Cesium carbonate → 7-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3H-isoindol-1-one

HRID 1045927Notes

Reaction equation

HRID 1045927 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](I)[C:5]([Cl:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]2[C:19]=1[C:18](=[O:20])[N:17]([CH3:21])[CH2:16]2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([NH:10][C:11]2[CH:12]=[CH:13][CH:14]=[C:15]3[C:19]=2[C:18](=[O:20])[N:17]([CH3:21])[CH2:16]3)[C:5]([Cl:9])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 450887127-Amino-2-methyl-2,3-dihydro-1H-isoindol-1-oneHCID 534009652,5-Dichloro-4-iodopyridine

Product 1

HCID 866551387-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3H-isoindol-1-oneYield 71.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,5-dichloro-4-iodopyridine (0.2 g, 0.73 mmol), 7-amino-2-methyl-3H-isoindol-1-one (0.118 g, 0.73 mmol), palladium(II) acetate (6.56 mg, 0.03 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.025 g, 0.04 mmol) and cesium carbonate (0.476 g, 1.46 mmol) were suspended in dioxane (5 mL). The mixture was heated at 100° C. for 30 minutes in a microwave reactor and then allowed to cool to room temperature. The mixture was loaded onto an SCX column and the product eluted first with MeOH and then with a 7M solution of NH3 in MeOH. Fractions containing product were combined and evaporated. A solid recovered from the top of the column was washed with water, dried in vacuo, and combined with the evaporated residue to afford 7-[(2,5-dichloropyridin-4-yl)amino]-2-methyl-3H-isoindol-1-one (0.160 g, 71% yield); 1H NMR spectrum: (300 MHz, DMSO) δ 3.07 (3H, s), 4.50 (2H, s), 7.25-7.28 (1H, m), 7.48 (1H, s), 7.56-7.63 (2H, m), 8.36 (1H, s), 9.80 (1H, s); Mass spectrum: m/z (ESI+) (M+H)+=308.01 and 309.97 and 311.99.

Workup

  1. temperatureto cool to room temperature
  2. washthe product eluted first with MeOH
  3. additionFractions containing product
  4. customevaporated
  5. customA solid recovered from the top of the column
  6. washwas washed with water
  7. customdried in vacuo

Sources & evidence

ORD record
ord-19c0e7c2969548c7ae577ac0b5213d53
Source dataset
uspto-grants-2013_10
Patent number
US08569298B2

Reaction notes

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