Triethylamine hydrochloride → HCID 58905361, compound

HRID 1293228Notes

Reaction equation

HRID 1293228 reaction equation
[C:1]([C:3]1[CH:27]=[CH:26][C:6]([CH2:7][NH:8][C:9](=[O:25])[C:10]2[CH:15]=[C:14]([F:16])[CH:13]=[N:12][C:11]=2[O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[CH:5][CH:4]=1)#[N:2].[N-:28]=[N+:29]=[N-:30].[Na+].Cl.C(N(CC)CC)C>CN1CCCC1=O.ClCCl>[F:16][C:14]1[CH:13]=[N:12][C:11]([O:17][C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)=[C:10]([CH:15]=1)[C:9]([NH:8][CH2:7][C:6]1[CH:5]=[CH:4][C:3]([C:1]2[N:28]=[N:29][NH:30][N:2]=2)=[CH:27][CH:26]=1)=[O:25]

Participants

6

Reactant 3

HCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 57572340HCID 57572340, compound

Product 1

HCID 58905361HCID 58905361, compoundYield 51%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of N-(4-cyanobenzyl)-5-fluoro-2-(4-fluorophenoxy)nicotinamide (step 1, 220 mg, 0.60 mmol) in 1-methyl-pyrrolidin-2-one (5 mL) were added sodium azide (117 mg, 1.8 mmol) and triethylamine hydrochloride (248 mg, 1.8 mmol) at room temperature. This mixture was heated at 150° C. for 18 h. The reaction mixture was diluted with dichloromethane (100 mL), and the solution was washed with saturated sodium dihydrogenphosphate solution (50 mL). The organic phase was dried (sodium sulfate) and concentrated. The residue was purified by flash column chromatography on silica gel (50 g) eluting with dichloromethane/methanol/acetic acid (100/5/0.5) to give off white solids. The solids were triturated with ethyl acetate to afford 125 mg (50%) of the title compound as white solids: 1H-NMR (DMSO-d6) δ 9.18 (1H, t, J=5.8 Hz), 8.14 (1H, d, J=2.8 Hz), 7.99 (1H, dd, J=8.2, 2.8 Hz), 7.90 (2H, d, J=8.2 Hz), 7.51 (2H, d, J=8.2 Hz), 7.22–7.15 (4H, m), 4.56 (2H, d, J=5.8 Hz); MS (ESI) m/z 409 (M+H)+, 407 (M−H)−.

Workup

  1. washthe solution was washed with saturated sodium dihydrogenphosphate solution (50 mL)
  2. dry with materialThe organic phase was dried (sodium sulfate)
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography on silica gel (50 g)
  5. washeluting with dichloromethane/methanol/acetic acid (100/5/0.5)
  6. customto give off white solids
  7. customThe solids were triturated with ethyl acetate

Sources & evidence

ORD record
ord-6e8906b487b94839a7e261ca45ece202
Source dataset
uspto-grants-2007_07
Patent number
US07238714B2

Reaction notes

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