Home Cart 0 Sign in  
X

[ CAS No. 1003012-75-6 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
3d Animation Molecule Structure of 1003012-75-6
Chemical Structure| 1003012-75-6
Chemical Structure| 1003012-75-6
Structure of 1003012-75-6 * Storage: {[proInfo.prStorage]}
Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Quality Control of [ 1003012-75-6 ]

Related Doc. of [ 1003012-75-6 ]

Alternatived Products of [ 1003012-75-6 ]

Product Details of [ 1003012-75-6 ]

CAS No. :1003012-75-6 MDL No. :MFCD08558991
Formula : C6H9N3O2 Boiling Point : -
Linear Structure Formula :- InChI Key :BVADIEGMRNCQSZ-UHFFFAOYSA-N
M.W :155.15 Pubchem ID :19576680
Synonyms :

Calculated chemistry of [ 1003012-75-6 ]

Physicochemical Properties

Num. heavy atoms : 11
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.5
Num. rotatable bonds : 2
Num. H-bond acceptors : 3.0
Num. H-bond donors : 0.0
Molar Refractivity : 41.93
TPSA : 63.64 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.47 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.22
Log Po/w (XLOGP3) : 1.1
Log Po/w (WLOGP) : 1.37
Log Po/w (MLOGP) : 1.25
Log Po/w (SILICOS-IT) : -1.36
Consensus Log Po/w : 0.72

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 1.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -1.7
Solubility : 3.1 mg/ml ; 0.02 mol/l
Class : Very soluble
Log S (Ali) : -2.03
Solubility : 1.45 mg/ml ; 0.00935 mol/l
Class : Soluble
Log S (SILICOS-IT) : -0.6
Solubility : 39.1 mg/ml ; 0.252 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 2.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.16

Safety of [ 1003012-75-6 ]

Signal Word:Warning Class:
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313 UN#:
Hazard Statements:H315-H319 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 1003012-75-6 ]

* 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 [ 1003012-75-6 ]

[ 1003012-75-6 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 1003012-75-6 ]
  • [ 857267-04-0 ]
YieldReaction ConditionsOperation in experiment
98.54% With 5%-palladium/activated carbon; hydrogen In methanol at 20 - 50℃; for 14h; Large scale; b Reaction Scheme 1 - Step b A 0.5 kilolitre clean and dry pressure reactor was charged with i-isopropyl-3-nitro-ifT- pyrazole (2) (14.5 Kg) at 25-30 °C. Methanol (130.5 L) was charged at 25-30 °C under a nitrogen atmosphere. The reaction mixture was stirred for 30 minutes at 25-30 °C. Then 5% Pd/C (4.35 Kg) (50% wet) suspended in methanol (14.5 L) was charged at 25- 30 °C under nitrogen. The reaction mixture was degassed under vacuum and filled with an argon atmosphere (50 Psi) three times. The reaction mixture was degassed under vacuum and filled with a hydrogen atmosphere (50 Psi) three times. Then the reaction mixture was stirred under hydrogen pressure (100 Psi) at room temperature for 14 hours. The temperature was gradually raised up to 55 °C. The absence of l - i so pro py 1 -3 - n i t ro - z H- pyr azo 1 e (2) was confirmed by HPLC (Limit: NMT 1.0 %). If, for a given run, the reaction mixture did not comply with the HPLC limit, it was maintained at room temperature under stirring until the desired HPLC purity was achieved. After completion of the reaction, the reaction mixture was cooled to 25-30 °C. The reaction mixture was degassed under vacuum and filled with a nitrogen atmosphere three times. The reaction mixture was filtered through a candy nutch filter, followed by a micro filter and the bed was washed with methanol (29.0 L). 90-95 % of the solvent was distilled off under vacuum at below 40-45 °C and the resultant mixture was co- distilled with acetonitrile at below 40-45 °C to afford the product. Final Product: i-isopropyl-3-amino-iiT-pyrazole (3) Greenish black liquid Output: 11.5 Kg Yield: 98.54 % lH NMR (DMSO-d6; 400 MHz): 1.35 (d, 6H), 4.18 (sept, lH), 4.45 (br s, 2H), 5.37 (s, lH), and 7.28 (s, lH). MS: (M+H+) = 126.17 HPLC purity: 98.61 % HPLC [X-bridge C18 column, 4.6 x 150 mm, 3.5 pm, mobile phase A = 10 mM ammonium bicarbonate in water, mobile phase B = acetonitrile, gradient programme (time/% B) = 0/10, 7/90, 15/90, 15.01/10; flow rate 1 mL per minute, temp = 25 °C): Rt = 3.84 minutes]
97% With hydrazine In methanol; water; ethyl acetate for 0.5h; 56 The 1-isopropyl-3-nitro-1H-pyrazole (145 mg, 0.94 mmol) was dissolved in ethyl acetate (4 mL) and methanol (4 mL) was added. While stirring, a 50% slurry of raney nickel in water (1 mL) was added followed by hydrazine (300 μL). Immediate effervescence was observed. The reaction continued to stir and bubble for 30 min. The reaction was passed through a plug of celite and concentrated in vacuo to give the desired product 1-isopropyl-1H-pyrazol-3-ylamine (114 mg, 97%) as a clear oil: ESI-LRMS m/e calcd for C6H11N3 [M+] 125.10, found 126.20 [M+H+].
90.9% With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 12h; B Step B: 1-isopropyl-1H-pyrazol-3-amine To a solution of 1-isopropyl-3-nitro-pyrazole (15 g, 96.68 mmol, 1 eq) in MeOH (150 mL) was added Pd/C (3 g, 10 wt.% loading on activated carbon) under N2. The reaction mixture was stirred at 25 °C for 12 hours under H2(30 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuum. The residue was purified by silica gel column chromatography (Petroleum ether: Ethyl acetate, 30:1 to 2:1) to give the title compound (11 g, 90.90% yield) as a brown oil.1H NMR (400 MHz, CDCl3): d 7.16 (d, 1 H), 5.57 (d, 1 H), 4.32-4.21 (m, 1 H), 3.60 (br s, 2 H) and 1.44 (d, 6 H).
85% With iron In ethanol at 80℃; for 1h;
83% With palladium on activated carbon; hydrogen In methanol at 20℃; for 24h; 2 Step 2: 3-Amino-l-(propan-2-yl)-lH-pyrazole Into a 250-mL round-bottom flask was placed a solution of l-isopropyl-3-nitro-lH-pyrazole (10.8 g, 69.6 mmol) in MeOH (100 mL). Then Pd/C (10% wt, 1.5 g) was added. The flask was evacuated and flushed three times with hydrogen. The mixture was stirred for 24 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting filtrate was concentrated under vacuum. This resulted in 7.27 g (83%) of the title compound as yellow oil. MS-ESI: 126.1 (M+l).
83% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 24h; 2 Step 2: 3-Amino- 1-(propan-2-yl)-1H-pyrazole Into a 250-mL round-bottom flask, was placed a solution of 1-isopropyl-3-nitro-1H-pyrazole (10.8 g, 69.6 mmol) in MeOH (100 mL). Then Pd/C (10% wt., 1.5 g) was added. The flask was evacuated and flushed three times with hydrogen. The mixture was stirred for 24 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting filtrate was concentrated under vacuum. This resulted in 7.27 g (83%) of the title compound as yellow oil. MS-ESI: 126.1(M+1).
83% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 24h; 2 Step 2: 3-Amino-i -(propan-2-yl)- 1 H-pyrazole Into a 250-mL round-bottom flask, was placed a solution of i-isopropyl-3-nitro-1H-pyrazole (10.8 g, 69.6 mmol) in MeOH (100 mL). Then Pd/C (10% wt, 1.5 g) was added. The flask was evacuated and flushed three times with hydrogen. The mixture was stirred for 24 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting mixture was concentratedunder vacuum. This resulted in 7.27 g (83%) of the title compound as yellow oil. MS-ESI: 126.1(M+ 1).
83% With palladium 10% on activated carbon; hydrogen In methanol at 20℃; for 24h; 2 Step 2: 3-Amino-l-(propan-2-yl)-lH-pyrazole Into a 250-mL round-bottom flask, was placed a solution of 1 -isopropyl-3 -nitro-lH-pyrazole (10.8 g, 69.6 mmol) in MeOH (100 mL). Then Pd/C (10% wt, 1.5 g) was added. The flask was evacuated and flushed three times with hydrogen. The mixture was stirred for 24 h at RT under an atmosphere of hydrogen. The solids were filtered out. The resulting mixture was concentrated under vacuum. This resulted in 7.27 g (83%) of the title compound as yellow oil. MS-ESI: 126.1 (M+l).
66% With palladium 10% on activated carbon; hydrogen In methanol at 25℃; for 2h; Inert atmosphere; B Step B: i-Isopropyl-iH-pyrazol-3-amine To a solution of i-isopropyl-3-nitro-iH-pyrazole (29.2 g, 188.20 mmol, 1 eq) in MeOH (400 mL) was added Pd/C (3 g, 10 wt % loading on activated carbon) under N2. The suspension was degassed in vacuo and purged with H2 several times. The reaction mixture was stirred at 25 °C for 2 hours under H2 (30 psi). The reaction mixture was filtered and the filtrate was concentrated in vacuo to give the title compound (15.81 g, 66 % yield, 98.2 % purity on LCMS) as a brown oil. NMR (400 MHz, CDCl3) d 7-15 (d, l H), 5-55 (d, l H), 4-30-4-20 (m, i H), 3.61 (s, 2 H) and 1.43 (d, 6 H). (0813) LCMS: m/z 126.2 (M+H)+ (ES+).
29% With hydrazine In methanol at 50℃; for 1h; 14 Pyrazole xxxiv (2 g, 13.98 mmol) is dissolved in methanol (20 mL) and hydrazine (90%, 0.5 mL, 13.98 mmol) is added. Raney nickel (0.5 g) is added slowly. The temperature is raised to 50 °C for one hour, then the reaction is cooled and the mixture filtered through HighFlow. The filtrate is concentrated and purified by flash column chromatography (20% ethyl acetate in hexanes) to give xxxv in 29% yield.
With iron; ammonium chloride In ethanol; water at 60℃; for 16h; B Step B: 1-Isopropyl-1H-pyrazol-3-amine To a solution of 1-isopropyl-3-nitro-1H-pyrazole (50 g, 322.26 mmol, 1 eq) and NH4Cl (86 g, 1.61 mol, 5 eq) in EtOH (500 mL) and H2O (300 mL) was added Fe (36 g, 644.52 mmol, 2 eq) as powder in portions at 60 °C. The reaction mixture was stirred at 60 °C for 16 hours, and then concentrated under reduced pressure to remove EtOH. The residue was diluted with H2O (1 L) and extracted with EtOAc (3 x 1 L). The combined organic layers were washed with brine (2 x 500 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give the title compound (39 g, crude) as a blue oil, which was used directly into the next step. 1H NMR (CDCl3) d 7.15 (d, 1 H), 5.55 (d, 1 H), 4.31-4.20 (m, 1 H), 3.60 (br s, 2 H) and 1.43 (d, 6 H). LCMS: m/z 126.2 (M+H)+ (ES+).

Reference: [1]Current Patent Assignee: ROCHE HOLDING AG; DISHMAN PHARMACEUTICALS & CHEMICALS LIMITED - WO2020/79207, 2020, A1 Location in patent: Page/Page column 19-21
[2]Current Patent Assignee: ROCHE HOLDING AG - US2008/21032, 2008, A1 Location in patent: Page/Page column 55
[3]Current Patent Assignee: ROCHE HOLDING AG - WO2019/211463, 2019, A1 Location in patent: Page/Page column 163
[4]Wang, Tao; Banerjee, Daliya; Bohnert, Tonika; Chao, Jianhua; Enyedy, Istvan; Fontenot, Jason; Guertin, Kevin; Jones, Howard; Lin, Edward Y.; Marcotte, Douglas; Talreja, Tina; Van Vloten, Kurt [Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 15, p. 2985 - 2990]
[5]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2019/23147, 2019, A1 Location in patent: Page/Page column 439; 440
[6]Current Patent Assignee: NOVARTIS AG; Novartis (w/o Sandoz) - WO2019/23145, 2019, A1 Location in patent: Page/Page column 432; 433
[7]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2019/79119, 2019, A1 Location in patent: Page/Page column 447; 448
[8]Current Patent Assignee: Novartis (w/o Sandoz); NOVARTIS AG - WO2020/86728, 2020, A1 Location in patent: Page/Page column 265-266
[9]Current Patent Assignee: ROCHE HOLDING AG - WO2019/166627, 2019, A1 Location in patent: Page/Page column 103-104
[10]Current Patent Assignee: CLAVIUS PHARMACEUTICALS - WO2019/5241, 2019, A1 Location in patent: Paragraph 0088
[11]Current Patent Assignee: SYNCOM B.V.; ROCHE HOLDING AG - WO2020/104657, 2020, A1 Location in patent: Page/Page column 69
  • 2
  • [ 26621-44-3 ]
  • [ 75-26-3 ]
  • [ 1003012-75-6 ]
YieldReaction ConditionsOperation in experiment
86% Into a 250-mL round-bottom flask was placed a solution of 3-nitro-lH-pyrazole (10 g, 88.4 mmol) in DMF (100 mL). This was followed by the addition of NaH (60% wt, 3.9 g, 97.5 mmol) in portions at 0C. The resulting solution was stirred for 0.5 h at 0C. This was followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0C in 10 min. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x100 mL of ethyl acetate. The organic layers were combined and dried over anhydrous Na2S04, then concentrated under vacuum. The residue was applied onto a silica gel column and eluted with a gradient of ethyl acetate/petroleum ether (1 :5 to 1 :3). This resulted in 11.8 g (86%) of the title compound as yellow oil. MS-ESI: 156.1 (M+l).
86% Into a 250-mL round-bottom flask, was placed a solution of <strong>[26621-44-3]3-nitro-1H-pyrazole</strong> (10 g, 88.4 mmol) in DMF (100 mL). This was followed by the addition of NaH (60% wt. oil dispersion, 3.9 g, 97.5 mmol) in portions at 0C. The resulting solution was stirred for 0.5 h at 0C. Thiswas followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0C in 10 mm. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water. The resulting solution was extracted with 3x100 mL of ethyl acetate. The organic layers were combined and dried over anhydrous Na2SO4, and then concentrated under vacuum. The residue was eluted from silica gel and eluted with a gradientof ethyl acetate/petroleum ether (1:5 to 1:3). This resulted in 11.8 g (86%) of the title compound as yellow oil. MS-ESI: 156.1 (M+1).
86% Into a 250-mL round-bottom flask, was placed a solution of <strong>[26621-44-3]3-nitro-1H-pyrazole</strong> (10 g, 88.4mmol) in DMF (100 mL). This was followed by the addition of NaH (60%, 3.9 g) in portions at0C. The resulting solution was stirred for 0.5 h at 0C. This was followed by the addition of 2-bromopropane (14.1 g, 114.6 mmol) dropwise with stirring at 0C in 10 mm. The resulting solution was stirred for 16 h at RT and then was quenched by the addition of 100 mL of water.
73% <strong>[26621-44-3]3-Nitro-1H-pyrazole</strong> xxxiii (5 g, 44.2 mmol) is dissolved in dimethylformamide (50 mL) and cesium carbonate (14 g, 43 mmol) is added. The reaction is stirred for thirty minutes at room temperature, and isopropyl bromide (5 mL, 53.3 mmol) is added. The reaction is stirred at room temperature for 12 hours, after which wafter (100 mL) is added and the reaction mixture is stirred for 10 minutes. The mixture is extracted into ethyl acetate (3 x 100 mL), and the organic layer is washed with brine and concentrated prior to purification by flash column chromatography (20% ethyl acetate in hexanes) to give xxxiv in 73% yield.;1]
71% To a mixture of 3-nitro-iH-pyrazole (30 g, 265.31 mmol, 1 eq) in DMF (300 mL) was added NaH (11.14 g, 278.58 mmol, 60% purity in mineral oil, 1.05 eq) in portions at o C. Then the reaction mixture was stirred at o C for 0.5 hour. 2-Bromopropane (39.16 g, 318.37 mmol, 1.2 eq) was added and the resulting mixture was warmed to 25 C for 12 hours. The reaction mixture was quenched with water (500 mL) and extracted with EtOAc (3 x 300 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous Na2S04, filtered and concentrated in vacuo. The residue was purified by chromatography (Si02, petroleum ether: ethyl acetate, 50:1 to 2:1) to give the title compound (29.2 g, 71 %) as a yellow oil. (0810) NMR (400 MHz, CDCI3) d 749 (d, 1 H), 6.90 (d, 1 H), 4-634-56 (m, 1 H) and 1.58 (d, 6 H).
43.73% To a solution of <strong>[26621-44-3]3-nitro-1H-pyrazole</strong> (25 g, 221.09 mmol, 1 eq) in DMF (300 mL) was added NaH (10.61 g, 265.31 mmol, 60 wt.% in mineral oil, 1.2 eq) at 0 C under N2. The suspension was stirred at 0 C for 0.5 hour, then 2-bromopropane (27.19 g, 221.09 mmol, 1 eq) was added dropwise to the reaction mixture at 0 C. The reaction mixture was stirred at 15 C for 12 hours. The reaction mixture was quenched with saturated aqueous NH4Cl solution (200 mL), diluted with water (500 mL) and extracted with EtOAc (3 × 500 mL). The organic phases were washed with brine (500 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by column chromotography (SiO2, Petroleum ether: Ethyl acetate, 1:0 to 5 :1) to give the title compound (15 g, 43.73% yield) as a yellow oil.1H NMR (400 MHz, CDCl3): d 7.49 (d, 1 H), 6.89 (d, 1 H), 4.65-4.54 (m, 1 H) and 1.57 (d, 6 H).

  • 3
  • [ 75-30-9 ]
  • [ 26621-44-3 ]
  • [ 1003012-75-6 ]
  • 2-isopropyl-3-nitro-1H-pyrazole [ No CAS ]
  • 4
  • [ 1003012-75-6 ]
  • [ 1696838-10-4 ]
YieldReaction ConditionsOperation in experiment
Multi-step reaction with 3 steps 1.1: palladium 10% on activated carbon; hydrogen / methanol / 24 h / 20 °C 2.1: hydrogenchloride / water / 0.5 h / 0 °C 2.2: 1 h / 0 - 20 °C 3.1: ammonia / dichloromethane / 1 h / 0 °C
Multi-step reaction with 3 steps 1.1: ammonium chloride; iron / ethanol; water / 16 h / 60 °C 2.1: hydrogenchloride; sodium nitrite / acetonitrile; water / 0.67 h / 0 °C 2.2: 1.33 h / 0 °C / 775.74 Torr 3.1: tetrahydrofuran / 2.75 h / 0 - 20 °C
Multi-step reaction with 3 steps 1.1: 5%-palladium/activated carbon; hydrogen / methanol / 14 h / 20 - 50 °C / 2585.81 - 5171.62 Torr / Large scale 2.1: sulfuric acid / acetonitrile; water / 0.5 h / -5 - 0 °C / Large scale 2.2: -5 - 0 °C / Large scale 2.3: 0.5 h / -5 - 0 °C / Large scale 3.1: isopropylmagnesium chloride / 2-methyltetrahydrofuran; n-heptane; tetrahydrofuran / 1.58 h / 10 °C 3.2: 1.32 h 3.3: 1.18 h / 20 °C
Same Skeleton Products
Historical Records