Toluene → HCID 178439704, compound

HRID 2266999Notes

Reaction equation

HRID 2266999 reaction equation
[C:1]([C:4]1[CH:26]=[CH:25][C:7]([O:8][CH2:9][C:10]2[CH:24]=[CH:23][C:13]([O:14][C:15]3[N:22]=[CH:21][CH:20]=[CH:19][C:16]=3[C:17]#[N:18])=[CH:12][CH:11]=2)=[C:6]([CH2:27][CH2:28][CH3:29])[C:5]=1[OH:30])(=[O:3])[CH3:2].Cl.C(N(CC)CC)C.[N-:39]=[N+:40]=[N-:41].[Na+].C1(C)C=CC=CC=1.[C:50](OCC)(=[O:52])[CH3:51]>>[C:50]([C:7]1([O:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:14][C:15]3[C:16]([C:17]4[NH:41][N:40]=[N:39][N:18]=4)=[CH:19][CH:20]=[CH:21][N:22]=3)=[CH:23][CH:24]=2)[CH:25]=[CH:26][C:4]([C:1](=[O:3])[CH3:2])=[C:5]([OH:30])[CH:6]1[CH2:27][CH2:28][CH3:29])(=[O:52])[CH3:51]

Participants

6

Reactant 5

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 59599533HCID 59599533, compound

Product 1

HCID 178439704HCID 178439704, compoundYield 40%

Conditions

Temperature
130 °C

Procedure

Mix 2-[4-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenoxy]-nicotinonitrile (0.16 g, 0.40 mmol), triethylamine hydrochloride (1.11 g, 8.05 mmol), sodium azide (0.52 g, 8.05 mmol) and toluene (6 mL) in a pressure vessel. Seal and heat to 130° C. for 6 hrs. Concentrate under reduced pressure to give a residue. Dilute with ethyl acetate (25 mL) and wash with 1N hydrochloric acid (3×50 mL). Dry over magnesium sulfate, filter, and concentrate to give a residue. Purification by flash chromatography, using 40:1 Chydrochloric acid3/methanol+1% acetic acid to 20:1 chloroformchloroform/methanol+1% acetic acid as a gradient eluent gives the title compound (0.07 g, 40%): MS (m/z): 444.1 (M−1). 1H NMR (DMSO-d6) 12.88 (s, 1H), 8.57 (d, J=7.4 Hz, 1H), 8.32 (d, J=5.0 Hz, 1H), 7.84 (d, J=9.2 Hz, 1H), 7.54 (d, J=8.2 Hz, 2H), 7.38 (dd, J=5.0 Hz, 7.4 Hz, 1H), 7.29 (d, J=8.2 Hz, 2H), 6.79 (d, J=9.2 Hz, 1H), 5.31 (s, 2H), 2.62 (t, J=7.4 Hz, 2H), 2.60 (s, 3H), 1.57-1.47 (m, 2H), 0.90 (t, J=7.4 Hz, 3H).

Workup

  1. customSeal
  2. concentrationConcentrate under reduced pressure
  3. customto give a residue
  4. washwash with 1N hydrochloric acid (3×50 mL)
  5. dry with materialDry over magnesium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-ee850b59fab84a4cbde5f89ea4d24c59
Source dataset
uspto-grants-2010_12
Patent number
US07858646B2

Reaction notes

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