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Chemical Structure| 59673-74-4 Chemical Structure| 59673-74-4

Structure of 59673-74-4

Chemical Structure| 59673-74-4

6-Amino-1H-indazol-3-ol

CAS No.: 59673-74-4

4.5 *For Research Use Only !

Cat. No.: A103630 Purity: 95%

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Product Details of [ 59673-74-4 ]

CAS No. :59673-74-4
Formula : C7H7N3O
M.W : 149.15
SMILES Code : OC1=NNC2=C1C=CC(N)=C2
MDL No. :MFCD07781650
InChI Key :RVEOZWSYDIHKIB-UHFFFAOYSA-N
Pubchem ID :108801

Safety of [ 59673-74-4 ]

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

Computational Chemistry of [ 59673-74-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 2.0
Num. H-bond donors 3.0
Molar Refractivity 42.52
TPSA ?

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

74.93 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.35
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

0.85
Log Po/w (WLOGP)?

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

0.86
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.

0.6
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

0.83
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.7

Water Solubility

Log S (ESOL):?

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

-1.91
Solubility 1.85 mg/ml ; 0.0124 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.

-2.01
Solubility 1.47 mg/ml ; 0.00985 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

-1.96
Solubility 1.65 mg/ml ; 0.011 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.

-6.61 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

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)

1.79

Application In Synthesis of [ 59673-74-4 ]

* 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 [ 59673-74-4 ]

[ 59673-74-4 ] Synthesis Path-Downstream   1~24

  • 2
  • [ 59673-74-4 ]
  • 4-bromo-Ν-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine [ No CAS ]
  • 4-bromo-Ν-α-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-Ν-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
11% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; for 16.0h; A solution of 4-bromo-Nu-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine (1500 mg, 3 mmol) and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> (555 mg, 24 mmol) in ethyl acetate (21 ml) was treated with N, N-diisopropylethylamine (1.4 ml, 7.8 mmol).The suspension was treated with a 2,4, 6-tripropyl-l, 3,5,2, 4,6-trioxatriphosphinane-2, 4,6 trioxide solution (50% in dimethylformamide, 2.2 ml, 3.7 mmol) and up added to the solution with dimethylformamide, and then stirred at RT for 16 h.The reaction mixture was stirred in ethyl acetate, washed twice with water and once with aqueous saturated sodium chloride solution.The organic phase was dried with sodium sulfate and the solvent removed.The crude product was stirred with acetonitrile and suction filtered.The residue was twice purified by preparative HPLC separated (eluent: acetonitrile / water with 0.1% TFA (gradient)).The crude product was stirred with methanol and sucked.This gave 202 mg (11% d. Th.) Of the title compound.
11% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; for 16.0h; A solution of 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine (1500 mg, 3 mmol) and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazole-3-one</strong> (555 mg, 24mmol) in ethyl acetate (21 ml) was treated with N, N-diisopropylethylamine (1.4 ml, 7.8 mmol). Thesuspension was treated with a 2,4, 6-tripropyl-1, 3,5,2, 4,6-trioxatriphosphinane 2, 4,6 trioxidesolution (50% in dimethylformamide, 2.2 ml, 3.7 mmol) and up added to the solution withdimethylformamide, and then stirred at RT for 16 h. The reaction mixture was stirred in ethylacetate, washed twice with water and once with sodium chloride solution. The organic phase wasdried with sodium sulfate and the solvent removed. The crude product was stirred with acetonitrileand suction filtered. The residue was twice purified by preparative HPLC separated (eluent:acetonitrile / water gradient, 0.1% TFA). The crude product was stirred with methanol and suctionfiltered. This gave 202 mg (11% theoretical value)of the title compound.
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; for 16.0h; Containing 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine (1500 mg, 3 have mozambican ear) and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> (555 mg, 24 have mozambican ear) in ethyl acetate (21 ml) solution with in N, N-diisopropyl ethylamine (1.4 ml, 7.8 have mozambican ear) blend. For the suspension 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphorinane-2,4,6-trioxide solution (50% in DMF in, 2.2 ml, 3.7 have mozambican ear) DMF until the blending and dissolving, and then the the mixture to the stirring the mixture at room temperature for up to 16 hours. Stirring the reaction mixture in ethyl acetate, and secondary washing with water and a saturated sodium chloride aqueous solution. The organic phase with sodium sulfate drying and removing the solvent. The crude product using acetonitrile stirring and suction filtered. The residual quality by preparative HPLC to be separated and secondary (eluents: acetonitrile/water with 0.1% trifluoro acetic acid the gradient). The crude product is used for methanol stirring and suction filtered. This generating 202 mg (theoretical value of 11%) the subject compound.
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; N,N-Diisopropylethylamine is added to a solution of 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> in ethyl acetate. A 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide solution (50% in dimethylformamide) is added to the reaction mixture, and the mixture is then stirred overnight at RT. The reaction mixture is worked up by methods known to those skilled in the art and the residue is separated by means of preparative HPLC. This gives the title compound.

  • 3
  • [ 59673-74-4 ]
  • (2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-[2'-chloro-4'-(isopropylcarbamoyl)biphenyl-4-yl]propanoic acid [ No CAS ]
  • tert-butyl [trans-4-({(2S)-3-[4'-(isopropylcarbamoyl)-2'-methylbiphenyl-4-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With N-ethyl-N,N-diisopropylamine; In ethyl acetate; for 3.0h;Reflux; A solution of (2S ) - 2- [(trans-4- [(tert-butoxycarbonyl) amino] methyl} cyclohexyl) carbonyl] - amino} -3- [4 '-(isopropylcarbamoyl) - 2'-methylbiphenyl-4-yl] propanoic acid (150 mg, 0:26 mmol) and 6-amino-l,2-dihydro-3 / i-indazol-3-one (53 mg, 0:28 mmol) in ethyl acetate (3 ml) was treated with N, Ndiisopropylethylamine(0:11 mL, 0.77 mmol). Then, 2,4,6-tripropyl-l, 3,5,2,4,6-trioxatriphosphinane2,4,6-trioxide solution (50% in ethyl acetate, 0:46 ml, 0.77 mmol) and refluxed for 3 h , Thereaction mixture was mixed with water, the precipitate is suctioned and dried via lyophilization.This gave 102 mg (55% d. Th.) Of the title compound.
  • 4
  • [ 59673-74-4 ]
  • ethyl 6-({(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-[4'-(cyclobutylcarbamoyl)-2'-methylbiphenyl-4-yl]propanoyl}amino)-1H-indol-2-carboxylate [ No CAS ]
  • tert-butyl [trans-4-({(2S)-3-[4'-(cyclobutylcarbamoyl)-2'-methylbiphenyl-4-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
29% 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 20.0℃; A solution of (2S )- 2- [(ira Ae4- [(ieri-butoxycarbonyl) amino] methyl} cyclohexyl) - carbonyl] amino} -3- [4 '-(cyclobutylcarbamoyl) - 2'-methylbiphenyl-4-yl] propanoic acid (80 mg, 0:14 mmol) in DMF (1.5mL) was added 6-amino-l, 2-dihydro-3 / i-indazol-3-one (40 mg, 0:27 mmol) and N, Ndiisopropylethylamine(0.07 mL, 0:41 mmol). The solution was treated with HATU (77 mg, 0:41mmol) and then stirred overnight at RT. The solvent was removed and the residue dissolved in alittle DMSO / acetonitrile, filtered through a Millipore filter and purified by preparative HPLC(eluent: gradient of acetonitrile / water with 0.1% trifluoroacetic acid). This gave 28 mg (29% d.Th.) Of the title compound.
  • 5
  • [ 59673-74-4 ]
  • N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-L-phenylalanine [ No CAS ]
  • N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With N-ethyl-N,N-diisopropylamine; HATU; In ethyl acetate; for 6.0h;Reflux; N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-L-phenylalanine (1.91 g, 3.6 mmol), 6-amino-l, 2-dihydro-3 -indazol-3-one (0:55 g, 3.60 mmol) and N, N- diisopropylamine (1.9 ml, 10.8 mmol)were suspended in 23 ml of ethyl acetate and 2,4,6-tripropyl-l, 3,5,2 , 4,6-trioxatriphosphinane-2,4,6-trioxide (50% in ethyl acetate, 5.73 g, 9.0 mmol). The mixture was then refluxed for 3 h,additional 6-amino-l, 2-dihydro-3 / i-indazol3-one (0.14g, 0.90 mmol), N, N-diisopropylamine (0:47ml, 2.70 mmol) and 2,4,6 added -Tripropyl1,3,5, 2,4, 6-trioxatriphosphinane-2,4,6-trioxide (50% inethyl acetate, 1:43 g, 2.25 mmol) and refluxed for another 3 h. The reaction mixture was treatedwith water, the phases were separated and the aqueous phase extracted three times with ethylacetate. The precipitated in two phases solid was suction filtered and dried under high vacuum.This gave 1:35 g (57%.
  • 6
  • [ 59673-74-4 ]
  • 3-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine [ No CAS ]
  • 3-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; at 20.0℃; for 50.0h;Reflux; Example 150A 3-Bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide 3-Bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine, <strong>[59673-74-4]6-amino-1H-indazol-3(2H)-one</strong> and N,N-diisopropylethylamine are suspended in ethyl acetate, and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% in ethyl acetate) is added. The reaction mixture is then heated under reflux for 2 h and stirred at RT for a further 48 h. The reaction mixture is worked up by methods known to those skilled in the art and the residue is separated by means of preparative HPLC. This gives the title compound.
  • 7
  • [ 59673-74-4 ]
  • tert-butyl [trans-4-({(2S)-3-[2'-methyl-5'-(morpholin-4-ylsulphonyl)biphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
  • 8
  • [ 59673-74-4 ]
  • tert-butyl [trans-4-({(2S)-3-[2'-methyl-5'-(pyrrolidin-1-ylsulphonyl)biphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
  • 9
  • [ 59673-74-4 ]
  • tert-butyl [trans-4-({(2S)-3-[5'-(benzylsulphamoyl)-2'-methylbiphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
  • 10
  • [ 59673-74-4 ]
  • tert-butyl [trans-4-({(2S)-3-[5'-(dimethylsulphamoyl)-2'-methylbiphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}carbamoyl)cyclohexyl]methyl}carbamate [ No CAS ]
  • 11
  • [ 59673-74-4 ]
  • tert-butyl 4-[5-(3-{(2S)-2-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]amino}-3-oxo-3-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propyl}phenyl)pyrimidin-2-yl]piperazine-1-carboxylate [ No CAS ]
  • 12
  • [ 59673-74-4 ]
  • N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-3-(3-methylpyridin-4-yl)-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
  • 13
  • [ 59673-74-4 ]
  • N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-3-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
  • 14
  • [ 59673-74-4 ]
  • N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-3-{6-[3-(dimethylamino)propoxy]pyridin-3-yl}-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
  • 15
  • [ 59673-74-4 ]
  • trans-4-(aminomethyl)-N-{(2S)-3-[2'-methyl-5'-(morpholin-4-ylsulphonyl)biphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}cyclohexanecarboxamide hydrochloride [ No CAS ]
  • 16
  • [ 59673-74-4 ]
  • trans-4-(aminomethyl)-N-{(2S)-3-[2'-methyl-5'-(pyrrolidin-1-ylsulphonyl)biphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}cyclohexanecarboxamide hydrochloride [ No CAS ]
  • 17
  • [ 59673-74-4 ]
  • trans-4-(aminomethyl)-N-{(2S)-3-[5'-(benzylsulphamoyl)-2'-methylbiphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}cyclohexanecarboxamide hydrochloride [ No CAS ]
  • 18
  • [ 59673-74-4 ]
  • trans-4-(aminomethyl)-N-{(2S)-3-[5'-(dimethylsulphamoyl)-2'-methylbiphenyl-3-yl]-1-oxo-1-[(3-oxo-2,3-dihydro-1H-indazol-6-yl)amino]propan-2-yl}cyclohexanecarboxamide hydrochloride [ No CAS ]
  • 19
  • [ 59673-74-4 ]
  • N-alpha-[trans-4-(aminomethyl)cyclohexyl]carbonyl}-3-(3-methylpyridin-4-yl)-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide hydrochloride [ No CAS ]
  • 20
  • [ 59673-74-4 ]
  • N-alpha-[trans-4-(aminomethyl)cyclohexyl]carbonyl}-3-[2-(4-methylpiperazin-1-yl)pyridin-4-yl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide hydrochloride [ No CAS ]
  • 21
  • [ 59673-74-4 ]
  • N-alpha-[trans-4-(aminomethyl)cyclohexyl]carbonyl}-3-{6-[3-(dimethylamino)propoxy]pyridin-3-yl}-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide hydrochloride [ No CAS ]
  • 22
  • [ 59673-74-4 ]
  • 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine [ No CAS ]
  • 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; Example 81A 4-Bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide N,N-Diisopropylethylamine is added to a solution of 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> in ethyl acetate. A 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide solution (50% in dimethylformamide) is added to the reaction mixture, and the mixture is then stirred overnight at RT. The reaction mixture is worked up by methods known to those skilled in the art and the residue is separated by means of preparative HPLC. This gives the title compound.
  • 23
  • [ 59673-74-4 ]
  • N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-L-phenylalanine [ No CAS ]
  • N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
57% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; diisopropylamine; In ethyl acetate; for 6.0h;Reflux; Example 5A N-alpha-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide N-[(trans-4-[(tert-Butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-4-iodo-L-phenylalanine (1.91 g, 3.6 mmol), <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> (0.55 g, 3.60 mmol) and N,N-diisopropylamine (1.9 ml, 10.8 mmol) were suspended in 23 ml of ethyl acetate and admixed with 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% in ethyl acetate, 5.73 g, 9.0 mmol). This was followed by refluxing for 3 h, addition of further <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> (0.14 g, 0.90 mmol), N,N-diisopropylamine (0.47 ml, 2.70 mmol) and 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide (50% in ethyl acetate, 1.43 g, 2.25 mmol) and refluxing once again for 3 h. The reaction mixture was admixed with water, the phases were separated and the aqueous phase was extracted three times with ethyl acetate. The solid precipitated in the two phases was filtered off with suction and dried under high vacuum. This gave 1.35 g (57% of theory) of the title compound.
  • 24
  • [ 59673-74-4 ]
  • 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine [ No CAS ]
  • 4-bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
11% With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine; In ethyl acetate; N,N-dimethyl-formamide; at 20.0℃; for 16.0h; Example 14A 4-Bromo-N-alpha-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-N-(3-oxo-2,3-dihydro-1H-indazol-6-yl)-L-phenylalaninamide N,N-Diisopropylethylamine (1.4 ml, 7.8 mmol) was added to a solution of 4-bromo-N-[(trans-4-[(tert-butoxycarbonyl)amino]methyl}cyclohexyl)carbonyl]-L-phenylalanine (1500 mg, 3 mmol) and <strong>[59673-74-4]6-amino-1,2-dihydro-3H-indazol-3-one</strong> (555 mg, 24 mmol) in ethyl acetate (21 ml). A 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane 2,4,6-trioxide solution (50% in dimethylformamide, 2.2 ml, 3.7 mmol) and, until dissolution, dimethylformamide were added to the suspension, and the mixture was then stirred at RT for 16 h. The reaction mixture was stirred into ethyl acetate, and washed twice with water and once with aqueous sodium chloride solution. The organic phase was dried with sodium sulphate and the solvent was removed. The crude product was stirred with acetonitrile and filtered off with suction. The residue was separated twice by means of preparative HPLC (eluent: acetonitrile/water gradient, 0.1% TFA). The crude product was stirred with methanol and filtered off with suction. This gave 202 mg (11% of theory) of the title compound. 1H-NMR (400 MHz, DMSO-d6): delta=ppm 0.69-0.89 (m, 2H), 1.04-1.29 (m, 3H), 1.37 (s, 9H), 1.67 (m, 4H), 2.04-2.17 (m, 1H), 2.75 (m, 3H), 2.94-3.07 (m, 1H), 4.54-4.75 (m, 1H), 6.68-6.83 (m, 1H), 6.96 (dd, 1H), 7.25 (d, 2H), 7.39-7.56 (m, 3H), 7.84 (s, 1H), 8.09 (d, 1H), 10.20 (s, 1H), 11.08 (br. s, 1H). LC-MS (Method 1): Rt=1.00 min; MS (ESIpos): m/z=614 [M+H]+.
 

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[ 59673-74-4 ]

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