Benzonitrile, 4-bromo- → HCID 178461986, compound

HRID 1983593Notes

Reaction equation

HRID 1983593 reaction equation
[CH3:1][CH:2]1[S:6][C:5]([NH:7][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:19])([F:18])[F:17])[CH3:9])=[N:4][C:3]1=[O:20].Br[C:22]1[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(C)C=CC=CC=1>[CH3:1][C:2]1([C:22]2[CH:29]=[CH:28][C:25]([C:26]#[N:27])=[CH:24][CH:23]=2)[S:6][C:5]([NH:7][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:16]([F:18])([F:17])[F:19])[CH3:9])=[N:4][C:3]1=[O:20]

Participants

6

Reactant 3

HCID 12162Benzonitrile, 4-bromo-HCID 178418261HCID 178418261, compoundHCID 178435108HCID 178435108, compound

Product 1

HCID 178461986HCID 178461986, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
95 °C

Procedure

To a mixture of 5-methyl-2-((S)-1-(2-(trifluoromethyl)phenyl)ethylamino)thiazol-4(5H)-one (0.2000 g, 0.662 mmol), 4-bromobenzonitrile (0.301 g, 1.65 mmol), Pd2(dba)3 (0.0303 g, 0.0331 mmol), (S)-2-(diphenylphosphino)-1-(2-(diphenylphosphino)-naphthalen-1-yl)naphthalene (0.0618 g, 0.0992 mmol), and LiN(TMS)2 (0.277 g, 1.65 mmol) was added toluene (8 mL) in a glove box. The mixture was gradually heated to 95° C. and stirred overnight. The reaction was quenched with NH4Cl (5 mL), and the reaction mixture was extracted three times with ethylacetate (30 mL). The organic phase was dried over Na2SO4, filtered and concentrated under vacuum. The crude was purified by chromatography on silica gel using 22% ethylacetate/hexane to remove the impurities and then 36% ethylacetate/hexane to obtain the product as a light yellow solid. MS (ESI, pos. ion) m/z: 404 (M+1), 402 (M-1). 1H NMR (CDCl3, 400 MHz): δ1.71-1.78 (m, 3H), 1.98-2.09 (m, 3H), 5.05 (q, J=8 Hz, 1H), 7.39-7.68 (m, 7H), 7.84 (d, J=8 Hz, 1H), 10.97 (s, 1H). % de (by 1H NMR): 48%.

Workup

  1. customThe reaction was quenched with NH4Cl (5 mL)
  2. extractionthe reaction mixture was extracted three times with ethylacetate (30 mL)
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude was purified by chromatography on silica gel using 22% ethylacetate/hexane
  7. customto remove the impurities

Sources & evidence

ORD record
ord-438920d83bbb4ce6b5680b84ed52f181
Source dataset
uspto-grants-2009_06
Patent number
US07541474B2

Reaction notes

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