Ethyl Acetate → (+/-)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-(6-fluoro-pyridin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indole-7-carbonitrile

HRID 2427272Notes

Reaction equation

HRID 2427272 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH:12]1[CH2:25][C:15]2[NH:16][C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][C:22]=3[C:14]=2[CH2:13]1.Br[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>CN(C=O)C>[O:11]=[C:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:2](=[O:1])[N:3]1[CH:12]1[CH2:25][C:15]2[N:16]([CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([F:34])[N:29]=3)[C:17]3[CH:18]=[CH:19][C:20]([C:23]#[N:24])=[CH:21][C:22]=3[C:14]=2[CH2:13]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 139852182-(Bromomethyl)-6-fluoropyridineHCID 581494122-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-1,2,3,4-tetrahydrocyclopenta[b]indole-7-carbonitrile

Product 1

HCID 59242740(+/-)-2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-4-(6-fluoro-pyridin-2-ylmethyl)-1,2,3,4-tetrahydro-cyclopenta[b]indole-7-carbonitrileYield 88.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Dissolve (±)-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1,2,3,4-tetrahydro-cyclopenta[b]indole-7-carbonitrile (6.88 g, 21.0 mmol) and 2-bromomethyl-6-fluoro-pyridine (3.99 g, 21.0 mmol) in DMF (80 mL). Add cesium carbonate (7.51 g, 23.1 mmol, 1.10 equivalents) and stir the reaction mixture at room temperature under nitrogen for 48 h. Dilute the reaction with ethyl acetate, wash with water (3×), dry over anhydrous sodium sulfate, filter, and concentrate to obtain a semi-solid (8.10 g). Purify the crude product on a 120 g silica gel column eluting with 0 to 100% ethyl acetate/hexanes to obtain 6.7 g of a tan/brown solid. Suspend the product in ether (100 mL) at room temperature overnight. Filter the solid, rinse with ether, and dry under high vacuum to obtain the title compound as a tan solid (5.70 g, 62%). LCMS 437.1 (M+1).

Workup

  1. additionDilute
  2. washwash with water (3×)
  3. dry with materialdry over anhydrous sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate

Sources & evidence

ORD record
ord-78b001d6bc40448483b4b15b06168c20
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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