HCID 46183920, compound → HCID 59222966, compound

HRID 1467410Notes

Reaction equation

HRID 1467410 reaction equation
[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[CH:25][N:24]=3)=[C:18]([CH:33]=[CH2:34])[CH:17]=1)=[N:5][CH:6]=[N:7]2>[Pd].C(OCC)(=O)C>[F:1][C:2]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:3]=1[C:4]([NH:13][CH2:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:26]=[CH:25][N:24]=3)=[C:18]([CH2:33][CH3:34])[CH:17]=1)=[N:5][CH:6]=[N:7]2

Participants

4

Reactant 1

HCID 46183920HCID 46183920, compound

Product 1

HCID 59222966HCID 59222966, compoundYield 30.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

(5,8-Difluoroquinazolin-4-yl)-{2-[4-(4-trifluoromethyl-pyridin-2-yloxy)-3-vinylphenyl]-ethyl}-amine (250 mg), 10% Pd—C (100 mg) and ethyl acetate (10 mL) were added to a 230 mL Corning shaker bottle filled with nitrogen gas. The bottle was evacuated, then charged with hydrogen (55 psi starting pressure) and shaken overnight. The reaction mixture was filtered through Celite, and concentrated in vacuo. The residue was purified by reverse phase chromatography (C-18 solid phase with acetonitrile/water eluent, 0.5% H3PO4) to provide (5,8-difluoroquinazolin-4-yl)-{2-[3-ethyl-4-(4-trifluoromethylpyridin-2-yloxy)-phenyl]-ethyl}-amine as a white powder (77 mg), M.P. 121-122°. 1H NMR (CDCl3): δ 8.69 (s, 1H), 8.31 (d, 1H), 7.36 (m, 1H), 7.22 (m, 1H), 7.17 (m, 2H), 7.13 (s, 1H), 7.00 (m, 2H), 6.76 (bm, 1H), 3.95 (m, 2H), 3.04 (t, 2H), 2.55 (q, 2H), 1.16 (t, 3H). MS: m/z 474.

Workup

  1. additionfilled with nitrogen gas
  2. customThe bottle was evacuated
  3. additioncharged with hydrogen (55 psi starting pressure)
  4. filtrationThe reaction mixture was filtered through Celite
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by reverse phase chromatography (C-18 solid phase with acetonitrile/water eluent, 0.5% H3PO4)

Sources & evidence

ORD record
ord-a9798abbb795491c8276cd695a36e634
Source dataset
uspto-grants-2015_04
Patent number
US09000162B2

Reaction notes

Loading…