2,2-Difluoroacetohydrazide → 7-bromo-1-(difluoromethyl)-8-phenyl-4H-pyrido[2,3-b][1,2,4]triazolo[4,3-d][1,4]oxazine
Reaction equation
[Br:1][C:2]1[C:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:5]2[NH:10][C:9](=S)[CH2:8][O:7][C:6]=2[N:12]=1.[F:19][CH:20]([F:25])[C:21]([NH:23][NH2:24])=O>C1(C)C(C)=CC=CC=1>[Br:1][C:2]1[C:3]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:4][C:5]2[N:10]3[C:21]([CH:20]([F:25])[F:19])=[N:23][N:24]=[C:9]3[CH2:8][O:7][C:6]=2[N:12]=1Participants
4
Procedure
A mixture of 6-bromo-7-phenyl-1H-pyrido[2,3-b][1,4]oxazine-2(3H)-thione (0.21 g, 0.654 mmol) and 2,2-difluoroacetohydrazide (0.14 g, 1.3 mmol) in xylene (6 ml) was heated at 150 degree under microwave for 60 min. The reaction solution was concentrated and the residue was partitioned between ethyl acetate (10 ml) and water (10 ml). The organic phase was separated and the aqueous phase was extracted with ethyl acetate (10 ml). The combined organic phase was concentrated and purified by column (biotage 25 g) eluted with ethyl acetate/cyclohexane (0-60%) to afford product (55 mg). 1H NMR (500 MHz, CDCl3) 8.09 (s, 1H), 7.4-7.55 (m, 5H), 7.06 (t, 1H), 5.66 (s, 2H).
Workup
- temperaturewas heated at 150 degree under microwave for 60 min
- concentrationThe reaction solution was concentrated
- customthe residue was partitioned between ethyl acetate (10 ml) and water (10 ml)
- customThe organic phase was separated
- extractionthe aqueous phase was extracted with ethyl acetate (10 ml)
- concentrationThe combined organic phase was concentrated
- custompurified by column (biotage 25 g)
- washeluted with ethyl acetate/cyclohexane (0-60%)
Sources & evidence
- ORD record
- ord-75fa7c5eccc24c41b28851281d2c880a
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221838B2
Reaction notes
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