2-(AMINOMETHYL)-4-BROMOANILINE

In a 500 ml three-necked flask was added 5.9 grams (molecular weight 196, 0.030 mol) of 2-amino-5-bromobenzonitrile, followed by addition of 45 ml of anhydrous tetrahydrofuran, stirred and cooled to 0 ° C. 40 ml of borane tetrahydrofuran (concentration 1M) was slowly added to the three bottles at 0 ° C under nitrogen protection and with stirring. Stir at room temperature for three days. Cold to 0 ° C, add 20 ml of absolute ethanol, Drink dry 1200 ml of HCl gas. Then concentrated, cooled to 25 ° C, Add 30 ml of isopropyl ether to precipitate the product. The solid product was then added to 50 ml of aqueous ammonia under cooling and under nitrogen, stirred, extracted with ethyl acetate, The solvent was evaporated to give a solid product which was dried to give 5.4 g, molecular weight 200, yield 89.6percent.Preparation 24: 6-(4, 4, 5, 5-tetramethyl-1 , 3, 2-dioxaborolan-2-yl)-3, 4- dihydroquinazolin-2(1 H)-one; Step 1 : 2-(aminomethyl)-4-bromoaniline; A solution of borane dimethyl sulfide complex (10 M, 10.2 ml) was added dropwise to a suspension of 2-amino-5-bromobenzonitrile (10 g, 0.102 mol) in tetrahydrofuran (400 ml_) at 0 10048] To accomplish the synthesis of the desired compounds 6a-f, synthesis of the key intermediate (10) was required, which in turn was envision from the l3uchwald- Hartwig coupling reaction of 6-bromo-3, 4-dihydroquinazo- lin-2(1H)-one (9) (H. Venkatesan, F. M. Hocutt, T. K. Jones, M. H. Rabinowitz, I Org. Chem., 75, 3488 (2010)—incor- porated herein by reference in its entirety) with tert-butyl piperazine-1 -carboxylate. Thus the synthesis of compound (9) was commenced with the reduction of bromobenzonitrile with borane to afford diamine (8), which was reacted with triphosgene to get the desired bromide (9) in 23percent overall yield from (7). However, the l3uchwald-Hartwig coupling of bromides 9 with tert-butyl piperazine- 1 -carboxylate, under different reaction conditions (PdCl2dppf, KOAc, DMF, 80° C.; Pd(PPh3)4, toluene, ethanol, Na2CO3, reflux) were not successful; the desired 10 was not observed in any case (scheme 1).

Molecular Weight:201.06
XLogP3:1.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:199.99491
Monoisotopic Mass:199.99491
Topological Polar Surface Area:52
Heavy Atom Count:10
Complexity:108
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes