CHROMAN-4-YLAMINE

Chroman-4-amine :; Chroman-4-one (3 g, 20.1 mmol), titanium(IV) isopropoxide (12.0 niL, 40.2 mmol) and2 M solution of ammonia in ethanol (60.6 mL, 121.2 mmol) were stirred at room temperature for 6 h. The reaction was cooled to 0 °C and sodium borohydride was added portionwise during 10 min. (1.14 g, 30.2 mmol); the resultant mixture was stirred at rt for an additional 3 h. The reaction was quenched by pouring it into ammonium hydroxide (2 M, 60 mL), the precipitate that formed was filtered off and washed with ethyl acetate (15 mL x 3). The organic layer was separated and the remaining aqueous layer was extracted with ethyl acetate (15 mL x 2). The combined organic extracts were washed with 1 M HCl (25 mL). The acidic aqueous extracts were washed with ethyl acetate (50 mL), then treated with aqueous sodium hydroxide (2 M) to pH 10-12, and extracted with ethyl acetate (40 mL x 3). The combined organic extracts were washed with brine, dried (NaPreparation 65 [0380] Preparation II-General procedure: At ambient temperature, 210 mL (210 mmoles, 2 eq.) of a 1M solution of BH3.THF in THF are added in the course of 10 minutes to a solution of 27 g (105 mmoles, 1 eq.) of the mixture of oximes 62 in 114 mL of THF. The solution obtained is heated at 70 C. for 212 h. After HPLC monitoring, the mixture is returned to ambient temperature. A 2N solution of HCl in ether (2 eq.) is added carefully to the mixture. The mixture is heated for 1 h at 40 C. Filtration of the solid yields 11.8 g of the hydrochloride of intermediate 48.2. 0.250 g (1.130 mmol) of 3-(methylsulfanyl)-6-(trifluoromethyl)-1, 2, 4-triazine-5-amine and 0.337 g (2.260 mmol) of General procedure: To a stirred solution of arylamine and salicylaldehyde(1 eq) in dry DCE (10 v) was added tri acetoxyborohydride (2eq) followed by acetic acid (1 eq) at 0C and the reaction wasstirred at RT for 4h. After completion the reaction mixturewas poured into ice cold water, basified by using aq. Na2CO3solution (pH=8) and extracted with chloroform, washed theextract with water, brine solution dried the extract overanhy.Na2SO4 and concentrated to get the crude product.Crude product was purified by column chromatography.R)-2-(9-(pyridin-2-yl)-6-oxaspiro[4.5]decan-9-yl)acetaldehyde 5a (20 mg, 0.08 mmol, prepared by a method disclosed in the patent application ") and 1-[2-(3, 4-Dihydro-2H-chromen-4-ylamino)-4-methylpyrimidin-5-yl]ethanone (ex.:1.83) (0288) 0.22 g (1.21 mmol) of 1-[4-methyl-2-(methylsulfanyl)pyrimidin-5-yl]ethanone is initially charged in 7 mL of dichloromethane and cooled down to about 0-5 C., then 0.428 g (1.81 mmol) of meta-chloroperbenzoic acid (73%) is added while stirring. The mixture is then stirred for 2 hours and allowed to come to room temperature (about 20 C.) within that period. Subsequently, 0.252 g (1.69 mmol) of

Molecular Weight:149.19
XLogP3:0.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:149.084063974
Monoisotopic Mass:149.084063974
Topological Polar Surface Area:35.2
Heavy Atom Count:11
Complexity:138
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes