HCID 46184153, compound → HCID 46183673, compound

HRID 2386910Notes

Reaction equation

HRID 2386910 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:19][CH2:20][NH:21][C:22]2[C:31]3[C:26](=[C:27]([F:33])[CH:28]=[CH:29][C:30]=3[F:32])[N:25]=[CH:24][N:23]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=1.[C:34]([Cu])#[N:35]>CN(C=O)C>[F:32][C:30]1[CH:29]=[CH:28][C:27]([F:33])=[C:26]2[C:31]=1[C:22]([NH:21][CH2:20][CH2:19][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[C:13]([C:15]([F:18])([F:17])[F:16])[CH:12]=[CH:11][N:10]=3)=[C:2]([CH:3]=1)[C:34]#[N:35])=[N:23][CH:24]=[N:25]2

Participants

4

Reactant 2

HCID 46184153HCID 46184153, compoundHCID 178418546HCID 178418546, compound2×

Product 1

HCID 46183673HCID 46183673, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of {2-[3-bromo-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-(5,8-difluoroquinazolin-4-yl)-amine) (137 mg, 0.26 mmol), CuCN (164 mg, 1.83 mmol) and DMF (10 mL) was heated at 126° for 3 h, then heated at reflux overnight. After addition of more CuCN (100 mg), the reaction was heated at reflux 2 h, then concentrated in vacuo. The residue was partitioned between water (10 mL) and EtOAc (10 mL). The aqueous layer was extracted with EtOAc (2×10 mL) and the pooled organic fractions were dried (Na2SO4), filtered through a silica gel/Celite plug and concentrated in vacuo to provide 5-[2-(5,8-difluoroquinazolin-4-ylamino)-ethyl]-2-(4-trifluoromethylpyridin-2-yloxy)-benzonitrile (70 mg) as an off-white powder (94% purity by LC), 57% yield, M.P. 157-159°. 1H NMR (CDCl3): δ 8.7 (bs, 1H), 8.29 (d, 1H), 7.62 (d, 1H), 7.57 (dd, 1H), 7.38 (m, 1H), 7.29 (s, 1H), 7.27 (s, 1H), 7.26 (m, 1H), 7.04 (m, 1H), 6.76 (bm, 1H), 3.96 (m, 2H), 3.10 (t, 2H). MS: m/z 471.

Workup

  1. temperaturewas heated at 126° for 3 h
  2. temperatureheated
  3. temperatureat reflux overnight
  4. temperaturethe reaction was heated
  5. temperatureat reflux 2 h
  6. concentrationconcentrated in vacuo
  7. customThe residue was partitioned between water (10 mL) and EtOAc (10 mL)
  8. extractionThe aqueous layer was extracted with EtOAc (2×10 mL)
  9. dry with materialthe pooled organic fractions were dried (Na2SO4)
  10. filtrationfiltered through a silica gel/Celite plug
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-96b421c058b54833aa2e04014c4876a3
Source dataset
uspto-grants-2012_09
Patent number
US08268843B2

Reaction notes

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