Water → 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528578Notes

Reaction equation

HRID 528578 reaction equation
[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][N:8]([C:23]2[S:24][CH:25]=[CH:26][N:27]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH:19]([CH3:21])[CH2:18][O:17][C:16]=3[CH:22]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.F[C:31]1[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:32]=1[C:33]#[N:34].C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C)C=O>[C:33]([C:32]1[CH:35]=[C:36]([C:39]([F:40])([F:41])[F:42])[CH:37]=[CH:38][C:31]=1[N:20]1[CH:19]([CH3:21])[CH2:18][O:17][C:16]2[CH:22]=[C:12]([S:9]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:29][CH:28]=3)[C:23]3[S:24][CH:25]=[CH:26][N:27]=3)(=[O:11])=[O:10])[CH:13]=[CH:14][C:15]1=2)#[N:34]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 5210162-Fluoro-5-(trifluoromethyl)benzonitrileHCID 89761641HCID 89761641, compound

Product 1

HCID 897616224-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 56%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (900 mg, 2.08 mmol) and 2-fluoro-5-(trifluoromethyl)benzonitrile (546 mg, 2.49 mmol, Alfa Aesar) in dimethylformamide (20 mL) was added Cs2CO3 (1.35 g, 4.16 mmol, GLR) and the mixture was heated at 90° C. for 3 h. The reaction mixture was cooled to room temperature and water (200 mL) was added. The aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was further purified by column chromatography (silica gel 100-200 mesh and 0-3% methanol in dichloromethane) to obtain 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-3-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (700 mg, 56%) as off white solid. 1H NMR (400 MHz, DMSO) δ 8.50 (s, 1H), 8.17 (d, J=8.7 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.44 (d, J=3.6 Hz, 1H), 7.35 (d, J=3.6 Hz, 1H), 7.30-7.12 (m, 4H), 6.85 (d, J=8.7 Hz, 2H), 6.55 (d, J=8.6 Hz, 1H), 5.02 (s, 2H), 4.23 (m, 2H), 4.19-4.06 (m, 1H), 3.70 (s, 3H), 1.21-1.09 (m, 3H); MS (ESI, positive ion) m/z 601.1 (M+H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted with ethyl acetate (2×100 mL)
  3. dry with materialThe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customto obtain the crude material which
  7. customwas further purified by column chromatography (silica gel 100-200 mesh and 0-3% methanol in dichloromethane)

Sources & evidence

ORD record
ord-efb73131d98d433ea76fde024dc6bba2
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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