2-Amino-5-methylpyridine → 2-Methyl-N-(5-methylpyridin-2-yl)-7-(4-(methylsulfonyl)-phenoxy)-3-oxoisoindoline-5-carboxamide

HRID 1177357Notes

Reaction equation

HRID 1177357 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Al](Cl)(C)C.[CH3:13][N:14]1[C:22](=[O:23])[C:21]2[C:16](=[C:17]([O:28][C:29]3[CH:34]=[CH:33][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:31][CH:30]=3)[CH:18]=[C:19]([C:24](OC)=[O:25])[CH:20]=2)[CH2:15]1>ClCCCl.C(Cl)Cl>[CH3:13][N:14]1[C:22](=[O:23])[C:21]2[C:16](=[C:17]([O:28][C:29]3[CH:30]=[CH:31][C:32]([S:35]([CH3:38])(=[O:37])=[O:36])=[CH:33][CH:34]=3)[CH:18]=[C:19]([C:24]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)=[O:25])[CH:20]=2)[CH2:15]1

Participants

6

Reactant 3

HCID 153482-Amino-5-methylpyridineHCID 79147ChlorodimethylaluminumHCID 667555411h-Isoindole-5-carboxylic acid,2,3-dihydro-2-methyl-7-[4-(methylsulfonyl)phenoxy]-3-oxo-,methyl ester

Product 1

HCID 667555652-Methyl-N-(5-methylpyridin-2-yl)-7-(4-(methylsulfonyl)-phenoxy)-3-oxoisoindoline-5-carboxamideYield 85%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-methyl-2-aminopyridine (144 mg, 1.33 mmol) in DCE at 0° C. was added Al(CH3)2Cl drop-wise. The reaction was stirred at room temperature for 20 minutes followed by the addition of methyl 2-methyl-7-(4-(methylsulfonyl)phenoxy)-3-oxoisoindoline-5-carboxylate. After stirring the reaction at room temperature for 14 hours, it was diluted with CH2Cl2 and quench with potassium sodium tartrate tetrahydrate (20% w/w) (1 mL) slowly. The solution was washed with brine, dried over Na2SO4, and concentrated. The crude sample was introduced into a silica gel column and eluted with 5-10% MeOH/CHCl3 to provide the product (40 mg, 85% yield) as a white solid. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 2.33 (s, 3 H) 3.10 (s, 3 H) 3.19-3.33 (m, 3 H) 4.40 (s, 2 H) 7.19 (d, J=8.67 Hz, 2 H) 7.53-7.66 (m, 1 H) 7.82 (s, 1 H) 7.97 (d, J=8.67 Hz, 2 H) 8.10-8.17 (m, 1 H) 8.19 (s, 2 H) 8.81 (s, 1H); LC-MS (ESI)+ m/z=452.00 (M+H)+.

Workup

  1. stirringAfter stirring
  2. customthe reaction at room temperature for 14 hours
  3. customquench with potassium sodium tartrate tetrahydrate (20% w/w) (1 mL) slowly
  4. washThe solution was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. additionThe crude sample was introduced into a silica gel column
  8. washeluted with 5-10% MeOH/CHCl3

Sources & evidence

ORD record
ord-1f2aa664d0154d52a0140324e2ef3118
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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