent NaHCO3 solution (5 ml), dried over MgSO4, and concentrated to afford 8 (13 mg, 87percent yield) as a white solid. 1H NMR (300 MHz, CDCl3) delta 6.68 (d, 1H, J=8.1 Hz), 5.21 (d, 1H, J=8.1 Hz), 4.64 (m, 1H), 4.40 (m, 1H), 3.86 (dd, 1H, J=2.7 Hz, 9.3 Hz), 3.76 (s, 3H), 3.56 (dd, 1H, J=3.3 Hz, 9.3 Hz), 3.50 (m, 1H), 2.33-2.10 (br. m, 2H), 1.45 (s, 9H), 1.14 (s, 9H).

References: [1]Patent: US2004/138493,2004,A1 .Location in patent: Page 20.
[2]Organic letters,2001,vol. 3,p. 1285 - 1286.

13
[ 17114-97-5 ]
(2S,3S)-2-((tert-butoxycarbonyl)amino)-4,4,4-trifluoro-3-methyl-butanoic acid [ No CAS ]
Boc-TFV(2S,3S)-Ser(Ot-Bu)-OMe(2S) [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 1722 - 1725.

14
[ 17114-97-5 ]
(2S,3R)-2-((tert-butoxycarbonyl)amino)-4,4,4-trifluoro-3-methyl-butanoic acid [ No CAS ]
Boc-TFV(2S,3R)-Ser(Ot-Bu)-OMe(2S) [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 1722 - 1725.

15
[ 17114-97-5 ]
[ 888725-63-1 ]
Boc-TFV(2R,3S)-Ser(Ot-Bu)-OMe(2S) [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 1722 - 1725.

16
[ 17114-97-5 ]
(2R,3R)-2-((tert-butoxycarbonyl)amino)-4,4,4-trifluoro-3-methylbutanoic acid [ No CAS ]
Boc-TFV(2R,3R)-Ser(Ot-Bu)-OMe(2S) [ No CAS ]

References: [1]Journal of Organic Chemistry,2002,vol. 67,p. 1722 - 1725.

17
[ 1694-92-4 ]
[ 17114-97-5 ]
[ 468773-16-2 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5183 - 5189.
[2]Tetrahedron,2002,vol. 58,p. 3159 - 3170.

18
[ 5720-05-8 ]
[ 17114-97-5 ]
3-tert-butoxy-2-p-tolylamino-propionic acid methyl ester [ No CAS ]

References: [1]Tetrahedron Letters,2003,vol. 44,p. 1691 - 1694.

19
[ 17114-97-5 ]
[ 618884-61-0 ]
[ 618884-62-1 ]

References: [1]Organic Letters,2003,vol. 5,p. 4421 - 4424.

20
[ 17114-97-5 ]
[ 752244-63-6 ]
methyl (2S)-3-tert-butoxy-2-((S)-2-(tert-butoxycarbonyl)amino-4-(perfluorophenyl)butanamido)propanoate [ No CAS ]

References: [1]Journal of Organic Chemistry,2004,vol. 69,p. 5468 - 5470.

21
[ 17114-97-5 ]
[ 467217-77-2 ]
[ 847778-78-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

22
[ 17114-97-5 ]
[ 618884-60-9 ]
[ 618884-62-1 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

23
[ 1011478-20-8 ]
[ 17114-97-5 ]
(S)-3-tert-butoxy-2-[3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3-methyl-biphenyl-4-carbonyl]-amino}-propionic acid methyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; triethylamine; In dichloromethane; for 16h;	(1 ) (S)-3-tert-Butoxy-2-{r3'-(4-chloro-2,5-dimethyl-benzenesulfonylamino)-3-methyl- biphenyl-4-carbonyll-amino}-propionic acid methyl ester (18)To a stirred mixture of the acid 16 from step 4 of Example 45 (1 g, 2.33 mmol), (S)-2-Amino- 3-tert-butoxy-propionic acid methyl ester hydrochloride (739 mg, 3.49 mmol), triethylamine (1.3 ml, 9.3 mmol) and HOBt monohydrate (356 mg, 2.33 mmol) in DCM (20 ml) is added solid EDC hydrochloride (535 mg, 2.79 mmol) and stirring is continued for 16 hours. The mixture is diluted with DCM (50 ml) and washed twice with 2N-HCI (50 ml), water (50 ml), 10percent sodium carbonate (50 ml) and brine (20 ml). The organic phase is then dried over sodium sulphate and concentrated to give the title product 18 as white foam which is directly used in the next step.Optionally, the crude can be further purified by silica gel chromatography using cyclohexane / ethyl acetate from 5percent to 50percent) MS (ESI): 587-589 [M+H]+

References: [1]Patent: WO2008/28937,2008,A1 .Location in patent: Page/Page column 57.

24
[ 17114-97-5 ]
[ 856865-69-5 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5183 - 5189.

25
[ 17114-97-5 ]
[ 856865-91-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5183 - 5189.

26
[ 17114-97-5 ]
(S)-2-{(S)-3-tert-Butoxy-2-[methyl-(2-nitro-benzenesulfonyl)-amino]-propionylamino}-4-methyl-pentanoic acid [ No CAS ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 5183 - 5189.

27
[ 17114-97-5 ]
[ 847778-79-4 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

28
[ 17114-97-5 ]
[ 847778-82-9 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

29
[ 17114-97-5 ]
[ 847778-83-0 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

30
[ 17114-97-5 ]
[ 847778-81-8 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.

31
[ 17114-97-5 ]
[ 618884-64-3 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.
[2]Organic Letters,2003,vol. 5,p. 4421 - 4424.

32
[ 17114-97-5 ]
[ 618884-65-4 ]

References: [1]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.
[2]Journal of Organic Chemistry,2005,vol. 70,p. 1389 - 1399.
[3]Organic Letters,2003,vol. 5,p. 4421 - 4424.

33
[ 17114-97-5 ]
[ 468773-61-7 ]