Ethyl Acetate → 4'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amide

HRID 1641250Notes

Reaction equation

HRID 1641250 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][CH:29]=1)[C:5]([NH:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([O:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:10][CH:9]=1)=[O:6].[F:30][C:31]1[CH:36]=[CH:35][C:34](B(O)O)=[C:33]([CH3:40])[CH:32]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(OCC)(=O)C>O1CCOCC1>[N:21]1([CH2:20][CH2:19][O:18][C:11]2[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:8]([NH:7][C:5]([C:4]3[CH:3]=[C:2]([C:34]4[CH:35]=[CH:36][C:31]([F:30])=[CH:32][C:33]=4[CH3:40])[CH:29]=[CH:28][CH:27]=3)=[O:6])=[CH:9][CH:10]=2)[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 2734665(4-Fluoro-2-methylphenyl)boronic acidHCID 595531183-bromo-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide

Product 1

HCID 595532284'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amideYield 69.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

3-Bromo-N-[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-benzamide (600 mg, 1.31 mmol), 4-fluoro-2-methylphenyl boronic acid (271 mg, 1.98 mmol), cesium carbonate (730 mg, 2.24 mmol) and tetrakis triphenylphosphine palladium(0) (25 mg) in dioxane (10 ml) are heated to 100° C. under a nitrogen atmosphere for 16 hours. The mixture is cooled to room temperature then poured into ethyl acetate (100 ml). The organic layer is washed with water (100 ml), dried over anhydrous sodium sulfate and evaporated to dryness. The residue is then purified by column chromatography on silica gel to give 4′-fluoro-2′-methyl-biphenyl-3-carboxylic acid[4-(2-morpholin-4-yl-ethoxy)-naphthalen-1-yl]-amide as pale purple needles (0.44 g). Mp: 95-7° C. 1H NMR 300 MHz (CDCl3) δ 8.35(d, 1H, J=7.5 Hz), 7.85-8.1(m, 5H), 7.75(d, 1H, J=7.5 Hz), 7.5-7.63(m, 4H), 7.2(m, 1H), 6.9-7.05(m, 2H), 6.85(d, 1H, J=12 Hz), 4.3(t, 2H), 3.75(m, 4H), 2.98(t, 2H), 2.6(m, 4H), 2.3(s, 3H).

Workup

  1. washThe organic layer is washed with water (100 ml)
  2. dry with materialdried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is then purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-3d0b9344922844fc8eae75af045432e2
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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