Boron tribromide → 3-(3-Amino-6-chloro-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-1-yl)phenol

HRID 1662220Notes

Reaction equation

HRID 1662220 reaction equation
B(Br)(Br)Br.[Cl:5][C:6]1[CH:14]=[C:13]2[C:9]([C:10]([NH2:33])=[N:11][C:12]2([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([O:31]C)[CH:26]=2)[C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[C:8]([F:34])[CH:7]=1>C(Cl)Cl>[NH2:33][C:10]1[C:9]2[C:13](=[CH:14][C:6]([Cl:5])=[CH:7][C:8]=2[F:34])[C:12]([C:25]2[CH:26]=[C:27]([OH:31])[CH:28]=[CH:29][CH:30]=2)([C:15]2[CH:20]=[CH:19][N:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[N:11]=1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 585795226-chloro-4-fluoro-1-(3-methoxyphenyl)-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine

Product 1

HCID 585794803-(3-Amino-6-chloro-4-fluoro-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-1-yl)phenolYield 24%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Boron tribromide (0.472 mL, 4.99 mmol) was added to a solution of 6-chloro-4-fluoro-1-(3-methoxyphenyl)-1-(2-(trifluoromethyl)pyridin-4-yl)-1H-isoindol-3-amine (870 mg, 2.00 mmol) in DCM (10 mL) at 0° C. under an argon atmosphere. The cooling bath was removed and the resulting mixture was stirred at rt for 45 min. The mixture was cooled to 0° C. and subsequently ice was added. The pH was adjusted to ˜8 with 4 M aq NaOH. The DCM was removed in vacuo and the resulting residue was extracted with EtOAc. The combined organics were dried over Na2SO4, concentrated and purified on a silica gel column eluted with 0-10% 0.1M NH3 in MeOH in DCM to afford 200 mg (24%) of the title compound.

Workup

  1. customThe cooling bath was removed
  2. temperatureThe mixture was cooled to 0° C.
  3. additionsubsequently ice was added
  4. customThe DCM was removed in vacuo
  5. extractionthe resulting residue was extracted with EtOAc
  6. dry with materialThe combined organics were dried over Na2SO4
  7. concentrationconcentrated
  8. custompurified on a silica gel column
  9. washeluted with 0-10% 0.1M NH3 in MeOH in DCM

Sources & evidence

ORD record
ord-b4e3b539b93b4640ab6b2d1106ba2ee5
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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