Cesium carbonate → HCID 89761206, compound

HRID 528629Notes

Reaction equation

HRID 528629 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[C:12]2[S:13][CH:14]=[CH:15][N:16]=2)(=[O:10])=[O:9])=[CH:4][C:3]=1[OH:26].C(=O)([O-])[O-].[Cs+].[Cs+].Br[C:34]1[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][C:35]=1[O:42][CH3:43]>[Cu]I>[C:38]([C:37]1[CH:40]=[CH:41][C:34]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)[C:12]3[S:13][CH:14]=[CH:15][N:16]=3)(=[O:9])=[O:10])=[CH:4][C:3]=2[OH:26])=[C:35]([O:42][CH3:43])[CH:36]=1)#[N:39]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 225911814-Bromo-3-methoxybenzonitrileHCID 89761412HCID 89761412, compound

Product 1

HCID 89761206HCID 89761206, compound

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
110 °C

Procedure

A microwave vial was charged with 4-amino-3-hydroxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)benzenesulfonamide (0.185 g, 0.472 mmol) (INTERMEDIate AD), cesium carbonate (0.384 g, 1.179 mmol), 4-bromo-3-methoxybenzonitrile (0.05 g, 0.236 mmol, Combi Blocks) and copper(i) iodide (0.011 g, 0.059 mmol). The vial was sealed and flushed with argon, and wrapped with aluminum foil to exclude light, then DMF (0.5 mL) was added. The reaction was heated to 110° C. for 2 hr to give intermediate 4-((4-cyano-2-methoxyphenyl)amino)-3-hydroxy-N-(4-methoxybenzyl)-N-(thiazol-2-yl)benzenesulfonamide. The reaction was cooled to rt, and chloroacetic acid chloride was added dropwise (0.038 ml, 0.472 mmol). The solution was maintained at rt for 30 min. At this time, 10 mL of saturated ammonium chloride solution was added, and the mixture was further diluted with 10 mL of DCM. The layers were separated and the aqueous layer was extracted with DCM (2×10 mL). To the aqueous layer was added n-(2-hydroxyethyl)ethylenediaminetriacetic acid, trisodium salt hydrate (500 mg, Sigma Aldrich) to aqueous to decomplex Cu from the product. The resulting aqueous solution was extracted with DCM (1×10 mL). The combined organics were dried (Na2SO4), filtered, and concentrated in vacuo. The crude product, 4-(4-cyano-2-methoxyphenyl)-N-(4-methoxybenzyl)-3-oxo-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (0.133 g, 0.236 mmol, 100% yield) was taken forward without further purification.

Workup

  1. customThe vial was sealed
  2. customflushed with argon
  3. additionDMF (0.5 mL) was added

Sources & evidence

ORD record
ord-ed6f2ddb7f7a4c11a342116b2c0e01ee
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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