Sodium hydride → HCID 59161209, compound

HRID 545555Notes

Reaction equation

HRID 545555 reaction equation
[H-].[Na+].[C:3]([C:5]1[CH:6]=[C:7]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]1[CH2:12][CH2:11][CH:10]([NH:18][C:19](=[O:23])[CH:20]([CH3:22])[CH3:21])[CH2:9][C:8]2=1)#[N:4].Cl.Cl[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=1>CN(C=O)C>[C:3]([C:5]1[CH:6]=[C:7]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:26][C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][N:28]=1)[C:13]1[CH2:12][CH2:11][CH:10]([NH:18][C:19](=[O:23])[CH:20]([CH3:21])[CH3:22])[CH2:9][C:8]2=1)#[N:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 57431662N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramideHCID 574316752-(Chloromethyl)-5-fluoropyridine hydrochloride

Product 1

HCID 59161209HCID 59161209, compoundYield 53.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Suspend sodium hydride (60% in oil, 80 mg, 1.99 mmol) in DMF (2 mL) and chill to 0° C. Add a solution of N-(6-cyano-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-isobutyramide (253 mg, 0.90 mmol) in DMF (2 mL) slowly via syringe, and allow to stir 30 min before warming to ambient temperature for 60 min. Add 2-chloromethyl-5-fluoro-pyridine hydrochloride salt (180 mg, 0.99 mmol) and stir the reaction for about 12 h. Quench the reaction with saturated aqueous ammonium chloride (5 mL). Add ethyl acetate (50 mL) and wash the solution with water (50 mL), then brine (2×50 mL). Separate the organic phase and dry over magnesium sulfate, filter, and evaporate under reduced pressure. Titurate the resulting residue with diethyl ether (10 mL) for 5 min and then filter to afford 187 mg (53%) of the title compound as a light yellow solid. mp 235-238° C. (dec); MS (ESI): m/z [391 C23H23FN4O+H]+; 1H NMR (300 MHz, CDCl3): δ 8.43s, 1H), 7.78 (s, 1H), 7.38-7.25 (m, 3H), 6.67 (dd, J=8.6, 4.2 Hz, 1H), 5.58 (d, J=7.8 Hz, 1H), 5.35 (s, 2H), 4.40 (br s, 1H), 3.14 (dd, J=15.4, 5.0 Hz, 1H), 2.79 (br s, 2H), 2.60 (dd, J=15.4, 7.6 Hz, 1H), 2.34 (pentet, J=6.8 Hz, 1H), 2.15 (br s, 1H), 2.02-1.95 (m, 1H), 1.16 (d, J=6.9 Hz, 6H).

Workup

  1. temperaturebefore warming to ambient temperature for 60 min
  2. customthe reaction for about 12 h
  3. customQuench
  4. customthe reaction with saturated aqueous ammonium chloride (5 mL)
  5. washAdd ethyl acetate (50 mL) and wash the solution with water (50 mL)
  6. customSeparate the organic phase
  7. dry with materialdry over magnesium sulfate
  8. filtrationfilter
  9. customevaporate under reduced pressure
  10. customfor 5 min
  11. filtrationfilter

Sources & evidence

ORD record
ord-312c49fe2a6d4fb6a7367f7c5b87a027
Source dataset
uspto-grants-2011_05
Patent number
US07935722B2

Reaction notes

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