4-Bromoanisole → HCID 57978150, compound

HRID 1866063Notes

Reaction equation

HRID 1866063 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1.[Br:15][C:16]1[CH:17]=[C:18](/[C:22](/[C:30]2[C:31]([C:36]#[N:37])=[N:32][CH:33]=[CH:34][CH:35]=2)=[N:23]\S(C(C)(C)C)=O)[CH:19]=[CH:20][CH:21]=1>C1COCC1>[Br:15][C:16]1[CH:17]=[C:18]([C:22]2([C:7]3[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=3)[C:30]3[C:31](=[N:32][CH:33]=[CH:34][CH:35]=3)[C:36]([NH2:37])=[N:23]2)[CH:19]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 77304-BromoanisoleHCID 57978154HCID 57978154, compoundHCID 178418339Butyllithium

Product 1

HCID 57978150HCID 57978150, compoundYield 14%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Butyllithium (2.5 M in hexanes, 0.947 mL) was added dropwise to a solution of 4-bromoanisole (483 mg, 2.58 mmol) in anhydrous THF at −78° C. under an atmosphere of argon. The mixture was stirred at that temperature for 30 min and then a solution of N-[(1E)-(3-bromophenyl)(2-cyanopyridin-3 -yl)methylene]-2-methypropane-2-sulfinamide (Example 2, 840 mg, 2.15 mmol) in THF (10 mL) was added dropwise. Stirring was continued for 3 h at −78° C., and then for 1 h at −25° C. The reaction was quenched by the addition of water, the mixture was diluted with ethyl acetate and washed with water, dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (20 mL) and to this was added 2 M hydrochloric acid in diethyl ether (2.5 mL). The mixture was stirred at room temperature for 22 h and then concentrated. The residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate, dried over sodium sulfate and concentrated. Purification by column chromatography using a gradient of increasing concentration of ethyl acetate in dichloromethane (0-50%) and finally 5% of 2 M ammonia in methanol in ethyl acetate-dichloromethane (45:50) gave 115 mg (14% yield) of the title compound. 1H NMR (CDCl3) δ 8.62 (dd, 1H), 7.88 (dd, 1H), 7.46 (t, 1H), 7.37 (m, 2H), 7.26 (m, 1H), 7.21 (m, 2H), 7.14 (t, 1H), 6.81 (m, 2H), 3.78 (s, 3H); MS (ESI) m/z 394, 396 [M+1]+.

Workup

  1. stirringStirring
  2. waitwas continued for 3 h at −78° C.
  3. waitfor 1 h at −25° C
  4. customThe reaction was quenched by the addition of water
  5. additionthe mixture was diluted with ethyl acetate
  6. washwashed with water
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. dissolutionThe residue was dissolved in methanol (20 mL)
  10. additionto this was added 2 M hydrochloric acid in diethyl ether (2.5 mL)
  11. stirringThe mixture was stirred at room temperature for 22 h
  12. concentrationconcentrated
  13. customThe residue was partitioned between dichloromethane and saturated aqueous sodium hydrogen carbonate
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated
  16. customPurification by column chromatography
  17. temperatureof increasing concentration of ethyl acetate in dichloromethane (0-50%) and finally 5% of 2 M ammonia in methanol in ethyl acetate-dichloromethane (45:50)

Sources & evidence

ORD record
ord-d64e0b571eee46d197c16ecf887e3385
Source dataset
uspto-grants-2009_12
Patent number
US07629356B2

Reaction notes

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