4-Iodopyridine → 1-(3-Bromophenyl)-1-pyridin-4-yl-1H-isoindol-3-amine

HRID 2264727Notes

Reaction equation

HRID 2264727 reaction equation
C([Li])(C)(C)C.I[C:7]1[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=1.[Br:13][C:14]1[CH:15]=[C:16]([C:20]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]#[N:35])=[N:21]S(C(C)(C)C)=O)[CH:17]=[CH:18][CH:19]=1>O1CCCC1>[Br:13][C:14]1[CH:15]=[C:16]([C:20]2([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=3)[C:28]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:34]([NH2:35])=[N:21]2)[CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 3

HCID 6094924-IodopyridineHCID 72335434N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamideHCID 178418306HCID 178418306, compound

Product 1

HCID 595962471-(3-Bromophenyl)-1-pyridin-4-yl-1H-isoindol-3-amineYield 61%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of tert-butyllithium (1.7 M in pentane, 3.5 mL, 6.0 mmol) in tetrahydrofuran (20 mL) at −105° C. was a solution of 4-iodopyridine (0.68 g, 3.3 mmol) in tetrahydrofuran (10 mL) added drop wise. Next was a solution of N-[(3-bromophenyl)(2-cyanophenyl)methylene]-2-methylpropane-2-sulfinamide (1.2 g, 3.0 mmol) in tetrahydrofuran (10 mL) added. After 1 h at −105° C. was the reaction quenched by addition of water. The resulting mixture was partitioned between ethyl acetate and water, the organic phase was dried over magnesium sulfate and evaporated. The residue was dissolved in methanol (25 mL) and treated with hydrochloric acid (2 M in diethylether, 3.0 mL, 6.0 mml) over night. The reaction mixture was concentrated and then partitioned between aqueous saturated sodium bicarbonate and chloroform, the organic phase was dried over magnesium sulfate and concentrated. Purification by column chromatography using a stepwise gradient of methanol in ethyl acetate (5-10%) with 1% triethylamine afforded the title compound (0.66 g, 61%). 1H NMR (CDCl3) δ 8.56-8.48 (m, 2 H), 7.60-7.38 (m, 6 H), 7.27-7.21 (m, 3 H), 7.21-7.14 (m, 1 H), 5.16 (br s, 2 H); MS (AP) m/z 364, 366 [M+1]+.

Workup

  1. customat −105° C.
  2. additionadded drop wise
  3. additionadded
  4. customthe reaction quenched by addition of water
  5. customThe resulting mixture was partitioned between ethyl acetate and water
  6. dry with materialthe organic phase was dried over magnesium sulfate
  7. customevaporated
  8. dissolutionThe residue was dissolved in methanol (25 mL)
  9. additiontreated with hydrochloric acid (2 M in diethylether, 3.0 mL, 6.0 mml) over night
  10. concentrationThe reaction mixture was concentrated
  11. custompartitioned between aqueous saturated sodium bicarbonate and chloroform
  12. dry with materialthe organic phase was dried over magnesium sulfate
  13. concentrationconcentrated
  14. customPurification by column chromatography

Sources & evidence

ORD record
ord-84cade0650fa4cccae259058a42f5ca4
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

Loading…