326827-21-8|3-Amino-5-cyclobutyl-1H-pyrazole| Ambeed

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

Quality Control of [ 326827-21-8 ] Purity: 97% SDS Specification

COA

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

NMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

CNMR

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

HPLC

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

LC-MS

Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.

1-2 Day Shipping
High Quality
Technical Support

Product Details of [ 326827-21-8 ]

CAS No. :	326827-21-8
Formula :	C₇H₁₁N₃
M.W :	137.18
SMILES Code :	NC1=NNC(=C1)C1CCC1
MDL No. :	MFCD08061045
InChI Key :	DELFRVWPWUEOHU-UHFFFAOYSA-N
Pubchem ID :	22176774

Safety of [ 326827-21-8 ]

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

Computational Chemistry of [ 326827-21-8 ] Show Less

Physicochemical Properties

Num. heavy atoms	10
Num. arom. heavy atoms	5
Fraction Csp3	0.57
Num. rotatable bonds	1
Num. H-bond acceptors	1.0
Num. H-bond donors	2.0
Molar Refractivity	40.27
TPSA ? Topological Polar Surface Area: Calculated from Ertl P. et al. 2000 J. Med. Chem.	54.7 Å²

Lipophilicity

Log P_o/w (iLOGP)? iLOGP: in-house physics-based method implemented from Daina A et al. 2014 J. Chem. Inf. Model.	0.99
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	0.99
Log P_o/w (WLOGP)? WLOGP: Atomistic method implemented from Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.	1.27
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.	0.87
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	1.53
Consensus Log P_o/w? Consensus Log P_o/w: Average of all five predictions	1.13

Water Solubility

Log S (ESOL):? ESOL: Topological method implemented from Delaney JS. 2004 J. Chem. Inf. Model.	-1.62
Solubility	3.3 mg/ml ; 0.0241 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.	-1.73
Solubility	2.57 mg/ml ; 0.0187 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	-1.72
Solubility	2.59 mg/ml ; 0.0189 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	Yes
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.	-6.43 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	0.0 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)	2.07

Application In Synthesis of [ 326827-21-8 ]

* 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 [ 326827-21-8 ]

[ 326827-21-8 ] Synthesis Path-Downstream 1~29

1
[ 586-75-4 ]
[ 326827-21-8 ]
4-bromo-<i>N</i>-[1-(4-bromo-benzoyl)-5-cyclobutyl-1<i>H</i>-pyrazol-3-yl]-benzamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3367 - 3380.

2
[ 918538-05-3 ]
[ 326827-21-8 ]
[ 1001353-97-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With N-ethyl-N,N-diisopropylamine; potassium iodide; In N,N-dimethyl-formamide; at 20℃; for 2h;	Example 041A: To potassium iodide (932 mg, 5.6 mmol) in DMF (5 mL) was added 2,4-dichloropyrrolo[ l,2-fJ[ l ,2,4]triazine (Mastalerz, et al. US20070004731 Al ) (1.06 g, 5.6 mmol). The mixture was stirred for 5 min, then 5-cyclobutyl- l H- pyrazol-3-amine (938 mg, 6.7 mmol) and diisopropylethylamine (0.98 mL, 5.6 mmol) were added and the mixture was stirred at rt for 2 h. Water was then added and precipitate was collected by filtration to afford 2-chloro-N-(5-cyclobutyl- 1 H-pyrazol- 3-yl)pyrrolo[l ,2-f][ l,2,4]triazin-4-amine ( 1.78 g, quantitative). LCMS (ESI) m/z 289 (M + Hf .
81.5%	With N-ethyl-N,N-diisopropylamine; In isopropyl alcohol; at 20℃; for 22h;	191A. 2-Chloro-N-(5-cyclobutyl-1H-pyrazol-3-yl)pyrrolo[1,2-f][1,2,4]triazin-4-amine 5-Cyclobutyl-1H-pyrazol-3-amine (see J. Med. Chem., 2001, 44(26), 4628-4660) (89 mg, 0.65 mmol) is dissolved in isopropyl alcohol (2-3 mL), N,N-diisopropylethylamine (174 muL, 1.0 mmol) is then added, followed by the compound from 1B (85 mg, 0.45 mmol). The reaction mixture is then stirred at RT for 22 h and the solid precipitate is collected by filtration, washed with a few mL of cold isopropyl alcohol, and dried in vacuo to give 106 mg (81.5%) of the title compound as a solid: MS: 289, 291 (M+H)+, LC/MS ret. t=2.02 min.; HPLC (Method D) ret. time 15.35 min.

References: [1]Patent: WO2011/88045,2011,A1 .Location in patent: Page/Page column 179-180.
[2]Patent: US2008/9497,2008,A1 .Location in patent: Page/Page column 82.

3
[ 326827-21-8 ]
4-bromo-N-(5-cyclobutyl-1H-pyrazol-3-yl)benzamide [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2004,vol. 47,p. 3367 - 3380.

4
[ 2033-24-1 ]
[ 104-88-1 ]
[ 326827-21-8 ]
[ 817640-91-8 ]

Yield	Reaction Conditions	Operation in experiment
59%	In ethanol; at 75℃; for 0.5h;	To <strong>[326827-21-8]5-cyclobutyl-1H-pyrazol-3-ylamine</strong> (1.0 g, 7.3 mmol) in EtOH (20 mL) was added 4-chlorobenzaldehyde (1.1 g, 8.0 mmol) followed by Meldrum's Acid (1.1 g, 8.0 mmol). The reaction mixture was then heated to 75 C. (oil bath). After 30 min, the reaction was cooled to room temperature, the solid was filtered off, and then washed with MeOH (5 mL) and hexanes (10 mL). The solid was collected and dried under reduced pressure to give the title compound (1.3 g, 59% yield) as a colorless solid. 500 MHz 1H NMR (DMSO-d6) d 12.0 (s, 1H), 10.3 (s, 1H), 7.34 (d, J=8.7 Hz, 2H), 7.11 (d, J=8.3 Hz, 2H), 4.20 (dd, J=7.1, 4.2 Hz, 1H), 3.17 (dddd, J=8.7, 8.7, 8.7, 8.7 Hz, 1H), 2.84 (dd, 15.8, 7.1 Hz, 1H), 2.44 (dd, J=16.2, 4.6 Hz, 1H), 2.09-1.87 (m, 4H), 1.83-1.69 (m, 1H), 1.68-1.61 (m, 1H). 13C NMR (125 Mz, DMSO-d6) d 169.8, 149.5, 144.1, 142.8, 131.7, 129.4, 129.2, 101.1, 41.3, 33.9, 31.0, 28.8, 28.4, 18.7. LRMS m/z (APCI+) 303 (M+1).

References: [1]Patent: US2004/266815,2004,A1 .Location in patent: Page 12.

5
[ 118431-89-3 ]
[ 326827-21-8 ]

Yield	Reaction Conditions	Operation in experiment
91%	With hydrazine; In ethanol; at 75℃; for 14h;	To an aliquot of the crude 3-cyclobutyl-3-oxo-propionitrile (10.0 g, 81.3 mmol) prepared above in EtOH (300 mL) was added hydrazine. The resulting mixture was heated to 75 C. (oil bath). After 14 hr, the reaction was cooled to room temperature and concentrated under reduced pressure. The resulting oil was taken up in EtOAc and washed with saturated aqueous NaHCO3 solution. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered through a pad of diatomaceous earth, and concentrated under reduced pressure. Purification of this material was accomplished by flash column chromatography on a Biotage 75S MPLC system (A Dynax Corp., Charlottesville, Va.), eluting with 100 EtOAc (2 L) and 10% MeOH/CH2Cl2 (2 L). The product-containing fractions were collected and concentrated to give the title compound (10.0 g, 91% yield) as a brown oil. 400 MHz 1H NMR (CDCl3) d 5.47 (s, 1H), 5.25 (bs, 3H), 3.40 (dddd, J=8.3, 8.3, 8.3, 8.3 Hz, 1H), 2.34-2.27 (m, 2H), 2.16-1.88 (m, 4H). LRMS m/z (APCI+) 138 (M+1).
	With hydrazine; In ethanol; at 60℃; for 24h;	General procedure: A solution of 50 mg (0.34 mmol) of 3-oxo-3-phenylpropanenitrile and 11.6 mg (0.36 mmol) of hydrazine and 0.024 mL of acetic acid (0.37 mmol) in 3 mL of anhydrous ethanol was heated at 60 C for 24 hr. The mixture was cooled to ambient temperature and the solvent removed in vacuo. The residue was taken up in ethyl acetate, washed with saturated sodium bicarbonate. The organic layer was washed with brine and dried over MgSO4, filtered and evaporated. The solid residue waswashedwithethyl ether and dried in vacuo to give 45 mg (82%) of 3-phenyl-1H-pyrazol-5-amine.

References: [1]Patent: US2004/266815,2004,A1 .Location in patent: Page 11-12.
[2]Bioorganic and Medicinal Chemistry Letters,2018,vol. 28,p. 3736 - 3740.

6
[ 1204245-22-6 ]
[ 326827-21-8 ]
[ 1204243-98-0 ]

Yield	Reaction Conditions	Operation in experiment
21%	With N-ethyl-N,N-diisopropylamine; potassium iodide; In N,N-dimethyl-formamide; at 20℃; for 4h;	Example 27Preparation of (4-(5-cyclobutyl- 1 H-pyrazol-3-ylamino)pyrrolo? ,2-fl F 1 ,2,4~\|triazin-2- yl)(4-fluorophenyl)methanone[00272] To (4-chloropyrrolo[l,2-fJ[l,2,4]triazin-2-yl)(4-fluorophenyl)methanone (69 mg, 0.25 mmol), in DMF (2 mL) was added S-cyclobutyl-lH-pyrazol-S-amine (34 mg, 0.25 mmol), diisopropylethylamine (0.050 mL, 0.29 mmol) and potassium iodide (41 mg, 0.25 mmol) and the mixture was stirred for 4 h at rt. Acetic acid (0.2 mL) was added followed by 1 mL of dimethylsulfoxide and the mixture was purified by preparative HPLC (Varian diphenyl reverse phase column, eluted with gradient of solvent B - 0.05% HOAC/CH3CN and solvent A = 0.05% HOAc/H2O). Fractions containing the desired material were combined and concentrated and then the residue was dissolved in a minimum volume of ethyl acetate. Upon the addition of hexanes, a solid formed which was filtered and dried to afford (4-(5-cyclobutyl-lH-pyrazol-3- ylamino)pyrrolo[l,2-fJ[l,2,4]triazin-2-yl)(4-fluorophenyl)methanone (20 mg, 21 %). 1H NMR (300 MHz, DMSO-^6) delta 1.74-2.47 (m, 6H), 3.4 (m, IH), 6.54 (s, IH), 6.85 (m, IH), 7.30-7.43 (m, 3H), 7.88 (s, IH), 8.13 (m, 2H), 10.88 (s, IH), 12.25 (s, IH); LC-MS (ESI) m/z 377 (M + H)+.

References: [1]Patent: WO2010/2472,2010,A1 .Location in patent: Page/Page column 106-107.

7
[ 326827-21-8 ]
(S)-1-(4-(5-cyclobutyl-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)pyrrolidine-2-carboxamide [ No CAS ]

References: [1]Patent: US2008/9497,2008,A1 .

8
[ 326827-21-8 ]
(R)-1-(4-(5-cyclobutyl-1H-pyrazol-3-ylamino)pyrrolo[1,2-f][1,2,4]triazin-2-yl)pyrrolidine-2-carboxamide [ No CAS ]

References: [1]Patent: US2008/9497,2008,A1 .

9
[ 326827-21-8 ]
[ 1315590-93-2 ]

References: [1]Patent: WO2011/88045,2011,A1 .

10
[ 326827-21-8 ]
[ 1315590-94-3 ]

References: [1]Patent: WO2011/88045,2011,A1 .

11
[ 326827-21-8 ]
[ 1315585-50-2 ]

References: [1]Patent: WO2011/88045,2011,A1 .

12
[ 796095-89-1 ]
[ 326827-21-8 ]
1-[4-[(5-cyclobutyl-1H-pyrazol-3-yl)amino]-6-(phenylmethyl)-2-pyrimidinyl]-2-azetidinecarboxamide [ No CAS ]

References: [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 948 - 952.

13
[ 796095-89-1 ]
[ 326827-21-8 ]
2-chloro-N-(3-cyclobutyl-1H-pyrazol-5-yl)-6-(phenylmethyl)-4-pyrimidinamine [ No CAS ]

References: [1]ACS Medicinal Chemistry Letters,2013,vol. 4,p. 948 - 952.

14
4-(benzenesulfonyl)-2,6-dichloropyridine [ No CAS ]
[ 326827-21-8 ]
(4-benzenesulfonyl-6-chloropyridin-2-yl)-(5-cyclobutyl-1H-pyrazol-3-yl)amine [ No CAS ]

References: [1]Bioorganic and Medicinal Chemistry Letters,2014,vol. 24,p. 5818 - 5823.

15
[ 16234-14-3 ]
[ 326827-21-8 ]
C₁₃H₁₂ClN₅S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 5121 - 5136.

16
[ 326827-21-8 ]
C₂₃H₃₁N₇O₂S [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 5121 - 5136.

17
[ 326827-21-8 ]
2-(4-aminopiperidin-1-yl)-N-(5-cyclobutyl-1H-pyrazol-3-yl)thieno[3,2-d]pyrimidin-4-amine [ No CAS ]

References: [1]Journal of Medicinal Chemistry,2015,vol. 58,p. 5121 - 5136.

18
[ 3932-97-6 ]
[ 934-22-5 ]
[ 326827-21-8 ]
N²-(1H-benzo[d]imidazol-6-yl)-N⁴-(5-cyclobutyl-1H-pyrazol-3-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14 mg		Example 297: Preparation of N2-(lH-benzo[d]imidazol-6-yl)-N4-(5-cyclobutyl-lH-pyrazol- 3-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine2,4-Dichloro-5-(trifluoromethyl)pyrimidine (0.087 g, 0.401 mmol), 5-cyclobutyl-lH- pyrazol-3-amine (0.055 g, 0.401 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.077 ml,0.441 mmol) were mixed in acetonitrile (2 ml). The mixture was microwaved at 80 C for 20 min and then concentrated. lH-benzo[d]imidazol-6-amine (0.053 g, 0.401 mmol) and acetic acid (0.024 g, 0.401 mmol) were added. The mixture was microwaved at 110 C for 20 min and then concentrated. 14 mg of product was recovered after automated reverse phase chromatography (water-MeCN). MS calcd for [Ci9Hi7F3N8+H]+: 415.16, found 415.20.

References: [1]Patent: WO2016/33100,2016,A1 .Location in patent: Page/Page column 227.

19
6-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-3,4-dihydroquinolin-2(1H)-one [ No CAS ]
[ 326827-21-8 ]
6-((4-((5-cyclobutyl-1H-pyrazol-3-yl)amino)-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(1H)-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
14 mg	With N-ethyl-N,N-diisopropylamine; In N,N-dimethyl-formamide; at 130℃; for 0.5h;Microwave irradiation;	Example 271: Preparation of 6-((4-((5-cydobutyl-lH-pyrazol-3-yl)amino)-5- (trifluorometh l) rimidin-2-yl)amino)-3,4-dihydroquinoli -2(lH)-one.6-((4-Chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)-3,4-dihydroquinolin-2(lH)-one (0.060 g, 0.175 mmol), 5-cyclobutyl-lH-pyrazol-3-amine (0.024 g, 0.175 mmol) and N-ethyl-N- isopropylpropan-2-amine (0.034 ml, 0.193 mmol) were mixed in DMF (2 ml). The mixture was microwaved at 130 C for 30 min and then concentrated. 14 mg of product was recovered after automated reverse phase chromatography (water- 10% THF in MeCN). MS calcd for[C2iH2oF3N70+H]+: 444.18 found 444.15.

References: [1]Patent: WO2016/33100,2016,A1 .Location in patent: Page/Page column 217.

20
[ 326827-21-8 ]
C₂₅H₃₄IN₃O₄ [ No CAS ]