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[ CAS No. 15754-60-6 ] {[proInfo.proName]}

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Product Details of [ 15754-60-6 ]

CAS No. :15754-60-6 MDL No. :MFCD12192641
Formula : C7H12N2 Boiling Point : -
Linear Structure Formula :- InChI Key :QUSOBKIKODRYSH-UHFFFAOYSA-N
M.W : 124.18 Pubchem ID :13469815
Synonyms :

Calculated chemistry of [ 15754-60-6 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 9
Num. arom. heavy atoms : 5
Fraction Csp3 : 0.57
Num. rotatable bonds : 1
Num. H-bond acceptors : 1.0
Num. H-bond donors : 0.0
Molar Refractivity : 37.79
TPSA : 17.82 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) : -6.26 cm/s

Lipophilicity

Log Po/w (iLOGP) : 1.88
Log Po/w (XLOGP3) : 1.12
Log Po/w (WLOGP) : 1.64
Log Po/w (MLOGP) : 1.08
Log Po/w (SILICOS-IT) : 0.92
Consensus Log Po/w : 1.33

Druglikeness

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

Water Solubility

Log S (ESOL) : -1.66
Solubility : 2.71 mg/ml ; 0.0218 mol/l
Class : Very soluble
Log S (Ali) : -1.09
Solubility : 10.1 mg/ml ; 0.0817 mol/l
Class : Very soluble
Log S (SILICOS-IT) : -1.58
Solubility : 3.3 mg/ml ; 0.0265 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 1.15

Safety of [ 15754-60-6 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 15754-60-6 ]

* 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.

  • Upstream synthesis route of [ 15754-60-6 ]
  • Downstream synthetic route of [ 15754-60-6 ]

[ 15754-60-6 ] Synthesis Path-Upstream   1~4

  • 1
  • [ 102-52-3 ]
  • [ 7400-27-3 ]
  • [ 15754-60-6 ]
YieldReaction ConditionsOperation in experiment
89% With hydrogenchloride In ethanolHeating / reflux A mixture of 1 , 1 ,3,3-tetramethoxypropane (37 g, 226 mmol), tert-butyl-hydrazine hydrochloride (28 g, 226 mmol) and cone HCl (60 mL, 720 mmol) in EtOH (300 mL) was heated at reflux overnight. The mixture was poured into water and the resulting mixture was extracted with ether. The combined organics were washed with brine, dried (MgSO4) and concentrated in vacuo to give 1-tert-butyl-lH-pyrazole (25 g, 89percent yield). 1H NMR (400 MHz, OMSO-Cl6): δl.n (s, 1 H), 7.38 (s, 1 H), 6.17 (s, 1 H), 1.47 (s, 9 H); MS (ESI) m/z: 125.1 [M+H]+.
89% With hydrogenchloride In ethanol; waterReflux A mixture of 1,1,3,3-tetramethoxypropane (3.7 g, 22.6 mmol), tert-butylhydrazinehydrochloride (2.8 g, 22.6 mmol), and conc. HCl (6 mL, 72 mmol) in EtOH (30 mL) was heated at reflux overnight. The reaction mixture was poured into water and the resulting mixture wasextracted with ether (30 mL x 3). The combined organics was washed with brine (20 mL), dried over MgSO4, and concentrated under reduced pressure to afford 1-tert-butyl-1H-pyrazole as awhite solid (2.5 g, 89percent). MS (ESI) m/z: 125 [M+H].
72%
Stage #1: With hydrogenchloride In ethanol; water at 50℃; for 2 h; Reflux; Industry scale
Stage #2: With sodium hydroxide In water
To a mixture of 1 ,1 ,3,3-tetramethoxypropane (3.82kg, 23.27mol) and tert- butylhydrazine hydrochloride (2.9kg, 23.27mol) in ethanol (24.54kg), cone HCI (4.72kg ,46.55mol) was added, keeping the temperature below 50°C. The reaction mixture was then rapidly heated to reflux. After ca. 2h the reaction was sampled and analysed by NMR. Pass criteria was <3.0percent starting material remaining. On receipt of a pass result the solution is cooled, diluted with water (8.29kg) and evaporated in vacuo (T<50°C, p<-0.08MPa) until approximately all of the original ethanol was removed. The solution was basified with 10M NaOH(aq), extracted with EtOAc (1 1 .1 1 kgx2) and the organic phase washed with saturated ammonium chloride solution (4.3ml/g x 2) and brine (4.3ml/g), then evaporated to give the title compound (2.08kg, 72percentyield) as a brown liquid (GC purity 99.70percenta/a).
72% With hydrogenchloride In ethanol; water at 50℃; for 0.2 h; Reflux; Industrial scale Stage a)
Preparation of 1-(1,1-Dimethylethyl)-1H-pyrazole (Intermediate 9)
To a mixture of 1,1,3,3-tetramethoxypropane (3.82 kg, 23.27 mol) and tert-butylhydrazine hydrochloride (2.9 kg, 23.27 mol) in ethanol (24.54 kg), conc HCl (4.72 kg, 46.55 mol) was added, keeping the temperature below 50° C.
The reaction mixture was then rapidly heated to reflux.
After ca.
2 h the reaction was sampled and analysed by NMR.
Pass criteria was <3.0percent starting material remaining.
On receipt of a pass result the solution is cooled, diluted with water (8.29 kg) and evaporated in vacuo (T<50° C., p<-0.08 MPa) until approximately all of the original ethanol was removed.
The solution was basified with 10M NaOH(aq), extracted with EtOAc (11.11 kg*2) and the organic phase washed with saturated ammonium chloride solution (4.3 ml/g*2) and brine (4.3 ml/g), then evaporated to give the title compound (2.08 kg, 72percent yield) as a brown liquid (GC purity 99.70percent a/a).
21.9 g With hydrogenchloride In ethanol for 2 h; Reflux To a stirred mixture of 34.48 g of 1,1,3,3-tetramethoxy-propane and 26.20 g tert.butyihydrazine hydrochloride in 230 mL ethanol was added 40.0 mL conc. hydrochloric acid dropwise below 50 00, then the mixture was stirred under reflux for 2 h. The reaction mixture was diluted with water. The solvent was almost removed by destillation and the aqueous residue extracted with diethylether. The combined aqueous phases were basified with iON sodium hydroxide solution and extracted with diethylether. The combined organic phases were washed with saturated brine, dried over sodium sulfate, filtered and concentrated in vacuo to yield 21.90 g of 1-tert-butyl-pyrazole as oil.Analysis: HPLC-MS: R1 = 0.412 mm (method A), M+H = 125

Reference: [1] Patent: WO2008/33999, 2008, A2, . Location in patent: Page/Page column 83
[2] Patent: WO2014/1377, 2014, A1, . Location in patent: Page/Page column 104
[3] Patent: WO2011/134971, 2011, A1, . Location in patent: Page/Page column 15; 16
[4] Patent: US2013/40984, 2013, A1, . Location in patent: Paragraph 0478-0479
[5] Patent: WO2017/42100, 2017, A1, . Location in patent: Page/Page column 42; 43
  • 2
  • [ 288-13-1 ]
  • [ 507-20-0 ]
  • [ 15754-60-6 ]
Reference: [1] Bulletin de la Societe Chimique de France, 1986, # 1, p. 129 - 132
  • 3
  • [ 15754-60-6 ]
  • [ 70951-85-8 ]
YieldReaction ConditionsOperation in experiment
93.4% With N-Bromosuccinimide In dichloromethane at 0 - 20℃; Industry scale To an ice cooled solution (0°C to 10°C) of 1 -(tert-butyl)pyrazole (1.75kg, 14.09mol) in dichloromethane (12.9kg) was added NBS (2.63kg ,14.79mol) portionwise. The solution was stirred at 0°C until the content of 1-(ie f-butyl)pyrazole <30percent (GC), then warmed to RT and stirred until the sample taken shows <1.0percent by GC. On receipt of a pass result, 10percent sodium bisulfite aqueous was added to the reaction mixture until Kl-starch did not turn to blue. The organic phase was then washed with 5percent NaCI solution and brine in sequence, then evaporated to give the title compound as a brown liquid (2.67kg, 93.4percentyield; GC purity 99.1 percenta/a).
85% With bromine; sodium carbonate In dichloromethane at 20℃; To a suspension OfNa2CO3 (36 g, 339 mmol) in CH2Cl2 (300 mL) was added l-t- butyl-lH-pyrazoIe from Example B19 (21 g, 170 mmol) and Br2 (9 mL), and the resulting mixture was stirred at RT overnight. The solid was removed by Filtration and the filter cake was washed with CH2Cl2. The filtrates were washed with water and brine, dried (MgSO4), and concentrated to give crude 4-bromo-l- λ-butyl-lH-pyrazole (29 g, 85percent), used without further purification. 1H NMR (300 MHz, CDC13): δ 7.49 (s, 1 H), 7.45 (s, 1 H), 1.53 (s, 9 H); MS (ESI) m/z: 203 [M+H]+.
85% With sodium carbonate decahydrate; bromine In dichloromethane at 20℃; To a suspension of Na2CO3 (3.6 g, 33.9 mmol) in CH2Cl2 (30 mL) was added 1-tert-butyl-1H-pyrazole (2.1 g, 17 mmol) and Br2 (0.9 mL). The mixture was stirred at roomtemperature overnight. The formed solid was removed by filtration and the filter cake waswashed with CH2Cl2 (30 mL). The filtrates were washed with water (20 mL) and brine (20 mL), dried (MgSO4), and concentrated under reduced pressure to afford crude 4-bromo-1-tert-butyl-1H-pyrazole (2.9 g, 85percent), which was used in next step without further purification. MS (ESI)m/z: 203 [M+H]+.
7.402 g With N-Bromosuccinimide In dichloromethane at 20℃; for 18 h; Intermediate 10: 4-Bromo-1-(1,1-dimethylethyl)-1H-pyrazole[0393]1-(1,1-dimethylethyl)-1H-pyrazole (6.1 g, 49.1 mmol) in dichloromethane (DCM) (200 ml) was added N-bromosuccinimde (8.74 g, 49.1 mmol). This was warmed to ambient temperature and stirred for 18 h. There was no starting material present and so the reaction mixture was quenched with aqueous sodium thiosulfate. The organics were washed with water (2×500 ml) and passed through a hydrophobic frit. The filtrate was concentrated in vacuo to yield an orange-brown oil which turned purple on standing (7.402 g).[0395]LCMS (Method B): Rt=1.03 min, MH+=203, 205
34 g With N-Bromosuccinimide In dichloromethane at 0 - 10℃; for 0.5 h; To a mixture of 21.9 g of 1-tert-butyl-pyrazole in 150 mL DOM was added 31.5 g Nbromosuccinimide in portions between 0 and 10 00 The resulting mixture was stirred for 30 mm. The reaction mixture was allowed to reach ambient temperature. The precipitate was filtered off and washed with DOM. The combined organic extracts were washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated in vacuo to yield 34.0 g of 4-bromo-1-tert-butyl-pyrazole as oil.Analysis: HPLC-MS: R1 = 1 .35 mm (method B), M+H = 203 I 205

Reference: [1] Patent: WO2011/134971, 2011, A1, . Location in patent: Page/Page column 16; 17; 72
[2] Patent: WO2008/33999, 2008, A2, . Location in patent: Page/Page column 84
[3] Patent: WO2014/1377, 2014, A1, . Location in patent: Page/Page column 104
[4] Patent: US2013/40984, 2013, A1, . Location in patent: Paragraph 0393-0395
[5] Patent: WO2017/42100, 2017, A1, . Location in patent: Page/Page column 43
  • 4
  • [ 15754-60-6 ]
  • [ 1256359-15-5 ]
Reference: [1] Patent: US2013/40984, 2013, A1,
[2] Patent: US2013/40984, 2013, A1,
[3] Patent: WO2014/1377, 2014, A1,
[4] Patent: WO2017/42100, 2017, A1,
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