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Chemical Structure| 2644-70-4 Chemical Structure| 2644-70-4

Structure of 2644-70-4

Chemical Structure| 2644-70-4

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Product Details of [ 2644-70-4 ]

CAS No. :2644-70-4
Formula : ClH5N2
M.W : 68.51
SMILES Code : NN.[H]Cl
English Name :Hydrazine hydrochloride
MDL No. :MFCD00044368
InChI Key :BIVUUOPIAYRCAP-UHFFFAOYSA-N
Pubchem ID :115031

Safety of [ 2644-70-4 ]

Computational Chemistry of [ 2644-70-4 ] Show Less

Physicochemical Properties

Num. heavy atoms 3
Num. arom. heavy atoms 0
Fraction Csp3 None
Num. rotatable bonds 0
Num. H-bond acceptors None
Num. H-bond donors None
Molar Refractivity 14.49
TPSA ?

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

52.04 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

None
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

None
Log Po/w (WLOGP)?

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

None
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.

None
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

None
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

None

Water Solubility

Log S (ESOL):?

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

None
Solubility None mg/ml ; None mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

None
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

None
Solubility None mg/ml ; None mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

None
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

None
Solubility None mg/ml ; None mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

None

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

None
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

None
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

None
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

None
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

None
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

None
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

None
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

None
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

None 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

None
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

None
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

None
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

None
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

None

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

None alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

None 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
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)

None

Application In Synthesis of [ 2644-70-4 ]

* 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 [ 2644-70-4 ]

[ 2644-70-4 ] Synthesis Path-Downstream   1~14

  • 1
  • [ CAS Unavailable ]
  • [ 2644-70-4 ]
  • [ 742058-27-1 ]
YieldReaction ConditionsOperation in experiment
70% In methanol for 1h; Heating / reflux; 1-1 5-(4-Benzyloxyphenyl)-1H-pyrazole-3-carboxylic acid methyl ester A mixture of sodium 3-(4-benzyloxyphenyl)-1-methoxycarbonyl-3-oxopropen-1-olate (starting compound 1A) (0.500 g, 1.496 mmol), hydrazine monohydrochloride (0.330 g, 4.82 mmol) and methanol (15 mL) was heated at reflux for 1 hour. After cooled to room temperature, the mixture was diluted with water (15 mL). The resulting precipitate was collected by filtration, washed with 50 % methanol/water, and dried under reduced pressure to give 5-(4-benzyloxyphenyl)-1H-pyrazole-3-carboxylic acid methyl ester (0.324 g, 70 %) as a colorless solid.
  • 2
  • [ 220435-92-7 ]
  • [ 2644-70-4 ]
  • [ 1309326-96-2 ]
YieldReaction ConditionsOperation in experiment
In ethanol; ethyl acetate 68 2-Chloro-4-(1H-pyrazol-3-yl)-benzoic Acid, Methyl Ester EXAMPLE 68 2-Chloro-4-(1H-pyrazol-3-yl)-benzoic Acid, Methyl Ester To a suspension of 2-chloro-4-(3-dimethylamino-2-propen-1-on-1-yl)-benzoic acid, methyl ester (13.67g) in ethanol (53 ml) was added hydrazine monohydrochloride (7.0 g). The mixture was heated in an oil bath at 75-80° C. for one hour. The solvent was removed in vacuo. The resulting residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, and the solvent removed in vacuo to yield the tide compound as a crude solid (12 g). A purified sample had a melting point of 130-131° C.
  • 3
  • [ 220435-92-7 ]
  • [ 2644-70-4 ]
  • [ 220436-03-3 ]
YieldReaction ConditionsOperation in experiment
In ethanol; ethyl acetate 19 2-Chloro-4-(1H-pyrazol-3-yl)-benzoic acid, methyl ester EXAMPLE 19 2-Chloro-4-(1H-pyrazol-3-yl)-benzoic acid, methyl ester To a suspension of 2-chloro-4-(3-dimethylamino-2-propen-1-on-1-yl)-benzoic acid, methyl ester (13.67 g) in ethanol (53 ml) was added hydrazine monohydrochloride (7.0 g). The mixture was heated in an oil bath at 75-80° C. for one hour. The solvent was removed in vacuo. The resulting residue was dissolved in ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, and the solvent removed in vacuo to yield the title compound as a crude solid (12 g). A purified sample had a melting point of 130-131° C.
  • 4
  • [ 136-95-8 ]
  • [ 2644-70-4 ]
  • [ 615-21-4 ]
YieldReaction ConditionsOperation in experiment
With hydrazine hydrate In ethylene glycol 1 2-HYDRAZINOBENZOTHIAZOLE EXAMPLE 1: 2-HYDRAZINOBENZOTHIAZOLE To a slurry of 30 g. (0.2 mole) 2-aminobenzothiazole in 150 ml. ethylene glycol was added 23.7 g. (0.4 mole) 85% hydrazine hydrate and 13.7 g. (0.2 mole) hydrazine monohydrochloride. The mixture was stirred under a nitrogen atmosphere and heated at a temperature of 140°C. for 2 hours. The product crystallized on cooling. After addition of 50 ml. water and stirring, the material was filtered, washed with 100 ml. water in three portions, and dried in vacuo at 60°C.
  • 5
  • [ 1477-42-5 ]
  • [ 2644-70-4 ]
  • [ 20174-68-9 ]
YieldReaction ConditionsOperation in experiment
89% With hydrazine hydrate In water; ethylene glycol 16 4-METHYL-2-HYDRAZINOBENZOTHIAZOLE EXAMPLE 16: 4-METHYL-2-HYDRAZINOBENZOTHIAZOLE 4-Methyl-2-aminobenzothiazole (8.21 g.; 0.05 mole), hydrazine monohydrochloride (1.14 g.; 0.017 mole), 85% hydrazine hydrate (1.96 g.; 0.033 mole), and 41 ml. of ethylene glycol were mixed, and the mixture heated under N2 atmosphere to 140°C. These reaction conditions were continued for 15 hours; the reaction mixture was then permitted to cool slowly to romm temperature and, for convenience only, stored overnight under N2 atmosphere. Water (45 ml.) was added to the reaction mixture in the morning to force crystallization. The reaction mixture was then filtered to separate the desired 4-methyl-2-hydrazinobenzothiazole compound. It was dried in vacuo overnight at 60°C. The yield was 8.00 g., 89% yield, m.p. 143°-51°C. Non-aqueous titration showed the product to be 85.8% pure.
  • 6
  • [ 2644-70-4 ]
  • [ 20914-27-6 ]
  • [ 68569-77-7 ]
  • [ 57-14-7 ]
YieldReaction ConditionsOperation in experiment
In ethanol VII 1-(2,6-dimethylphenyl)-1-methyl-2-aminoguanidine.HCl EXAMPLE VII 1-(2,6-dimethylphenyl)-1-methyl-2-aminoguanidine.HCl To 8.2 g of 1-(2,6-dimethylphenyl)-1-methylcyanamide dissolved in 30 ml of ethanol, 3.4 g of hydrazine.hydrochloride are added. The mixture is refluxed for 20 hours followed by evaporation. The residue is recrystallized from ethanol/ether. Yield: 7.8 g; melting point: 187°-188°C. By using 1.1-dimethyl-hydrazine instead of hydrazine.hydrochloride 1-(2,6-dimethylphenyl)-1-methyl-2-dimethylaminoguanidine is obtained as an oily substance. Rf in methanol:acetic acid (98:2) = 0.63 (SiO2).
In ethanol VII 1-(2,6-dimethylphenyl)-1-methyl-2-aminoguanidine.HCl EXAMPLE VII 1-(2,6-dimethylphenyl)-1-methyl-2-aminoguanidine.HCl To 8.2 g of 1-(2,6-dimethylphenyl)-1-methylcyanamide dissolved in 30 ml of ethanol, 3,4 g of hydrazine.hydrochloride are added. The mixture is refluxed for 20 hours followed by evaporation. The residue is recrystallized from ethanol/ether. Yield: 7.8 g; melting point: 187°-188° C. By using 1.1-dimethyl-hydrazine instead of hydrazine. hydrochloride 1-(2,6-dimethylphenyl)-1-methyl-2-dimethylaminoguanidine is obtained as an oily substance. Rf in methanol:acetic acid (98:2) = 0.63 (SiO2).
  • 7
  • [ 22359-38-2 ]
  • [ 2644-70-4 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride In water pptn. of N2H4*HCl by addn. of HCl to an acidic soln.;;
  • 8
  • [ 608880-86-0 ]
  • [ 2644-70-4 ]
  • [ 75-05-8 ]
  • [ 1150263-29-8 ]
YieldReaction ConditionsOperation in experiment
24.78% Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.25h; Stage #2: methyl 3-(4-methoxypyridin-2-yl) propionate In tetrahydrofuran at -78 - 20℃; for 0.666667h; Stage #3: hydrazine hydrochloride; acetonitrile more than 3 stages; 9 Acetonitrile (1.078 mL, 20.64 mmol, 1.3eq) was added dropwise to lithium diisopropylamide (10.32 mL, 20.64 mmol, 1.3eq) in THF (10OmL) at -780C over a period of 5 mins under nitrogen. The resulting solution was stirred at -78 0C for 10 mins. Methyl 3-(4-methoxypyridin-2-yl)propanoate (3.1g, 15.88 mmol, leq) was added in one portion and the reaction was stirred for 30 mins before being allowed to warm to ambient temperature. After stirring for 10 mins, a further 1.3 equivalents of acetonitrile anion was added to the reaction flask at -78 0C. The reaction was allowed to warm back up to ambient temperature and stirred for 1 h. The reaction mixture was diluted with ethanol (100 mL) and hydrazine hydrochloride (2.83 g, 41.29 mmol, 2.6eq) was added. The reaction was heated at reflux for 3 h until formation of pyrazole was complete. The resulting mixture was evaporated to dryness and the residue was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM with ammonia. Pure fractions were evaporated to dryness to afford 5-(2-(4-methoxypyridin-2-yl)ethyl)-lH-pyrazol-3-amine (859mg, 24.78 %) as a yellow gum.IH NMR (400.132 MHz, DMSO) δ 2.79 - 2.87 (2H, m), 2.87 - 2.96 (2H, m), 3.83 (3H, s), 6.73 (IH, s), 6.77 - 6.81 (IH, m), 6.83 (IH, d), 7.33 (IH, s), 8.30 (IH, d). MS: m/z 219 (MH+)
  • 9
  • [ 2644-70-4 ]
  • [ 75-05-8 ]
  • [ 193151-11-0 ]
  • [ 1000895-59-9 ]
YieldReaction ConditionsOperation in experiment
38% Stage #1: acetonitrile; 3-(3-cyano-phenyl)-propionic acid methyl ester With sodium hydride In 1,4-dioxane at 20℃; for 0.166667h; Heating / reflux; Stage #2: hydrazine hydrochloride In 1,4-dioxane; ethanol Heating / reflux; 10 Sodium hydride (60%, 3.Og, 75.6mmol) was added to a stirred solution of methyl 3-(3- cyanophenyl)propanoate (11.9g, 63.0mmol) in dry 1,4 dioxane (35OmL) and dry acetonitrile (3.95mL, 75.6mmol) under nitrogen to give a cloudy grey mixture. This was stirred at room temperature for 10 mins and then refluxed under nitrogen overnight to give a dark orange solution. The reaction mixture was cooled and ethanol (25mL) was added followed by hydrazine monohydrochloride (8.635g, 126mmol). The reaction mixture was refluxed overnight. The reaction mixture was cooled, filtered, and evaporated to dryness to afford crude 3-[2-(5-amino-2H-pyrazol-3-yl)ethyl]benzonitrile (16g). Purified by flash silica chromatography, eluted isocratically with 8% MeOH in DCM. Pure fractions evaporated to dryness to afford 3-[2-(5-amino-2H-pyrazol-3-yl)ethyl]benzonitrile as an orange gum, (5.1g, 38%). IH NMR (399.9 MHz, DMSOd6) δ 2.73 - 2.76 (2H, m), 2.88 - 2.92 (2H, m), 4.07 - 4.08 (IH, m), 4.50 (2H, s), 5.17 (IH, s), 7.47 - 7.51 (IH, m), 7.55 - 7.58 (IH, m), 7.64 - 7.66 (2H, m) MS: m/z 213.41 (MH+)
  • 10
  • [ 2644-70-4 ]
  • [ 59938-06-6 ]
  • [ CAS Unavailable ]
YieldReaction ConditionsOperation in experiment
86% In ethanol; water; ethyl acetate 14.B Preparation of Substituted Quinolines 88 Step B: Preparation of 3-trifluoromethyl-1H-pyrazole 86a. To a stirred solution of hydrazine monochloride (6.62 g, 1.6 eq.) in EtOH (300 mL) was added dropwise compound 84 (10.16 g, 1 eq.) in EtOH (200 mL). The reaction mixture was refluxed for 6 hrs and evaporated to dryness. Water and EtOAc were added to the residue. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 86a as a brown solid in 86% yield. 1H NMR (CDCl3, 376 MHz) δ 6.66 (d, J=2.30 Hz, 1H), 7.72 (d, J=2.30 Hz, 1H); 19F NMR (CDCl3, MHz) δ 61.41 (s, 3F).
86% In ethanol; water; ethyl acetate 19.A.B Method A Step B: Preparation of 3-trifluoromethyl-1H-pyrazole 233a. To a stirred solution of hydrazine monochloride (6.62 g, 1.6 eq.) in EtOH (300 mL) was added dropwise compound 231 (10.16 g, 1 eq.) in EtOH (200 mL). The reaction mixture was refluxed for 6 hrs and evaporated to dryness. Water and EtOAc were added to the residue. The organic layer was washed with water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 233a as a brown solid in 86% yield. 1H NMR (CDCl3, 376 MHz) δ (ppm) 6.66 (d, J=2.30 Hz, 1H), 7.72 (d, J=2.30 Hz, 1H); 19F NMR (CDCl3, MHz) δ (ppm) 61.41 (s, 3F).
  • 11
  • [ 2644-70-4 ]
  • [ 38664-64-1 ]
  • [ 49633-25-2 ]
YieldReaction ConditionsOperation in experiment
94% With sulfuric acid In water 14.D Preparation of Substituted Quinolines 88 Step D: Preparation of 3-isopropyl-1H-pyrazole 86b. Compound 85 (6.6 g, 1 eq.) was added dropwise to a stirred solution of hydrazine monochloride (3.2 g, 1 eq.), sulfuric acid (1.13 mL) and H2O (6 mL). The reaction mixture was stirred at 68° C. for 2 hrs. The mixture was then neutralized with 1N NaOH and extracted with diethyl ether. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 86b as a beige solid in 94% yield. 1H NMR (DMSO-d6, 400 MHz) δ 1.17 (s, 3H), 1.19 (s, 3H), 2.87-2.93 (m, 1H), 5.99 (s, 1H), 7.40 (s, 1H). 1.39-1.43 (t, J=7.04 Hz, 3H), 4.08-4.13 (q, J=7.04 Hz, 2H), 5.86 (d, J=12.40 Hz, 1H), 7.90 (d, J=12.40 Hz, 1H).
94% With sulfuric acid In water 19.A.D Method A Step D: Preparation of 3-isopropyl-1H-pyrazole 233b. Compound 232 (6.6 g, 1 eq.) was added dropwise to a stirred solution of hydrazine monochloride (3.2 g, 1 eq.), sulfuric acid (1.13 mL), and H2O (6 mL). The reaction mixture was stirred at 68° C. for 2 hrs. The mixture was then neutralized with 1N NaOH and extracted with diethyl ether. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to yield compound 233b as a beige solid in 94% yield. 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.17 (s, 3H), 1.19 (s, 3H), 2.87-2.93 (m, 1H), 5.99 (s, 1H), 7.40 (s, 1H). 1.39-1.43 (t, J=7.04 Hz, 3H), 4.08-4.13 (q, J=7.04 Hz, 2H), 5.86 (d, J=12.40 Hz, 1H), 7.90 (d, J=12.40 Hz, 1H).
  • 12
  • [ 718619-80-8 ]
  • [ 2644-70-4 ]
  • [ 718619-81-9 ]
YieldReaction ConditionsOperation in experiment
100% Stage #1: hydrazine hydrochloride With triethylamine In dichloromethane for 0.5h; Stage #2: 2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzoic acid pentafluorophenyl ester In dichloromethane for 5h; 69.6; 141.1 Example 69; 2-{5-[2-(4-Ethyl-2-fluoro-phenylamino)-3,4-difluoro-phenyl]-[1,3,4]oxadiazol-2-ylamino}-ethanol; Step 6 To a stirring solution of hydrazine hydrochloride (0.68g, 9.87 mmol) in dichloromethane (50 ML) was added triethylamine (2.63 mL, 18.84 mmol) and allowed to stir for 30 minutes. 2- (4-ethyl-2-fluoro-phenylamino)-3, 4-difluoro- benzoic acid pentafluorophenyl ester (4.14g, 8.79 mmol) was added and the mixture was allowed to stir an additional 5 hours. The reaction mixture was partitioned between dichloromethane and water. Organics were washed twice with water, twice with brine, twice with saturated NAHCO3 and a final wash with brine. Organics were collected, dried over NA2SO4, filtered and concentrated in vacuo. Afforded 2- (4-ETHYL-2-FLUORO-PHENYLAMINO)-3, 4-DIFLUORO-BENZOIC acid hydrazide 6 (3.07g, >100% yield due to solvents remaining) as a yellow solid.
  • 13
  • [ 14011-37-1 ]
  • [ CAS Unavailable ]
  • [ 85230-37-1 ]
YieldReaction ConditionsOperation in experiment
92% Stage #1: diethyl oxalacetate sodium salt In benzene for 0.333333h; Stage #2: With acetic acid for 0.5h; Stage #3: hydrazine hydrochloride at 100℃; for 24.5h; Heating / reflux; 1 Example 1; 5-HYDROXY-LH-PYRAZOLE-3-CARBOXYLIC acid ethyl ester Diethyloxalacetate, sodium salt (14. 53 g, 69. 15 mmol) was dissolved in 100 mL of benzene and stirred for 20 min. To the solution was added 100 ML of acetic acid and the reaction mixture was stirred for a further 30 min. Hydrazine monohydrochloride (9. 47 g, 138 mmol) was added and the reaction mixture was stirred for an additional 30 min. The reaction was brought to reflux at 100 C for 24 h. The reaction was then removed from heat and cooled to room temperature and extracted with ethyl acetate and washed with 10% hydrochloric acid, saturated sodium bicarbonate solution, water and then brine. The solvent was removed IN VACUO TO yield an oily solid which was then triturated with a 2 : 1 mixture of diethyl ether : hexanes to yield 3 (10. 00 g, 92%) as an off-white solid : LRMS (electrospray) ; m/z [M+H1+ = 157.
  • 14
  • [ 2644-70-4 ]
  • [ 140233-87-0 ]
  • [ 1352994-46-7 ]
YieldReaction ConditionsOperation in experiment
88% Stage #1: 3,3'-diamino-2,2',4,4',6,6'-hexanitrodiphenylamine With sodium hydroxide In water at 80℃; for 0.5h; Stage #2: hydrazine hydrochloride In water at 20℃; for 1h;
 

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