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Chemical Structure| 35344-95-7 Chemical Structure| 35344-95-7
Chemical Structure| 35344-95-7

1H-Pyrazole-4-carboxaldehyde

CAS No.: 35344-95-7

4.5 *For Research Use Only !

Cat. No.: A435381 Purity: 97%

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Product Details of [ 35344-95-7 ]

CAS No. :35344-95-7
Formula : C4H4N2O
M.W : 96.09
SMILES Code : O=CC1=CNN=C1
MDL No. :MFCD02179514
InChI Key :LRGBDJBDJXZTTD-UHFFFAOYSA-N
Pubchem ID :5130673

Safety of [ 35344-95-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H332-H335
Precautionary Statements:P280-P305+P351+P338-P310

Computational Chemistry of [ 35344-95-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 7
Num. arom. heavy atoms 5
Fraction Csp3 0.0
Num. rotatable bonds 1
Num. H-bond acceptors 2.0
Num. H-bond donors 1.0
Molar Refractivity 23.98
TPSA ?

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

45.75 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.23
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

-0.95
Log Po/w (WLOGP)?

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

0.22
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.

-1.04
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

1.2
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

-0.07

Water Solubility

Log S (ESOL):?

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

-0.3
Solubility 48.2 mg/ml ; 0.501 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.

0.47
Solubility 286.0 mg/ml ; 2.98 mol/l
Class?

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

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

-1.1
Solubility 7.69 mg/ml ; 0.08 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

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.

-7.56 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

2.0
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)

1.0

Application In Synthesis of [ 35344-95-7 ]

* 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 [ 35344-95-7 ]

[ 35344-95-7 ] Synthesis Path-Downstream   1~30

  • 2
  • [ 431-67-4 ]
  • [ 35344-95-7 ]
  • [ 102807-90-9 ]
  • 3
  • [ 136609-85-3 ]
  • [ 35344-95-7 ]
  • 5-methyl-6<2-(4-pyrazolyl)-5-benzimidazoyl>-2,3,4,5-tetrahydro-pyridazin-3-one [ No CAS ]
  • 5
  • [ 35344-95-7 ]
  • C4H3N2O(1-)*K(1+) [ No CAS ]
  • 6
  • [ 626-05-1 ]
  • [ 35344-95-7 ]
  • [ 815608-05-0 ]
  • 7
  • 1-(1-ethoxyethyl)-1H-pyrazole-4-carbaldehyde [ No CAS ]
  • [ 35344-95-7 ]
  • 8
  • [ 2075-45-8 ]
  • [ 68-12-2 ]
  • [ 35344-95-7 ]
  • 9
  • [ 14538-51-3 ]
  • [ 35344-95-7 ]
  • 4-(1,3-dihydroxy-4,4,5,5-tetramethylimidazolidin-2-yl)pyrazole [ No CAS ]
  • 10
  • [ 952674-99-6 ]
  • [ 35344-95-7 ]
  • [ 952675-00-2 ]
YieldReaction ConditionsOperation in experiment
36% With dmap; In 1,1-dichloroethane; at 0 - 20℃; for 3h; Step I. 1-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong>; 2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (0.8 g, 1.9 mmol) was added to a solution of <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (0.6 g, 6.2 mmol) and DMAP (1.5 g, 12 mmol) in DCE (70 mL) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. The solvent was concentrated and the product was purified by flash chromatography on silica gel using DCM/EtOAc (1:1) as eluent to provide the title compound as white solid. Yield: 0.34 g (36percent); MS (ESI) (M+H)+=465.0.
36% With dmap; In 1,1-dichloroethane; at 0 - 20℃; for 3h; Step I. 1-({2-tert-butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong>2-tert-Butyl-1-[(4,4-difluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (0.8 g, 1.9 mmol) was added to a solution of <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (0.6 g, 6.2 mmol) and DMAP (1.5 g, 12 mmol) in DCE (70 mL) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 3 h. The solvent was concentrated and the product was purified by flash chromatography on silica gel using DCM/EtOAc (1:1) as eluent to provide the title compound as white solid. Yield: 0.34 g (36percent); MS (ESI) (M+H)+=465.0.
  • 11
  • [ 952675-18-2 ]
  • [ 35344-95-7 ]
  • 1-({2-tert-butyl-1-[(trans-4-fluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-1H-pyrazole-4-carbaldehyde [ No CAS ]
YieldReaction ConditionsOperation in experiment
28% With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20℃; for 3h; Step B: 1-({2-tert-Butyl-1-[(trans-4-fluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong>; 2-tert-Butyl-1-[(4-fluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (400 mg, 1.03 mmol), <strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> (300 mg, 3.09 mmol) (see Example 126, step H for preparation) and DMAP (catalytic) were stirred in 10 mL of DCM containing DIPEA (0.90 mL, 5.15 mmol) at rt for 3 h. The solution washed with saturated aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by flash chromatography on silica gel using hexanes/EtOAc (1:1) as eluent. Yield: 131 mg (28percent). 1H NMR (400 MHz, CHLOROFORM-D) delta 1.16-1.26 (m, 2H), 1.35-1.48 (m, 2H), 1.54-1.56 (m, 9H), 1.72 (dd, J=8.69, 3.03 Hz, 2H), 1.95-2.04 (m, 1H), 2.11-2.19 (m, 2H), 4.17-4.21 (m, 2H), 4.37-4.46 (m, 1H), 4.50-4.59 (m, 1H), 7.44 (d, J=8.59 Hz, 1H), 7.96 (dd, J=8.69, 1.86 Hz, 1H), 8.08 (s, 1H), 8.44 (d, J=1.37 Hz, 1H), 8.64 (s, 1H), 9.91 (s, 1H).
28% With N-ethyl-N,N-diisopropylamine;dmap; In dichloromethane; at 20℃; for 3h; Step B: 1-({2-tert-Butyl-1-[(trans-4-fluorocyclohexyl)methyl]-1H-benzimidazol-5-yl}sulfonyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong>2-tert-Butyl-1-[(4-fluorocyclohexyl)methyl]-1H-benzimidazole-5-sulfonyl chloride (400 mg, 1.03 mmol), <strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> (300 mg, 3.09 mmol) (see Example 126, step H for preparation) and DMAP (catalytic) were stirred in 10 mL of DCM containing DIPEA (0.90 mL, 5.15 mmol) at rt for 3 h. The solution was washed with saturated aqueous NaHCO3 solution, brine and dried over anhydrous MgSO4. The crude product was purified by flash chromatography on silica gel using hexanes/EtOAc (1:1) as eluent. Yield: 131 mg (28percent). 1H NMR (400 MHz, CHLOROFORM-D) delta 1.16-1.26 (m, 2H), 1.35-1.48 (m, 2H), 1.54-1.56 (m, 9H), 1.72 (dd, J=8.69, 3.03 Hz, 2H), 1.95-2.04 (m, 1H), 2.11-2.19 (m, 2H), 4.17-4.21 (m, 2H), 4.37-4.46 (m, 1H), 4.50-4.59 (m, 1H), 7.44 (d, J=8.59 Hz, 1H), 7.96 (dd, J=8.69, 1.86 Hz, 1H), 8.08 (s, 1H), 8.44 (d, J=1.37 Hz, 1H), 8.64 (s, 1H), 9.91 (s, 1H).
  • 12
  • [ 24424-99-5 ]
  • [ 35344-95-7 ]
  • [ 821767-61-7 ]
YieldReaction ConditionsOperation in experiment
76% dmap; In acetonitrile; at 20℃; for 0.5h; 4-FORMYL-PYRAZOLE-1-CARBOXYLIC acid tert-butyl ester (56). To a solution of 55 (0.31 g, 3.26 mmol) in acetonitrile (30 ml) was added BOC anhydride (0.71 g, 3.26 mmol) followed by DMAP (0.02 g). After 30 minutes of stirring at room temperature, the solvent was evaporated, water and EtOAc were added. Organic layer was separated, washed with 0.5 N HCl (10 ml) and brine (15 ml), dried (NA2S04) and concentrated to give 0.41 g (76percent yield) of the desired product which was used in the next step to prepare di-Boc-protected 2 without purification.
71% With dmap; In acetonitrile; at 20℃; 1003831 Step A: Boc2O (2183 mg, 10.0 mmol) was added to a stirred solution of iH<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (961 mg, 10.0 mmol) in acetonitrile (30 mL) at room temperature, followed by 4-dimethylaminopyridine (?DMAP?) (61.1 mg, 0.500 mmol). After stirring overnight, the reaction was concentrated to dryness and partitioned between ethyl acetate (30 mL) and water (30 mL). The organics were isolated and washed with 0.5N HCL (30 mL) and with brine (30 mL). The organics were isolated, dried (Mg504), filtered and concentratedan oil, which was loaded onto a Biotage 40M column with 4/1 hexanes/ethyl acetate and eluted with the same solvent. Product containing fractions were pooled and concentratedan oil, which eventually solidified to a solid, tert-butyl 4-formyl-1H-pyrazole-1-carboxylate(1.4 g, 71percent).
  • 13
  • [ 153687-35-5 ]
  • [ 35344-95-7 ]
YieldReaction ConditionsOperation in experiment
With trifluoroacetic acid; for 2h;Heating / reflux; 1H-PYRAZOLE-4-CARBALDEHYDE (55). To a solution of 1- (4-METHOXY-BENZYL)-1H- pyrazole (0.21 mol) (Synth. Commun. 1990, 20/18 ; 2849) in dry DMF (235 ml) was added POCL3 (1.5 eq. ) dropwise at room temperature. The mixture was then heated at 95°C for 16 hrs. After cooling to room temperature, the reaction mixture was neutralized by adding ice and saturated sodium carbonate solution. EtOAc (800 ml) was added and the organic layer was separated and washed several times with water. After drying (Na2SO4), the solvent was removed and the crude product was purified over silica gel to give 16.4 g (35percent yield) desired aldehyde 1-(4-METHOXY-BENZYL)-LH- pyrazole-4-carbaldehyde. It was heated with 150 ml TFA for 2 hrs. TFA was evaporated and the basified crude product was purified on silica gel to give 5.3 g of 55.
  • 14
  • [ 594-70-7 ]
  • [ 35344-95-7 ]
  • [ 204707-17-5 ]
YieldReaction ConditionsOperation in experiment
226.3 mg(51%) With acetic acid; In ethanol; Example 12 Production of alpha-(4-pyrazolyl)-N-t-butylnitrone To a suspension of 1,1-dimethylnitroethane (546.0 mg, 5.29 mmol) and zinc (515.5 mg, 7.89 mmol) in ethanol (3.0 ml) was added acetic acid (950.0 mg, 15.8 mmol) dropwise at 5° C. while stirring. The mixture was stirred at room temperature for 45 minutes. After cooling the mixture to 5° C. again, <strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (255.4 mg, 2.66 mmol) was added dropwise to the mixture while stirring and stirred at room temperature overnight. Zinc acetate in the mixture was filtered off and the filtrate was concentrated and purified by silica gel chromatography (chloroform/methanol=10/1). Yield: 226.3 mg(51percent) 1H-NMR(CDCl3) 1.60(s, 9H), 6.56(d, 1H, J=2.0 Hz), 7.64(d, 1H, J=2.0 Hz), 7.71(s, 1H), 8.43(brs, 1H)
  • 15
  • [ 945466-97-7 ]
  • [ 35344-95-7 ]
  • (6R,7S,7aS)-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)-2-[(1H-pyrazol-4-ylmethyl)amino]hexahydro-3H-pyrrolizin-3-one [ No CAS ]
  • (6R,7S,7aS)-2-[bis(1H-pyrazol-4-ylmethyl)amino]-6-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)-hexahydro-3H-pyrrolizin-3-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
22%; 48% To a solution of 20mg (0.04 mmol) (6R3 75, 7a5)-2-amino-6-{(lR)-l-[3,5- bis(trifluoromethyl)phenyl]ethoxy}-7-(4-fluorophenyl)hexahydro-3H-pyrrolizin-3-one in 1 mL anhydrous dichloromethane and 7 muL (0.04 mmol) DIEA under nitrogen atmosphere was added crushed 4A molecular sieves followed by 40 mg (0.04 mmol) aromatic heterocyclic aldehyde . After 5 minutes of stirring, the solution was then treated with 40 mg (0.2 mmol) Na(OAc)3BH and the resulting suspension stirred vigorously at room temperature, overnight. The mixture was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane (2 x 5 mL). The organics were combined and treated as stated in Example 3, step E. The residue was purified by preparative TLC plate eluding with methanol/dichloromethane (1/9) to afford two products. The less polar product was found to be the mono substituted compound 5.3 mg (22percent),MS: 571 (MH)+,and the slightly more polar product 11.2 mg (48percent) was di-substituted,MS: 651 (MH)+. Conversion to the HCl salts of each were accomplished according to the procedure for Example GJM-5, step C.
  • 16
  • [ 7051-34-5 ]
  • [ 35344-95-7 ]
  • [ 1082065-99-3 ]
YieldReaction ConditionsOperation in experiment
56% Preparation 53: 1 -Cyclopropylmethyl- 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> <n="62"/>--61-Add lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (0.200 g, 2.08 mmol) to a suspension of sodium hydride (0.092 g, 2.29 mmol) in DMF (3 mL) at 0 0C. Stir for 20 min. at 0 0C. Add a solution of l-(bromomethyl)cyclopropane (0.295 g, 2.18 mmol) in DMF (4 mL) dropwise to the reaction mixture. Stir reaction to ambient temperature for 18 hr. Quench with aqueous saturated sodium bicarbonate solution and add ethyl acetate. Separate organic layer. Extract aqueous layer twice with ethyl acetate, dry combined organics (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0: 100 to 60:40 ethyl acetate:hexanes) to give the title preparation (175 mg, 56percent). GC-MS: m/z = 150 [M+].
  • 17
  • [ 35344-95-7 ]
  • [ 540-51-2 ]
  • [ 1082065-98-2 ]
YieldReaction ConditionsOperation in experiment
97% With potassium carbonate; In acetonitrile; at 150℃; for 0.333333h;Microwave irradiation; Preparation 12: 1 -(2-Hydroxy-ethyl)- lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>Combine lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (0.110 g, 1.14 mmol), 2-bromoethanol(0.172 g, 1.37 mmol), and potassium carbonate (0.236 g, 1.71 mmol) in acetonitrile (2 mL). Heat in microwave at 150 0C for 20 min. Cool to room temperature and filter, wash with acetonitrile. Concentrate filtrate to give l-(2-hydroxy-ethyl)-lH-pyrazole-4- carbaldehyde (0.155 g, 97percent). GC-MS (m/z): 140 (M+).
97% With potassium carbonate; In acetonitrile; at 150℃; for 0.333333h;Microwave irradiation; Preparation 52: l-(2-Hydroxy-ethyl)-lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> Combine lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (0.110 g, 1.14 mmol), 2-bromoethanol(0.172 g, 1.37 mmol), and potassium carbonate (0.236 g, 1.71 mmol) in acetonitrile (2 mL). Heat in microwave at 150 0C for 20 min.. Cool to room temperature and filter, washing with acetonitrile. Concentrate filtrate to give the title preparation (0.155 g, 97percent). GC-MS: m/z = 140 [M+].
89% With potassium carbonate; In acetonitrile; at 150℃; for 0.666667h;Sealed tube; Microwave irradiation; 1-(2-Hydroxyethyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> In a 30-mL sealed tube, <strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (500 mg, 5.20 mmol, 1.00 equiv), potassium carbonate (1.08 mg, 7.80 mmol, 1.50 equiv) and 2-bromoethan-1-ol (775.3 mg, 6.20 mmol, 1.19 equiv) were mixed in CH3CN (10 mL) at room temperature. The reaction mixture was then irradiated with microwave for 40 min at 150° C. After the reaction was done, the reaction mixture was cooled to room temperature, filtered through a celite pad and the filtrate was concentrated under reduced pressure. The residue was purified in a silica gel column eluting with dichloromethane/methanol (1percent to 5percent gradient) to afford 1-(2-hydroxyethyl)-<strong>[35344-95-7]1H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong></strong> (650 mg, 89percent) as yellow solid. MS: m/z=140.8 [M+H]+
69% With potassium carbonate; In acetonitrile; at 150℃; for 0.5h;Microwave irradiation; 1H-Pyrazole-4-carboxaldehyde (0.50 g, 5.21 mmol), 2-bromoethanol (1.30 g, 10.41 mmol) and potassium carbonate (0.79 g, 5.73 mmol) combined with acetonitrile (5 mL) in a microwave vial. The microwave vial was heated at 150 °C in a microwave for 30 minutes. The reaction mixture was filtered and the solvent evaporated under reduced pressure. The residue was purified by flash column chromatography eluting with 0- 100percent ethyl acetate in iso-hexane to afford the title compound (0.50 g, 69percent). 1HNMR (400 MHz, CDCl3): delta 9.86 (s, 1 H); 8.02 (s, 1 H); 7.99 (s, 1 H); 4.33-4.25 (m, 2 H); 4.05 (t, J = 4.8 Hz, 2 H).

  • 18
  • [ 433-06-7 ]
  • [ 35344-95-7 ]
  • [ 790254-33-0 ]
YieldReaction ConditionsOperation in experiment
42% Preparation 55: 1 -(2,2,2-Trifluoro-ethyl)- 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> Add 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (0.40Og, 4.16 mmol) as a solution in DMF (2 mL) dropwise to a suspension of sodium hydride (0.333 g, 8.32 mmol) in DMF (5 mL) at 0 0C. Stir for 15 min. at 0 0C. Add 2,2,2-trifluoroethyl-p-toluenesulfonate (1.27 g, 5.00 mmol) and DMF (3 mL) to the reaction mixture. Heat to 60 0C for 18 hr. Quench with aqueous saturated sodium bicarbonate solution and add ethyl acetate. Separate organic layer. Extract aqueous layer twice with ethyl acetate, wash combined organics with brine, dry (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0: 100 to 100:0 ethyl acetate:hexanes) to give the title preparation (309 mg, 42%). GC-MS: m/z = 178 [M+].
  • 19
  • [ 4333-56-6 ]
  • [ 35344-95-7 ]
  • [ 1082066-00-9 ]
YieldReaction ConditionsOperation in experiment
8.82% With potassium carbonate; In N,N-dimethyl-formamide; at 110℃; for 16h;Sealed tube; To the stirred solution of lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> 19-4 (200 mg, 2.08 mmol) in DMF (2 ml) in a sealed tube were added potassium carbonate (719.19 mg, 5.20 mmol, 314.06 uL) and bromocyclopropane 19-5 (251.80 mg, 2.08 mmol, 166.76 uL). The reaction mixture was heated at H0C for 16 hours and then cooled to room temperature, diluted with ethyl acetate, washed with water, brine, dried over sodium sulfate and concentrated under reduced pressure. The crude material was purified by column chromatography to afford l-cyclopropylpyrazole-4-carbafdehyde 19-6 (25 mg, 183.62 umol, 8.82% yield) as gum. NMR (400 MHz, DMSO-d6) d 9.75 (s, 1H), 8.53 (s, 1H), 7.95 (s, 1 1 1 ), 3.86-3.82 (m, 1 1 1 ), 1. 10-1.08 (m, 2) 1 ).. 1.03-0.98 (m, 21 1).
With potassium carbonate; In N,N-dimethyl-formamide; at 130℃; for 18h; Preparation 54: 1 -Cyclopropyl- 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>Dissolve lH-<strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> in N,N-dimethylformamide (1.9 mL). Add potassium carbonate (0.539 g, 3.90 mmol) and cyclopropylbromide (0.346 g, 2.86 mmol). Heat in a pressure tube to 130 0C for 18 hr. Cool to ambient temperature and add DCM and water. Separate layers and extract water layer 3 times with DCM. Wash combined DCM layers with brine, dry (magnesium sulfate), filter, and concentrated to give the free base of the title preparation. GC-MS: m/z = 136 [M+].
  • 20
  • [ 35344-95-7 ]
  • [ 137049-02-6 ]
  • [ 1082066-05-4 ]
YieldReaction ConditionsOperation in experiment
80% With triethylamine; In dichloromethane; at 20℃; for 18h; Preparation 61 : l-(l,2-Dimethyl-lH-imidazole-4-sulfonyl)-l H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>Dissolve lH-<strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> (0.150 g, 1.56 mmol) in DCM (5 mL). Add triethylamine (240 muL, 1.72 mmol) and l,2-dimethyl-lH-imidazole-4-sulfonyl chloride (0.334g, 1.72 mmol). Stir at ambient temperature for 18 hr. Concentrate, and purify via silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate: hexanes to give the title preparation (317mg, 80percent). GC-MS: m/z = 254 [M+].
  • 21
  • [ 19788-37-5 ]
  • [ 35344-95-7 ]
  • [ 1082065-96-0 ]
YieldReaction ConditionsOperation in experiment
91% Preparation 50: l-(3,5-Dimethylisoxazol-4-ylmethyl)-lH-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> Add N,N-dimethylformamide (3 mL) to sodium hydride (0.092 g, 2.29 mmol) and stir at 0 0C. Add l-H-<strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> (0.200 g, 2.08 mmol) and stir at 0 0C for 20 min.. Dissolve 4-chloromethyl-3,5-dimethylisoxazole (0.318 g, 2.18 mmol) in N,N-dimethylformamide (4 mL) and add to reaction mixture. Stir reaction at room temperature for 18 hr. Quench with aqueous saturated sodium bicarbonate solution. Add ethyl acetate and separate organic layer. Extract aqueous layer twice with ethyl acetate. Dry combined organic layers (magnesium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 25:75 to 75:25 ethyl acetate:hexanes), to give the title preparation (387 mg, 91percent). GC-MS: m/z = 205 [M+].
  • 22
  • [ 25676-75-9 ]
  • [ 35344-95-7 ]
  • [ 1082066-49-6 ]
YieldReaction ConditionsOperation in experiment
20% With dimethylaminoacetic acid; potassium carbonate;copper(l) iodide; In dimethyl sulfoxide; at 110℃; for 66h; Preparation 62: 1 -(I -Methyl- lH-imidazol-4-y I)- 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>In an oven-dried flask, combine 4-bromo-l -methyl- lH-imidazole (0.200 g, 1.24mmol), copper (I) iodide (0.022g, 0.113 mmol), N,N-dimethylglycine (0.023 g, 0.226 mmol), and potassium carbonate (0.312 g, 2.26 mmol). Purge with nitrogen 3 times.Add l-H-<strong>[35344-95-7]pyrazole-4-carboxaldehyde</strong> (0.109 g, 1.13 mmol), and DMSO (1.7 mL). Heat to 110 0C for 48 hr. Cool to ambient temperature and partition between ethyl acetate and water. Separate organic layer and extract aqueous layer twice with ethyl acetate. Dry <n="64"/>--63-combined organic layers (magnesium sulfate), filter and concentrate. Add copper (I) iodide (0.022 g, 0.113 mmol), N,N-dimethylglycine (0.023 g, 0.226 mmol), potassium carbonate (0.312 g, 2.26 mmol), and DMSO (1.7 mL). Purge with nitrogen 3 times. Heat to 110 0C for 18 hr. Cool to ambient temperature and partition between ethyl acetate and water. Separate organic layer and extract aqueous layer twice with ethyl acetate. Dry combined organic layers (magnesium sulfate), filter, concentrate, and purify (silica gel chromatography, eluting with 50:50 to 100:0 ethyl acetate: hexanes) to give the title preparation (39 mg, 20percent). GC-MS: m/z = 176 [M+].
  • 23
  • [ 19686-73-8 ]
  • [ 35344-95-7 ]
  • [ 1082066-01-0 ]
YieldReaction ConditionsOperation in experiment
73% With potassium carbonate; In acetonitrile; at 150℃; for 0.333333h;Microwave irradiation; Preparation 56: Racemic l-(2-Hydroxy-propyl)-l H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong>Combine 1 H-<strong>[35344-95-7]pyrazole-4-carbaldehyde</strong> (0.150g, 1.56 mmol), racemic l-bromo-2- propanol (0.26Og, 1.87 mmol), and potassium carbonate (0.323g, 2.34 mmol) in <n="63"/>--62-acetonitrile (2 mL). Heat in microwave at 150 0C for 20 min.. Filter, wash with acetonitrile and concentrate filtrate. Purify via silica gel chromatography, eluting with 0: 100 to 100:0 ethyl acetate:hexanes) to give the title preparation (177 mg, 73percent). GC- MS: m/z = 154 [M+].
  • 24
  • copper(II) choride dihydrate [ No CAS ]
  • [ 21050-13-5 ]
  • [ 35344-95-7 ]
  • [ 1310-73-2 ]
  • (Ph3PNPPh3)3[Cu3(μ3-O)(μ-4-CHO-pyrazolate)3Cl3]Cl [ No CAS ]
  • 25
  • [ 1056249-32-1 ]
  • [ 35344-95-7 ]
  • C18H13N5O [ No CAS ]
  • 26
  • [ 7703-74-4 ]
  • [ 35344-95-7 ]
  • 2,6-bis(4-formylpyrazolylmethyl)pyridine [ No CAS ]
  • 27
  • [ 1018720-28-9 ]
  • [ 35344-95-7 ]
  • C17H19N5O [ No CAS ]
  • 28
  • [ 911491-26-4 ]
  • [ 35344-95-7 ]
  • [ 911491-63-9 ]
  • 29
  • [ 1194-02-1 ]
  • [ 35344-95-7 ]
  • [ 1152958-56-9 ]
YieldReaction ConditionsOperation in experiment
With sodium hydride; In N,N-dimethyl-formamide; mineral oil; at 60℃; for 6h;Inert atmosphere; To a mixture of 4-fluorobenzonitrile (2.49 g, 20.6 mmol) and 4-formylpyrazole (1.98 g, 20.6 mmo) in 50 mL of DMF at 0 0C was added 95percent sodium hydride (0.54 g, 22.7 mmol) under nitrogen. The mixture was heated to 60 0C for 6 hours and cooled to room temperature, Water was added carefully and the mixture was then extracted with ethyl acetate. The combined extracts were washed with water and brine, and then dried over sodium sulfate, filtered, and concentrated in vacuo to provide crude 4~(4-formyMH-pyrazol-l-yl)benzonitrile.
  • 30
  • [ 503555-59-7 ]
  • [ 35344-95-7 ]
  • [ 1273318-79-8 ]
 

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Technical Information

Categories

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