Diisopropylethylamine → 4'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amide

HRID 1171419Notes

Reaction equation

HRID 1171419 reaction equation
[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH2:20])=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=2)[C:31](O)=[O:32])=[C:24]([CH3:37])[CH:23]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C)C=O.C(OCC)(=O)C>[CH3:1][S:2][C:3]1[N:8]=[C:7]([O:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([NH:20][C:31]([C:30]3[CH:29]=[C:28]([C:25]4[CH:26]=[CH:27][C:22]([F:21])=[CH:23][C:24]=4[CH3:37])[CH:36]=[CH:35][CH:34]=3)=[O:32])=[CH:12][CH:11]=2)[CH:6]=[CH:5][N:4]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 549122783-(4-Fluoro-2-methylphenyl)benzoic acidHCID 595533854-(2-Methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-ylamine

Product 1

HCID 595531874'-Fluoro-2'-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amideYield 13.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

4-(2-Methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-ylamine (320 mg, 1 mmol), 3-(4-fluoro-2-methylphenyl)benzoic acid (230 mg, 1.0 mmol), HBTU (569 mg, 1.5 mmol) and diisopropylethylamine (0.53 ml, 3.0 mmol) are stirred at room temperature in anhydrous dimethylformamide (5 ml) for 1 day. The mixture is then poured into ethyl acetate (100 ml) and washed with water (100 ml). The organic layer is then dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with 20-30-40% ethyl acetate in hexanes to give product as a pink solid recrystallized from ethyl acetate/hexanes to give 4′-fluoro-2′-methyl-biphenyl-3-carboxylic acid [4-(2-methylsulfanylpyrimidin-4-yloxy)-naphthalen-1-yl]-amide as pink crystals (67 mg). 1H NMR 400 MHz (CDCl3) 8.30 (d, 1H, J=6 Hz), 8.14 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.86-7.92 (m, 4H), 7.44-7.56 (m, 4H), 7.28 (d, 1H, J=8.4), 7.18 (m, 1H), 6.9-6.97 (m, 2H), 6.46 (d, 1H, J=5.6 Hz), 2.23 (d, 6H).

Workup

  1. washwashed with water (100 ml)
  2. dry with materialThe organic layer is then dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is purified by column chromatography on silica gel
  5. washeluted with 20-30-40% ethyl acetate in hexanes
  6. customto give product as a pink solid
  7. customrecrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-806a58d08833408cab90a008f7713fa9
Source dataset
uspto-grants-2010_11
Patent number
US07829560B2

Reaction notes

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