Hydrochloric Acid → 1-(3-Bromophenyl)-1-(3-fluoropyridin-4-yl)-1H-isoindol-3-amine

HRID 2264734Notes

Reaction equation

HRID 2264734 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.[Br:20][C:21]1[CH:22]=[C:23]([C:27]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[C:41]#[N:42])=[N:28]S(C(C)(C)C)=O)[CH:24]=[CH:25][CH:26]=1.Cl>O1CCCC1.O>[Br:20][C:21]1[CH:22]=[C:23]([C:27]2([C:19]3[CH:18]=[CH:17][N:16]=[CH:15][C:14]=3[F:13])[C:35]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:41]([NH2:42])=[N:28]2)[CH:24]=[CH:25][CH:26]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 677943-FluoropyridineHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 595962811-(3-Bromophenyl)-1-(3-fluoropyridin-4-yl)-1H-isoindol-3-amineYield 64%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

To a −78° C. solution of diisopropylamine (0.77 mL, 5.50 mmol) in tetrahydrofuran (10 mL) was n-butyllithium (2.5 M in hexane, 2.20 mL, 5.50 mmol) added, the mixture was stirred 0.5 h and then a solution of 3-fluoropyridine (0.47 mL, 5.50 mmol) in tetrahydrofuran (2 mL) was added and after another 0.5 h N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (Scheme #5, N) (1.95 g, 5.0 mmol) in tetrahydrofuran (5 mL) was added. After 1.5 h at −78° C. water was added, the mixture was extracted with ethyl acetate, the organic phase was dried over magnesium sulfate and concentrated. The residue was dissolved in methanol (40 mL) and treated with hydrochloric acid (2 M in diethylether, 5 mL, 10.0 mmol) over night. After evaporation, the residue was partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and evaporated. Purification of the residue by column chromatography using a stepwise gradient of methanol in chloroform (0-10%) as the eluent gave the title compound (1.22 g, 64%). 1H NMR (CDCl3) δ 8.43 (d, J=2.78 Hz, 1 H), 8.35 (d, J=5.05 Hz, 1 H), 7.76 (d, J=8.08 Hz, 1 H), 7.60-7.50 (m, 3 H), 7.45-7.37 (m, 2 H), 7.37-7.33 (m, 1 H), 7.20-7.13 (m, 2 H), 5.37 (br s, 2 H); MS (AP) m/z 382, 384 [M+1]+.

Workup

  1. customTo a −78° C.
  2. additionadded
  3. additionwas added
  4. extractionthe mixture was extracted with ethyl acetate
  5. dry with materialthe organic phase was dried over magnesium sulfate
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in methanol (40 mL)
  8. customAfter evaporation
  9. customthe residue was partitioned between aqueous saturated sodium bicarbonate and chloroform
  10. dry with materialthe organic phase was dried over magnesium sulfate
  11. customevaporated
  12. customPurification of the residue by column chromatography

Sources & evidence

ORD record
ord-bcf62904e0d640428114bec23bfc6c3c
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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