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

HRID 1171419ノート

反応式

HRID 1171419 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-806a58d08833408cab90a008f7713fa9
出典データセット
uspto-grants-2010_11
特許番号
US07829560B2

反応ノート

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