Hydrochloric Acid → 1-(2-Bromopyridin-4-yl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine

HRID 1662191Notes

Reaction equation

HRID 1662191 reaction equation
C([Li])CCC.Br[C:7]1[N:12]=[C:11]([CH3:13])[C:10]([O:14][CH3:15])=[C:9]([CH3:16])[CH:8]=1.[Br:17][C:18]1[CH:23]=[C:22](/[C:24](/[C:32]2[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=2[C:39]#[N:40])=[N:25]\S(C(C)(C)C)=O)[CH:21]=[CH:20][N:19]=1.Cl.C(OCC)C>C1COCC1.CO>[Br:17][C:18]1[CH:23]=[C:22]([C:24]2([C:7]3[CH:8]=[C:9]([CH3:16])[C:10]([O:14][CH3:15])=[C:11]([CH3:13])[N:12]=3)[C:32]3[C:33](=[C:34]([F:38])[CH:35]=[CH:36][CH:37]=3)[C:39]([NH2:40])=[N:25]2)[CH:21]=[CH:20][N:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 3283Diethyl EtherHCID 58579482(NE)-N-[(2-bromo-4-pyridinyl)-(2-cyano-3-fluorophenyl)methylidene]-2-methylpropane-2-sulfinamideHCID 593275316-Bromo-3-methoxy-2,4-dimethylpyridineHCID 178418339Butyllithium

Product 1

HCID 585794841-(2-Bromopyridin-4-yl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amineYield 103%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (0.229 mL, 0.57 mmol) was added to 6-bromo-3-methoxy-2,4-dimethylpyridine (124 mg, 0.57 mmol) in THF (7 mL) at −78° C. under nitrogen atmosphere. The reaction was stirred for 30 min before (E)-N-((2-bromopyridin-4-yl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (180 mg, 0.44 mmol) in THF (2 mL) was added. The reaction was kept at −78° C. for 1 hour and then allowed to reach room temp. Methanol (5 mL) was added followed by hydrochloric acid in diethylether (1.323 mL, 1.32 mmol) and the reaction mixture was stirred 1 hour at room temperature. NaHCO3(sat) was added and the mixture was extracted with EtOAc (×2). The combined organic phases were dried and concentrated to give the title compound (200 mg, 97%), which was used without further purification. MS (ES+) m/z 441, 443 [M+1]+.

Workup

  1. additionwas added
  2. customto reach room temp
  3. extractionthe mixture was extracted with EtOAc (×2)
  4. customThe combined organic phases were dried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-40f229d7bc18434c9908ccc830853080
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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