2-Imidazolidinone → 1-((1S)-1-{2-[(2R)-4-(6-Cyano-1-benzothien-3-yl)-2-methylpiperazinyl]ethyl}-3,4-dihydro-1H-2-benzopyran-6-yl)-2-imidazolidinone

HRID 2056774Notes

Reaction equation

HRID 2056774 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[C@H:10]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][N:16]([C:19]4[C:23]5[CH:24]=[CH:25][C:26]([C:28]#[N:29])=[CH:27][C:22]=5[S:21][CH:20]=4)[CH2:15][C@H:14]3[CH3:30])[O:9][CH2:8][CH2:7][C:6]=2[CH:31]=1.[NH:32]1[CH2:36][CH2:35][NH:34][C:33]1=[O:37].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.ClCCl.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:28]([C:26]1[CH:25]=[CH:24][C:23]2[C:19]([N:16]3[CH2:17][CH2:18][N:13]([CH2:12][CH2:11][C@H:10]4[C:5]5[CH:4]=[CH:3][C:2]([N:32]6[CH2:36][CH2:35][NH:34][C:33]6=[O:37])=[CH:31][C:6]=5[CH2:7][CH2:8][O:9]4)[C@H:14]([CH3:30])[CH2:15]3)=[CH:20][S:21][C:22]=2[CH:27]=1)#[N:29]

Participants

8

Reactant 4

HCID 84532-ImidazolidinoneHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 693073673-((3R)-4-{2-[(1S)-6-Bromo-3,4-dihydro-1H-2-benzopyran-1-yl]ethyl}-3-methylpiperazinyl)-1-benzothiophene-6-carbonitrile

Product 1

HCID 693078161-((1S)-1-{2-[(2R)-4-(6-Cyano-1-benzothien-3-yl)-2-methylpiperazinyl]ethyl}-3,4-dihydro-1H-2-benzopyran-6-yl)-2-imidazolidinone

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

3-((3R)-4-{2-[(1S)-6-Bromo-3,4-dihydro-1H-2-benzopyran-1-yl]ethyl}-3-methylpiperazinyl)-1-benzothiophene-6-carbonitrile (0.36 g, 0.73 mmol)was dissolved in dry toluene (15 mL) and degassed. 2-Imidazolidinone (0.071 g, 0.82 mmol), tris(dibenzylideneacetone)dipalladium (34 mg), (+/−)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (47 mg) and caesium carbonate (0.34 g, 1.05 mmol)were added and the mixture heated under reflux with stirring, under a nitrogen atmosphere, for 2 days. The reaction was cooled to room temperature, diluted with dichloromethane, filtered through celite and washed with water. The organic extracts were dried (MgSO4), filtered and evaporated in vacuo. Purification by LC-MS yielded the title compound as the free base. M+H=502.

Workup

  1. customdegassed
  2. temperaturethe mixture heated
  3. temperatureunder reflux
  4. filtrationfiltered through celite
  5. washwashed with water
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customPurification by LC-MS

Sources & evidence

ORD record
ord-08be77cba73f4cf48204bfe2c56ec191
Source dataset
uspto-grants-2008_02
Patent number
US07335660B2

Reaction notes

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