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Chemical Structure| 1190320-08-1 Chemical Structure| 1190320-08-1

Structure of 1190320-08-1

Chemical Structure| 1190320-08-1

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Product Details of [ 1190320-08-1 ]

CAS No. :1190320-08-1
Formula : C8H6FN3
M.W : 163.15
SMILES Code : NC1=NC=NC2=CC=C(F)C=C12
MDL No. :MFCD12024574
InChI Key :ARIXAZJLBIBWSR-UHFFFAOYSA-N
Pubchem ID :46835706

Safety of [ 1190320-08-1 ]

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

Computational Chemistry of [ 1190320-08-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 12
Num. arom. heavy atoms 10
Fraction Csp3 0.0
Num. rotatable bonds 0
Num. H-bond acceptors 3.0
Num. H-bond donors 1.0
Molar Refractivity 43.9
TPSA ?

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

51.8 Ų

Lipophilicity

Log Po/w (iLOGP)?

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

1.44
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

1.38
Log Po/w (WLOGP)?

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

1.78
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.

1.5
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

1.63
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.55

Water Solubility

Log S (ESOL):?

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

-2.34
Solubility 0.75 mg/ml ; 0.0046 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.

-2.07
Solubility 1.39 mg/ml ; 0.00849 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

-3.24
Solubility 0.0941 mg/ml ; 0.000577 mol/l
Class?

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

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
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.

-6.32 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)

1.51

Application In Synthesis of [ 1190320-08-1 ]

* 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 [ 1190320-08-1 ]

[ 1190320-08-1 ] Synthesis Path-Downstream   1~7

  • 1
  • [ 61272-77-3 ]
  • [ 77287-34-4 ]
  • [ 1190320-08-1 ]
YieldReaction ConditionsOperation in experiment
80% at 200.0℃; for 1.0h;Microwave irradiation; Sealed vial; General procedure: Method A: Benzonitriles were suspended in formamide (40 equiv) and InCl3 (1 equiv), or not, in a sealed vial and were irradiated at 400 W under microwaves. The residue was cooled to room temperature, filtrated, washed with water and dried.
  • 2
  • [ 1190320-08-1 ]
  • 6′-bromo-8′-methyl-2′H-spiro[cyclohexane-1,3′-imidazo[1,5-a]pyridine]-1′,5′-dione [ No CAS ]
  • 6'-[(6-fluoroquinazolin-4-yl)amino]-8'-methyl-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; To a solution of 100 mg (321 pmol) 6-bromo-8-methyl-2H-spiro[cyclohexane-1 3- imidazo[1,5-a]pyridine]-1,5-dione (GAS-No: 1849592-70-6; PGT Int. AppI. (2015), WO 2015200481) and 57.7 mg (353 pmol) <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS-No: 1190320-08-1) in 12 mL 1 ,4-dioxane was added 314 mg cesium carbonate and the mixture was degassed and purged with argon several times. 19.9 mg 4,5-bis(diphenylphosphino)-9,9-dim ethylxanthene, 16.4 mg 2-(dicyclohexyl-phosphino)-2,4,6-triisopropylbiphenyl, 7.7 mg palladium(ll)acetate and 31.5 mg tris(dibenzylideneacetone)dipalladium(0) were added and the mixture was stirred at 1000 for 2 hours. The m ixture was concentrated and the residue purified by flash chromatography (Biotage SNAP Ultra cartridge silica 25 g, ethanol:dichloromethane) and crystallization from ethanol to give 73 mg (55%) of the titlecompound.LG-MS: m/z = 394.3[M÷H].1HNMR (400 MHz, DMSO-d6), 6 [ppm]= 1.24 (1H), 1.51 (2H), 1.59-1.81 (5H), 2.52 (3H*),3.02(2H), 7.85(1H), 7.95 (1H), 8.12(1H), 8.62 (1H), 8.79(1H), 9.33 (1H), 10.25(1H)*: at least partially hidden by solvent or water signal
  • 3
  • [ 1190320-08-1 ]
  • 6'-bromo-8'-methyl-2'H-spiro[cyclopentane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
  • 6'-[(6-fluoroquinazolin-4-yl)amino]-8'-methyl-2'H-spiro[cyclopentane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
31% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 105.0℃; for 2.0h;Inert atmosphere; To a solution of 6?-bromo-8?-methyl-2?H-spiro[cyclopentane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?5?- dione (GAS 1849592-55-7; PGT Int. AppI. (2015), WO 2015200481, 100 mg, 337 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 60.4 mg, 370 pmol) in 1,4-dioxane (12 mL)was added cesium carbonate (329 mg, 1 .01 mmol) and the mixture was degassed and purged with argon several times. 4, 5-Bis(diphenylphosphino)-9,9-dimethylxanthene (20.8 mg, 36.0 pmol), 2-(dicyclohexyl-phosphino)-2,4,6-triisopropylbiphenyl (17.2 mg, 36.0 pmol), palladium(ll)acetate (8.08 mg, 36.0 pmol) and tris(dibenzylideneacetone)dipalladium(0) (33.0 mg, 36.0 pmol) were added and the mixture was stirred at 1050 for2 hours. The reaction mixture was diluted with a mixture of dichloromethane/methanol, anorganic salts were filtered off and the filtrate was concentrated. The residue was purified by preperative TLG (ethanol: dichloromethane) and the obtained material was taken up in dichloromethane/methanol and stirred at RT. The solid was isolated by centrifugation and dried to give 42 mg (31% yield) of the title compound.LG-MS: m/z = 380.1 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.717 (4.64), 1.731 (5.23), 1.748 (4.64), 1.762(4.15), 1 .844 (5.33), 1.855 (5.53), 1 .874 (4.44), 1 .993 (6.32), 2.331 (3.36), 2.336 (1 .38),2.518 (16.00), 2.523 (10.67), 2.673 (3.06), 2.678 (1.38), 2.805 (2.96), 2.825 (5.53), 2.842(5.04), 2.857 (5.23), 2.877 (2.47), 3.297 (1 .09), 3.368 (1.68), 5.758 (2.57), 7.811(2.07),7.818 (2.37), 7.834 (4.44), 7.840 (4.94), 7.855 (3.16), 7.862 (3.36), 7.922 (5.04), 7.935(5.33), 7.944 (3.85), 7.957 (3.36), 8.141 (4.54), 8.147 (4.74), 8.164 (4.64), 8.170 (4.44), 8.546 (0.59), 8.606 (10.77), 8.776 (12.74), 9.352 (1.88), 10.042 (1.98).
  • 4
  • [ 1190320-08-1 ]
  • 6'-bromo-4-hydroxy-8'-methyl-4-(trifluoromethyl)-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
  • (cis)-6'-[(6-fluoroquinazolin-4-yl)amino]-4-hydroxy-8'-methyl-4-(trifluoromethyl)-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
3% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; To a solution of (cis)-6?-bromo-4-hydroxy-8?-methyl-4-(trifluoromethyl)-2?H-spiro[cyclohexane- 1,3?-imidazo[1,5-a]pyridine]-1?,5?-dione (prepared according to example 127b, 100 mg, 253 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 45.4 mg, 278 pmol) in 1,4-dioxane (10 mL) was added cesium carbonate (247 mg, 759 pmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene (15.7 mg, 27.1 pmol), 2-(dicyclohexyl-phosphino)-2,4,6- triisopropylbiphenyl (12.9 mg, 27.1 pmol), palladium(ll)acetate (6.08 mg, 27.1 pmol) and tris(dibenzylideneacetone)dipalladium(0) (24.8 mg, 27.1 pmol) were added and the mixturewas stirred at 1 00cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo, taken up in dichloromethane/ethanol again and stirred at RT. The solid was filtered off under vacuo and dried to give 4 mg (3% yield) of the title compound.LG-MS: m/z = 478.5 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.232 (2.49), 1.360 (1.55), 1.427 (6.02), 1.458(6.11), 1.818 (5.42), 1.853 (6.88), 1.937 (4.47), 1 .964 (6.11), 1.997 (2.92), 2.326 (5.33),2.381 (8.86), 2.668 (5.33), 3.440 (3.78), 3.466 (5.68), 3.499 (3.18), 5.758 (6.37), 5.991(3.10), 6.008 (12.99), 7.830 (2.41), 7.852 (4.73), 7.868 (3.18), 7.935 (5.33), 7.949 (5.42),7.958 (4.22), 7.971 (3.27), 8.030 (2.92), 8.150 (4.47), 8.168 (4.73), 8.615 (1.55), 8.643(15.66), 8.797 (16.00), 9.351 (10.67), 10.469 (9.81), 10.605 (1.72).
  • 5
  • [ 1190320-08-1 ]
  • 6'-bromo-8'-methyl-2'H-spiro[cyclobutane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
  • 6'-[(6-fluoroquinazolin-4-yl)amino]-8'-methyl-2'H-spiro[cyclobutane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
49% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; To a solution of 6?-bromo-8?-methyl-2?H-spiro[cyclobutane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?5?- dione (prepared according to example 146a, 100 mg, 353 pmol) and 6-fluoroquinazolin-4- amine (GAS 1190320-08-1, 63.4 mg, 389 pmol) in 1 ,4-dioxane (7.0 mL) was added cesium carbonate (345 mg, 1 .06 mmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (21 .9 mg, 37.8 pmol), 2-(dicyclohexyl-phosphino)-2,4, 6-triisopropylbiphenyl (18.0 mg, 37.8 pmol), palladium(ll)acetate (8.48 mg, 37.8 pmol) and tris(dibenzylideneacetone)dipalladium(0) (34.6 mg, 37.8 pmol) were added and the mixture was stirred at 100cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up inmethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 66.0 mg (49 % yield) of the title compound.LG-MS: m/z = 366.5 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.929 (0.53), 1.951 (0.59), 2.146 (0.57), 2.159 (0.57), 2.172 (0.53), 2.327 (1.55), 2.331 (1.49), 2.342 (0.77), 2.364 (1.28), 2.377 (1.06),2.388 (0.80), 2.401 (0.69), 2.470 (16.00), 2.665 (0.86), 2.669 (1.12), 2.673 (0.84), 3.404 (0.65), 3.429 (1.24), 3.456 (1.12), 3.482 (0.55), 7.825 (0.49), 7.832 (0.57), 7.848 (1.06), 7.855 (1.16), 7.869 (0.77), 7.875 (0.82), 7.935 (1.35), 7.948 (1.39), 7.958 (1.00), 7.972(0.86), 8.179 (1.08), 8.186 (1.14), 8.203 (1.12), 8.210 (1.06), 8.610 (4.59), 8.789 (4.79), 9.399 (2.65), 10.207 (2.41).
  • 6
  • [ 1190320-08-1 ]
  • 6-bromo-8-methyl-2H-spiro[imidazo[1,5-a]pyridine-3,3’-thietane]-1,5-dione [ No CAS ]
  • 6-[(6-fluoroquinazolin-4-yl)amino]-8-methyl-2H-spiro[imidazo[1,5-a]pyridine-3,3'-thietane]-1,5-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
37% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; To a solution of 6-bromo-8-methyl-2H-spiro[imidazo[1 ,5-a]pyridine-3,3?-thietane]-l ,5-dione(prepared according to example 173a, 100 mg, 332 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong>(GAS 1190320-08-1, 59.6 mg, 365 pmol) in 1 ,4-dioxane (6.6 mL) was added cesiumcarbonate (325 mg, 996 pmol) and the mixture was degassed and purged with argon severaltimes. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (20.6 mg, 35.5 pmol), 2-(dicyclohexyl-phosphino)-2,4, 6-triisopropylbiphenyl (16.9 mg, 35.5 pmol),palladium(ll)acetate (7.98 mg, 35.5 pmol) and tris(dibenzylideneacetone)dipalladium(0) (32.5 mg, 35.5 pmol) were added and the mixture was stirred at 100cC for 2 hours. The mixture was concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 50.0 mg (37%yield) of the title compound.LC-MS: m/z = 384.2 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.035 (0.41), 1.052 (0.83), 1.070 (0.44), 2.323(0.59), 2.327 (0.82), 2.332 (0.68), 2.454 (16.00), 2.522 (1.84), 2.665 (0.57), 2.669 (0.77),2.673 (0.58), 3.308 (4.03), 4.688 (4.06), 4.714 (4.09), 5.758 (0.40), 7.832 (0.61), 7.839(0.72), 7.855 (1.31), 7.861 (1.44), 7.877 (0.95), 7.883 (1.06), 7.941 (1.74), 7.955 (1.77),7.964 (1.24), 7.977 (1.13), 8.215 (1.30), 8.222 (1.37), 8.239 (1.34), 8.246 (1.31), 8.609 (5.84), 8.796 (6.05), 9.413 (3.39), 10.774 (3.27).
  • 7
  • [ 1190320-08-1 ]
  • (cis)-6’-bromo-4-hydroxy-8’-methyl-4-(pentafluoroethyl)-2’H-spiro[cyclohexane-1,3’-imidazo[1,5-a]pyridine]-1‘,5’-dione [ No CAS ]
  • (cis)-6'-[(6-fluoroquinazolin-4-yl)amino]-4-hydroxy-8'-methyl-4-(pentafluoroethyl)-2'H-spiro[cyclohexane-1,3'-imidazo[1,5-a]pyridine]-1',5'-dione [ No CAS ]
YieldReaction ConditionsOperation in experiment
55% With tris-(dibenzylideneacetone)dipalladium(0); palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; XPhos; In 1,4-dioxane; at 100.0℃; for 2.0h;Inert atmosphere; To a solution of (cis)-6?-bromo-4-hydroxy-8?-methyl-4-(pentafluoroethyl)-2? Hspiro[cyclohexane-1 ,3?-imidazo[l ,5-a]pyridine]-1 ?,S?-dione (prepared according to example191 b, 100 mg, 225 pmol) and <strong>[1190320-08-1]6-fluoroquinazolin-4-amine</strong> (GAS 1190320-08-1, 40.3 mg,247 pmol) in 1 ,4-dioxane (9 mL) was added cesium carbonate (220 mg, 674 pmol) and the mixture was degassed and purged with argon several times. 4,5-Bis(diphenylphosphino)-9,9- dimethylxanthene (13.9 mg, 24.0 pmol), 2-(dicyclohexyl-phosphino)-2,4,6- triisopropylbiphenyl (11 .5 mg, 24.0 pmol), palladium(ll)acetate (5.40 mg, 24.0 pmol) andtris(dibenzylideneacetone)dipalladium(0) (22.0 mg, 24.0 pmol) were added and the mixture was stirred at 1000 for 2 hours. The mixture was filtered, concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol:dichloromethane). The isolated product was taken up in ethanol and stirred at RT. The solid was filtered off under vacuo and dried to give 68 mg (55% yield) of the title compound.LG-MS: m/z = 528.1 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.231 (0.92), 1.440 (3.58), 1.471 (3.62), 1.905(2.66), 1 .934 (4.08), 1.973 (2.48), 2.001 (3.07), 2.034 (1.24), 2.332 (1 .88), 2.336 (0.83),2.371 (0.69), 2.518 (12.61), 2.523 (7.43), 2.539 (0.96), 2.673 (1.97), 2.678 (0.87), 3.458(1.60), 3.468 (1.83), 3.490 (3.16), 3.502 (2.98), 3.523 (1.79), 3.534 (1.38), 6.115 (10.54),7.823 (1 .51), 7.829 (1.79), 7.845 (2.93), 7.852 (3.35), 7.867 (2.29), 7.873 (2.57), 7.934(4.03), 7.948 (4.08), 7.957 (2.98), 7.971 (2.70), 8.130 (3.07), 8.137 (3.26), 8.154 (3.21), 8.161 (3.12), 8.634 (14.72), 8.795 (16.00), 9.351 (7.79), 10.487 (7.06).
 

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