7-AMINO-3,4-DIHYDRO-2H-ISOQUINOLIN-1-ONE

4C (700 mg, 3.6 mmol) was stirred in MeOH (25 mL) with 10percent Pd/C(cat.) under H2 (60 psi) for 1 h. The reaction was filtered through Celite and concentrated in vacuo to give 4D (500 mg, 86percent yield). Intermediate 1; [00191] Intermediate 1C (700mg, 3.6 mmol) was stirred in MeOH (25ml) with 10percent Pd/C (cat.) under Hspecific examples include: 3, 4-Dihydro-5-nitro-1(2H)-isoquinolinone, 3, 4-Dihydro-7-nitro-1(2H)-isoquinolinone, 5-Amino-3, 4-dihydro-1(2H)-isoquinolinone, 7-Amino-3, 4-dihydroisoquinolin-1(2H)-one (1.20 g, 7.4 mmol), 2-bromo-1-cyclopropylethan-1-one (1.32 g, 8.1 mmol), DIEA (1.91 g, 14.8 mmol), Add to toluene (20 mL), and stir the reaction at 95 C for 6 hours.Concentrated and purified by silica gel column chromatography (PE: EA = 1: 1) was purified to give the title compound (1.50 g of, 83.0% yield).To a stirred solution of 21 3-(2, 6-dichlorophenyl)-7-methylsulfanyl-2H-pyrimido[5, 4-e][1, 3]oxazin-4-one (200 mg, 0.59 mmol, 1.0 eq) in 24 toluene (15 mL) was added 25 m-CPBA (203 mg, 1.18 mmol, 2.0 eq) and allowed to stir at rt for 30 min. 227 7-Amino-3, 4-dihydro-2H-isoquinolin-1-one (100 mg, 0.590 mmol, 1.0 eq) and 27 DIPEA (300 mg, 2.36 mmol, 4.0 eq) were added and allowed to stir at rt for 2 h. Progress of reaction was monitored by LCMS. After completion of reaction solvent was removed under reduced pressure, residue was diluted with water (20 mL) and extracted with CH2Cl2 (50 mL×3). Combined organic layer was washed with water (20 mL×3), dried over anhydrous Na2SO4 and concentrated under reduced pressure. Crude residue was purified by reversed phase chromatography to obtain 228 3-(2, 6-dichlorophenyl)-7-((1-oxo-1, 2, 3, 4-tetrahydroisoquinolin-7-yl)amino)-2, 3-dihydro-4H-pyrimido[5, 4-e][1, 3]oxazin-4-one (13 mg, 4.8%). (0360) LCMS: 456 [M+1]+ (0361) 1H NMR (400 MHz, DMSO-d6): delta 10.51 (br s, 1H), 8.86 (s, 1H), 8.22 (br s, 1H), 7.95 (br s, 1H), 7.83 (dd, J=1.97, 8.11 Hz, 1H), 7.59-7.71 (m, 2H), 7.48-7.56 (m, 1H), 7.28 (d, J=8.33 Hz, 1H), 5.75 (s, 2H), 3.35 (d, J=3.95 Hz, 2H), 2.86 (t, J=6.58 Hz, 2H).

Molecular Weight:162.19
XLogP3:0.6
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Exact Mass:162.079312947
Monoisotopic Mass:162.079312947
Topological Polar Surface Area:55.1
Heavy Atom Count:12
Complexity:193
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes