Dimethylformamide → HCID 67023339, compound

HRID 63482Notes

Reaction equation

HRID 63482 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH:12]1[CH2:17][CH2:16][C:15](=[O:18])[NH:14][C:13]1=[O:19])[CH2:5]2.[CH3:20][N:21](C=O)C>C1(P([C-]2C=CC=C2)C2C=CC=CC=2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N>[O:19]=[C:13]1[CH:12]([N:6]2[CH2:5][C:4]3[C:8](=[CH:9][CH:10]=[C:2]([C:20]#[N:21])[CH:3]=3)[C:7]2=[O:11])[CH2:17][CH2:16][C:15](=[O:18])[NH:14]1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 690490113-(5-Bromo-1-oxoisoindolin-2-yl)piperidine-2,6-dione

Product 1

HCID 67023339HCID 67023339, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst2×HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)Catalyst2×HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×

Conditions

Temperature
120 °C

Procedure

A mechanically stirred mixture of 3-(5-bromo-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione (25.2 g, 78 mmol), bis(diphenylphosphino)ferrocene (2.0 g), tris(dibenzylideneacetone)dipalladium (2.0 g) and zinc cyanide (9.4 g, 80 mmol) in DMF (300 mL) was heated to 120° C. and stirred at this temperature for 19 hours. The reaction mixture was cooled to 40° C., and another 9.4 g of zinc cyanide, 2 g of bis(diphenylphosphino)ferrocene and 2 g of tris(dibenzylideneacetone)dipalladium were added. The mixture was stirred at 120° C. for 2 hours, cooled to room temperature and quenched with water (900 mL). The solid was filtered, washed with additional water and air dried overnight. The solid was stirred in hot acetic acid (200 mL) for 20 minutes. The solid was filtered, washed with additional acetic acid, ethyl acetate and hexanes, and air dried to give 30.8 g of crude 2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindole-5-carbonitrile as a gray solid; 1H NMR (DMSO-d6) δ 1.99-2.06 (m, 1H), 2.35-2.45 (m, 1H), 2.57-2.63 (m, 1H), 2.86-2.98 (m, 1H), 4.42 (d, J=17.7 Hz, 1H), 4.55 (d, J=17.7 Hz, 1H), 5.15 (dd, J=13.2 Hz, J=5.1 Hz, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.99 (dd, J=7.8 Hz, J=0.9 Hz, 1H), 8.16 (s, 1H), 11.03 (s, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to 40° C.
  2. stirringThe mixture was stirred at 120° C. for 2 hours
  3. temperaturecooled to room temperature
  4. customquenched with water (900 mL)
  5. filtrationThe solid was filtered
  6. washwashed with additional water and air
  7. customdried overnight
  8. stirringThe solid was stirred in hot acetic acid (200 mL) for 20 minutes
  9. filtrationThe solid was filtered
  10. washwashed with additional acetic acid, ethyl acetate and hexanes, and air
  11. customdried

Sources & evidence

ORD record
ord-4027989c0fc247c582c72d8be3f28576
Source dataset
uspto-grants-2016_09
Patent number
US09447070B2

Reaction notes

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