Acetic Acid → HCID 49836386, compound

HRID 1825723Notes

Reaction equation

HRID 1825723 reaction equation
C([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]#[N:18])=[CH:14][CH:15]=2)[C:10]([C@H:19]2[CH2:23][CH2:22][C@@H:21]([N:24]([CH2:26]C3C=CC=CC=3)[CH3:25])[CH2:20]2)=[CH:9]1)(OC(C)(C)C)=O.C=O.C(O)(=O)C>[Pd].C(Cl)Cl.CO>[CH3:25][N:24]([CH3:26])[C@@H:21]1[CH2:22][CH2:23][C@H:19]([C:10]2[C:11]3[C:16](=[CH:15][CH:14]=[C:13]([C:17]#[N:18])[CH:12]=3)[NH:8][CH:9]=2)[CH2:20]1

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 712FormaldehydeHCID 49836270HCID 49836270, compound

Product 1

HCID 49836386HCID 49836386, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A mixture of cis-1-BOC-3-[3-(N-benzyl-N-methylamino)-cyclopentyl]-1H-indole-5-carbonitrile (500 mg, 1.2 mMol), 10% palladium on carbon (200 mg), formaldehyde (1.2 mL of 30% aqueous, 12 mMol), and acetic acid (0.1 mL) in methylene chloride (10 mL) and methanol (20 mL) was stirred under hydrogen (balloon pressure) for 4 h. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was dissolved in methylene chloride (10 mL) and trifluoroacetic acid (3 mL) and stirred for 18 h. The solution was concentrated in vacuo, and the residue was dissolved in ethyl acetate. The ethyl acetate solution was washed with aqueous NaHCO3, and then brine, and dried over magnesium sulfate. The solution was concentrated to give the crude product which was purified by preparative HPLC to give cis-3-(3-dimethylaminocyclopentyl)-1H-indole-5-carbonitrile (120 mg, 40%).

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was dissolved in methylene chloride (10 mL)
  4. stirringtrifluoroacetic acid (3 mL) and stirred for 18 h
  5. concentrationThe solution was concentrated in vacuo
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washThe ethyl acetate solution was washed with aqueous NaHCO3
  8. dry with materialbrine, and dried over magnesium sulfate
  9. concentrationThe solution was concentrated
  10. customto give the crude product which
  11. customwas purified by preparative HPLC

Sources & evidence

ORD record
ord-89a9ae03613045738035fe4a18f197ad
Source dataset
uspto-grants-2006_05
Patent number
US07049314B2

Reaction notes

Loading…