Sodium hydride → HCID 58382965, compound

HRID 1506722Notes

Reaction equation

HRID 1506722 reaction equation
[CH2:1]([N:3]([CH2:25][CH3:26])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:19][CH3:20])[CH:16]=3)[NH:11][C:10]=2[C:9]2[CH:21]=[CH:22][CH:23]=[CH:24][C:8]=2[S:7]1)=[O:5])[CH3:2].S(C1C=CC(C)=CC=1)(O[CH2:31][CH2:32][F:33])(=O)=O.[H-].[Na+]>CN(C=O)C>[CH2:25]([N:3]([CH2:1][CH3:2])[C:4]([CH:6]1[C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([O:19][CH3:20])[CH:16]=3)[N:11]([CH2:31][CH2:32][F:33])[C:10]=2[C:9]2[CH:21]=[CH:22][CH:23]=[CH:24][C:8]=2[S:7]1)=[O:5])[CH3:26]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2560192-Fluoroethyl p-ToluenesulfonateHCID 58382955HCID 58382955, compound

Product 1

HCID 58382965HCID 58382965, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (+−)-8-methoxy-6,11-dihydro-5-thia-11-aza-benzo[a]fluorene-6-carboxylic acid diethyl amide (51) (150 mg, 0.41 mmol; prepared according to Example 17(b)) in anhydrous DMF (4 ml) was added 2-fluoroethyl tosylate (166 mg, 0.82 mmol), prepared as described in L. Cronin et al (J. Org. Chem. 2004; 69: 5934-5946) followed by sodium hydride 60% dispersion in mineral oil (34 mg, 0.82 mmol) under nitrogen. The reaction mixture was heated at 80° C. for 1 h. After cooling, the solvents were removed in vacuo, the residue quenched with water (30 ml), extracted with DCM (2×30 ml), dried (MgSO4) and solvents removed in vacuo. The residue was purified by column chromatography on silica, eluting with 5-10% EtOAc/CH2Cl2. The crude solid was quenched with ether/pet. spirit, filtered, dried in vacuo (45° C.) to give the title compound (non-radioactive tetracyclic indole imaging agent) (77 mg, 46%) as a pale brown solid. The structure was confirmed by 1H NMR (300 MHz, CDCl3) δ 1.12 (t, J=7.0 Hz, 3H), 1.36 (t, J=7.0 Hz, 3H), 3.25-3.70 (m, 4H), 3.83 (s, 3H), 4.45-4.70 (m, 2H), 4.80 (t, J=5.2 Hz, 1H), 4.96 (t, J=5.2 Hz, 1H), 5.09 (s, 1H), 6.84-6.93 (m, 2H), 7.13-7.32 (m, 3H), 7.46 (m, 1H), 7.58 (d, J=8.0 Hz, 1H).

Workup

  1. customprepared
  2. temperatureAfter cooling
  3. customthe solvents were removed in vacuo
  4. customthe residue quenched with water (30 ml)
  5. extractionextracted with DCM (2×30 ml)
  6. dry with materialdried (MgSO4) and solvents
  7. customremoved in vacuo
  8. customThe residue was purified by column chromatography on silica
  9. washeluting with 5-10% EtOAc/CH2Cl2
  10. customThe crude solid was quenched with ether/pet
  11. filtrationspirit, filtered
  12. customdried in vacuo (45° C.)

Sources & evidence

ORD record
ord-36115d26da09498d86b3ecfc30623983
Source dataset
uspto-grants-2015_12
Patent number
US09220795B2

Reaction notes

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