Tetrahydrofuran → 2-Amino-1,2,3,4-tetrahydrocyclopenta[b]indole-7-carbonitrile

HRID 2427257Notes

Reaction equation

HRID 2427257 reaction equation
C1COCC1.O=C1C2C(=CC=CC=2)C(=O)[N:8]1[CH:17]1[CH2:30][C:20]2[NH:21][C:22]3[CH:23]=[CH:24][C:25]([C:28]#[N:29])=[CH:26][C:27]=3[C:19]=2[CH2:18]1.O.NN>C(O)C>[NH2:8][CH:17]1[CH2:30][C:20]2[NH:21][C:22]3[CH:23]=[CH:24][C:25]([C:28]#[N:29])=[CH:26][C:27]=3[C:19]=2[CH2:18]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 24654Hydrazine hydrate (1:1)HCID 581494122-(1,3-Dioxo-1,3-dihydro-2H-isoindol-2-yl)-1,2,3,4-tetrahydrocyclopenta[b]indole-7-carbonitrile

Product 1

HCID 468355392-Amino-1,2,3,4-tetrahydrocyclopenta[b]indole-7-carbonitrile

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

In a three neck round bottomed flask, equipped with a mechanical stirrer, prepare a mixture of THF (3100 ml) and ethanol (550 ml). To this mixture add crude 2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-1,2,3,4-tetrahydro-cyclopenta[b]indole-7-carbonitrile (170 g, 0.52 mol) and stir for 15 min. Add hydrazine hydrate (90 ml, 1.9 mol) and stir the mixture at room temperature for 16 h. Check by LC/MS to confirm that no starting material remains. Filter the crude reaction in vacuo and wash the solid with THF (2×200 mL). Collect the mother liquors and remove the solvent under vacuum. Purify by silica gel filtration (1.5″ high, very wide SiO2 pad) using (2 M NH3/MeOH)/CH2Cl2 (3-10%). Collect the fractions containing product and remove the solvent. Add acetonitrile (180 ml) and reflux the mixture for 15 min and then cool to room temperature. Collect a brown solid by filtration and dry in vacuo overnight at 40° C. to give the racemic title compound, 55 g (60%). GC-MS: 198 (M+), 196 (M−);

Workup

  1. customIn a three neck round bottomed flask, equipped with a mechanical stirrer
  2. customprepare
  3. filtrationFilter the crude
  4. customreaction in vacuo
  5. washwash the solid with THF (2×200 mL)
  6. customCollect the mother liquors
  7. customremove the solvent under vacuum
  8. filtrationPurify by silica gel filtration (1.5″ high, very wide SiO2 pad)
  9. customCollect the fractions
  10. additioncontaining product
  11. customremove the solvent
  12. temperatureAdd acetonitrile (180 ml) and reflux the mixture for 15 min
  13. customCollect a brown solid
  14. filtrationby filtration
  15. customdry in vacuo overnight at 40° C.

Sources & evidence

ORD record
ord-4aa23e9c16af416b8552077fa7339335
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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