Cesium carbonate → 4-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

HRID 528648Notes

Reaction equation

HRID 528648 reaction equation
[CH3:1][O:2][C:3]1[CH:31]=[CH:30][C:6]([CH2:7][N:8]([C:25]2[S:26][CH:27]=[CH:28][N:29]=2)[S:9]([C:12]2[CH:13]=[CH:14][C:15]3[NH:20][CH2:19][CH:18]([CH2:21][O:22][CH3:23])[O:17][C:16]=3[CH:24]=2)(=[O:11])=[O:10])=[CH:5][CH:4]=1.[Cl:32][C:33]1[CH:34]=[CH:35][C:36](F)=[C:37]([CH:40]=1)[C:38]#[N:39].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[Cl:32][C:33]1[CH:34]=[CH:35][C:36]([N:20]2[CH2:19][CH:18]([CH2:21][O:22][CH3:23])[O:17][C:16]3[CH:24]=[C:12]([S:9]([N:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:31][CH:30]=4)[C:25]4[S:26][CH:27]=[CH:28][N:29]=4)(=[O:11])=[O:10])[CH:13]=[CH:14][C:15]2=3)=[C:37]([C:38]#[N:39])[CH:40]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 936535-Chloro-2-fluorobenzonitrileHCID 89761839N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide

Product 1

HCID 897619324-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamideYield 87.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (150 mg, 0.324 mmol) and 5-chloro-2-fluorobenzonitrile (50.55 mg, 0.324 mmol, Aldrich) in DMF (5.0 mL) was added Cs2CO3 (210 mg, 7.95 mmol) and the reaction mixture was heated at 80° C. for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane) to obtain 4-(4-chloro-2-cyanophenyl)-N-(4-methoxybenzyl)-2-(methoxymethyl)-N-(thiazol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazine-7-sulfonamide (170 mg, 87.6%) as an off white solid. m/z (ESI) 596.8 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (2×50 mL)
  2. dry with materialThe combined organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the crude material which
  6. customwas purified by column chromatography (silica gel 100-200 mesh and 0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-55051fc73f1140019de144b22dc24e4e
Source dataset
uspto-grants-2016_05
Patent number
US09346798B2

Reaction notes

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