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

HRID 528575Notes

Reaction equation

HRID 528575 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][CH2:19][CH:18]([CH3:21])[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+]>CN(C=O)C>[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[CH2:19][CH:18]([CH3:21])[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

5

Reactant 3

HCID 10796Cesium carbonateHCID 5210162-Fluoro-5-(trifluoromethyl)benzonitrileHCID 89761908N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897619014-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (INTERMEDIATE AE) (1.3 g, 3.02 mmol) and 2-fluoro-5-(trifluoromethyl)benzonitrile in DMF (20 ml) was added Cs2CO3 (1.8 g, 5.56 mmol) at 25° C. and the reaction mixture was stirred at 90° C. for 2 h. The reaction mixture was poured into ice water and the resulting mixture was extracted with EtOAc. The layers were separated and the organic layer was washed with water, dried over sodium sulfate and concentrated. The resulting residue was purified by silica gel column chromatography using a gradient of 0-50% EtOAc in hexanes to afford 1.2 g of 4-(2-cyano-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-2-methyl-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide as off white solid in 75% yield. 1H-NMR (400 MHz, DMSO): 6.44 (s, 1H), 8.12 (d, J=8.8 Hz, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.75-7.77 (m, 1H), 7.43-7.44 (m, 1H), 7.19-7.25 (m, 4H), 6.78-6.86 (m, 3H), 5.02 (s, 2H), 4.37-4.42 (m, 1H), 3.89-3.92 (m, 1H), 3.70 (s, 3H), 3.55-3.61 (m, 1H), 1.35 (s, 3H); m/z (ESI, positive ion) 601.0 (M+H)

Workup

  1. extractionthe resulting mixture was extracted with EtOAc
  2. customThe layers were separated
  3. washthe organic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0fe7147ebfeb4427a228e793f606363b
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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