3-(tert-Butyl)-1H-pyrazole-4-carbaldehyde

Cat.NO.:A199538 Purity:97%

Product Details of [ 1001020-17-2 ]

CAS No. :	1001020-17-2
Formula :	C₈H₁₂N₂O
M.W :	152.19
SMILES Code :	O=CC1=CNN=C1C(C)(C)C
MDL No. :	MFCD07186448
InChI Key :	JQCJTNPAWAQSFC-UHFFFAOYSA-N
Pubchem ID :	3159701

Safety of [ 1001020-17-2 ]

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

Computational Chemistry of [ 1001020-17-2 ] Show Less

Physicochemical Properties

Num. heavy atoms	11
Num. arom. heavy atoms	5
Fraction Csp3	0.5
Num. rotatable bonds	2
Num. H-bond acceptors	2.0
Num. H-bond donors	1.0
Molar Refractivity	43.25
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	45.75 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	1.12
Log P_o/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry	1.39
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.52
Log P_o/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.	0.44
Log P_o/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	2.13
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.32

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.86
Solubility	2.08 mg/ml ; 0.0137 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (Ali)? Ali: Topological method implemented from Ali J. et al. 2012 J. Chem. Inf. Model.	-1.95
Solubility	1.69 mg/ml ; 0.0111 mol/l
Class? Solubility class: Log S scale Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly	Very soluble
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com	-2.38
Solubility	0.639 mg/ml ; 0.0042 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	Yes
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.	-6.24 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)	1.7

Application In Synthesis of [ 1001020-17-2 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

Downstream synthetic route of [ 1001020-17-2 ]

[ 1001020-17-2 ] Synthesis Path-Downstream 1~4

1
pinacolone semicarbazone [ No CAS ]
[ 68-12-2 ]
[ 1001020-17-2 ]

Yield	Reaction Conditions	Operation in experiment
6%		b) 3-Te/t-butyM /-/-pyrazole-4-carbaldehydePhosphorus oxychloride (18.2 ml_, 195 mmol) was added portionwise to DMF (30 ml_, 387 mmol) at < 5 0C. Pinacolone semicarbazone (15.4 g, 97.6 mmol) was added over 1 h maintaing the temperature at < 5 0C. The reaction mixture became very thick so an additional quantity of DMF (10 mL) was added. The mixture was heated to 60 0C for 3.5 h then allowed to cool and poured into ice. The reaction was neutralised using sodium hydroxide (40 g, 1 mol) in water (130 mL) then heated at 60 0C for 5 min. The mixture was <n=”66″/>cooled in an ice bath and acidified to pH 6 and the product extracted into EtOAc. The EtOAc was dried over MgSO4 and concentrated onto silica. The crude product was purified by flash chromatography using elutants EtOAc/heptane. Trituration in diethyl ether gave a white solid (1.02 g, 6.1 mmol, 6 %). 1 H NMR (400MHz, CDCI3): delta 1.48 (s, 9H), delta 8.07 (s, 1 H)1 delta 10.06 (s, 1 H) delta 10.25 (b, 1 H).

References: [1]Patent: WO2008/3452,2008,A1 .Location in patent: Page/Page column 64-65.

2
[ 1001020-17-2 ]
[ 1001020-10-5 ]
2-(2-(3-tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 3h;	Example 78 2-(2-(3-7erf-butyl-4-formyl-1H-pyrazol-1-vnacetan?ido)-N-nnethyl-4,5.6,7- tetrahvdrobenzofblthiophene-3-carboxannide3-Terf-butyl-1H-pyrazole-4-carbaldehyde (150 mg, 0.986 mmol), 2-(2-bromoacetamido)- N-methyl-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxannide (490 mg, 1.478 mmol) and potassium carbonate (545 mg, 3.94 mmol) were mixed with DMF (5 ml_) and heated for 3 h at 60 0C. The reaction was partitioned between water and EtOAc. Organics were combined and purified by chromatography (0-60%, EtOAc/heptane) to give the title product as a white solid (360 mg, 0.894 mmol, 91 %). MS (ESI): m/z 403.6 [M + H]+.

References: [1]Patent: WO2008/3452,2008,A1 .Location in patent: Page/Page column 71.

3
[ 1001020-17-2 ]
[ 1001020-23-0 ]
2-(2-(3-tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%		Example 842-(2-(3-rert-butyl-4-formyl-1H-pyrazol-1-vhacetamido)-N-(2-hvdroxyethvn-4.5.6.7- tetrahvdrobenzofbithiophene-3-carboxamide <n=”78″/>2-(2-Bromoacetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3- carboxamide (1.66 g, 4.60 mmol), 3-tert-butyl-1 H-pyrazole-4-carbaldehyde (1.75 g, 11.49 mmol) and potassium carbonate (2.54 g, 18.38 mmol) were mixed with DMF (20 ml_) and heated at 70 CC for 2 h. On cooling, the reaction was partitioned between EtOAc and water. The organics were washed with brine, dried over MgSO4 and concentrated directly onto silica for chromatographic purification (0-100 % EtOAc/heptane). Concentration in vacuo yielded a white solid (1.64 g, 3.79 mmol, 83 %). MS (ESI): m/z 433.5 [M + H]+.

References: [1]Patent: WO2008/3452,2008,A1 .Location in patent: Page/Page column 76-77.

4
[ 1001020-17-2 ]
[ 74-88-4 ]
C₉H₁₄N₂O [ No CAS ]
C₉H₁₄N₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With potassium carbonate; In N,N-dimethyl-formamide; at 85℃; for 3h;	A mixture of A-i (750 mg, 4.93 mmol), A-2 (0.46 mL, 7.39 mmol) and K2C03 (2.72 g, 19.71 mmol) in 10 mL DMF is heated at 85 C for 3 hours. The reaction mixture is diluted with EtOAc, washed with water, brine, dried over Na2SO4, concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with 10-100% EtOAc in heptane to yield Intermediates A and B as a 10:1 mixture by 1HNMR.

References: [1]Patent: WO2018/111803,2018,A1 .Location in patent: Page/Page column 17; 18.

Details

Reviews

There are no reviews yet.

Be the first to review “3-(tert-Butyl)-1H-pyrazole-4-carbaldehyde”

Products