6-Bromoquinazoline

General procedure: A mixture of 8-(4-chlorophenyl)-2-((2, 2, 2- trifluoroethyl)amino)pyrido[4, 3-i/]pyrimi-din-7(d7/)-one (100 mg, 0.28 mmol, 1.0 equiv), 5-bromo-2-methyl-2H-indazole (119 mg, 0.56 mmol, 2.0 equiv.), Cul (5.4 mg, 0.028 mmol, 0.1 equiv.), N1, A2-dimethylcy cl ohexane-l, 2-diamine (8.1 mg, 0.056 mmol, 0.2 equiv.), CS2CO3 (276 mg, 0.847 mmol, 3.0 equiv.) and dioxane (2 mL) was stirred at l00C under N2 atmosphere for l6h. The crude mixture was concentrated under reduced pressure, and the resulting residue was purified by flash column chromatography on silica gel to yield 8-(4- chlorophenyl)-6-(2-methyl-2H-indazol-5-yl)-2-((2, 2, 2- tri fl uoroethyl )am i no)py ri do[-/, 3-6/]pyrimidin-7(6//)-one (Example 123).6-Bromoquinazoline 29a (418 mg, 2 mmol, prepared according to the known method disclosed in 'Science of Synthesis, 2004, 16, 573-749), bis(pinacolato)diboron (609 mg, 7.4 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium (292 mg, 0.40 mmol) and potassium acetate (588 mg, 6.00 mmol) were dissolved successively in 20 mL of dimethyl ether under an argon atmosphere. The reaction solution was heated to 80C, and stirred for 4 hours. The reaction was stopped, and the reaction solution was cooled to room temperature and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by CombiFlash rapid preparation instrument with elution system B to obtain the title product 29b (450 mg), yield: 87.9%. MS m/z (ESI): 257.1 [M+1].The A9-1 (63mg, 0.30mmol) was dissolved in dioxane (5mL), was added bis (pinacolato) borate (91mg, 0.36mmol), KOAc (59mg, 0.60mmol), Pd (dppf) 2Cl2 (25mg, 0.03mmol), purged with nitrogen, 90 stirred for 4 hours, cooled to room temperature, suction filtered through Celite, the filterWas spin dried to give crude black oil (183mg), was used directly in the next step.Example 163 6-{4-[l-{[(3S)-l-(Cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-(trifluoromethyl)- lH-benzimidazol-2-yl] phenyl} quinazoline1 - { [(3 S)- 1 -(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl} -2-[4-(4, 4, 5 , 5-tetramethyl- 1 , 3 , 2- dioxaborolan-2-yl)phenyl]-5-(trifluoromethyl)-lH-benzimidazole (120 mg, 0.167 mmol) was dissolved in 1 , 4-dioxane (1.5 mL) in a 5 mL microwave vial. To this was added 6- bromoquinazoline (34.9 mg, 0.167 mmol), PdCl2(dppf)-CH2Cl2 adduct (6.81 mg, 8.34 muiotaetaomicron), and 2.0 M aqueous potassium carbonate (0.250 mL, 0.501 mmol) with stirring. The vial was purged with nitrogen, sealed and heated at 100 C for six hours. The reaction mixture was allowed to cool and the pH was adjusted to 7 with 1 N HC1. The reaction mixture was extracted with DCM (3 x 50 mL) and the combined extracts were dried over sodium sulfate, filtered and evaporated to dryness. The crude product was dissolved in DMSO (1.5 mL) and purified by preparative reverse phase HPLC. The appropriate fractions were combined, the pH adjusted to 7 with saturated aqueous NaHC03, and extracted with DCM (3 x 25 mL). The combined DCM extracts were dried over sodium sulfate, filtered and evaporated to dryness to afford 29 mg of the titled compound as an off- white solid. (LCMS m/z 542.3, M+H).PREPARATION EXAMPLE 3Preparation of 6-(2-fluoro-4-methyl-5-((2, 2, 2-trifluoroethyl)thio)phenyl)quinazoline (compound No. 31-1 )A mixed solution comprising 0.11 g of

Molecular Weight:209.04
XLogP3:1.7
Hydrogen Bond Acceptor Count:2
Exact Mass:207.96361
Monoisotopic Mass:207.96361
Topological Polar Surface Area:25.8
Heavy Atom Count:11
Complexity:140
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes