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Chemical Structure| 41036-32-2 Chemical Structure| 41036-32-2

Structure of H-D-Ala-OBzl·TosOH
CAS No.: 41036-32-2

Chemical Structure| 41036-32-2

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Product Details of [ 41036-32-2 ]

CAS No. :41036-32-2
Formula : C17H21NO5S
M.W : 351.42
SMILES Code : O=S(C1=CC=C(C)C=C1)(O)=O.C[C@@H](N)C(OCC2=CC=CC=C2)=O
MDL No. :MFCD00039092
InChI Key :NWOPHJSSBMABBD-DDWIOCJRSA-N
Pubchem ID :2802425

Safety of [ 41036-32-2 ]

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

Computational Chemistry of [ 41036-32-2 ] Show Less

Physicochemical Properties

Num. heavy atoms 24
Num. arom. heavy atoms 12
Fraction Csp3 0.24
Num. rotatable bonds 5
Num. H-bond acceptors 6.0
Num. H-bond donors 2.0
Molar Refractivity 91.09
TPSA ?

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

115.07 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

3.02
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

-0.14
Log Po/w (WLOGP)?

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

3.25
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.

2.26
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

1.37
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.95

Water Solubility

Log S (ESOL):?

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

-1.97
Solubility 3.76 mg/ml ; 0.0107 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.

-1.82
Solubility 5.29 mg/ml ; 0.0151 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

-2.57
Solubility 0.955 mg/ml ; 0.00272 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

Yes
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.

-8.54 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

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

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)

3.1

Application In Synthesis of [ 41036-32-2 ]

* 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 [ 41036-32-2 ]

[ 41036-32-2 ] Synthesis Path-Downstream   1~54

  • 1
  • [ 41036-32-2 ]
  • (S)-2-tert-Butoxycarbonylamino-heptanedioic acid 7-benzyl ester [ No CAS ]
  • [ 18814-51-2 ]
  • 3
  • [ 1676-90-0 ]
  • [ 41036-32-2 ]
  • [ 92398-55-5 ]
  • 6
  • [ 41036-32-2 ]
  • Boc-D-Arg(NO2) [ No CAS ]
  • [ 92261-84-2 ]
  • 8
  • [ 41036-32-2 ]
  • [ 3401-36-3 ]
  • [ 132343-11-4 ]
  • 9
  • [ 41036-32-2 ]
  • [ 49827-15-8 ]
  • [ 171557-07-6 ]
  • 10
  • [ 41036-32-2 ]
  • C9H15BrO4 [ No CAS ]
  • (2R)-2-(3-Bromo-2-methylpropionylamino)propionic acid benzyl ester [ No CAS ]
  • 12
  • [ 41036-32-2 ]
  • [ 100-52-7 ]
  • (R)-2-[1-Phenyl-meth-(E)-ylidene]-amino}-propionic acid benzyl ester [ No CAS ]
  • 13
  • [ 41036-32-2 ]
  • [ 186753-98-0 ]
  • [ 263010-60-2 ]
  • 14
  • [ 5068-28-0 ]
  • [ 41036-32-2 ]
  • Boc-Cys(SBn)-D-Ala-OBn [ No CAS ]
  • 15
  • [ 1147-76-8 ]
  • [ 41036-32-2 ]
  • [ 736145-05-4 ]
  • 16
  • [ 185990-56-1 ]
  • [ 41036-32-2 ]
  • [ 908589-92-4 ]
  • 17
  • [ 27460-85-1 ]
  • [ 41036-32-2 ]
  • [ 947509-47-9 ]
  • 18
  • [ 41036-32-2 ]
  • [ 436848-62-3 ]
  • [ 947189-25-5 ]
  • 19
  • [ 69651-48-5 ]
  • [ 41036-32-2 ]
  • [ 947509-48-0 ]
  • 20
  • [ 41036-32-2 ]
  • (R)-2-[(Diphenyl-phosphinoyl)-phenyl-methyl]-amino}-propionic acid benzyl ester [ No CAS ]
  • 24
  • [ 41036-32-2 ]
  • [ 374756-15-7 ]
  • 25
  • [ 782493-67-8 ]
  • [ 41036-32-2 ]
  • C33H42F3N3O4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium tris(acetoxy)borohydride; triethylamine; In 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran; at 20℃; for 168h; EXAMPLE 76 Step A: D-alanine benzylester p-toluenesulfonic acid salt (22mg, 0. 062MMOL), triethylamine (9. 0muL, 0. 062MMOL), and sodium triacetoxyborohydride (22mg, 0. LOMMOL) were added to a stirring solution of 1-((1R,3S)-3-isopropyl-3-[6-(trifluoromethyl)-2H-1, 3-benzoxazin-3 (4H)- yl] carbonyl} cyclopentyl) piperidin-4-one (19MG, 0.021mmol) in DCM (LOML). The reaction mixture was stirred at rt for 96h, however, the reaction had not gone to completion. Another 39mg (0. 1 LMMOL) OF L- alanine BENZYLESTERP-TOLUENESULFONIC acid salt and 15, UL (0. 1 LMMOL) of triethylamine was added to the reaction mixture. After stirring for an additional 72h at rt, the reaction mixture was diluted with dichloromethane (50ML), washed with sodium bicarbonate solution (1 x 50ML) and brine (1 x 50ML), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by preparatory TLC (silica gel, 0. 25% ammonium hydroxide, 2.25% MeOH, 97.5% DCM) afforded the desired product. ESI-MS calculated for C33H42F3N304 : 601. 70, found 602 (M + H).
With sodium tris(acetoxy)borohydride; triethylamine; In dichloromethane; at 20℃; for 168h; Step A: D-alanine benzylester p-toluenesulfonic acid salt (22 mg, 0.062 mmol), triethylamine (9.0 muL, 0.062 mmol), and sodium triacetoxyborohydride (22 mg, 0.10 mmol) were added to a stirring solution of 1-((1R,3S)-3-isopropyl-3-[6-(trifluoromethyl)-2H-1,3-benzoxazin-3(4H)-yl]carbonyl}cyclopentyl)piperidin-4-one (19 mg, 0.021 mmol) in DCM (10 mL). The reaction mixture was stirred at rt for 96 h, however, the reaction had not gone to completion. Another 39 mg (0.11 mmol) of L-alanine benzylester p-toluenesulfonic acid salt and 15 muL (0.11 mmol) of triethylamine was added to the reaction mixture. After stirring for an additional 72 h at rt, the reaction mixture was diluted with dichloromethane (50 mL), washed with sodium bicarbonate solution (1×50 mL) and brine (1×50 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by preparatory TLC (silica gel, 0.25% ammonium hydroxide, 2.25% MeOH, 97.5% DCM) afforded the desired product. ESI-MS calculated for C33H42F3N3O4: 601.70. found 602 (M+H).
  • 26
  • dibenzylphosphoryl-L-alanyl-L-proline [ No CAS ]
  • [ 41036-32-2 ]
  • dibenzylphosphoryl-L-alanyl-L-prolyl-D-alanine benzylester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With benzotriazol-1-ol; In ethyl acetate; N,N-dimethyl-formamide; Example 14 Dibenzylphosphoryl-L-alanyl-L-prolyl-D-alanine L-arginine salt: Dibenzylphosphoryl-L-alanyl-L-proline (1.4 g, 3.2 m mole), HOBt (476 mg, 3.5 m mole) and D-alanine benzylester p-toluene sulfonic acid salt (1.3 g, 3.5 m mole) were dissolved in DMF (5 ml), and WSC (0.64 ml) was added thereto while cooling to -15 C. The reaction was carried out for 3 hours under cooling and then overnight at room temperature. To the reaction solution ethyl acetate (100 ml) was added and the mixture was washed with 1N hydrochloric acid, 5% sodium bicarbonate and water in order. The mixture was dried with anhydrous sodium sulfate and the thus obtained solution was distilled under reduced pressure to give an oily dibenzylphosphoryl-L-alanyl-L-prolyl-D-alanine benzylester material.
With benzotriazol-1-ol; In ethyl acetate; N,N-dimethyl-formamide; EXAMPLE 14 Dibenzylphosphoryl-L-alanyl-L-prolyl-D-alanine L-arginine salt: Dibenzylphosphoryl-L-alanyl-L-proline (1.4 g, 3.2 m mole), HOBt (476 mg, 3.5 m mole) and D-alanine benzylester p-toluene sulfonic acid salt (1.3 g, 3.5 m mole) were dissolved in DMF (5 ml), and WSC (0.64 ml) was added thereto while cooling to -15 C. The reaction was carried out for 3 hours under cooling and then overnight at room temperature. To the reaction solution ethyl acetate (100 ml) was added and the mixture was washed with 1N hydrochloric acid, 5% sodium bicarbonate and water in order. The mixture was dried with anhydrous sodium sulfate and the solvent was distilled off under reduced, pressure to give oily dibenzylphosphoryl-L-alanyl-L-prolyl-D-alanine benzylester.
  • 27
  • [ 926309-49-1 ]
  • [ 41036-32-2 ]
  • (R)-2-[(2R,3S,4R,5R)-5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-2-azido-3,4-dihydroxy-tetrahydro-furan-2-ylmethoxy]-hydroxy-phosphorylamino}-propionic acid benzyl ester ammonium salt [ No CAS ]
YieldReaction ConditionsOperation in experiment
7% With dicyclohexyl-carbodiimide; In water; tert-butyl alcohol; EXAMPLE 6 General Procedure monobasic Salts The appropriate amino acid ester (7 mol equivalent) was added to a solution of the nucleoside 5'-monophosphate species (1 mol equivalent) and DCC (5 mol. equivalent) in tert-BuOH (5 mL) and H2O (2 mL) and the resulting mixture was stirred and heated at reflux for 4 h. The solvent was removed in vacuo to afford the desired salt which was purified as described. ; step 2-azido-cytidine 5'-O-(benzyloxy-D-alaninyl)phosphate The title compound was prepared as described in Example 5 utilizing azido-cytidine monophosphate (100 mg, 0.294 mmol), <strong>[41036-32-2]D-alanine benzyl ester tosylate</strong> salt (14m 368.83 mg, 2.058 mmol), DCC (302.82 mg, 1.47 mmol) in tert-BuOH (5 mL) and H2O. The crude was purified by column chromatography eluting with a gradient starting from iso-PrOH, to iso-PrOH/conc. NH4OH/H2O (90:7:3, 85:10:5 and 80:12:8) to I-68 afford a white solid (7.8 mg, 0.0139 mmol, 7%). 31P NMR (D2O): delta6.52; 1H NMR (D2O): delta7.63 (1H, d, H6-cytidine, J=7.8 Hz), 7.25 (5H, CH-benzyl), 5.91 (1H, d, H1'-cytidine, J=3.0 Hz), 5.86 (1H, d, H5-cytidine, J=7.8 Hz), 5.00 (2H, s, CH2-benzyl), 4.25-4.13 (2H, m, H2'-cytidine, H3'-cytidine), 3.84 (2H, m, CH2 (2H, m, H5'-cytidine), 3.71 (1H, m, CHalpha), 1.37 (3H, d, CH3-lateral chain); MS (ES) m/e: 524.0 (M-, 100%); Accurate mass: C19H23N7O9P required 524.1295 found 524.1295.
  • 28
  • [ 41036-32-2 ]
  • [ 770-12-7 ]
  • phenyl (benzyloxy-D-alaninyl)phosphorochloridate [ No CAS ]
  • 29
  • [ 41036-32-2 ]
  • [ 6622-55-5 ]
  • [ 1214259-11-6 ]
  • 30
  • [ 1708-29-8 ]
  • [ 41036-32-2 ]
  • [ 1257236-54-6 ]
YieldReaction ConditionsOperation in experiment
78% Ozone gas was passed into a mixture of 2,5-dihydrofuran (1.994 g, 28.46 mmol), methanol (24 ml_),DCM (100 mL) at -60C,(containing a trace of sudan red), until the red colour disappeared leaving a greyish solution. After removal of excess ozone with nitrogen, sodium cyanotrihydroborate (1.252 g, 19.92 mmol) was added to the solution and the mixture stirred at -500C for 10mins. A solution benzyl (2R)-2-aminopropanoate p-toluenesulfonate salt (5 g, 14.23 mmol) in methanol (10OmL) was added dropwise and the stirring continued at 00C overnight. Acetic acid (0.815 mL, 14.23 mmol) was added and the mixture evaporated. The residue was dissolved in DCM (20OmL) and washed with saturated aqueous NaHCO3 solution. The organic extracts were dried over Na2SO4, filtered and evaporated to an oil. The crude product was purified by flash silica chromatography, elution gradient 15 to 50% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford benzyl (2R)-2-morpholin- 4-ylpropanoate (2.75 g, 78 %) as a orange oil; m/z: 250.17 (MH+).
  • 31
  • [ 1292320-84-3 ]
  • [ 41036-32-2 ]
  • [ 1292320-87-6 ]
YieldReaction ConditionsOperation in experiment
51% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In dichloromethane; at 20℃; for 24h; III. Dipeptides for absolute configuration determination and alpha/gamma-peptide studies.A number of alpha/gamma-dipeptides were prepared using Fmoc-AMCP and standard coupling reagents. However, all proved recalcitrant to crystallization from a wide range of solvent mixtures via slow evaporation. Boc-AMCP was therefore obtained and dipeptides using either D or L forms of Alanine benzyl ester tosylate were prepared (Scheme 5-3). Scheme 5-3. (a) Coupling of Boc-AMCP to LAla-OBn tosylate; (b) Coupling of Boc-AMCP to DAla-OBn tosylate.BocNH-AMCP-DAla-OBnThe couplings proceeded in moderate yields to provide useful amounts of both dipeptides. The dipeptides were isolated and several crystallization trials were set up using slow evaporation from mixtures of chloroform, ethyl acetate, methanol, heptane, and pentane. A mixture of ethyl acetate and heptane yielded large needles for the Boc-NH-AMCP-DAla-OBn dipeptide. These diffracted into the space group PI and the X-ray crystal structure was solved. The absolute configuration of the AMCP residue was shown to be (R,R) for the ring stereocenters, resulting from the Michael addition using the (S) catalyst. The relative configuration of the stereocenters is trans.
  • 32
  • [ 15761-38-3 ]
  • [ 41036-32-2 ]
  • N-t-butoxycarbonyl-L-alanyl-D-alanine benzyl ester [ No CAS ]
  • 33
  • [ 41036-32-2 ]
  • L-alanyl-D-alanine benzyl ester hydrochloride [ No CAS ]
  • 34
  • [ 41036-32-2 ]
  • C24H36N4O7 [ No CAS ]
  • 35
  • C20H31N5O8 [ No CAS ]
  • [ 41036-32-2 ]
  • [ 1428244-75-0 ]
  • 36
  • [ 352356-38-8 ]
  • [ 41036-32-2 ]
  • Boc-ACHC-<SUP>D</SUP>Ala-OBn [ No CAS ]
  • 38
  • [ 41036-32-2 ]
  • Boc-ACHC-<SUP>D</SUP>Ala-ACHC-<SUP>D</SUP>Ala-OBn [ No CAS ]
  • 39
  • [ 41036-32-2 ]
  • Boc-<SUP>D</SUP>Ala-(1R, 2S)-ACHC-<SUP>D</SUP>Ala-(1R, 2S)-ACHC-<SUP>D</SUP>Ala-OBn [ No CAS ]
  • 40
  • [ 53267-93-9 ]
  • [ 41036-32-2 ]
  • C25H32N2O6 [ No CAS ]
  • 41
  • [ 41036-32-2 ]
  • C20H24N2O4 [ No CAS ]
  • 42
  • [ 41036-32-2 ]
  • C22H26N2O5 [ No CAS ]
  • 43
  • [ 41036-32-2 ]
  • [ 55721-65-8 ]
  • Boc-D-Ile-D-Ala-OBn [ No CAS ]
  • 44
  • [ 13139-16-7 ]
  • [ 41036-32-2 ]
  • Boc-L-Ile-D-Ala-OBn [ No CAS ]
  • 45
  • [ 338-69-2 ]
  • [ 104-15-4 ]
  • [ 100-51-6 ]
  • [ 41036-32-2 ]
  • 46
  • [ 20312-37-2 ]
  • [ 41036-32-2 ]
  • C16H23NO4 [ No CAS ]
YieldReaction ConditionsOperation in experiment
98% With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; In acetonitrile; at 0 - 20℃; To a soln of D-Alanine benzyl ester p-toluene sulfonate (58.50 g, 167 mmol) in acetonitrile anhyd (100 mL) was dropwised DIPEA (44.97 g, 348 mmol) in acetonitrile anhyd (50 mL) at 0 C. The mixture was added D-O-leucine (20.00 g, 151 mmol) in acetonitrile anhyd (50 mL), EDCI hydrochloride (34.81 g, 182 mmol) and HOBt (20.45 g, 151 mmol) and stirred at r.t. over night. The reaction mixture was then evaporated concentrated under reduced pressure. The residue was washed sequentially 10% citric acid (3 × 300 mL), sat. NaHCO3 soln (3 × 300 mL) and brine (3 × 300 mL). The organic layer was dried over Na2SO4, filtered and concentrated under redued pressure. The crude residue was purified by silica gel chromatography (hexane-EtOAc, 9:1) and recrystallized from EtOAc-hexane as a white solid; yield: 43.58 g (98%); mp 60.5-61.7 C, [a]D25 +47.29 (c 1.00, CHCl3). IR (KBr film):3385, 3323, 2956, 2870, 1743, 1643, 1529, 1464, 1398, 1294, 1163, 1083, 742, 697. 1H NMR (CDCl3, 400 MHz): delta = 0.94 (d, J=2.4 Hz, 3H), 0.96 (d, J=2.4 Hz, 3H), 1.43 (d, J=7.2 Hz, 3H), 1.43-1.66 (m, 2H), 1.84-1.86 (m, 1H), 2.82 (s, 1H), 4.14-4.17 (m, 1H), 4.63-4.66 (m, 1H), 5.14 (dd, J=12.4, 5.2 Hz, 2H), 6.99 (d, J=11.5 Hz, 1H), 7.33-7.39 (m, 5H). ESI-MS: m/z [M+H]+ calcd for C16H24NO4: 294.1705; found: 294.1737.
  • 47
  • [ 41036-32-2 ]
  • C33H56N2O7Si [ No CAS ]
  • 48
  • [ 41036-32-2 ]
  • [ 173918-07-5 ]
  • 49
  • [ 41036-32-2 ]
  • [ 173918-12-2 ]
  • 50
  • [ 41036-32-2 ]
  • L-OTBDMS-valine-L-valine-D-O-leucine-D-alanine-L-O-valine-L-valine-D-O-leucine-D-alanine benzyl ester [ No CAS ]
  • 51
  • [ 41036-32-2 ]
  • [ 173918-09-7 ]
  • 52
  • [ 41036-32-2 ]
  • C71H120N6O19Si [ No CAS ]
  • 53
  • [ 41036-32-2 ]
  • C65H106N6O19 [ No CAS ]
  • 54
  • trans-2-(1H-benzo[d]imidazol-2-yl) cyclopropane-1-carboxylic acid [ No CAS ]
  • [ 41036-32-2 ]
  • trans-(2-(1H-benzo[d]imidazol-2-yl)cyclopropane-1-carbonyl)-D-alanine benzyl [ No CAS ]
YieldReaction ConditionsOperation in experiment
With N-ethyl-N,N-diisopropylamine; 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℃; for 2h; D-Alanine benzyl tosylate (1.75 g, 5.0 mmol), trans-2-(1H-benzo[d]imidazol-2-yl) cyclopropane-1-carboxylic acid (1.11 g, 5.5 mmol), and HATU (2.09 g, 5.5 mmol) were dissolved in DMF (30 mL), and then DIPEA (2.61 mL, 15 mmol) was added thereto, followed by stirring at room temperature for two hours. A saturated aqueous sodium hydrogen carbonate solution was added to a reaction liquid, the mixture was stirred for a while, and then extraction was performed with ethyl acetate. A separated organic layer was washed with a saturated saline solution and dried over anhydrous sodium sulfate, an insoluble substance was filtered, and then a solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate) to obtain Diastereomer A (upper spot on TLC (ethyl acetate), white amorphous, 562 mg, 31%) and Diastereomer B (lower spot on TLC (ethyl acetate), white amorphous, 401 mg, 22%) of a title compound. Diastereomer A 1H NMR (CD3OD, 400 MHz): delta = 1.39 (d, 3H, J = 7Hz), 1.5-1.7 (m, 2H), 2.3-2.4 (m, 1 H), 2.5-2.6 (m, 1H), 4.47 (q, 1H, J = 8Hz), 5.13 (d, 1H, J = 12Hz), 5.19 (d, 1H, J = 12Hz), 7.1-7.2 (m, 2H), 7.3-7.6 (m, 7H). 2H cannot be observed. Diastereomer B 1H NMR (CD3OD, 400 MHz): delta = 1.39 (d, 3H, J = 7Hz), 1.5-1.7 (m, 2H), 2.3-2.4 (m, 1H), 2.5-2.6 (m, 1 H), 4.47 (q, 1H, J = 8Hz), 5.13 (s, 2H), 7.1-7.4 (m, 7H), 7.4-7.5 (m, 2H). 2H cannot be observed.
 

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