4-Bromobenzenesulfonamide → (cis) 4-(4-(4-Chloroindolin-1-yl)-2-(2,6-dimethylmorpholine-4-carbonyl) thiazol-5-yl)benzenesulfonamide

HRID 1051884Notes

Reaction equation

HRID 1051884 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][N:6]2[C:11]1[N:12]=[C:13]([C:16]([N:18]2[CH2:23][C@@H:22]([CH3:24])[O:21][C@@H:20]([CH3:25])[CH2:19]2)=[O:17])[S:14][CH:15]=1.BrC1N=C(C(N2C[C@@H](C)O[C@@H](C)C2)=O)SC=1.Br[C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH2:52])(=[O:51])=[O:50])=[CH:45][CH:44]=1.C([O-])(=O)C.[K+]>CC(N(C)C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH2:5][N:6]2[C:11]1[N:12]=[C:13]([C:16]([N:18]2[CH2:23][C@H:22]([CH3:24])[O:21][C@H:20]([CH3:25])[CH2:19]2)=[O:17])[S:14][C:15]=1[C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH2:52])(=[O:51])=[O:50])=[CH:45][CH:44]=1

Participants

7

Reactant 4

HCID 696964-BromobenzenesulfonamideHCID 517044Potassium AcetateHCID 118444685(cis) (4-(4-Chloroindolin-1-yl)thiazol-2-yl) (2,6-dimethylmorpholino) methanoneHCID 118444688(cis) (4-Bromothiazol-2-yl) (2,6-dimethylmorpholino)methanone

Product 1

HCID 71735883(cis) 4-(4-(4-Chloroindolin-1-yl)-2-(2,6-dimethylmorpholine-4-carbonyl) thiazol-5-yl)benzenesulfonamideYield 26%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (cis) (4-(4-chloroindolin-1-yl)thiazol-2-yl) (2,6-dimethylmorpholino) methanone (Step-2, of compound 45, 0.6 g, 1.59 mmol in dimethyl acetamide (10 ml) were added 4-bromobenzenesulfonamide (0.41 g, 1.75 mmol) and potassium acetate (0.31 g, 3.18 mmol) at 25° C. in a tube, the nitrogen gas was bubbled through reaction mixture for 15 minutes. To this was added palladium (II) acetate (0.03 g, 0.16 mmol) under nitrogen and the tube was sealed. The reaction mixture was heated at 150° C. for 18 hr under stirring. The progress of reaction was monitored by TLC. The reaction mixture was cooled to 25° C. and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (30 ml), reaction mixture was washed with water (2×10 ml), dried over sodium sulphate and concentrated under reduced pressure to obtain a crude product; which was purified by preparative HPLC to obtain the title compound (0.22 g, 26.0%). MS: m/z 533 (M+1).

Workup

  1. customthe nitrogen gas was bubbled through reaction mixture for 15 minutes
  2. customthe tube was sealed
  3. customThe progress of reaction
  4. temperatureThe reaction mixture was cooled to 25° C.
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate (30 ml)
  7. customreaction mixture
  8. washwas washed with water (2×10 ml)
  9. dry with materialdried over sodium sulphate
  10. concentrationconcentrated under reduced pressure
  11. customto obtain a crude product
  12. customwhich was purified by preparative HPLC

Sources & evidence

ORD record
ord-fe5f68ab3d744a6a902fedfd003cacd8
Source dataset
uspto-grants-2016_07
Patent number
US09388196B2

Reaction notes

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