Hydrochloride methanol → 1-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amine

HRID 1662197Notes

Reaction equation

HRID 1662197 reaction equation
C([Li])(C)(C)C.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:19]=[C:20](/[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:22][CH:23]=1.Cl.CO>C1COCC1>[Br:17][C:18]1[CH:19]=[C:20]([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:22][CH:23]=1

Participants

6

Reactant 4

HCID 21893726Hydrochloride methanolHCID 58579486HCID 58579486, compoundHCID 593275316-Bromo-3-methoxy-2,4-dimethylpyridineHCID 178418306HCID 178418306, compound

Product 1

HCID 585795341-(3-Bromophenyl)-4-fluoro-1-(5-methoxy-4,6-dimethylpyridin-2-yl)-1H-isoindol-3-amineYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

tert-Butyllithium (1.040 mL, 1.77 mmol) was added dropwise to THF (5 mL) at −100° C. under an argon atmosphere. A solution of 6-bromo-3-methoxy-2,4-dimethylpyridine (191 mg, 0.88 mmol) in THF (3 ml) was added dropwise followed by the addition of (E)-N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (300 mg, 0.74 mmol) in THF (7 ml). The resulting reaction mixture was left on the thawing cooling bath for 30 min then the cooling bath was removed and the mixture was stirred at r.t. for 1 h. Hydrogen chloride-methanol solution (3.54 mL, 4.42 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. The mixture was concentrated under reduced pressure and the residue was purified on a silica gel column eluted with 0-10% 0.1 M NH3 in MeOH in DCM to give the title compound (272 mg, 84%). MS (ES+) m/z 440, 442 [M+1]+.

Workup

  1. customThe resulting reaction mixture
  2. waitwas left on the thawing
  3. temperaturecooling bath for 30 min
  4. customthe cooling bath was removed
  5. stirringthe resulting mixture was stirred at r.t. for 1 h
  6. concentrationThe mixture was concentrated under reduced pressure
  7. customthe residue was purified on a silica gel column
  8. washeluted with 0-10% 0.1 M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-be94451a988240a79721990a1fc634a4
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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