Home Cart Sign in  
Chemical Structure| 37091-73-9 Chemical Structure| 37091-73-9

Structure of 37091-73-9

Chemical Structure| 37091-73-9

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 37091-73-9 ]

CAS No. :37091-73-9
Formula : C5H10Cl2N2
M.W : 169.05
SMILES Code : C[N+]1=C(Cl)N(C)CC1.[Cl-]
MDL No. :MFCD09039290
InChI Key :AEBBXVHGVADBHA-UHFFFAOYSA-M
Pubchem ID :10176306

Safety of [ 37091-73-9 ]

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

Computational Chemistry of [ 37091-73-9 ] Show Less

Physicochemical Properties

Num. heavy atoms 9
Num. arom. heavy atoms 0
Fraction Csp3 0.8
Num. rotatable bonds 0
Num. H-bond acceptors 0.0
Num. H-bond donors 0.0
Molar Refractivity 49.56
TPSA ?

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

6.25 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

-1.85
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

1.18
Log Po/w (WLOGP)?

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

-3.59
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.

1.23
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

0.28
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.

-1.63
Solubility 3.95 mg/ml ; 0.0234 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.

-0.91
Solubility 20.9 mg/ml ; 0.124 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

-1.44
Solubility 6.14 mg/ml ; 0.0363 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

Low
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.

-6.49 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

2.0 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)

3.11

Application In Synthesis of [ 37091-73-9 ]

* 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 [ 37091-73-9 ]

[ 37091-73-9 ] Synthesis Path-Downstream   1~36

  • 1
  • [ 80-73-9 ]
  • [ 79-37-8 ]
  • [ 37091-73-9 ]
  • 2
  • [ 80-73-9 ]
  • [ 37091-73-9 ]
YieldReaction ConditionsOperation in experiment
96.6% With phosgene; In tetrachloromethane; at 5 - 50℃; for 5.5h; For 1000 ml three port in the reaction bottle, by adding 1,3-dimethyl-2-imidazolidinone (34.2 g, 0.3 mol), carbon tetrachloride (400 ml), stirring slowly dropwise solid phosgene carbon tetrachloride solution (containing solid phosgene 30 g, 0.1 mole, carbon tetrachloride 100 ml), the reaction mixture is kept below 5 C, violent mixing 0.5 hours, the reaction at room temperature 1 hour, heating to 50 C, maintain 4 hours. To be the reaction product is cooled to room temperature, filter, a small amount of carbon tetrachloride washing, get a pure white crystalline product chloropivaloyl 1,3-dimethyl-2-chlorotrifluoromethylbenzene imidazoline 49 g, yield of 96.6%,
70.1% With oxalyl dichloride; In benzene; at 20℃; for 5h;Inert atmosphere; Under an inert atmosphere, 1,3-Dimethyl-2-imidazolidinone (7.0 mL, 64 mmol) was dissolved in anhydrous benzene (25 mL). To this oxalyl chloride (7.2 mL, 80 mmol) was added, and the solution was refluxed for 5 hours, and allowed to sit at room temperature overnight. The solution was filtered quickly to give 2-chloro-1,3-dimethylimidazolinium chloride (7.5815 g, 44.85 mmol) in 70.1% yield.
53% With Phthaloyl dichloride; at 140℃; for 5h; 1,3-dimethyl-2-imidazolidinone 3.50g (30.7 mmol), and the mixture was heated for 5 hours and stirred at 140 of chloride phthalic acid 6.54g (32.4 mmol). After cooling, the crystal upon addition of 1,4-dioxane 25mL precipitated, filtered with a glass filter, washed twice with 1,4-dioxane 10 mL, washed once with ether 5 mL, and dried under vacuum. To give 2-chloro-1,3-dimethyl imidazolium chloride 2.72g (53% yield).
With oxalyl dichloride; In chloroform; for 20h;Reflux; Inert atmosphere; Schlenk technique; To a solution of 1,3-dimethyl-2-imidazolidinone (1.0 mL, 9.3 mmol) dissolved in dry CHCl3 (20 mL) was added oxalyl chloride (3.9 mL,44.7 mmol) dropwise. The yellow solution was stirred at reflux for 20 h. The solvent was removed under vacuum. The remaining solid was washed twice with Et2O
With oxalyl dichloride; In toluene; at 80℃; for 12h;Inert atmosphere; General procedure: N,N?-Disubstituted cyclic urea (6 mmol) was dissolved in toluene (50 mL) and oxalyl chloride (7.6 g, 5.2 mL, 60 mmol) was added. The resulting mixture was stirred at 80 C for 12 h. The white precipitate was then filtered off under an inert atmosphere, washed with anhydrous Et2O, and dried in vacuo to give the pure chloride as a white solid.
With oxalyl dichloride; In dichloromethane; at 0 - 20℃; for 6h;Inert atmosphere; General procedure: A solution of urea (50mmol) in dry CH2Cl2 (10mL) was added dropwise at 0C under an Argon atmosphere to a solution of freshly distilled oxalyl chloride (55 mmoL) in dry CH2Cl2 (25ml). The reaction mixture was allowed to reach rt. and was stirred at rt 6h. The solvent was then evaporated under reduced pressure to afford a brown solid which was washed with dry Et2O (4×20mL) to give a white solid.
With oxalyl dichloride; In toluene; at 60℃; for 20h;Inert atmosphere; Cooling with ice; General procedure: 1 ml urea derivatives dissolved in 400 ml toluene. 1.2 mol oxalyl chloride dissolved in toluene and then instilled to previous system in ice bath, protected by nitrogen and with strongly stirred. Then stirred in room temperature for 2h and heated in 60 for 20h. The mixture was cooled and filtered in reduced pressure, washed by ethyl acetate to get white solid. Needle-like crystal was harvested with 95%-97% yields after crystallization via ethyl acetate and acetonitrile.

References: [1]Patent: CN105367478,2016,A .Location in patent: Paragraph 0021; 0027; 0028.
[2]European Journal of Inorganic Chemistry,2005,p. 3815 - 3824.
[3]Chemistry - A European Journal,2016,vol. 22,p. 16187 - 16199.
[4]Synthesis,2009,p. 2267 - 2277.
[5]Helvetica Chimica Acta,1985,vol. 68,p. 1543 - 1556.
[6]Journal of Organic Chemistry,2018,vol. 83,p. 13051 - 13062.
[7]Tetrahedron Letters,2011,vol. 52,p. 3723 - 3725.
[8]Angewandte Chemie - International Edition,2014,vol. 53,p. 11907 - 11911.
    Angew. Chem.,2014,vol. 126,p. 12101 - 12105,5.
[9]Journal of the American Chemical Society,2006,vol. 128,p. 14185 - 14191.
[10]Patent: JP5782331,2015,B2 .Location in patent: Paragraph 0031.
[11]Synlett,2003,p. 369 - 371.
[12]Chemical Communications,2002,p. 1618 - 1619.
[13]Synthesis,2008,p. 917 - 920.
[14]Journal of the American Chemical Society,2009,vol. 131,p. 2882 - 2892.
[15]European Journal of Inorganic Chemistry,2011,p. 1302 - 1314.
[16]Inorganica Chimica Acta,2011,vol. 374,p. 546 - 557.
[17]European Journal of Inorganic Chemistry,2012,p. 4833 - 4845.
[18]European Journal of Inorganic Chemistry,2013,p. 163 - 171.
[19]Tetrahedron,2013,vol. 69,p. 8943 - 8951.
[20]Organic Letters,2014,vol. 16,p. 2790 - 2793.
[21]Dalton Transactions,2016,vol. 45,p. 16966 - 16983.
[22]Angewandte Chemie - International Edition,2017,vol. 56,p. 3360 - 3363.
    Angew. Chem.,2017,vol. 129,p. 3408 - 3412,5.
[23]Organometallics,2018,vol. 37,p. 1172 - 1180.
[24]Journal of Physical Organic Chemistry,2018,vol. 31.
[25]Journal of Molecular Liquids,2019,vol. 277,p. 280 - 289.
[26]Tetrahedron Letters,2013,vol. 54,p. 6959 - 6963.
  • 3
  • [ 37091-73-9 ]
  • natrium-(cis,cis,cis,trans-2,4,6,8-cyclononatetraenid) [ No CAS ]
  • 2-(2,4,6,8-Cyclononatetraen-1-yl)-1,3-dimethylimidazoliniumchlorid [ No CAS ]
  • 4
  • [ 37091-73-9 ]
  • sodium (2Z,4Z,6Z,8E)-cyclonona-2,4,6,8-tetraenide [ No CAS ]
  • 2-chloro-2-(cyclonona-2,4,6,8-tetraen-1-yl)-1,3-dimethylimidazolidine [ No CAS ]
  • 5
  • [ 37091-73-9 ]
  • [ 86196-90-9 ]
  • 6
  • [ 1911-01-9 ]
  • [ 37091-73-9 ]
  • [ 82464-49-1 ]
  • 7
  • [ 65523-28-6 ]
  • [ 37091-73-9 ]
  • [ 82464-49-1 ]
  • 8
  • [ 5345-47-1 ]
  • [ 37091-73-9 ]
  • [ 14667-47-1 ]
  • 9
  • [ 10420-89-0 ]
  • [ 37091-73-9 ]
  • 1,3-dimethyl-2-[(1S)-1-(1-naphthyl)ethylimino]imidazolidine [ No CAS ]
  • 10
  • [ 55-21-0 ]
  • [ 37091-73-9 ]
  • 2-benzoylimino-1,3-dimethylimidazolidine [ No CAS ]
  • 12
  • [ 19131-99-8 ]
  • [ 37091-73-9 ]
  • N-[(S)-1-phenylethyl]-N,N',N''-trimethyl-N',N''-ethyleneguanidinium chloride [ No CAS ]
  • 13
  • [ 3886-69-9 ]
  • [ 37091-73-9 ]
  • 1,3-dimethyl-2-[(R)-1-phenylethylimino]imidazolidine [ No CAS ]
  • 14
  • [ 38235-77-7 ]
  • [ 37091-73-9 ]
  • Benzyl-(1,3-dimethyl-imidazolidin-2-ylidene)-((R)-1-phenyl-ethyl)-ammonium; chloride [ No CAS ]
  • 16
  • [ 37091-73-9 ]
  • [ 74400-91-2 ]
  • C17H40N6P(1+)*Cl(1-) [ No CAS ]
  • 17
  • [ 80-73-9 ]
  • [ 75-44-5 ]
  • [ 37091-73-9 ]
  • 18
  • [ 37091-73-9 ]
  • [ 479-27-6 ]
  • [ 501931-38-0 ]
  • 19
  • [ 6723-30-4 ]
  • [ 37091-73-9 ]
  • [ 592489-01-5 ]
  • 20
  • [ 6456-74-2 ]
  • [ 37091-73-9 ]
  • 2-(tert-butyloxycarbonylmethylimino)-1,3-dimethylimidazolidine [ No CAS ]
  • 21
  • [ 37091-73-9 ]
  • [ 75-31-0 ]
  • 2-(2-propylimino)-1,3-dimethylimidazolidine [ No CAS ]
  • 22
  • [ 37091-73-9 ]
  • [ 109-76-2 ]
  • [ 879132-89-5 ]
  • 24
  • [ 37091-73-9 ]
  • [ 107-11-9 ]
  • allyl-(1,3-dimethyl-imidazolidin-2-ylidene)-amine [ No CAS ]
  • 25
  • [ 37091-73-9 ]
  • [ 100-46-9 ]
  • [ 25653-11-6 ]
YieldReaction ConditionsOperation in experiment
100% With triethylamine; In dichloromethane; at 20℃; for 5h;Inert atmosphere; General procedure: To a solution of a 2-chloro-4,5-dihydroimidazolium chloride in CH2Cl2 was added Et3N followed by a primary amine at r.t. and the mixture was stirred at r.t. After the addition of ice-water and then 20percent aq NaOH solution, the mixture was extracted with toluene. The combined organic solution extracts were washed with H2O and brine to give a guanidine that was purified by column chromatography (silica gel or NH-silica gel) if necessary. An alkyl bromide was added to a solution of the guanidine in MeCN at r.t. and then the mixture was stirred at r.t. After evaporation of the solvent the residue was isolated either as the bromide by successively washing with hexane and Et2O or after purified by column chromatography (silica gel) if necessary as the hexafluorophosphate by treatment with aq NH4PF6 solution at r.t.
  • 26
  • [ 141-86-6 ]
  • [ 37091-73-9 ]
  • [ 873949-80-5 ]
  • 27
  • [ 1477-55-0 ]
  • [ 37091-73-9 ]
  • N1,N3-bis(1,3-dimethylimidazolidin-2-ylidene)-m-xylylene-α,α'-diamine [ No CAS ]
  • 28
  • [ 2026-48-4 ]
  • [ 37091-73-9 ]
  • 1,3-dimethyl-2-[(S)-1-hydroxymethyl-2-methylpropylimino]imidazolidine [ No CAS ]
  • 29
  • [ 929-59-9 ]
  • [ 37091-73-9 ]
  • 1-(1,3-dimethylimidazolidin-2-ylideneamino)-2-{2-[2-(1,3-dimethylimidazolidin-2-ylideneamino)ethoxy]ethoxy}ethane [ No CAS ]
  • 30
  • [ 3385-21-5 ]
  • [ 37091-73-9 ]
  • N1,N3-bis(1,3-dimethylimidazolidin-2-ylidene)cyclohexane-1,3-diamine [ No CAS ]
  • 31
  • [ 916162-84-0 ]
  • [ 37091-73-9 ]
  • [ 916162-85-1 ]
YieldReaction ConditionsOperation in experiment
65% In tetrahydrofuran; dichloromethane; for 6h;Heating / reflux; A mixture of lambda/-[1-(3,4-diaminophenyl)ethyl]-2-methylpropane-2-sulfiotanamide and GDI (569 mg, 3.51 mmol) in THF - DCM (10 ml - 10 ml) was refluxed for 6 hours. After cooling to the room temperture, water (10 mL) was added to the mixture. The mixture was extracted with EtOAc (150 ml) and organic layer was washed with brine (30 ml), dried over sodium sulfate and concentrated. The residue was recrystaliized from EtOAc to afford 430 mg (65percent) of the title compound as a pale brown solid. 1H NMR (300MHz,DMSO-d6) delta ppm 1.11 (9H, s), 1.38 (3H, d, J = 7.3 Hz), 4.37-4.28 (1H, m), 5.53 (1H, d, J = 6.6 Hz), 6.84(1H, d, J = 7.3 Hz), 6.93 (1 H, d, J = 8.1 Hz), 6.99 (1H, s), 10.54 (1H, br.s), 10.60 (1H, br.s). MS (ESI) m/z282 (M + H)+, 280 (M - H)".
  • 32
  • [ 37091-73-9 ]
  • [ 996-50-9 ]
  • 1,3-dimethyl-2-diethylaminoimidazolidinium chloride [ No CAS ]
  • 33
  • [ 109-01-3 ]
  • [ 37091-73-9 ]
  • (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid cyclohexylester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine; In (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy) cyclopenta [c]-pyrane-4-carboxylic acid; Example 9 A dichloromethane solution containing 400 mg of (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid described in Example 1 was cooled with ice followed by addition of 0.20 ml of 1-methylpiperazine, 2 ml of triethylamine and 301 mg of <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> and stirring for 15 hours at room temperature. The reaction mixture was then extracted with dichloromethane. After washing the organic phase with saturated aqueous sodium bicarbonate and brine, it was dried over anhydrous magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel chromatography to obtain a colorless powder from the dichloromethane-methanol elude in the form of (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid 4-methylpiperazylamide (264 mg, yield: 50percent). The physicochemical properties of this compound are described in Table 5, Compound No. 20. (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid cyclohexylester was produced in the same manner from (1S,4aS,6S,7R,7aR)-6,7-epoxy-1,4a,5,6,7,7a-hexahydro-7-methyl-1-(methylcarbamoyloxy)cyclopenta[c]-pyrane-4-carboxylic acid.
  • 34
  • 2,2-di-tert-butyl 1,2,2-cyclopropanetricarboxylate [ No CAS ]
  • N-(tert-butoxycarbonylmethyl)-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}amine [ No CAS ]
  • [ 37091-73-9 ]
  • (2RS)-2-[N-(carboxymethyl)-N-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}carbamoyl]cyclopropane-1,1-dicarboxylic acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With formic acid; triethylamine; In chloroform; EXAMPLE 1 Preparation of (2RS)-2-[N-(carboxymethyl)-N-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}carbamoyl]cyclopropane- 1,1-dicarboxylic acid 73 mg of N-(tert-butoxycarbonylmethyl)-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}amine obtained in Reference Example 1, 140 mg of 2,2-di-tert-butyl 1,2,2-cyclopropanetricarboxylate obtained in Reference Example 2 and 1.0 ml of triethylamine, were dissolved in 1 ml of chloroform, and a solution of 91 mg of <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> in 1 ml of chloroform, was added under cooling with ice, followed by stirring at the same temperature for 20 minutes and then stirring at room temperature for two hours. The reaction solution was poured into water and extracted with ethyl acetate. The extract solution was washed with a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The drying agent was filtered off, and then, the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1), to obtain 114 mg (yield: 98percent) of a tri-tert-butyl ester of the above identified compound as a colorless oily substance. 2 ml of formic acid was added to 78 mg of the above ester, followed by stirring at room temperature for 18 hours. The reaction solution was evaporated to dryness under reduced pressure to obtain 60 mg (yield: quantitative) of the above identified compound as a colorless oily substance. 1 H-NMR(CD3 OD) delta:0.80-1.05(3H, m), 1.50-1.90(2H, m), 2.00-3.40(6H, m), 3.60-4.60(3H, m), 6.95-7.50(13H, m). FAB-MS:548(M+H).
  • 35
  • hexane chloroform [ No CAS ]
  • N-(tert-butoxycarbonylmethyl)-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}amine [ No CAS ]
  • trimellitic anhydride [ No CAS ]
  • [ 37091-73-9 ]
  • [ 194921-12-5 ]
YieldReaction ConditionsOperation in experiment
42% With sodium bicarbonate; triethylamine; trifluoroacetic acid; In chloroform; EXAMPLE 3 Preparation of 4-[N-(carboxymethyl)-N-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}carbamoyl]phthalic acid 61 mg of N-(tert-butoxycarbonylmethyl)-{(1R,2R)-2-(2-fluoro-4-biphenylyl)-1-methyl-4-phenylbutyl}amine obtained in Reference Example 1, 39 mg of trimellitic anhydride and 85 mul of triethylamine, were dissolved in 3 ml of chloroform, and a solution of 91 mg of <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> in 1 ml of chloroform, was added under cooling with ice, followed by stirring at room temperature for two hours. To the reaction solution, 1 ml of a saturated sodium hydrogen carbonate aqueous solution was added, followed by vigorously stirring at room temperature for one hour. Then, it was acidified with 1N hydrochloric acid and extracted with ethyl acetate. The extract solution was washed with a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. To the residue, 2 ml of trifluoroacetic acid was added, followed by stirring at room temperature for one hour. Then, the reaction solution was concentrated under reduced pressure. The residue was purified by medium pressure liquid chromatography (Lobar column.(TM)., Size A, RP-8, manufactured by Merck Co.; acetonitrile/0.1percent trifluoroacetic acid aqueous solution=1/1), followed by treatment with chloroform-hexane to obtain 33 mg (yield: 42percent) of the above identified compound as white powder. 1 H-NMR(CD3 COCD3) delta:1.08(3H, d, J=6.3 Hz), 1.80-3.30(5H, m), 3.90-4.40(3H, m), 6.95-7.90(16H, m). FAB-MS:584(M+H).
  • 36
  • [ 194922-09-3 ]
  • dimethyl 2-(1-acetoxycarboxymethyl)-2,3-O-isopropylidene-L-tartarate [ No CAS ]
  • [ 37091-73-9 ]
  • trisodium (4R,5R)-4-[N-(carboxylatomethyl)-N-{(1R,2R)-1-methyl-2-(4-phenoxyphenyl)-4-phenylbutyl}carbamoylhydroxymethyl]-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With sodium hydroxide; triethylamine; In tetrahydrofuran; methanol; chloroform; EXAMPLE 8 Preparation of trisodium (4R,5R)-4-[N-(carboxylatomethyl)-N-{(1R,2R)-1-methyl-2-(4-phenoxyphenyl)-4-phenylbutyl}carbamoylhydroxymethyl]-2,2-dimethyl-1,3-dioxolane-4,5-dicarboxylate 11.6 mg of N-(methoxycarbonylmethyl)-{(1R,2R)-1-methyl-2-(4-phenoxyphenyl)-4-phenylbutyl}amine obtained in Example 51, 9.6 mg of dimethyl 2-(1-acetoxycarboxymethyl)-2,3-O-isopropylidene-L-tartarate obtained in Reference Example 6 and 20 mul of triethylamine, were dissolved in 0.5 ml of chloroform, and a solution of 9.7 mg of <strong>[37091-73-9]2-chloro-1,3-dimethylimidazolinium chloride</strong> in 0.5 ml of chloroform, was added under cooling with ice, followed by stirring at room temperature for 4 hours. The reaction solution was purified by silica gel thin layer chromatography (Kieselgel.(TM).60F254, Art.(TM).5744; hexane/acetone=2/1), to obtain 11.0 mg (yield: 53percent) of a condensate as a colorless foam. 10.0 mg of the above condensate was dissolved in 0.6 ml of tetrahydrofuran, and 60 mul of a 1N sodium hydroxide aqueous solution was added, followed by stirring at room temperature for 13 hours. The solvent was distilled off under reduced pressure, and then, methanol was added to the residue. Precipitated crystals were collected by filtration to obtain 5.7 mg (yield: 65percent) of the above identified compound as white powder. 1 H-NMR(CD3 OD) delta:0.79-1.00(3H, m), 1.32, 1.38, 1.49 and 1.68(total 6H, each s), 1.80-3.20(5H, m), 3.50-4.05(3H, m), 4,50-5.35(2H, m), 6.93-7.40(14H, m).
 

Historical Records

Categories