6-(TRIFLUOROMETHYL)URACIL

To a stirred solution of ethyl 4.4, 44rifluoro—3-oxobutanoate 101 (3 g. 1 &30 nim-ol) in ethin.iol (30 mL) under argon atmosphere were added urea 102- (978 mg, 16.30 mmol) and freshly prepared sodium ethoxide (750 mg of Na in 30 mL of EtOH) at Pt; the mixture was heated to 90 °C and stirred for 24 h. The reaction was monitored by TIE; after completion of the reaction, the volati Ic-s were removed in vacua, diluted with water (25 mL), acidified with 1 N SC1 UO niL) and extracted with EtOAc (2 x 40 niL). The comb med organic extracts were dried over sodium sulfate, filtered and concentrated in vacua to afford compound 103 (650 mg, 22percent) as a white solid. TL-C: 5percent CH3OR CK2CI2 (1?, : 0.3); ‘H-NMR (DMSO-percent, 500 MHz): 6 1107 (s. 114), i1.54(s. iS). 6.07 (s, 1HTo a stirred solution of ethyl 4.4, 44rifluoro-3-oxobutanoate 101 (3 g. 1 &30 nim-ol) in ethin.iol (30 mL) under argon atmosphere were added urea 102- (978 mg, 16.30 mmol) and freshly prepared sodium ethoxide (750 mg of Na in 30 mL of EtOH) at Pt; the mixture was heated to 90 C and stirred for 24 h. The reaction was monitored by TIE; after completion of the reaction, the volati Ic-s were removed in vacua, diluted with water (25 mL), acidified with 1 N SC1 UO niL) and extracted with EtOAc (2 x 40 niL). The comb med organic extracts were dried over sodium sulfate, filtered and concentrated in vacua to afford compound 103 (650 mg, 22%) as a white solid. TL-C: 5% CH3OR CK2CI2 (1?, : 0.3); 'H-NMR (DMSO-%, 500 MHz): 6 1107 (s. 114), i1.54(s. iS). 6.07 (s, 1H(Step 1) Methyl (2S)-2-(tert-butoxycarbonylamino)-3-[4-[2, 4-dioxo-6-(trifluoromethyl)-1H-pyrimidin-3-yl]phenyl]propanoate (0203) (0204) 6-(Trifluoromethyl)-1H-pyrimidine-2, 4-dione (1.00 g, 5.60 mmol) and [4-[(2S)-2-(tert-butoxycarbonylamino)-3-methoxy-3-oxo-propyl]phenyl]boronic acid (2.00 g, 6.20 mmol) were dissolved in methylene chloride (10 ml), copper(II) acetate (3.01 g, 15.1 mmol) and triethylamine (2.40 g, 2.40 mmol) were added thereto, and the resulting mixture was stirred at room temperature for 12 hours. The reaction liquid was filtered and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate=5:1 to 1:1) to obtain the title compound (750 mg, 29%) as a yellow crystal. (0205) 1H NMR (CD3OD, 400 MHz): delta 7.26 (d, J=8.0 Hz, 2H), 7.22 (d, J=8.0 Hz, 2H), 6.27 (s, 1H), 4.45-4.41 (m, 1H), 3.73 (s, 3H), 3.21-3.16 (m, 1H), 3.07-3.02 (m, 1H), 1.43 (s, 9H)

Molecular Weight:180.08
XLogP3:-0.3
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Exact Mass:180.01466183
Monoisotopic Mass:180.01466183
Topological Polar Surface Area:58.2
Heavy Atom Count:12
Complexity:268
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes