反応 #1017492

反応方程式

(2R,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1-trifluoropentan-2-ol

(2S,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1-trifluoropentan-2-ol

4-nitrobenzoyl isothiocyanate

N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride

N-ethyl-N-isopropylpropan-2-amine

4-nitrobenzoyl isothiocyanate

→

title compound

N-((4S,6R)-4-(6-bromo-3-fluoropyridin-2-yl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-yl)-4-nitrobenzamide

溶媒

MeCN

反応条件

後処理

1. 1
   workup.STIRRINGto stir for additional 20 min
2. 2
   温度the reaction mixture was heated to 70° C. for 1 h
3. 3
   その他The reaction mixture was partitioned between water and EtOAc
4. 4
   その他The organic layer was separated
5. 5
   洗浄washed with brine
6. 6
   乾燥dried over sodium sulfate
7. 7
   濃縮The filtrate was concentrated under reduced pressure
8. 8
   その他the crude material was purified by silica gel chromatography (0-60% EtOAc/hexanes)

実験手順

To a solution of (2R,4S)-4-amino-4-(6-bromo-3-fluoropyridin-2-yl)-1,1,1-trifluoropentan-2-ol (7f, 0.183 g, 0.553 mmol) in MeCN (3 mL) was added 4-nitrobenzoyl isothiocyanate (Matrix, 0.150 g, 0.719 mmol). The mixture was stirred at room temperature for 30 min. Additional 4-nitrobenzoyl isothiocyanate (30 mg) was added and the reaction was allowed to stir for additional 20 min. N1-((Ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (Aldrich, 0.170 g, 0.884 mmol) and N-ethyl-N-isopropylpropan-2-amine (0.241 mL, 1.382 mmol) was added and the reaction mixture was heated to 70° C. for 1 h. The reaction mixture was partitioned between water and EtOAc. The organic layer was separated washed with brine, and dried over sodium sulfate. The filtrate was concentrated under reduced pressure and the crude material was purified by silica gel chromatography (0-60% EtOAc/hexanes) to obtain the title compound as an off-white solid. MS m/z=505/507 [M]+/[M+2]+. Calculated: 505.2

出典