Home Cart Sign in  
Chemical Structure| 1151802-22-0 Chemical Structure| 1151802-22-0

Structure of 1151802-22-0

Chemical Structure| 1151802-22-0

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

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

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Alternative Products

Product Details of [ 1151802-22-0 ]

CAS No. :1151802-22-0
Formula : C12H19BN2O2
M.W : 234.10
SMILES Code : CC1(C)C(C)(C)OB(C2=CN(C3CC3)N=C2)O1
MDL No. :MFCD16659007
InChI Key :NLWYVKHISUTBMY-UHFFFAOYSA-N
Pubchem ID :59327133

Safety of [ 1151802-22-0 ]

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

Computational Chemistry of [ 1151802-22-0 ] Show Less

Physicochemical Properties

Num. heavy atoms 17
Num. arom. heavy atoms 5
Fraction Csp3 0.75
Num. rotatable bonds 2
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 67.46
TPSA ?

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

36.28 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

0.0
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

1.68
Log Po/w (WLOGP)?

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

1.45
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.

0.87
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

0.78
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

0.96

Water Solubility

Log S (ESOL):?

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

-2.44
Solubility 0.859 mg/ml ; 0.00367 mol/l
Class?

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

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.06
Solubility 2.06 mg/ml ; 0.00878 mol/l
Class?

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

-2.62
Solubility 0.567 mg/ml ; 0.00242 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.

-6.54 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

0.0
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)

3.04

Application In Synthesis of [ 1151802-22-0 ]

* 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 [ 1151802-22-0 ]

[ 1151802-22-0 ] Synthesis Path-Downstream   1~35

  • 1
  • [ 1151802-22-0 ]
  • [ 1161360-83-3 ]
  • [ 1161361-80-3 ]
YieldReaction ConditionsOperation in experiment
With sodium carbonate;tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; at 110℃; for 0.166667h; Example 6; Synthesis of 2-(3-chloro-5-( 1 -cyclopropyl- 1 H-pyrazol-4-yl)phenyl)-N-(4-(2-methylpyridin-4- yl)phenyl)propanamideA clear microwave vial was charged with 2-(3-bromo-5-chlorophenyl)-N-(4-(2- methylpyridin-4-yl)phenyl)propanamide (0.150 g, 0.349 mmol), l-cyclopropyl-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.0981 g, 0.419 mmol), tetrakis(triphenylphosphine)palladium (0.0202 g, 0.0175 mmol), sodium carbonate (0.349 ml, 0.698 mmol) and dioxane (4 mL). The vial was flushed with nitrogen and capped. The vial was heated in a Personal Chemistry SmithSynthesizer to 1100C for 10 minutes. The reaction mixture was diluted with ethyl acetate and water. The organic portion was washed with an aqueous saturated solution of sodium bicarbonate, then with water and then brine. The organic layer was then dried with sodium sulfate, reduced and purified by RP-HPLC using a gradient of 5percentACN 0.1percent TFA to 95percent ACN 0.1percent TFA in water 0.1percent TFA. The pure fractions were neutralized with ammonium hydroxide and the volatiles were removed under reduced pressure. The solid that crashed out of the aqueous layer was filtered off, washed with water and dried in <n="112"/>a vacuum oven at 45 degrees to give 2-(3-chloro-5-(l-cyclopropyl-lH-pyrazol-4-yl)phenyl)-N- (4-(2-methylpyridin-4-yl)phenyl)propanamide as an off-white solid.
  • 2
  • [ 1151802-23-1 ]
  • [ 73183-34-3 ]
  • [ 1151802-22-0 ]
YieldReaction ConditionsOperation in experiment
With sodium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In N,N-dimethyl-formamide; at 150℃; for 1h;Inert atmosphere; Sealed microwave vial; Bis(pinacolato)diboron (330 mg, 1.3 mmol), NaOAc (262 mg, 3.2 mmol), and Pd(dppf)Cl2-dichloromethane complex (89 mg, O. l lmmol) were combined in a microwave vial. 4-Bromo-l -cyclopropyl- lH-pyrazole and DMF (4 mL) were added and the vial was flushed with argon and sealed. The reaction mixture was heated in a microwave for 60 min at 150 0C. The reaction was diluted with 10 mL water and extracted 3 x 10 mL with EtOAc. The combined organic layers were dried over Na2Spsi4 and concentrated to yield 120 mg of the title compound as a dark oil, m/z 235.4 [M +H]+.
  • 4
  • [ 61676-62-8 ]
  • [ 1239363-40-6 ]
  • [ 1151802-22-0 ]
YieldReaction ConditionsOperation in experiment
83% Step 2In a flask 1-cyclopropyl-4-iodo-1H-pyrazole (405 mg, 1.73 mmol) was dissolved in THF (8.0 mL) and the solution cooled to 0° C.Isopropylmagnesium chloride (2.0 M in THF, 1.04 mL, 2.08 mmol) was added dropwise and the mixture stirred at 0° C. for 45 min, after which 2-isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.53 mL, 2.60 mmol) was added and the mixture allowed to warm to room temperature over 1 h.The mixture was quenched with 50percent sat aqueous NH4Cl and extracted with EtOAc.The organic extract was washed with sat.NaCl, dried over MgSO4 and the solution was concentrated.The residue was purified by SiO2 chromatography (20-50percent EtOAc/heptane) to afford 405 mg (83percent) of 1-cyclopropyl-1H-pyrazole-4-boronic acid pinacol ester as a colorless viscous oil.
  • 5
  • [ 61676-62-8 ]
  • [ 1151802-23-1 ]
  • [ 1151802-22-0 ]
YieldReaction ConditionsOperation in experiment
Step 1 : l-Cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyridaziiie To a 100 n L flask is added 4-bromo-l-cyclopropylpyrazol (6.57 g, 35.1 mmol) and anhydrous THF (30 niL). The solution is cooled to -78 °C under nitrogen; then n-butyl lithium (15.5 n L, 2.5 M in hexanes, 38.6 mmol) is added dropwise. The reaction mixture is stirred at the temperature for 1 hr, followed by addition of isopropyl boronate (9.17 g, 94.1 mmol) and stirred below -70 °C for 3 hours. The reaction is quenched with water (20 n L) and the resulted mixture is adjusted to pH 8-9 with aqueous hydrochloride solution (1 N). The combined organic phases are concentrated and used in next step without further purification (6.64 g, 81percent yield). (MS: [M+l] 235)
  • 6
  • [ 141-30-0 ]
  • [ 1151802-22-0 ]
  • [ 1440965-10-5 ]
YieldReaction ConditionsOperation in experiment
407 g With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium phosphate; In 1,4-dioxane; water; at 20 - 90℃;Inert atmosphere; 3-Chloro-6-(l-cyclopropy -lH-pyrazol-4-yl)pyridazine To a 100 mL round bottom flask is added the above solid (6.64 g, 28.4 mol), 3,6-dichoropyridazine (8.46 g, 56.8 mmol), Pd(dppf)Cl2 (1.04 g, 1.42 mol) potassium phosphate (18.1 g, 85.2 mmol), water (5 mL), and 1,4-dioxane (50 g) at room temperature under nitrogen. The reaction mixture is stirred at 90 °C overnight. After cooled to 30 °C, water (20 mL) is added. The aqueous phase is isolated and extracted with ethyl acetate (3 X 30 mL). The combined organic phases are concentrated and the residue is purified on a silica gel flash chromatography to provide a yellow solid (4.07 g, 65percent yield). (MS: [M+l] 222)
  • 7
  • [ 1151802-22-0 ]
  • [ 1440964-89-5 ]
  • 8
  • [ 1151802-22-0 ]
  • [ 1586045-04-6 ]
  • [ 1586040-71-2 ]
YieldReaction ConditionsOperation in experiment
Example 235 N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(1-cyclopropyl-1H-pyrazol-4-yl)thiazole-4-carboxamide 235 Following the procedure for Example 101 starting from tert-butyl ((3S,4R,7S)-7-(4-(2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate (Intermediate 99), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with <strong>[1151802-22-0]1-<strong>[1151802-22-0]cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong></strong> gave 235. 1H NMR (400 MHz, DMSO-d6) delta 9.75 (s, 1H), 8.44 (s, 1H), 8.22 (s, 1H), 8.03 (s, 1H), 7.90 (s, 1H), 4.92-4.83 (m, 1H), 4.59-4.40 (m, 1H), 4.32 (dd, J=22.2, 15.0 Hz, 1H), 4.19-3.93 (m, 1H), 3.80 (dd, J=7.4, 3.7 Hz, 1H), 3.77 (s, 3H), 3.38-3.31 (m, 1H), 2.12-2.03 (m, 1H), 1.87-1.66 (m, 5H), 1.17-0.96 (m, 4H). LCMS (ES+) m/z 446 (M+1).
  • 9
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
45% With chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl?)]palladium(II); caesium carbonate; In 1,4-dioxane; water; at 100℃; for 2h; Step 2. (S)-l-(6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-(quinazolin-2-yloxy)-3,4- dihydroquinolin-l(2H)-yl)ethanone [0344] A mixture of (S)-l-(6-bromo-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin-l(2H)- yl)ethanone (0.025 g, 0.061 mmol), l-cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)- lH-pyrazole (0.017 g, 0.073 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-l, - biphenyl)(2'-amino-l,r-biphenyl-2-yl) palladium(II) (XPhos 2nd generation precatalyst) (2.4 mg, 0.003 mmol), and cesium carbonate (0.059 g, 0.182 mmol) in 1 ,4-dioxane (2.0 mL) and water (0.40 mL) was heated at 100 °C for 2 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 25-100percent ethyl acetate-hexane) to afford (S)-l-(6-(l- cyclopropyl- 1 H-pyrazol-4-yl)-2-methyl-5-(quinazolin-2-yloxy)-3,4-dihydroquinolin- 1 (2H)- yl)ethanone (0.012 g, 45percent) as a white solid. MS (ESI, pos. ion) m/z 440. 1H NMR (300 MHz, DMSO-i/e) delta ppm 0.81 - 0.91 (m, 5 H), 1.07 (d, J=6.74 Hz, 3 H), 1.47 (m, 1 H), 2.03 (br dd, J=13.34, 6.89 Hz, 1 H), 2.18 (s, 3 H), 2.44 (m, 1 H), 3.55 - 3.67 (m, 1 H), 4.63 (m, 1 H), 7.41 (br s, 1 H), 7.51 - 7.70 (m, 3 H), 7.72 (s, 1 H), 7.91 (ddd, J=8.50, 7.04, 1.47 Hz, 1 H), 8.06 (s, 1 H), 8.10 (d, J=8.21 Hz, 1 H), 9.54 (s, 1 H). MS (ESI, pos. ion) m/z 440 [M+H]+.
  • 10
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-5-cyclopropoxy-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(5-cyclopropoxy-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
19% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; 1,2-dichloro-ethane; at 80℃;Inert atmosphere; Step 2. (S)-l-(5-cyclopropoxy-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-3,4- dihydroquinolin-l(2H)-yl)ethanone. [0392] A 1.5 mL reaction vial was charged with (S)-l-(6-bromo-5-cyclopropoxy-2-methyl-3,4- dihydroquinolin-l(2H)-yl)ethanone (0.019 g, 0.06 mmol) and 1 ,4-dioxane (50 \iL). 1 -cyclopropyl- 4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.2 M solution in 1 ,4-dioxane, 540 \iL, 0.108 mmol) and potassium carbonate (1 M solution in water, 180 \iL, 0.18 mmol) were added, and the reaction mixture was purged with nitrogen. [1 ,1'- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.02 M solution in 1,2-dichloroethane, 300 \iL, 0.006 mmol) was added, and the reaction was purged with nitrogen and heated to 80 °C on a heater shaker overnight. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution. The aqueous layer was separated and washed with ethyl acetate, and the combined organic layers were concentrated under a stream of nitrogen. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated in a Genevac to afford (S)-l-(5-cyclopropoxy-6-(l- cyclopropyl-lH-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-l(2H)-yl)ethanone (0.0039 g, 19percent). MS (ESI, pos. ion) m/z 352 [M+H]+.
  • 11
  • [ 1151802-22-0 ]
  • 4-[[(2S)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-5-yl]oxy]benzamide [ No CAS ]
  • (S)-4-(1-acetyl-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-1,2,3,4-tetrahydroquinolin-5-yloxy)benzamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
40% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃; Step 2. (S)-4-(l-acetyl-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-l,2,3,4-tetrahydroquinolin- 5-yloxy)benzamide [0496] A 50-mL, round-bottom flask was charged with (S)-4-(l-acetyl-6-bromo-2-methyl-l,2,3,4- tetrahydroquinolin-5-yloxy)benzamide (0.068 g, 0.17 mmol), l-cyclopropyl-4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.059 g, 0.25 mmol), [1,1'- bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.014 g, 0.02 mmol), potassium carbonate (0.070 g, 0.50 mmol), 1 ,4-dioxane (20 mL) and water (2 mL). The resulting mixture stirred overnight at 100 °C. After cooling to room temperature, the reaction mixture was passed through a short pad of celite, and the filtrate was concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with 1 : 1 , ethyl acetate/petroleum ether). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, XBridge Prep CI 8 OBD Column, 19x150mm 5um 13nm; mobile phase, water (0.05percent ammonium bicarbonate) and acetonitrile (15.0percent to 95percent acetonitrile in 12 min; flow rate: 20 mL/min); Detector, UV 254/220nm. This afforded (S)-4-(l-acetyl-6-(l-cyclopropyl- lH-pyrazol-4-yl)-2-methyl-l,2,3,4-tetrahydroquinolin-5-yloxy)benzamide (0.029 g, 40percent) as an off- white solid. 1H NMR(300 MHz, CD3OD) delta ppm 0.93-1.03 (m, 4 H), 1.15 (d, J=6.60 Hz, 3 H, 1.19- 1.42 (m, 1 H), 2.18-2.27 (m, 5 H), 2.67-2.75 (m, 1 H), 3.56-3.63 (m, 1 H), 4.77-4.79 (m, 1 H), 6.85- 6.88 (m, 2 H), 7.37 (m, 1 H), 7.63 (d, J=8.40 Hz, 1 H), 7.77 (s, 1 H), 7.81-7.85 (m, 2 H), 7.94 (s, 1 H). MS (ESI, pos. ion) m/z 431 [M+H]+.
  • 12
  • [ 1151802-22-0 ]
  • 1-[(2S)-6-bromo-2-methyl-5-[(4-methylpyridin-2-yl)oxy]-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one [ No CAS ]
  • 1-[(2S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-[(4-methylpyridin-2-yl)oxy]-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
53% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃;Inert atmosphere; Step 2. l-[(2S)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-[(4-methylpyridin-2-yl)oxy]- l,2,3,4-tetrahydroquinolin-l-yl]ethaii-l-one [0539] A 50-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen, and charged with l-[(2S)-6-bromo-2-methyl-5-[(4-methylpyridin-2-yl)oxy]-l, 2,3,4- tetrahydroquinolin-l-yl]ethan-l-one (11 1 mg, 0.30 mmol), 1,4-dioxane (15 mL), 1 -cyclopropyl-4- (tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole (139 mg, 0.59 mmol), [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (30 mg, 0.04 mmol), potassium carbonate (124 mg, 0.90 mmol), and water (5 mL). The resulting mixture stirred overnight at 100 °C. After cooling to room temperature, the solution was diluted with ethyl acetate (10 mL). The aqueous layer was separated and extracted with ethyl acetate (2 x 20 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1 : 1 , ethyl acetate/petroleum ether). The collected fractions were combined and concentrated under vacuum. The crude product was further purified by Prep-HPLC with the following conditions (Waters I): Column, SunFire Prep C18, 5um, 19x100mm; mobile phase, water (0.05percent ammonium bicarbonate) and acetonitrile (65percent to 85percent acetonitrile in 7 min, flow rate 20 mL/min); Detector, UV 220&254nm. This afforded l-[(2S)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-[(4- methylpyridin-2-yl)oxy]-l,2,3,4-tetrahydroquinolin-l-yl]ethan-l-one (63.6 mg, 53percent) as an off-white solid. 1H NMR (300 MHz, CD3OD) delta ppm 0.95-1.01 (m, 4H), 1.14 (d, J=6.30 Hz, 3H), 1.30-1.45 (m, 1H), 2.10-2.30 (m, 5H), 2.34 (s, 3H), 2.55-2.70 (m, 1H), 3.55-3.65 (m, 1H), 4.68-4.85 (m, 1H), 6.75 (s, 1H), 6.85-6.95 (m, 1H), 7.20-7.32 (m, 1H), 7.55-7.58 (m, 1H), 7.72 (s, 1H), 7.89-7.93 (m, 2H). MS (ESI, pos. ion) m/z 403[M+H]+.
  • 13
  • [ 1151802-22-0 ]
  • 1-[(2S)-6-bromo-5-(2,2-dichloroethoxy)-2-methyl-1,2,3,4-tetrahydroquinolin-1-yl]ethan-1-one [ No CAS ]
  • (S,E)-1-(5-(2-chlorovinyloxy)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
26% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 15h;Inert atmosphere; Step 2. (S,E)-l-(5-(2-chlorovinyloxy)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-3,4- dihydroquinolin-l(2H)-yl)ethanone [0575] A 50-mL round-bottom flask was purged and maintained with an inert atmosphere of nitrogen and charged with l-[(2S)-6-bromo-5-(2,2-dichloroethoxy)-2-methyl- 1,2,3,4- tetrahydroquinolin-l-yl]ethan-l-one (43 mg, 0.11 mmol), 1 -cyclopropyl-4-(tetramethyl- 1,3,2- dioxaborolan-2-yl)-lH-pyrazole (40 mg, 0.17 mmol), [1,1 '- bis(diphenylphosphino)ferrocene]dichloropalladium(II) (8 mg, 0.01 mmol), potassium carbonate (31 mg, 0.22 mmol), 1,4-dioxane (24 mL), and water (4 mL). The resulting mixture stirred for 15 h at 100 °C in an oil bath. After cooling to room temperature, the reaction mixture was passed a short pad of celite and concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with dichloromethane/methanol, 50: 1 then 20: 1) to afford (S,E)-l-(5-(2- chlorovinyloxy)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-l(2H)- yl)ethanone (12 mg, 26percent) as a white solid. 1H NMR(300 MHz, CD3OD) delta ppm 1.05-1.15 (m, 7 H), 1.35-1.58 (m, 1 H), 2.21 (s, 3 H), 2.25-2.50 (m, 2 H), 2.80-2.93 (m, 1 H), 3.65-3.75 (m, 1 H), 4.61 (s, 1 H), 4.70-4.85 (m, 1 H), 5.52 (d, J=4.20 Hz, 1 H), 6.52 (d, J=4.20 Hz, 1 H), 7.15-7.25 (m, 1 H), 7.54 (d, J=8.40 Hz, 1 H),7.89 (s, 1 H), 8.07 (s, 1 H). MS (ESI, pos. ion) m/z 372[M+H]+.
  • 14
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-2-methyl-5-(3-methylpyridin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(3-methylpyridin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
21% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; Step 3. (S)-l-(6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-(3-methylpyridin-2-yloxy)-3,4- dihydroquinolin-l(2H)-yl)ethanone [0602] A 100-mL, round-bottom flask was charged with (S)-l-(6-bromo-2-methyl-5-(3- methylpyridin-2-yloxy)-3,4-dihydroquinolin-l(2H)-yl)ethanone (0.129 g, 0.34 mmol), [Iota, - bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.025 g, 0.03 mmol), potassium carbonate (0.142 g, 1.03 mmol), l-cyclopropyl-4-(4,4,5,5-tetramethyl-l ,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.243 g, 1.04 mmol), 1.4-dioxane (10 mL) and water (2 mL). The resulting mixture stirred overnight at 100 °C. After cooling to room temperature, the reaction mixture was passed through a short pad of Celite, and the filtrate was concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with 50percent ethyl acetate-petroleum ether). The product was further purified by preparative-HPLC with the following conditions (Waters I): Column, SunFire Prep C18,19xl50mm; mobile phase, water (0.05percent ammonium bicarbonate) and acetonitrile (54percent to 80percent acetonitrile in 10 min, flow rate: 20 mL/min); Detector, UV 220&254nm. This afforded (S)- 1 -(6-( 1 -cyclopropyl- 1 H-pyrazol-4-yl)-2-methyl-5-(3-methylpyridin-2-yloxy)-3,4- dihydroquinolin-l(2H)-yl)ethanone (0.0285 g, 21percent) as an off-white solid. 1H NMR(300 MHz, CD3OD) delta ppm 1.00-1.03 (m, 4 H), 1.16 (d, J=6.60 Hz, 3 H), 1.32-1.42 (m, 1 H), 2.20-2.28 (m, 5 H), 2.48 (s, 3 H), 2.54-2.59 (m, 1 H), 3.57-3.64 (m, 1 H), 4.75-4.80 (m, 1 H), 6.95-7.00 (m, 1 H), 7.22-7.27 (m, 1 H), 7.54 (d, J=8.40 Hz, 1 H), 7.63 (s, 1 H), 7.72-7.77 (m, 2 H), 7.80 (s, 1 H). MS (ESI, pos. ion) m/z 403[M+H]+.
  • 15
  • [ 1151802-22-0 ]
  • 1-((S)-6-bromo-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
  • 1-((S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; Step 3. l-((S)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H- purin-2-yloxy)-3,4-dihydroquinoliii-l(2H)-yl)ethanone [0608] A 100-mL, round-bottom flask was charged with l-((S)-6-bromo-2-methyl-5-(7-(tetrahydro- 2H-pyran-2-yl)-7H-purin-2-yloxy)-3,4-dihydroquinolin-l(2H)-yl)ethanone (0.200 g, 0.41 mmol), [l, -bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.030 g, 0.04 mmol), potassium carbonate (0.170 g, 1.23 mmol), l-cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH- pyrazole (0.288 g, 1.23 mmol), 1 ,4-dioxane (20 mL), and water (2 mL). The resulting mixture stirred overnight at 100 °C. After cooling to room temperature, the reaction mixture was passed through a short pad of Celite, and the filtrate was concentrated under vacuum. The residue was purified by preparative thin layer chromatography (eluting with 1 :2, ethyl acetate/petroleum ether) to afford 1- ((S)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-(7-(tetrahydro-2H-pyran-2-yl)-7H-purin-2- yloxy)-3,4-dihydroquinolin-l(2H)-yl)ethanone (0.150 g, 71percent) as light yellow oil. MS (ESI, pos. ion) m/z 514[M+H]+.
  • 16
  • [ 1151802-22-0 ]
  • (S)-5-(1-allyl-1H-benzo[d]imidazol-2-yloxy)-6-bromo-2-methyl-1,2,3,4-tetrahydroquinoline [ No CAS ]
  • (E/Z)-(S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-5-((1-(prop-1-en-1-yl)-1H-benzo[d]imidazol-2-yl)oxy)-1,2,3,4-tetrahydroquinoline [ No CAS ]
YieldReaction ConditionsOperation in experiment
86% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; at 100℃; for 3h; Step 3. (E/Z)-(S)-6-(l-cyclopropyl-lH-pyrazol-4-yl)-2-methyl-5-((l-(prop-l-en-l-yl)-lH- benzo[d]imidazol-2-yl)oxy)-l,2,3,4-tetrahydroquinoline [0726] A mixture of (S)-5-(l-allyl-lH-benzo[d]imidazol-2-yloxy)-6-bromo-2-methyl-l ,2,3,4- tetrahydroquinoline (0.115 g, 0.29 mmol), l-cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan- 2-yl)-lH-pyrazole (0.269 g, 1.15 mmol), potassium carbonate (0.118 g, 0.85 mmol), and [Iota, - bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.023 g, 0.03 mmol) in 1,4-dioxane (10 mL) and water (3 mL) stirred for 3 h at 100 °C. The reaction mixture was cooled to room temperature, filtered through a short pad of Celite and concentrated under vacuum. The residue was purified via preparative thin layer chromatography (eluting with 1 :2, ethyl acetate/petroleum ether) to afford (S)-6-(l -eye lopropyl-lH-pyrazol-4-yl)-2-methyl-5-((l -(prop- 1-en- l-yl)-lH-benzo[d]imidazol-2-yl)oxy)-l ,2,3,4-tetrahydroquinoline (0.106 g, 86percent) as a red oil which is mixture of E and Z isomers. MS (ESI, pos. ion) m/z 426 [M+H]+.
  • 17
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With (chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II)); caesium carbonate; In 1,4-dioxane; water; at 100℃; for 16h; A mixture of (S)-1-(6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone (0.500 g, 1.858 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazole (0.457 g, 1.951 mmol), chloro(2-dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'- biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II) (XPhos 2nd generation precatalyst) (0.146 g, 0.186 mmol), and cesium carbonate (1.816 g, 5.57 mmol) in 1,4-dioxane (7.5 mL) and water (1.50 mL) was heated at 100 °C for 16 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100percent ethyl acetate-hexane) to afford (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone (0.335 g, 61percent) as an off-white solid. MS (ESI, pos. ion) m/z 297 [M+1]+.
  • 18
  • [ 1151802-22-0 ]
  • (S)-cyclopentyl 7-bromo-3-methyl-4-(2,2,2-trifluoroacetyl)-3,4-dihydroquinoxaline-1(2H)-carboxylate [ No CAS ]
  • (S)-cyclopentyl 7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
59% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; water; at 100℃; for 17h; A mixture of (S)-cyclopentyl 7-bromo-3-methyl-4-(2,2,2-trifluoroacetyl)-3,4- dihydroquinoxaline-1(2H)-carboxylate (0.250 g, 0.574 mmol), 1-cyclopropyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.148 g, 0.632 mmol), tris(dibenzylideneacetone)dipalladium (0.026 g, 0.029 mmol), X-Phos (0.027 g, 0.057 mmol) and cesium carbonate (0.561 g, 1.723 mmol) in 1,4-dioxane (5.0 mL) and water (1.0 mL) was heated at 100 °C for 17 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 25-100percent ethyl acetate-hexane) to afford (S)- cyclopentyl 7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)- carboxylate (0.124 g, 59 percent) as a yellow solid. MS (ESI, pos. ion) m/z 367 [M+1]+.
  • 19
  • [ 1151802-22-0 ]
  • (S)-1-acetyl-6-bromo-N-(4-fluorophenyl)-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide [ No CAS ]
  • (S)-1-acetyl-6-(1-cyclopropyl-1H-pyrazol-4-yl)-N-(4-fluorophenyl)-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; 1,2-dichloro-ethane; at 80℃; for 4h;Inert atmosphere; A reaction vial was charged with (S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3- b]pyrazin-1(2H)-yl)ethanone (0.1 M solution in 1,2-dichloroethane, 0.30 mL, 0.03 mmol) and N,N-diisopropylethylamine (0.052 mL, 0.300 mmol) was added. 1-Fluoro-4-isocyanatobenzene (0.017 mL, 0.150 mmol) was added neat, followed by the addition of a catalytic amount of DMAP (~1 mg), and the reaction was shaken at 50 °C overnight. The reaction was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated and extracted with ethyl acetate, and the combined organic layers were concentrated under a stream of nitrogen and vacuum to yield (S)-1-acetyl-6-bromo-N-(4- fluorophenyl)-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide. The crude product was dissolved in 1,4-dioxane (100 L), and 1-cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)-1H-pyrazole (0.2 M solution in 1,4-dioxane, 0.27 mL, 0.054 mmol), potassium carbonate (1.0 M solution in water, 0.090 mL, 0.090 mmol) and [1,1?- bis(diphenylphosphino) ferrocene]dichloropalladium(II) dichloromethane adduct (0.02 M solution in 1,2-dichloroethane, 150 muL, 0.003 mmol) were added. The reaction was purged with nitrogen, and heated to 80 °C on a heater shaker for 4 hours. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution and brine. The combined organic layers were concentrated in a Genevac. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated to afford (S)-1-acetyl-6-(1-cyclopropyl-1H-pyrazol-4-yl)-N-(4-fluorophenyl)-2-methyl-2,3- dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide. MS (ESI, pos. ion) m/z 435 [M+H]+.
  • 20
  • [ 1151802-22-0 ]
  • C12H15BrN2O2 [ No CAS ]
  • ethyl (S)-7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxaline-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With bis-triphenylphosphine-palladium(II) chloride; sodium hydrogencarbonate; In 1,4-dioxane; water; N,N-dimethyl-formamide; at 80℃;Inert atmosphere; General procedure: A 100 mL round bottomed flask fitted with a nitrogen inlet was charged with (S)-1- (6-bromo-4-(furan-2-carbonyl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)-2,2,2- trifluoroethanone (0.626 g, 1.5 mmol), 1,4-dioxane (15 mL), 4-(methylsulfonyl)phenylboronic acid (0.360 g, 1.8 mmol), and sodium bicarbonate as a 1M solution in water (4.5 mL, 4.5 mmol). The reaction mixture was purged with nitrogen. Bis(triphenylphosphine)palladium(II) dichloride (0.01 M solution in DMF, 7.5 mL, 0.075 mmol) was added, and the reaction mixture was purged with nitrogen and heated to 80 °C overnight. The reaction was diluted with ethyl acetate (30 mL) and washed with brine (15 mL). The aqueous layer was separated and washed with ethyl acetate (30 mL) and the combined organic layers were concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 1:1 hexanes? ethyl acetate) to afford (S)-furan-2-yl(3-methyl-7-(4-(methylsulfonyl)phenyl)-3,4- dihydroquinoxalin-1(2H)-yl)methanone (0.33 g, 55 percent yield) as a viscous yellow oil. MS (ESI, pos. ion) m/z 397 [M+1]+.
  • 21
  • [ 1151802-22-0 ]
  • (S)-(4-(benzo[d]oxazol-2-yl)-6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)(cyclopropyl)methanone [ No CAS ]
  • (S)-(4-(benzo[d]oxazol-2-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)(cyclopropyl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
69% With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; water; at 100℃; for 1.5h; A mixture of (S)-(4-(benzo[d]oxazol-2-yl)-6-bromo-2-methyl-3,4-dihydroquinoxalin- 1(2H)-yl)(cyclopropyl)methanone (0.019 g, 0.046 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.012 g, 0.051 mmol), tris(dibenzylideneacetone) dipalladium (2.1 mg, 2.3 mumol), 2-dicyclohexylphosphino-2?,4?,6?-triisopropylbiphenyl (XPhos) (2.2 mg, 4.6mumol) and cesium carbonate (0.045 g, 0.138 mmol) in dioxane (1.0 mL) and water (0.20 mL) was heated in the microwave at 100 °C for 1.5 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 50-100percent ethyl acetate- hexane) to afford (S)-(4-(benzo[d]oxazol-2-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4- dihydroquinoxalin-1(2H)-yl)(cyclopropyl)methanone (0.014 g, 69percent) as an off-white solid.1H NMR (300 MHz, DMSO-d6) delta ppm 0.65 - 1.05 (m, 11 H), 1.85 - 2.02 (m, 1 H), 3.58 - 3.80 (m, 1 H), 3.90 - 4.16 (m, 2 H), 5.02 - 5.18 (m, 1 H), 7.01 - 7.26 (m, 2 H), 7.31 (dd, J = 8.21, 1.76 Hz, 1 H), 7.35 - 7.58 (m, 3 H), 7.79 (s, 1 H), 8.18 (s, 1 H), 8.36 (d, J = 2.05 Hz, 1 H). MS (ESI, pos. ion) m/z 440 [M+H]+.
  • 22
  • [ 1151802-22-0 ]
  • (S)-1-(4-(benzo[d]isoxazol-3-yl)-6-bromo-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(4-(benzo[d]isoxazol-3-yl)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
22% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; 1,2-dichloro-ethane; at 80℃;Inert atmosphere; A 1.5 mL reaction vial was charged with (S)-1-(4-(benzo[d]isoxazol-3-yl)-6-bromo- 2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone (0.012 g, 0.03 mmol), 1-cyclopropyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.2 M in 1,4-dioxane, 225 muL, 0.03 mmol), and dioxane (0.1 mL). Potassium carbonate (1 M solution in water, 90 muL, 0.09 mmol) was added, and the reaction mixture was purged with nitrogen. [1,1?- Bis(diphenylphosphino)ferrocene]dichloropalladium(II) (0.02 M solution in 1,2-dichloroethane, 150 muL, 0.003 mmol) was added, the reaction was purged with nitrogen, and heated overnight at 80 °C on a heater shaker. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution. The aqueous layer was separated and washed with ethyl acetate and the combined organic layers were concentrated under a stream of nitrogen. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated in a Genevac to afford 1-[(2S)-4-[(furan-2- yl)carbonyl]-6-(5-methanesulfonylpyridin-2-yl)-2-methyl-1,2,3,4-tetrahydroquinoxalin-1- yl]ethan-1-one (0.0026 g, 22percent). MS (ESI, pos. ion) m/z 414 [M+H]+.
  • 23
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-4-(7-fluoro-1-methyl-1H-indazol-3-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethan-1-one [ No CAS ]
  • 1-[(2S)-6-(1-cyclopropyl-1H-pyrazol-4-yl)-4-(7-fluoro-1-methyl-1H-indazol-3-yl)-2-methyl-1,2,3,4-tetrahydroquinoxalin-1-yl]ethan-1-one [ No CAS ]
YieldReaction ConditionsOperation in experiment
27% With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium carbonate; In 1,4-dioxane; water; at 100℃; A 100-mL round-bottom flask was purged with an inert atmosphere of nitrogen and charged with (S)-1-(6-bromo-4-(7-fluoro-1-methyl-1H-indazol-3-yl)-2-methyl-3,4-dihydro quinoxalin-1(2H)-yl)ethan-1-one (46 mg, 0.11 mmol), 1-cyclopropyl-4-(4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl)-1H-pyrazole (77.6 mg, 0.33 mmol), [1,1?-bis(diphenylphosphino) ferrocene]dichloropalladium(II) (8 mg, 0.01 mmol), potassium carbonate (46 mg, 0.33 mmol), 1,4-dioxane (20 mL) and water (2 mL). The resulting mixture stirred overnight at 100 °C. After cooling to room temperature, the reaction mixture was filtered through a short pad of celite and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1:1, ethyl acetate/petroleum ether) to afford (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4- yl)-4-(7-fluoro-1-methyl-1H-indazol-3-yl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)ethanone (13.1 mg, 27percent) as a white solid.1H NMR(300 MHz, CDCl3) delta ppm 1.01-1.14 (m, 4H), 1.26 (d, J = 6.90 Hz, 3H), 2.32 (s, 3H), 3.55-3.65 (m, 1H), 3.67-3.75 (m, 1H), 3.90-4.01 (m, 1H), 4.23 (s, 3H), 6.76 (s, 1H), 6.85-6.98 (m, 2H), 7.01-7.15 (m, 3H), 7.49 (s, 1H), 7.56 (s, 1H). MS (ESI, pos. ion) m/z 445 [M+H]+.
  • 24
  • [ 1151802-22-0 ]
  • (S)-isopropyl 7-bromo-3-methyl-4-(methylcarbamoyl)-3,4-dihydropyrido[2,3-b]pyrazine-1(2H)-carboxylate [ No CAS ]
  • (S)-isopropyl 7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-4-(methylcarbamoyl)-3,4-dihydropyrido[2,3-b]pyrazine-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; water; 1,2-dichloro-ethane; at 80℃;Inert atmosphere; A reaction vial was charged with (S)-isopropyl 7-bromo-3-methyl-4- (methylcarbamoyl)-3,4-dihydropyrido[2,3-b]pyrazine-1(2H)-carboxylate (0.015 g, 0.04 mmol), <strong>[1151802-22-0]1-<strong>[1151802-22-0]cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong></strong> (0.2 M solution in 1,4-dioxane, 0.40 mL, 0.080 mmol), potassium carbonate (1.0 M solution in water, 0.120 mL, 0.120 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.02 M solution in 1,2-dichloroethane, 0.200 mL, 0.004 mmol). The reaction was purged with nitrogen and heated to 80 °C on a heater shaker overnight.. The reaction was diluted with ethyl acetate and washed with brine. The combined organic layers were concentrated under a stream of nitrogen. The crude product was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated to afford (S)-isopropyl 7-(1- cyclopropyl-1H-pyrazol-4-yl)-3-methyl-4-(methylcarbamoyl)-3,4-dihydropyrido[2,3-b]pyrazine- 1(2H)-carboxylate. MS (ESI, pos. ion) m/z 399 [M+H]+.
  • 25
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate; In 1,4-dioxane; 1,2-dichloro-ethane; at 80℃; A reaction vial was charged with (S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3- b]pyrazin-1(2H)-yl)ethanone (0.1 M solution in 1,2-dichloroethane, 0.30 mL, 0.03 mmol), 1,4- dioxane (100 L), <strong>[1151802-22-0]1-<strong>[1151802-22-0]cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong></strong> (0.2 M solution in 1,4-dioxane, 0.27 mL, 0.054 mmol), potassium carbonate (1.0 M solution in water, 0.090 mL, 0.090 mmol) and [1,1?-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane adduct (0.02 M solution in 1,2-dichloroethane, 150 muL, 0.003 mmol). The reaction was purged with nitrogen, and heated to 80 °C on a heater shaker overnight. The reaction was diluted with ethyl acetate and washed with 1 N aqueous sodium hydroxide solution and brine. The combined organic layers were concentrated under a stream of nitrogen and vacuum to yield (S)-1-(6-(1-cyclopropyl-1H-pyrazol-4-yl)-2-methyl-3,4-dihydropyrido[2,3- b]pyrazin-1(2H)-yl)ethanone. The crude product was dissolved in 1,2-dichloroethane (200 L), and N,N-diisopropylethylamine (0.052 mL, 0.300 mmol) was added. 2-Isocyanatopropane (0.020 mL, 0.200 mmol) was then added along with a catalytic amount of DMAP (~1 mg), and the reaction was shaken at 80 °C for 3 hours. The reaction was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The aqueous layer was separated and extracted with ethyl acetate and the combined organic layers were concentrated in a Genevac. The crude product was purified by mass triggered preparatory HPLC. The product- containing fractions were combined and concentrated to afford (S)-1-acetyl-6-(1-cyclopropyl- 1H-pyrazol-4-yl)-N-isopropyl-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide. MS (ESI, pos. ion) m/z 383 [M+H]+.
  • 26
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-2-methyl-3,4-dihydropyrido[2,3-b]pyrazin-1(2H)-yl)ethanone [ No CAS ]
  • (S)-1-acetyl-6-(1-cyclopropyl-1H-pyrazol-4-yl)-N-isopropyl-2-methyl-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide [ No CAS ]
  • 27
  • [ 1151802-22-0 ]
  • isopropyl (S)-4-acetyl-7-bromo-3-methyl-6-nitro-3,4-dihydroquinoxaline-1(2H)-carboxylate [ No CAS ]
  • isopropyl (S)-4-acetyl-7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-6-nitro-3,4-dihydroquinoxaline-1(2H)-carboxylate [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; XPhos; In 1,4-dioxane; water; at 90℃; for 16h; A mixture of isopropyl (S)-4-acetyl-7-bromo-3-methyl-6-nitro-3,4- dihydroquinoxaline-1(2H)-carboxylate (0.131 g, 0.327 mmol), 1-cyclopropyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.092 g, 0.392 mmol), cesium carbonate (0.319 g, 0.980 mmol), XPhos (0.016 g, 0.033 mmol) and tris(dibenzylideneacetone)dipalladium (0.015 g, 0.016 mmol) in 1,4-dioxane (3 mL) and water (0.6 mL) was heated for 16 h at 90 C. The reaction was cooled to rt and concentrated. The residue was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate solution. The organic phase was concentrated and the residue was purified by mass triggered preparatory HPLC. The product-containing fractions were combined and concentrated in a Genevac to afford isopropyl (S)-4-acetyl-7-(1- cyclopropyl-1H-pyrazol-4-yl)-3-methyl-6-nitro-3,4-dihydroquinoxaline-1(2H)-carboxylate. MS (ESI, pos. ion) m/z 428 [M+H]+.
  • 28
  • [ 1151802-22-0 ]
  • (S)-1-(6-bromo-4-(cyclopropanecarbonyl)-2-methyl-3,4-dihydroquinoxalin-1(2H)-yl)-2,2,2-trifluoroethanone [ No CAS ]
  • (S)-cyclopropyl(7-(1-cyclopropyl-1H-pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxalin-1(2H)-yl)methanone [ No CAS ]
YieldReaction ConditionsOperation in experiment
79% With (chloro(2-dicyclohexylphosphino-2?,4?,6?-triisopropyl-1,1?-biphenyl)[2-(2?-amino-1,1?-biphenyl)]palladium(II)); caesium carbonate; In 1,4-dioxane; water; at 100℃; for 16h;Microwave irradiation; A mixture of (S)-1-(6-bromo-4-(cyclopropanecarbonyl)-2-methyl-3,4-dihydro quinoxalin-1(2H)-yl)-2,2,2-trifluoroethanone (0.100 g, 0.256 mmol), 1-cyclopropyl-4-(4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.066 g, 0.281 mmol), chloro(2-dicyclohexyl phosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl)(2'-amino-1,1'-biphenyl-2-yl) palladium(II) (XPhos Precatalyst 2nd Generation) (10.06 mg, 0.013 mmol), and cesium carbonate (0.250 g, 0.767 mmol) in dioxane (2.0 mL) and water (0.40 mL) was heated in the microwave at 100 °C for 16 h. The reaction mixture was filtered through Celite and concentrated to afford an orange oil. This material was purified via column chromatography on silica gel (Biotage 25 g column, gradient elution with 25-100percent ethyl acetate-hexane) to afford (S)-cyclopropyl(7-(1-cyclopropyl-1H- pyrazol-4-yl)-3-methyl-3,4-dihydroquinoxalin-1(2H)-yl)methanone (0.065 g, 79percent) as a yellow solid. MS (ESI, pos. ion) m/z 323 [M+1]+.
  • 29
  • [ 1151802-22-0 ]
  • (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide [ No CAS ]
  • (9S)-5-(1-cyclopropyl-1H-pyrazol-4-yl)-N-(pyrazin-2-yl)-1,6,8-triazatricyclo[7.2.1.02,7]dodeca-2(7),3,5-triene-8-carboxamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
35% With tris-(dibenzylideneacetone)dipalladium(0); potassium dihydrogenphosphate; In 1,4-dioxane; water; at 90℃; for 15h; Pd2(dba)3 (0.087 g, 0.095 mmol) and X-phos (0.018 g, 0.047 mmol) was added to degassed solution of (4S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3-b][1,4]diazepine-5(2H)-carboxamide (0.3 g, 0.947 mmol), <strong>[1151802-22-0]1-<strong>[1151802-22-0]cyclopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole</strong></strong> (0.333 g, 1.421 mmol) and potassium dihydrogen phosphate (0.258 g, 1.894 mmol) in 1,4-dioxane (5 mL): water (1 mL) and heated to 90 C. for 15 hours. Cooled to room temperature and filtered through pad of celite. The filtrate was diluted with water (25 mL) and ethyl acetate (50 mL). The separated organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to get crude (TLC eluent: 10% MeOH in ethyl acetate; UV active; Rf0.30). The crude compound was purified by column chromatography using neutral alumina and eluted in 75% ethyl acetate in hexane to afford (4S)-7-(1-cyclopropyl-1H-pyrazol-4-yl)-N-(pyrazin-2-yl)-3,4-dihydro-1,4-methanopyrido[2,3b][1,4]diazepine-5(2H)-carboxamide (0.13 g, 0.332 mmol, 35.0% yield) off-white solid, LCMS (m/z): 389.32 [M+H]+. 1H NMR (400 MHz, CDCl3): delta ppm 14.14 (s, 1H), 9.60 (d, J=1.10 Hz, 1H), 8.61 (s, 1H), 8.29-8.33 (m, 2H), 8.03 (s, 1H), 7.47-7.58 (m, 1H), 7.13 (d, J=8.11 Hz, 1H), 5.66 (dd, J=6.03, 3.18 Hz, 1H), 3.73 (tt, J=7.43, 3.75 Hz, 1H), 3.08-3.34 (m, 3H), 2.99 (dd, J=11.95, 3.18 Hz, 1H), 2.32 (dddd, J=14.11, 10.00, 6.03, 4.06 Hz, 1H), 2.02-2.11 (m, 1H), 1.22-1.32 (m, 2H), 1.07-1.18 (m, 2H).
35% With tris-(dibenzylideneacetone)dipalladium(0); potassium dihydrogenphosphate; XPhos; In 1,4-dioxane; water; at 90℃; for 15h; Pd2(dba)3 (0.087 g, 0.095 mmol) and X-phos (0.018 g, 0.047 mmol) was added to degassed solution of (4,S)-7-chloro-N-(pyrazin-2-yl)-3,4-dihydro-l,4-methanopyrido[2,3- b][,4] diazepine-5(2H)-carboxamide (0.3 g, 0.947 mmol), l-cyclopropyl-4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)-lH-pyrazole (0.333 g, 1.421 mmol) and potassium dihydrogen phosphate (0.258 g, 1.894 mmol) in 1,4-dioxane (5 mL):water (1 mL) and heated to 90 C for 15 hours. Cooled to room temperature and filtered through pad of celite. The filtrate was diluted with water (25 mL) and ethyl acetate (50 mL). The separated organic layer was dried over anhydrous sodium sulfate, filtered and evaporated to get crude (TLC eluent: 10% MeOH in ethyl acetate; UV active; Rf-0.30). The crude compound was purified by column chromatography using neutral alumina and eluted in 75%) ethyl acetate in hexane to afford (4,S)-7-(l-cyclopropyl-lH-pyrazol-4-yl)-N-(pyrazin- 2-yl)-3,4-dihydro-l,4-methanopyrido [2,3b][l,4]diazepine-5(2H)-carboxamide (0.13 g, 0.332 mmol, 35.0 % yield) off-white solid, LCMS (m/z): 389.32 [M+H]+.1H NMR (400 MHz, CDC13): delta ppm 14.14 (s, 1H), 9.60 (d, J= 1.10 Hz, 1H), 8.61 (s, 1H), 8.29 - 8.33 (m, 2H), 8.03 (s, 1H), 7.47 - 7.58 (m, 1H), 7.13 (d, J = 8.11 Hz, 1H), 5.66 (dd, J = 6.03, 3.18 Hz, 1H), 3.73 (tt, J = 7.43, 3.75 Hz, 1H), 3.08 - 3.34 (m, 3H), 2.99 (dd, J = 11.95, 3.18 Hz, 1H), 2.32 (dddd, 7 =14.11, 10.00, 6.03, 4.06 Hz, 1H), 2.02 - 2.11 (m, 1H), 1.22 - 1.32 (m, 2H), 1.07 - 1.18 (m, 2H).
  • 30
  • [ 1244041-71-1 ]
  • [ 1151802-22-0 ]
  • C18H20N4O2S [ No CAS ]
  • 31
  • [ 1244041-71-1 ]
  • [ 1151802-22-0 ]
  • C13H12N4S [ No CAS ]
  • 32
  • [ 1151802-22-0 ]
  • (4S)-7-chloro-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b] [1,4]diazepine [ No CAS ]
  • (4S)-7-(1-cyclopropyl-1H-pyrazol-4-yl)-2,3,4,5-tetrahydro-1,4-methanopyrido[2,3-b][1,4]diazepine [ No CAS ]
YieldReaction ConditionsOperation in experiment
34.4% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; water; at 110℃; for 16h;Inert atmosphere; Tripotassium phosphate (6.51 g, 30.7 mmol) and l-cyclopropyl-4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)-lH-pyrazole (2.87 g, 12.27 mmol) were added to a stirred solution of (4S)-7-chloro-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3-b][l,4]diazepine (2 g, 10.22 mmol) in mixture of 1,4-Dioxane (40 mL), Water (10.00 mL) at RT. Purged with argon for 5 min, then added PdCl2(dppf)-CH2Cl2 adduct (0.835 g, 1.022 mmol) stirred the reaction mixture at 1 10 C for 16 h. Allowed the reaction mixture to RT, diluted with water (150 mL) extracted with Ethyl acetate (2x300 mL), washed with brine (200 mL). The combined organic layer was dried over Na2S04 and concentrated under reduced pressure to obtain crude compound. The crude product was purified by flash column chromatography (silica-gel: 100-200 mesh) and was eluted with 10% MeOH-DCM to afford (4S)-7-(l-cyclopropyl-lH-pyrazol-4-yl)-2,3,4,5-tetrahydro-l,4-methanopyrido[2,3- b][l,4]diazepine (1 g, 3.52 mmol, 34.4 % yield), LCMS (m/z): 268.13 [M+H]+
  • 33
  • [ 1151802-22-0 ]
  • 11-chloro-5-(dimethyl-1H-1,2,3-triazol-5-yl)-8-[(S)-oxan-4-yl(phenyl)methyl]-3,8,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaene [ No CAS ]
  • 11-(1-cyclopropyl-1H-pyrazol-4-yl)-5-(dimethyl-1H-1,2,3-triazol-5-yl)-8-[(S)-oxan-4-yl(phenyl)methyl]-3,8,10-triazatricyclo[7.4.0.02,7]trideca-1(13),2(7),3,5,9,11-hexaene [ No CAS ]
YieldReaction ConditionsOperation in experiment
61% With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate; In 1,4-dioxane; at 100℃; for 2h;Inert atmosphere; Dissolved (S)-7-chloro-3-(l,4-dimethyl-lH-l,2,3-triazol-5-yl)-5- (phenyl(tetrahydro-2H-pyran-4-yl)methyl)-5H-pyrrolo[2,3-b:4,5-b']dipyridine (47.3 mg, 0.1 mmol) and l-cyclopropyl-4-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-lH- pyrazole (46.8 mg, 0.200 mmol) in 1.7 mL of dioxane. Added PdCl2(dppf CH2Cl2Adduct (8.2 mg, 10.0 muetaiotaomicron) and 0.3 mL of sodium carbonate (300 mu, 0.300 mmol). Bubbled in argon for 2 min while sonicating. Heated at 100 °C for 2 h. The crude material was purified via preparative LC/MS with the following conditions: Column: XBridge C18, 19 x 200 mm, 5-muiotaeta particles; Mobile Phase A: 5:95 ACN: water with 0.1 percent trifluoroacetic acid; Mobile Phase B : 95 : 5 ACN: water with 0.1 percent trifluoroacetic acid; Gradient: 35-75percent B over 20 min, then a 5-min hold at 100percent B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 34.0 mg (61percent), and its estimated purity by LCMS analysis was 98percent. Two analytical LC/MS injections were used to determine the final purity. Injection 1 conditions: Column: Waters BEH CI 8, 2.0 x 50 mm, 1.7-muiotaeta particles; Mobile Phase A: 5:95 ACN:water with 10 mM NlrUOAc; Mobile Phase B: 95:5 ACN:water with 10 mM NH4OAc; Temperature: 50 °C; Gradient: 0-100percent B over 3 min, then a 0.5-min hold at 100percent B; Flow: 1.0 mL/min; Detection: UV at 220 nm. RT = 1.81 min, M+H = 545. Injection 2 conditions: Column: Waters BEH C18, 2.0 x 50 mm, 1.7-mupiiota particles; Mobile Phase A: 5:95 methanol: water with 10 mM NHiOAc; Mobile Phase B: 95:5 methanol: water with 10 mM NEUOAc; Temperature: 50 °C; Gradient: 0-100percent B over 3 min, then a 0.5-min hold at 100percent B; Flow: 0.5 mL/min; Detection: UV at 220 nm. RT = 3.15 min, M+H = 545. H NMR (500MHz, DMSO-de) delta 8.63 (s, 1H), 8.58 - 8.53 (m, 2H), 8.51 (br. s., 1H), 8.26 (s, 1H), 7.84 (d, J=7.7 Hz, 2H), 7.70 (d, J=8.1 Hz, 1H), 7.31 (t, J=7.5 Hz, 2H), 7.22 (t, J=7.2 Hz, 1H), 5.93 (br. s., 1H), 4.03 (s, 3H), 3.90 (dd, J=7.5, 3.5 Hz, 2H), 3.76 (d, J=10.6 Hz, 2H), 3.26 (t, J=l 1.4 Hz, 1H), 2.30 (s, 3H), 1.56 (d, J=10.6 Hz, 1H), 1.51 - 1.38 (m, 1H), 1.36 - 1.24 (m, 1H), 1.24 - 1.14 (m, 3H), 1.14 - 0.95 (m, 3H).
  • 34
  • [ 1151802-22-0 ]
  • (2E)-3-(4-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-3-yl)acrylic acid [ No CAS ]
  • 35
  • [ 1151802-22-0 ]
  • (2E)-3-[4-(1-cyclopropyl-1H-pyrazol-4-yl)pyridin-3-yl]-N-{4-[(morpholin-4-yl)methyl]phenyl}acrylamide [ No CAS ]
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 1151802-22-0 ]

Organoborons

Chemical Structure| 1002309-48-9

A111817 [1002309-48-9]

1-Cyclobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.97

Chemical Structure| 879487-10-2

A172495 [879487-10-2]

1-Isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.96

Chemical Structure| 1256359-15-5

A128505 [1256359-15-5]

1-(tert-Butyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.95

Chemical Structure| 827614-69-7

A297285 [827614-69-7]

1-Propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.95

Chemical Structure| 1175275-00-9

A279990 [1175275-00-9]

1-Cyclohexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.94

Related Parent Nucleus of
[ 1151802-22-0 ]

Pyrazoles

Chemical Structure| 1002309-48-9

A111817 [1002309-48-9]

1-Cyclobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.97

Chemical Structure| 879487-10-2

A172495 [879487-10-2]

1-Isopropyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.96

Chemical Structure| 1256359-15-5

A128505 [1256359-15-5]

1-(tert-Butyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.95

Chemical Structure| 827614-69-7

A297285 [827614-69-7]

1-Propyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.95

Chemical Structure| 1175275-00-9

A279990 [1175275-00-9]

1-Cyclohexyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole

Similarity: 0.94