6-CHLOROQUINAZOLIN-4-AMINE

synthesis of 4-amino-6-chloro-quinazolineA solution of 2-amino-5-chlorobenzonitrile (1.07 g, 7.0 mmol) in formamide (20 ml) was heated at 180 Example 4 - synthesis of 4-amino-6-chloro-quinazoline; A solution of 2-amino-5-chlorobenzonitrile (1.07 g, 7.0 mmol) in formamide (20 ml) was heated at 180 To a solution of 102 mg (282 pmol) 6-bromo-8-methyl-2, 3, 5, 6-tetrahydro-2H- spiro[im idazo[1 , 5-a]pyridine-3, 4-thiopyran]-1 , 5-dione 1 , 1 -dioxide (prepared according toexample 198a) and 55.8mg (311 pmol) To a solution of 101 mg (307 pmol) 6-bromo-8-methyl-2, 3, 5, 6-tetrahydro-2H- spiro[im idazo[1 , 5-a]pyridine-3, 4-thiopyran]-1 , 5-dione (prepared according to 96a)and 60.6mg (337 pmol) To a solution of (trans)-6-bromo-4-hydroxy-8-methyl-4-(pentafluoroethyl)-2H-spiro[cyclohexane-1 , 3-imidazo[1 , 5-a]pyridine]-1 , 5-dione (prepared according to example 191c, 100 mg, 225 pmol) and To a solution of 6-bromo-8-methyl-2H-spiro[imidazo[1 , 5-a]pyridine-3, 3-thietane]-1 , 5-dione1, 1-dioxide (prepared according to example 179a, 120 mg, 360 pmol) and 6- chloroquinazolin-4-amine (GAS 19808-35-6, 71.2 mg, 396 pmol) in 1, 4-dioxane (12 mL) was added cesium carbonate (352 mg, 1 .08 mmol) and the mixture was degassed and purged with argon several times. 4, 5-Bis(diphenylphosphino)-9, 9-dimethylxanthene (22.3 mg, 38.5 pmol), 2-(dicyclohexyl-phosphino)-2, 4, 6-triisopropylbiphenyl (18.4 mg, 38.5 pmol), palladium(ll)acetate (8.65 mg, 38.5 pmol) and tris(dibenzylideneacetone)dipalladium(0) (35.3 mg, 38.5 pmol) were added and the mixture was stirred at 100cC for 2 hours. The mixture was filtered and concentrated and the residue purified by flash chromatography (Biotage SNAP cartridge silica 25 g, ethanol: dichloromethane). The isolated product wastaken up in ethanol and stirred at RT. The solid was filtered off under vacuo, taken up in dichloromethane again and stirred at RT. The solid was filtered off under vacuo and dried to give 47.0 mg (29% yield) of the title compound.LG-MS: m/z = 432.3 [M÷H].1H-NMR (400 MHz, DMSO-d6) 6 [ppm]= 1.231 (0.57), 2.318 (0.47), 2.480 (16.00), 2.518(4.73), 2.522 (3.70), 2.659 (0.41), 3.205 (0.90), 3.565 (0.43), 4.406 (2.33), 4.446 (2.37), 5.574 (2.54), 5.614 (2.37), 7.878 (1.21), 7.901 (2.35), 7.941 (2.11), 7.946 (1.96), 7.963(1.06), 7.968 (1.02), 8.557 (2.27), 8.562 (2.25), 8.626 (4.32), 8.810 (4.81), 9.585 (2.27), 10.692 (2.50).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 To a solution of 100 mg (353 pmol) 6-bromo-8-methyl-2H-spiro[cyclobutane-1 3- imidazo[1, 5-a]pyridine]-1, 5-dione (prepared according to example 146a) and 69.8 mg (389 pmol) To a solution of 100 mg (369 pmol) 6-bromo-3, 3, 8-trimethyl-2, 3-dihydroimidazo[1, 5- a]pyridine-1, 5-dione (prepared according to POT Int. AppI. (2015), WO 2015200481) and 72.9mg (406 pmol)

Molecular Weight:179.60
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:179.0250249
Monoisotopic Mass:179.0250249
Topological Polar Surface Area:51.8
Heavy Atom Count:12
Complexity:164
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes