4-Bromo-1-fluoro-2-methoxybenzene → 1-(3-Bromophenyl)-4-fluoro-1-(4-fluoro-3-methoxyphenyl)-1H-isoindol-3-amine

HRID 1662203Notes

Reaction equation

HRID 1662203 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([F:13])=[C:9]([O:14][CH3:15])[CH:8]=1.[Br:16][C:17]1[CH:18]=[C:19](/[C:23](/[C:31]2[CH:36]=[CH:35][CH:34]=[C:33]([F:37])[C:32]=2[C:38]#[N:39])=[N:24]\S(C(C)(C)C)=O)[CH:20]=[CH:21][CH:22]=1.Cl.CO>C1COCC1>[Br:16][C:17]1[CH:18]=[C:19]([C:23]2([C:7]3[CH:12]=[CH:11][C:10]([F:13])=[C:9]([O:14][CH3:15])[CH:8]=3)[C:31]3[C:32](=[C:33]([F:37])[CH:34]=[CH:35][CH:36]=3)[C:38]([NH2:39])=[N:24]2)[CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 4

HCID 136049094-Bromo-1-fluoro-2-methoxybenzeneHCID 21893726Hydrochloride methanolHCID 58579486HCID 58579486, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 585795211-(3-Bromophenyl)-4-fluoro-1-(4-fluoro-3-methoxyphenyl)-1H-isoindol-3-amineYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

tert-Butyllithium (3.68 mL, 5.89 mmol) was added dropwise to THF (10 mL) at −100° C. under an argon atmosphere. A solution of 4-bromo-1-fluoro-2-methoxybenzene (0.604 g, 2.95 mmol) in THF (5 ml) was added dropwise followed by the addition of (E)-N-((3-bromophenyl)(2-cyano-3-fluorophenyl)methylene)-2-methylpropane-2-sulfinamide (1 g, 2.46 mmol) in THF (5 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 (11.78 mL, 14.73 mmol) was added and the resulting mixture was stirred at r.t. for 1 h. The mixture was concentrated and purified on a silica gel column eluting with 0-10% 0.1 M NH3 in MeOH in DCM to afford 0.98 g (93%) of the title compound. MS (ES+) m/z 429, 431 (M+H)+

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
  7. custompurified on a silica gel column
  8. washeluting with 0-10% 0.1 M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-f4a0b6a3fdb148d38ad3afc533dcbb22
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

Loading…